Wednesday, November 12, 2008
Glut corticoids - best we have
-control the inflammation process. Inhaled glucocorticoids have very mild adverse effects. Very well tolerated. Sometimes there’s some hoarseness but that resolves over time. Kids may have stunted growth but they catch up.
For pts with severe asthma, oral prednisone may be used for less than two weeks. But over extended period of time, we worry aobut systemic issues. We can review the side effects. The systemic side effects are the stress response primarily. That’s pretty much it. So glucocorticoids are a drug of first choice for control of asthma. There are some combinatino products, that purple discuss Advair. Two drugs. One is a long acting albuterol and the other is a glucocorticoid. Other drugs like Pulmicort is an inhaled glucocorticoid and can be used for long periods of time.
Mast Cell Stabalizers.
-Chromalin Sodium.
Mast cells are filled with granules, leukotryines and stabilizes the mast cell membrane so they don’t burst so easily in response to allergens. Used in peds and pts with exercise induced asthma. Virtually no side effects, a really nice controller. This is inhaled as well.
Leukotryine antagonists.
-also increasingly used for pts with allergy. Ltos of pts with allergy who are on leukotryine antagonists who have no asthma coupon? Growing use of this type of drug. Antileukotryines. Anti inflammatory mediators. If we block the receptors we block the leukotryines. Helps reduce the Eosinophils which infiltrate into the bronchi and cause swelling. Leukotryine inhibitors block all of that. All of these cells that come in and fix the situation actually make it worse. Fairly new in the late 1990s. One issue we should be aware of is the potential for liver injury. Pretty rare, but the risk is there.
Questions about rescuers, controllers, asthma, or respiratory drugs at all?
The next several lectures will seem to be disorganized, but it is for a reason. The book is arranged in a funky way. What She’s trying to do is separate the drugs that act on blood vessels as vasocontrisctors or vasodialators. Catagories of new drugs work on the heart as separate mechanisms and separate things. Some thigns will be repeating. Work both on blood vessels and the heart. Is a pretty complicated process managing blood fialure? And all that. Bear with me, by the Monday Dec 1st, we’ll have put the whole big picture together.
A couple of things on the blood vessels worksheet. Components of the vascular system are arteries, arterioles capillaries, veins and venules. Muscular, contract and dilate. So there is the center of where resistance will change. On the other hand, the veins and venules will not constrict so much they have a great stretch capacity. Where blood is pooled. Majority of blood is in the venous system. If I have a very wide tube, is fluid going to flow though it nicely or is it going to be kind of stuck? Great big vein, blood will go through very nicely. Nice good blood flow.
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Homework
1. What are the major components of the vascular system?
The vascular system is made up of the vessels that carry our blood. Arteries carry oxygen-rich blood away from the heart. Veins carry oxygen-poor blood back to your heart. There is one exception to that statement; when the blood starts its vascular system trip at the right side of the heart,
How do the following variables affect blood flow
a. diameter of the vessel
Vaso dilation: decreases resistance. So many of the vaso dialtors we talk about are used for HTN.
b. pressure gradient
c. vessel resistance
d. distrubution of pressure in the blood vessel:
Tissue necrosis is something you need to keep an eye out ofor. Epi, if IV comes out of vein and gets into the tissue you can get tissue necrosis. So another adverse effect of Epinephrine is crisis, constiction of arteries and we want to incrase BP we can increase it allot, way over what we want. This hypertensive state can actually cause cerebral hemmorhage. Pts who get this drug need continous CV monitoring. Its not to be given nonchalantly without monitoring BP, hear rate.
e. venous return.
3. Formula for regulation of blood pressur eis AP
What role the autonomic nervous system play in the blood pressure regulation
4. Review the nervous sytem worksheet and descrie what happens when each of the folliwng receptor types are stimulated
a. Alpha 1 If alpha one binds to the beta 1 receptors they constrict. So you will see epinephrine used in dental procedures in combination with a local anesthetic. They dilver the anesthetic to a certain spot and constrict the vessels around that spot to keep it right there. It constricts those vessels and prevents movement of tipopcal anesthesia.
Alpha one effect: Controls superficial bleeding. Put epinephrine to stop bleeding wounds.
Alpha one effect: helps treat anaphalyxis: a huge drop in BP, so by constircing the blood vessels, you push more blood to heart and increase the bp
Alpha one effect: nasal congestion. They are vaso constrictors in the nose and if they constrict, they use congestion. Not used as nasal decongestant. Epinephrine can be given in a viariaty of forms. Given topically, IV, IM, Sub Q, down the ET tube in codes in the delivery room. Can be inhaled. IN the nicu when we extibate babies and they have lots of stridor and constriciton, we give inhaled epi nebulized and it helps to constrict and reduces the constriction in their bronchi. But that’s actually a beta 2 effect.
Dopamine High doses: And then at high concentraitons: 18 to 20ish, dilation of renal vasculator in repsonse ot dopamine sitmulation, Beta 1 stimulation, and Alpha 1 stimulation. Peripheral vasoconstriction. High doses used in pts with shock and dramatically critical pts with awful cardiac output. Sick pts.
One common vaso constictor for all of them is Alpha 1, so blocking the alpha 1 receptors would cause vasodilation, and so it does. So our first vasodilator is an alpha blocker called Minpress or Vasowon?
b. Aphla 2
c. Beta 1Giving EPI can jump starrt the heart. A beta 1 affect. Hyperstimulation causes increased HR, dysrhythmias, and if there is narrowing of the coronary artery, then the increased work of the heart can cause aingina.
Dopamine High doses: And then at high concentraitons: 18 to 20ish, dilation of renal vasculator in repsonse ot dopamine sitmulation, Beta 1 stimulation, and Alpha 1 stimulation. Peripheral vasoconstriction. High doses used in pts with shock and dramatically critical pts with awful cardiac output. Sick pts.
d. Beta 2. Can be inhaled. IN the nicu when we extibate babies and they have lots of stridor and constriciton, we give inhaled epi nebulized and it helps to constrict and reduces the constriction in their bronchi. But that’s actually a beta 2 effect.
Hypoglycemia: beta 2 receptors in the liver. Breaking glygogen down, glycogenolysis, so we can creat glucose. So pts with DM, we want to monitor very carefully their glucose levels if they are on this drug. Everyone is thinking about arteries, hearts and lungs, but often we forget aobut monitoring the liver. Important for pts who are getting a lot of Epi. A while algo a baby was coded, and teacher was the nurse. She teasted the glucose and the baby’s glucose was 350, so lots of epi with ltos of stress caused huge glucose. Least of baby’s problems, but it had to be dealt with.
5. What is the result of domaine receptor activation?
Increase peripheral resistance which means I can constrict a tube or I could increase my cardiac output. How do I increase my cardiac output? I increase my heart rate, or the strength of the stroke of my heart. Increase contractility and squeeze more out with each contraction.
Changes in peripheral resistance: constriction and changes in diameter of the blood vessels.
Vaso constrictors and a couple of vasodialators.
Epinephrine and Domapmine: Ones you should HIGHLIGHT.
Remember the receptors times 2, are all of them. Alpha one alpha two beta one and beta two.
Drug interactions:
MAO inhibitors
Breaks down catecholamines to their inactive metabolites. So epinephrine, nor epinephrine, Dopamine. Monoaminone oxidase breaks down their catecoholamines. If you do this, the level of Epi goes UP. SO if MAO is given, much higher risk of seeing those adverse affects of Hypertension, tissue necrosisi, angina, dysrhytmias.
Need for FINAL
Trycyclic reactors Promote uptake of seratonin and catecolamines. This reuptake is a way to get rid of it in the synaptic cleft. So it’s the same effect as an Mao inhibitor. You have too much. And suppose you have a pt taking a beta blocker used for hypertension. What if a pt is on a beta blocker to reduce his BP but then you give epinephrine which is a beta agonist. You just cancel out the effect. So if she wants to give epinephrine to increase HR or BP because its low, she will override the beta blocker effect. Cancels it out. Same is true with Alpha Blockers.
MAO inhibitors
TCAs
Alpha inhibitors
Beta blockers.
Administeration:
Monitor IV sites
Very diluted 1 in 10,000. Make sure it’s the right dilution. Higher concentration given for other things. Always always.
Norepinephrine is similar to epi in almost all respect
Trigers Alpha 1, Alpha 2, Beta 1 and Beta 2.
Use epinephrine instead. Not one you need to highlight.
Dopamine:
-has a serious of effects that are dose related. Dopamine infusion seen in the ICU.
-Low doses: binds to dopamine receptors in the kidneys and increases renal perfusion by dilating renal vasculature.
-moderate doses: binds to the dopamine receptors in the kidneys AND to beta 1 recptors. So you get the dilation of renal vasculator AND increased HR. Moderate to high dose, you can measure HR to see if its working as well as urine output. What you really want if pt is in shock and has horrible cardiac output: BP.
Dopamine High doses: And then at high concentraitons: 18 to 20ish, dilation of renal vasculator in repsonse ot dopamine sitmulation, Beta 1 stimulation, and Alpha 1 stimulation. Peripheral vasoconstriction. High doses used in pts with shock and dramatically critical pts with awful cardiac output. Sick pts.
Measure urine output to see if renal is working
In some pts who have dopamine infusing through peripheral line, you can see a white streaking gioing through arm or leg. Reduced blood flow right around the vein in which its flowing. So if that extravagates, you have a problem.
So if moderate dose is given, stimulating Beta 1 recptors, HR ggoes up and you have a risk of Tachycardia and dysrhythmias. Then heart cant feed as well, asthrosclerosis, narrowing of artiers, you can get angina. A mismatch between work of heart and how well heart can feed itself with blood. Tlak more about it later. Don’t worry aobut it too much.
Contraindications: pts with dysrhytmias, or ventricular fibrilation should not receive dopamine or very carefully. Same with Epi or MAO inhibitors since its metabolized by same enzyme. Also TCAs, trycyclics.
Q: Why would dopamine have a complimentary effect with diuretics?
A. They both increase the urine out put. One uses dilation of renal vasculator, vs. soemting else. Work nicely together for pulmonary edema. Given by continous infusion sinc eits reapidly metabolized. Micrograms per kilo per minute. Weight based, minute to minute, in micrograms. Math of that is fun when pt is dying and you’re calculating micrograms per kilo per minute.
Vaso constirction in nose and that reduces congestion. Technically vaso constrictors.
Reduce the preload to the heart: more blood in this pool here, you have less returning to the heart. Less returning to heart is less out of the heart. Decreased cardiac output, decreased BP. This is an indirect effect of the veins. BP is direct.
So presosin
-is used for Pts with HTN primarily.
Adverse effects:
-orthostatic hypotension. Happens with first dose. Also start with low doses titrating up slowly to what pt can tolerate and what controls their BP. So don’t give targeted theraputic dose. So one issue with vasodilators is reflex tachycardia. And that is because right here in the aortic arch is a bar receptor. A pressure receptor. If you vasodialate and decrease the BP, then receptor says not enough pressure. One way to increase pressure is to increase the HR. So, for presosin this is very ture: drop in BP causes reflex tachycardia in order to bump pressure back up. So an effective drug, but it has this compensation effect by the body so higher HR is pretty normal.
- Constict Alpha 1 by stimulation, dilating in the nose vessels will cause congestion: the opoosite. Pseudoephedrine reduces congestion, the opposite would b etrue if we dilate. Nasal congestion is pretty common.
Administration: Drug is administered PO: start low doses, increase slowly. First dose don’t let pt stand up too quickly.
Indirect Vasodilators
Resurpine
Direct effect of dilation and oncstriction of these vessels. Also indirectly and how we do that is presynaptic neuron and post synaptic neuron. Precursors get taken into the presynaptic neuron, converted to Dopamine and then converted to nor epinephrine and converted to little vessicles. Under normal circumastances. Preoduce nor epinephrine and package in little vessicles. Sitmulus cause vessicles to go into surface where they pur contects into the cleft and transmission goes downstream.
Resurpine blocks production of dopamine in the production pathway. IT pokes holes in vessicles and nor epinephrine leaks out and then gets metabolized by MAO.
-prevents production of norpeinephrine
-pokes holes so norepinprine leaks out if its already. There.
So body doesn’t produce dopamine or nor epinephrine. So lower levels of nor epinephrine indirectly cause vaso dilation of the sympathetic nervous sytem. Indirect vasodilatory effect. Unfortonately respurpine goes directly int o the CNS because its very lipid soluble. So,. Which disease process did we talk about that we need to treat low levels of norepinpehrine and seratonin and dopamine? Which disease process do we need to boost concentrations in the synaptic cleft? Depression. Giving resurpine causes depression. Depleting suplly in synaptic cleft. Common, dramatic side effect of resupine. Not sued often for that reason.
-works in whole body, not just vasculator. A dramatic side effect is stimulation of intestinal motility. The Parasympathetic system gets a boost, and it seems that that increases gastric motlity and diarrhea is a horrible consequence.
-Depressed rats with diarrhea. Haha.
Guinethidine
-does not get through BBB blood brain barriar
-still horrendous diarrhea issue.
-Reduces sympathetic nervous system in body. Reduces Alpha 1 and auses vaso dilation.
-Used for: HTN,
-neither drug is popular.
Alpha 2 receptors:
A bit confusing and we don’t worry aobu them in the periphery, but we think about htem in the CNS. We are here with our neuron. Alpha 2 receptors are presynaptic receptors. So, there you can think of them as being part of a feedback mechanism. If a neuron receives allot of imput and puts allot of neurostramitter in a synaptic cleft, rush of activity, running from a bear tons of nor epinephrine in body. Tons of epinephrine in the body, escaped form bear and you need to settle. Down. High concentratin of norpehinephine and epi will bind ot alpha 2 receptor when concetration is high enough. And that signals to neuron that enough is enough and you can stop pouring so much out. Enough is enough.
-So, in the CNS there are signal from brainstem to cardiovascular system so that when you turn on the neurons in the brainstem you turn on the vascular system constict the blood vessels andc ause effects in the periphery. If you block the CNS stimulation you reduce the HR and constgriction and you get vasodilation. Alpha 2 receptors in the CNS and brainstem, turning those on will stop transmissoin in the CNS. So an alpha2 algonist that wokrs in the brain will turn this on which turns this off. This stops transmission and activaiton of the cardiovascular system and causes vasodialtion. AN that drug is called Claunadine.
Claunadine:
First mechanism: presynaptic neuron when it receives all ot of stimulation it pours a lot so fneurotramitter in cleft.
High neurotramitte rin cleft it duffises to alpha2 recptor
Pre synaptic neuron realizes enough is in cleft and turns it off.
So by turning on alpha2 you turn off the presynpatic neuron.~!
Now if you have a brainstem and utrni on the sympathetic system in the brain you turn signal in the heart and vessels to increae the HR and turn on the cardiovascular system. By turning one thing on you turn on another. Bu ti fyou turn on alpha2 recptorsi nthe brain you turn off the stimulation there. If you turn this one, that goes off in the brain. Vasodilation then occurs. Clear as mud.
AP=PR x CO
HR x SV
!!Claunadine: KNOW FOR EXAM of alpha 2? Agonists?
-used for HTN. Not sure of mechanism but used for pts with severe cancer pain.
-vasodilatory effect
-lipid soluble in CNS
-works rapidly
-Since it getes into CNS it has CNS effects like: sedation, dry mouth, does not have reliance on body position like raisoin does so you do Not have orthostatic hypotension. Acting in CNS not directly in the periphery so moving body do es not cause changes in bp. But if a pt has been on claunadine for a while and stop taking it suddenly, there is rebound hypertension that can be pretty significant that last for many days. So they are treated well, they should taper it over time, not abruptly stop it.
Guanamens and Guamycine
Similar effects to claunadine.
Methyldopa?
Similar to claunadine in mechanism
Use is an antihypertensive drug causing vasodilation works centrally, side effects of dry mouth, sexual dysfunction, and two side effects tahtare unique
-hemolytic anemia and hepatotoxicity: only drug with tehse side effects.
Renin angiogenesis system.
Lets talk about the system now. On Monday, we will cover the drugs associated with it.
So angiotensinogen:
-is converted to angiogenesis 1 by the enzyme renin.
Renin is a rate limiting step. So without renin, this reaction is very slow. Or doesn’t occur at all. Angiotesin 1 is inactive, but angiostenin 2 is highly active, and converted by angiostensin1-ase. Extremely rapid process. Renin is the rate limiting step. As soon as renin is there you have repid conversion to angiotensin 2. Renin
-released in kidney
-release triggered by:
* decreased BP and
* decreased sodium
*decreased blood volume
*decreaed kidney perfusion.
Low BP is going to be a pump in renin release to convert ot angiogenesis 1 and then rapidly to angiotesnin 2. So angiotensin’ job is to increase BP by vasoconstriction.
Aldosterone:
Renains water. Wherever sodium goes, water follows. Change in water and sodium and blood balance. Vasoconstriction happens very quickly.
Angiotensin 2 and aldosterone:
-cause cardiac remodeling which is not a good thing for pts who have these in consistently high levels. Vasculator changes as well as in thicking of the wall like athrosclerosis. Not a good thing.
Monday, December 8, 2008
Pharm: platelets: clotting
Platelet activation:
Receptors are long and sticky and binds to fibrinogen and little platelets stick together and that’s aggregation. These little bonds are the process of platelet aggregation. So what causes platelet aggregation? One biggy is collagen. No gaps or nicks, but as soon as vessels is injured hter ie exposure of sub endothelium and collagen sticks to injured spot. Collagen is great platelt acivator.
TXA2,
ADP-AdenosineDiphosphate,
PAF-platelet activating factor
Thrombin
GP: Glycoprotein
A clot is created but it is not stable. NO reinfocement and the clot might fall off if its not stabilized so the next step is coagulation which is the formation of fibrin and this is stringy fibers that reinforces the clot. There is an intrinsic pathway and an extrinsic pathway and it is a cascade. So once it starts it cascades to the final product.
Intrinsic pathway: all of the factors needed for cascade are already present intrinsically to the vascular system. What happens, is you have a factor activated to active factor: Factor A. And on goes a chain of stimulation. Last one is Factor 10.
Reponse to injury: thromboplastin is released. This stimulates a factor 7 to factor 7A, which stimulates factor 10 to become factor 10A.
KNOW: What intrinsic factor is, and that it means that it’s got factors already in the vasculator. Extrinsic needs thermoplastic form outside. And both of these converge on factor 10A.
What we are trying to produce is fibrin and factor 10A stimulates protrombinm to become thrombin. Thrombin stimulates fibrinogen to become fibrin. And all this fibrin is what goes to the clot to reinforce it.
Trigger pathway downstream. Body has set up mechanism to captivate and activate them if they wander away from the tissue site and that enzyme is called Antithrombin. It can inactivate 10A and Thrombin. It inactivates all of those little activated factors if they tend to wander away and that’s when heparin is going to come in.
Aterial Thrombus vs. Venus thrombus
Aerteria thrombus: starts from tissue injury, happens in arteries pretty locally since arteries are going out the the tissues. Tends to be a local effect. The injury stimulates platelet aggregation. Clot occludes the artery.
But If it’s a Venus thrombus, we treat with platelet drugs. So ant platelet drugs help with myocardial infarction and venus thrombus in the coagulation pathway: venus stasis. Some women get DVT in their legs because the blood flow has slowed down the the point the coagulation pathway has slowed down. Treat with anticoagulants like heparin.
KNOW: these drugs…
1. Heparin:
-animal bovine protiene. A long chain with a little active site in the middle.
-binds with ant thrombin and makes it better at inactivating thrombin and factor 10A. So heparin binds with ant thrombin which is the protein that inactivates all of these little factors and makes ant thrombin better, including most importantly 10 a and thrombin.
So here’s how it works….drawing of mechanism of action.
Kinetics and Dynamics of Heparin.
-Big molecule
-highly polar with ltos of negative charges
-PO: will not work, wont’ go through GI membranes
-Does not cross placenta. Due to membrane negative charge-
-No CNS
-Immediate onset of action. Short halflife of 1.5 hours. Give in repeated doses often.
-Variable and non-specific binding.: hard to tell how much active and available heparin you have. Hard to decide how much will be enough for pts.
-Hepatically metabolized: hepatic disease must be closely monitored.
-Renally excreted.
-Use: keep veins open, for initial treatment of DVT or PE (Pulmonary Embolus when a piece of clot breaks off and travels to lungs.) Venus problems can travel a long way, but arterial problems don’t travel so far.
-Side Effects: Bleeding in 10% of pts. Can be mild-severe, and can happen in any site in the body. Will see lots of bruises. Tachycardia. In situations where there is waay to much heparin there is an antidote called Protamine. This his positive charges, and it binds together with negative charge of heparin, and then it can’t do anything.
Heparine Induced Thrombocytopenia: Drop in Platelets. DON”T learn the mechanism. Know that a drop in platelets can be this, which can be fatal.
Hypersensitivity: Heparin is derived from animal extracts and this can cause a protein anaphylaxis reaction. There is a significant chance for fever, chills, etc…
IF there are two steps to hemostasis and blocking pathway, so if I give drugs that block platelet aggregation then pt is at much higher risk. Careful of anti-platelet and heparin. They have no way to coagulate anything. Aspirin/heparin, etc…
Monistering. Difficult to preduct how much is enough. APTT: Activated Partial trothomboplastin time. Typically this is 40%. Don’t memorize how to give it daily. Also moniter platelets.
Low molecular weight heparin: smaller molecules
-still has chain
-same activated site where it binds to ant thrombin.
-With short arms, low molecular weight heparin cannot activate thrombin. But it CAN activate factor 10A. It’s arms are too short. Like a T-rex!! It is still as effective as heparin at anticoagulation.
-Adverse effects: bleeding, thrombocytopenia, hypersensitivity. Less risk of all of these, except the risk for bleeding is the same. The differences between unfractionated heparins and low moleuclear weight are thse…
-does not bind indiscriminately to all proteins. Measure by body weight, give dose, and you know how much will be in their plasma. So you don’t need to moniter at all. It doesn’t bind so non-specifically. Much more specific molecule. Much more predictable kinetic profile so you know what you’re gonna get. You can give it on a fixed dose schedule and for heparin, it must be adjusted more or less depending on APTT. Has a longer halflife, so you can give it 1 or 2 times daily. It is sub Q, still not PO, and less likely to cause thrombocytopenia.
Low molecular weight heparin is much more expensive, though. However, pts can be given this and be sent home, and the hospitalization cost of monitoring pts with heparin treatment. So actually, how molecular weight heparin is still cheaper.
KNOW: Advantages of Lowmoleuclar weight heparin over heprain.
Direct Thrombin Inhibitors:
-Don’t need to know the name.
-(Heparin is the indirect thrombin inhibitor, because it must bind to ant thrombin first and then activate thrombin. Also, heparin can only act on Free Thrombin.)
-However, Direct thrombin inhibitors can directly act on free thrombin floating around in blood stream as well as thrombin that’s in a clot.
-Largely used for angioplasty, iv stuff in cardiology unit. Critical Care kind of drug. Extremely expensive. Not more effective than heparin.
-Adverse effects: backpain, decreased BP,
So those are the three types of anticoagulants given IV, SubQ or both.
One PO anticoagulant……
Warfarin:
-Cattle ate some spoiled clover and had a bleeding reaction. WARF came up with a synthetic form of spoiled clover and gave it to animals which caused hemorrhaging there too. Used in rat poison. In early 1950s a guy tried to commit suicide and took allot of rat posion, but didn’t die. But they did find out it had an anticoagulant effect.
-Mechanism of warfarin action is very different from heparin, low moleuclear wight heparin, or direct thombin inhibitors….
*Draws on board* Inactive factor becomes another factor…etc… Vitamin K is necessary to biosynthesize these inactivated factors. So it blocks biosynthesis. That’s a very different mechanism. Warfarin works on one side, and Heparin works on another side of the cascade:
From the intrinsic pathway, once it gets started there are inactive protiens witing to be activated and that activated factor activates another inactivated factor. This is the cascade effect. So one of the components of these factors, in order to be built by body they need vitamin K. Warfarin blocsk this biosynthesis, but warfarin blocsk Vitamin K so these can be synthesized.
-Effects of warfarin are not immediate.
-Once a factor is made and is circulating in the body, warfarin can’t do anything to it. Warfarin only affects factors that are BEING synthesized. So halflife of typical factor is a day or two. So you have to wait for old ones to die to see any effect. Allot of pts you have on Heparin and you have to switch to PO warfarin to get that going. You can gradually wean off the heparin to coumadin, but you can’t just send them out the door because there’s not a peak until several days have passed. Likewise, if a pt is finished taking warfarin, it will be several days until coagulation pathway is back to normal. Wait several days while the body is makin gnew factor. Still at risk for bleeding.
-Adverse effects: Bleeding is #1 problem/ antidote is Vitamin K: overcomes the inhibition of vitamin K from warfarin. Pts who are on warfarin are out in society and they must be advised to use a medical alert bracelet, in case they are in an accident and have a bleeding problem. Also causes birth defects like fetal hemorrhage, central birth defects, etc…because it passes right through the placenta.
-Must moniter the PT:
-prothrombin time. Average pt is 12 seconds. This was normalized to INR. (but you don’t need to know these specifics, like what the INR would be of pt.)
-Moniter also IR: the lab would giv eyou a figure of the Pts prothrombin time vs. the control’s prothrombin time. So institutions have normalized it as INR: normalized prothrombin time. Unanticoagulated blood as an INR of 1. A pt on warfarin you are shooting for 2-3. Some pts should be more than that. If the INR is too high, like 4, you need to cut back on warfarin.
-At home kits are available for pts so they don’t need to come in and get prothrombin time tests at doctor’s.
- Dependent on Cytochrome P450 mechanism.
-Hepatically metabolized.
-99% protein bound, so drug interactions are a major issue
-Non polar: easily absorbed through GI and Placenta. So for OB pts, it is better to give heparin.
-DVT or PE: use
-Every drug that a pt takes in addition must be okayed bythe doctor.
-Nursing considerations:
-Surgury, Peptic ulcer disease, moniter IV sites, moniter platelts, if warfarin moniter INR, educate them to look for bleeding and medical alert bracelets and pregnancy.
*now we draw a little table comparing heparin and warfarin*
HEPARIN
WARFARIN
MOA
Route
Onset
_________________________________________________________________________________
Only works on 10A.
Low moleculular weight heparin.
Know why these LMWH are more convenient and why they are the choice: don’t need to moniter, pts can go home on this drug, has a predicable plasma concentration. Longer halflife. Side effects are same as heparin. Thrombocytopenia which is less than heparin. Direc thrombin inhibitors.
Direct thrombin inhbitors: used in acute care setting
-inactivate thrombin both free and inbedded within.
-Don’t need to know Direct thrombin inhibitors specifically
Warfarin is a biggie. Number one adverse effect is bleeding. Know this drug.
Antiplatlet drugs:
-Aspirin.
-Know which mechanism and its side effect.
EPP
-Receptor antagonists and how those work and glycoprotein II and IIIa and how they work.
Other antipathetic drugs.
Thrombolytics: Don’t know any specifically like names but know what they do and where they are used.
-not in notes
-in anticoagulants worksheet.
-promote conversion of plasminogen to plasmin and that enzyme chews up clots. So if she gives this thormbolyticl ike streptokinase they are clot busters. Zbut you don’t need to know the names of any specifics. Given to babies with clots in their extremities.
Will make a study guide again.
Anemias: read about several. #2 most common and deadly disease in the world. Extremely common. Like iron deficiency. Common in underdeveloped countries. Can affect mortality and morbidity, particularly in vulnerable pts. Renal disease, congestive heart failure, cancer, etc… Can make quality of life awful. For the normal person who has had trauma and lost blood they can get over the hump and be healthy again.
What is anemia?
-The reduction in number of RBCs, size of RBCs or hemoglobin content of RBCs. Normal hemoglobin is 13 for men and 12 for women. Can be due to blood loss, hemolytic, bone marrow disfunciton. Deficincy anemais,
1. Iron
2. B12
3. Folic Acid.
There are two types of deficiency:
1. Microcytic
2. Macrocytic
Iron deficiency is a microcrystal anemia. Low hemoglobin you can’t carry oxygen well to the tissues. Most of the iron the body absorbs goes into the bone marrow. Osme goes to myoglobin and a tiny bit goes to make other enzymes that have iron in them. If a patients iron stores are low the amount of iron their body takes up will be high. IF the stores are high, uptake will be low. If you give allot of iron to a pt who has high iron store, they will not take up much of it. The iron cycle is this:
Iron from your diet binds with ferratin in the small intestine mucosal cells and sometimes it gets stored there. But sometimes it passes through and binds with transferrinand makes complex.
1. About 80% can go to the bone marrow. Then it can go to the bone marrow to make RBCs,
2. can go to the liver for storage for later, Liver is a high iron tissue,
3. it can go tot hmsucles to make myoglobin and
4 it goes to tissues to make enzymes.
Body loses some iron everyday, but very little. When The liver was discovered that it was iron rich. In early 1920s, Minot was working with iron deficint dogs and fed them raw liver. Minot did the same experiment with people. Both cured.
So when a pt has not a whole lot of iron, the RBCs lack enough iron and they tend to be small, thusmicrocytic anemia. Tend also to be hypo chromic or pale. Changes depending on what the body’s stores are. Most common causes of poisoning are iron poisining. But generally if stores are high the uptake will not be high. What you need to know is adverse effects:
Nausia, vomiting, diarrhea, constipation: will make people non-adherent. Constipation is a big deal. Heartburn, bloating, etc… Tricks to get pts around this issue: GI are not dangerous and become more tolerated over time. Iron supplements wont be taken if it makes them feel awful. Taken with food, and the risk is lower. Not the same adverse effects. Problem is that aborption goes down as well. If they take iron between meals, absorption goes up but also with adverse effects. Start taking drug with meals initially and then after a week take it between meals and that way hopefully the body will have grown accustomed and the side effects wont be quite so bad. Given in eavenly spaced daily doses because the body needs a steady continuous amount. Taken morning, noon, evening. Give moms vitron C. Ascoprbic acid boosts absorption and side effects. Also antacids. Tums or Prilosec and Zantac…that increases PH in stomach, acid content is reduced and iron is not well absorbed. Last one is tetracyclines, which we don’t need to know.
Depending on severity of anemia and causes, recover will take several weeks to several months. Next drug is parenteral. This is a dangerous medication of anyphylaxis. Encourages pts to take the drug Po. And if a pt cannto take po iron because of malabosprtion then they need something parenteral. When blood loss has been huge they can get iron detrate though IV. Po iron should be the best because of anyphylaxis. Can be fatal even when treated.
Vitamin B12 anemia: treating pts with raw liver in 1920s and minot has a student who studied pernicious anemia. Was a fatal disease. Lived 1-3 years. Noticed that pts don thave gastric acid. Pts who received gastric juices and raw hamburger survived.
So humans are dependent on getting B12 from soil, microorganisms, etc.. Anmials that eat the soil and microorganisms get it, and we get it from the animals we eat. Sometimes they live on legumes, etc.. or on leafy vegetables. And allot of strict vegetarians take vitamin supplements anyways. So we need vitamin B12 in order to synthesize dna. Rapidly growing cells are most effective: bone marrow, erythrocytes, plaetelets , wbcs and gi tracts. Rapidly growing cells are most effective.
Mechanism is this: Folic acid is inactive and it needs to become activated and that’s done by vitamin B12. So without, we don’t get active folic acid. And without active folic acid, we can’t synthesize DNA. There is an alternate pathway. This is the marjor and inor pathway. So you can bypass it but not enough to survive. What you need is for vitamin B12 to bind with intrinsic factor and that’s whats in gastric jucie. So vitamin B12 binds with intrinsic factor in the stomach and it can be transported through tissues that way. But if pts do not have any intrinsic factor ad you give them enough b12 youcan get them to absorb it. Elimination of B12 is very slow, so its developed slowly over months. The causes of B12 deficiency are reduced stomach acid, intrinsic factor, diseases like celiac disease which can contibute. Consequece; affects the high growth tissues, oral ulcerations, and bone marrow disfunction and what happens is the dnA replicates and the cell can’t multiply so you have these big cells called macrocytes.
IM, SubQ, pO, and intranasal gel.
Pain: didn’t read chpter 28. But read it before Wed class. On opiods.
What we did read for today, start on pg 54 of notes and down to section of opoids and skip pg. 59. Pain is a huge issue in the hospital. Affects millions of people. Know that pain is very subjective.
IF in doubt, remember rule number 1. If a pt claims pain, you must believe them. Most common pain is lower back pain. Gate controlled theory. Best explanation so far. Go up through the spinal cord and into the brain. Perception and stimulation. Stimulation of the nose receptors causes stimulation in the CNS. Chemicals called
bradykinens
prostoglandins
cytokines
substance P
CGRP
But there are lots of others. A complicated molecular system. After stimulation you’ve got transmission. Pain stimulus travels though spinal cord up into the brain. Third stage is perception.
Ouch that hurts that’s pain perception which happens nthe brain. Laswt is modulation. And what happens ist he brain siulates other nurons which release chemical inhiitorslike norpinephrine, seratonin and endogenous opoids. And those suppress the pain. A or C fibers. Just there for your interest. When you are assessing someones pain, its called the PQRST. P is for palliation, what causes your pain,
Q is quality
R is radiation
S is severity
T is for temporal. What happens over time.
Switch to pg 59.
Nsaids
Acetopmenophen is not an Nsaid. It is not.
Cyclooxygenaseinhibitors. The body take sarachadonic acid and two types of same enzyme. Cox 1 and Cox 2 synthesizes prostoglandins and thromboxine. Prostoglandins one of their functinos is increasing sensitivity to pain. So if we inhibit this enzyme we inhibit prostoglandin s ynthesis and indoing that youreduce the action of prostoglandins and suppress our sensitivity to pain. That’s the though process behind cox inhibitors. Cox 1 is presnt in almost all tissues thoughout the body and it is responbile for housekeeping chores of the body and it has a significan taction in the gastric mucosa and cox 1 is responsible for producing prostoglandins and thomboxanes.
Prostoglandins
-act on the gastric mucusa and increase bicoarbonate secreation, which is a base.
-And in doing sothey decreaes the acid content in the stomach which is protective.
-Also stimulates the rlease of mucus inth stomach which protects the stomach.
-Also decrease acid production
-increase gastric blood flow, perfusion of the stomach.
Cox 1
-Increase renal blood flow.
-Synthesizes trhomboxane which acauses platlet aggregation.
Cox 2’s prostoglandins
-Tissue injury
-Increased sensitivity to pain and inflammation.
-Affects set point for thermogregulation so those prostoglandins cause fever.
-Presnt in the kidneys and the prostoglanin synthesized from those Cox 2 increase renal blood flow.
NSAIDs.
-Aspirin: only one we need to know
-blocks cox 1 and cox 2
-well absorbed kinetically. Converted to an active metabolite. Elimination is dependent on ph. Aspirn is a weak acid and if you want to get rid of aspirn quickly youcan mekt he urin more basic and that will help get rid of aspirin. If aspirn blocks cox 1 then it would have a role in thromboxine synthesis blocking it, reducing platlet aggregation. Used prophylacitcally. Antiinflammation. Also bocks prostoglanin synthesisis at tissue site reducing pain. Sensitivity reducing paiat injury site and perception of pain in the CNS. Also works since cox two is presntinthe brain it also works as a fever reducer. We do not use aspirn in children at all anymore. Reyes syndrom/.
Dysmennorrea. Reduces pain in smooth muscle of uterous;
____________________________________________________________________
October 8 Wednesday
Lung Cancer and Breast Cancer
Types of Breast cancer: ductal and globular
Ductal Carcinoma in Situ DCIS
-others are being more selective in pt population
Ductal Breast Cancer
-more invasive. Insitu means it hasn’t started to invade the basement membrane. Ductal then has become invasive once its called breast cancer. Large nucleated cells filling the ducts. Once it becomes more advanced moving well beyond the ducts. More advanced. Subcategories of ductal breast cancer. Globular
Carcinoma in situ. Before it penetrates the basement membrane.
-No one treats this as a benign condition.
Infiltrating lobular
Pagets disease
-Description of the nipple. Ductal carcinoma that involves the areaola itself. Itching and oozing a common problem.
Inflammatory Breast cancer:
-Worst possible diagnosis
-Aggressive/Invasive
-Orange-peel skin overlying the tumor.
Half of women will be dead already by the time they reach 85. Chance getting it by 85 is 1:7. Live to age 79, risk is 1:15. Percent of women to die of breast cancer is 2.8% which is similar to chance of dying from a hip fracture. Risk of death by breast cancer decreases when you’re old, but only because you’ll probably die of something else first. May be more on our mind, since it affects younger people and its more on our mind.
Risk factors on pg. 106
Spending more time on genetics than anything else. Age is a risk factor and family history is certiantly a risk, even without knowing anything else about genetics. Definable genetical mutation, which is inherited. Mutation of the BRCA gene #1.
BRCA=breast cancer gene. This particular mutation is not one mutation, there are at least 17 mutations that can affect this gene. Another word is polymorphism. MOre and more when you look at the literature it means that a gene has many many possible mutations. Only a few mutations confer a significant enough risk for breast cancer. There’s a mutation and in different people it means different risks. If you look at BRCA mutation in general which is located on chromosome #17, and found in 1 in 500 women, you have a 40% risk in your lifetime of ovarian cancer.
Options include more frequent screening, diet and exercise, avoiding fatty foods, prophylactice removal of the breasts (both) which is the only kind of surgery where you don’t do anything with the lymph nodes. Gives you a 98% reduction in risk. But this person is also at risk for ovarian cancer, which could be a oopherectomy. Removed primary source of growth factor for breast cancer.
So
-double simple prophylactic mastectomy (cosmetic and breastfeeding issues)
- oopherectomy (no children, osteoperosis, and hot flashes…needing HRT)
-more frequent screening
BRCA 2 is a different gene.
-much higher risk for breast cancer
-not as high a risk for ovarian cancer
-men get this mutation
-increases risk for other cancers too, though.
Indications for Genetic screening in Breast cancer.
-90% is sporadic, rather than inherited. These mutations would be called aquired.
-Know that P53 is a significant risk.
-Women who inheret a BCRA, must be homozygous. Women who don’t inherent these mutations much less commonly aquire one. When you inheret a mutation of a gene you can be vulnerable to other mutations.
What cells in the body are going to have an inherited mutation? ….
Every cell ijn the body. You inheret the same DNA in every cell which makes the same perosn. You find an aquired mutation only in the tumor itself.
Methylation Problems
Early menarche or late menopause, high circulating levels of serum estradial or HRT. Estrogen is a growth factor for tumors. When we are talking about HRT we are talking about stimulating a cancer that was already there and making it grow faster. Lifetime exposure cause some carcinogenic effects over a lifetime. High levels of estrogen for 40 years, that may actually be a carcinogenic exposure over that many years. But if a women goes through menopause at age 52, its highly unlikely that estrogen caused the mutations, it was simply a growth factor. Birth control pills have finally been laid to rest as a risk factor for bresat cancer. If anything, the current forms of birth control are protected reducing the risk of breast cancer. With HRT we are stimulating a tumor that’s aready there.
Mitogenesis
-increases cell divisions
Mutogenesis
-of oxidative damage to the DNA.
WHI results: statistics can be a little misleading. If you have tumors and you take estrogens that cause tumor to grow over next few years. Look at the hazard ratio for breast cancer in year five.
No risk with abortions. Oral contraceptive use, and decreased risk of breat cancer with breastfeeding and pregnancy.
…
Pg. 108: Progressive cellular and tissue changes.
Why does pregnancy help prevent? Where the cells are most ready to divide. Cells that are most vulnerable are places where cells are ready to divide anyways. That’s true in the breast also. The portion of the total breast tissue hwere there is the most cell division is Lob 1. Active undifferentiated part of breast with high proliferation rates. Present in geastest amounts between onset of puberty and first child making this the most vulnerable time. Allows the cells to differentiate further into more mature cell types called Lob 2 and Lob 3.
Increased risk in breast cancer is called proliferate breast disease: Fibroadenoma also known as a cyst. Many women have fibro adenomas and cysts int heir breast and this is why…
However if the cyst if full of cells even if they are not cancerous yet they are called atypical hyperplasia this is a significant breast cancer. Women come sin the clinic feeling alump, and mamogram looks funny. They might do a digital mamogram and then an ultrasound. If the lump is full of fluid, they say it’s a cyst don’t worry about it, but if its solid on ultrasound, they are going to biopsy it. That’s how we get clinical evaluation of breats cancer. Past history of breast cancer increases risk for another one.
Gale model: one way women can type in their personal info and get some indication of what hteir risk factors are.
Mutations:
-Formation of oncogenes and mutation of sumor suppressor genes
_Aquired p53 mutation
-BRCA inheritance
-other gene mutations.
Bottom of page. 108: Atypical hyperplasia CIS eventually leading to invasive carcinoma.
Concept of the growth factors in a little bit more detail.
The most important growth factor in breast cancer is estrogen. Required for normal breast cell function. Activation of breast cells at puberty. In neoplastic cells, estrogen stimulation results in over stimulation of growth factor reduction resulting in uncontrolled proliferation.
Estrogen receptor positive…normal cells have estrogen receptors, but if the tumor hast retained its estrogen recetpors it is at least in that way more normal. A better chacne of controlling gtumor, slower growth, and we can block the cancer with Tomoxafin and blocking estrogen synthesiis then those tumors will not progress. That implies about ….
ER negative: Autocrine sitmulation. Don’t need estrogen and don’t care about oopherectomy, tomoxifin or drugs that block estrogen synthesis. That’s when we talk about ER positive and ER negative. Progesterone receptors…tumors are more responsive and slower growing. Insulin-like growth factors don’t have much to do with insulin. All called IGFs. Alpha, beta, gamma, and play a variety in diseases.
Epidermal growth factor: Her2/neu. Treated with HERCEPTIN which blocks the Her receptors and prevents the growth promoting effects of epidermal growth factor. You will see women who are on herceptin for breast cancer.
What we do in looking at brast cancer…usually occurs in upper, outer quadrant. Retaracting and making the breast look asymmetric. Mostly will be found when it’s a little lump. Second most common place is upper, inner. If you look closely you can see that the skin is starting to look different. Regional spread is to the axillary nodes. The amount spread to the nodes is related to how big the primary tumor is. Divided into three regions that help predict prognosis. If you don’t feel nodes, that doesn’t mean that there isn’t cancer there. You have to sample the nodes to make sure they are negative for cnacer.
Sentinal node: injecting dye and watcing for it go to into the sentinal node. If the node is negative, then you are fine. Spreads to lungs, bones, brain, adrenal glands, etc…
MRI better in mammography.
Excisional biopsy
Sentinal node
PET scanning
TNM tumor nodes metastises.
Receptors are long and sticky and binds to fibrinogen and little platelets stick together and that’s aggregation. These little bonds are the process of platelet aggregation. So what causes platelet aggregation? One biggy is collagen. No gaps or nicks, but as soon as vessels is injured hter ie exposure of sub endothelium and collagen sticks to injured spot. Collagen is great platelt acivator.
TXA2,
ADP-AdenosineDiphosphate,
PAF-platelet activating factor
Thrombin
GP: Glycoprotein
A clot is created but it is not stable. NO reinfocement and the clot might fall off if its not stabilized so the next step is coagulation which is the formation of fibrin and this is stringy fibers that reinforces the clot. There is an intrinsic pathway and an extrinsic pathway and it is a cascade. So once it starts it cascades to the final product.
Intrinsic pathway: all of the factors needed for cascade are already present intrinsically to the vascular system. What happens, is you have a factor activated to active factor: Factor A. And on goes a chain of stimulation. Last one is Factor 10.
Reponse to injury: thromboplastin is released. This stimulates a factor 7 to factor 7A, which stimulates factor 10 to become factor 10A.
KNOW: What intrinsic factor is, and that it means that it’s got factors already in the vasculator. Extrinsic needs thermoplastic form outside. And both of these converge on factor 10A.
What we are trying to produce is fibrin and factor 10A stimulates protrombinm to become thrombin. Thrombin stimulates fibrinogen to become fibrin. And all this fibrin is what goes to the clot to reinforce it.
Trigger pathway downstream. Body has set up mechanism to captivate and activate them if they wander away from the tissue site and that enzyme is called Antithrombin. It can inactivate 10A and Thrombin. It inactivates all of those little activated factors if they tend to wander away and that’s when heparin is going to come in.
Aterial Thrombus vs. Venus thrombus
Aerteria thrombus: starts from tissue injury, happens in arteries pretty locally since arteries are going out the the tissues. Tends to be a local effect. The injury stimulates platelet aggregation. Clot occludes the artery.
But If it’s a Venus thrombus, we treat with platelet drugs. So ant platelet drugs help with myocardial infarction and venus thrombus in the coagulation pathway: venus stasis. Some women get DVT in their legs because the blood flow has slowed down the the point the coagulation pathway has slowed down. Treat with anticoagulants like heparin.
KNOW: these drugs…
1. Heparin:
-animal bovine protiene. A long chain with a little active site in the middle.
-binds with ant thrombin and makes it better at inactivating thrombin and factor 10A. So heparin binds with ant thrombin which is the protein that inactivates all of these little factors and makes ant thrombin better, including most importantly 10 a and thrombin.
So here’s how it works….drawing of mechanism of action.
Kinetics and Dynamics of Heparin.
-Big molecule
-highly polar with ltos of negative charges
-PO: will not work, wont’ go through GI membranes
-Does not cross placenta. Due to membrane negative charge-
-No CNS
-Immediate onset of action. Short halflife of 1.5 hours. Give in repeated doses often.
-Variable and non-specific binding.: hard to tell how much active and available heparin you have. Hard to decide how much will be enough for pts.
-Hepatically metabolized: hepatic disease must be closely monitored.
-Renally excreted.
-Use: keep veins open, for initial treatment of DVT or PE (Pulmonary Embolus when a piece of clot breaks off and travels to lungs.) Venus problems can travel a long way, but arterial problems don’t travel so far.
-Side Effects: Bleeding in 10% of pts. Can be mild-severe, and can happen in any site in the body. Will see lots of bruises. Tachycardia. In situations where there is waay to much heparin there is an antidote called Protamine. This his positive charges, and it binds together with negative charge of heparin, and then it can’t do anything.
Heparine Induced Thrombocytopenia: Drop in Platelets. DON”T learn the mechanism. Know that a drop in platelets can be this, which can be fatal.
Hypersensitivity: Heparin is derived from animal extracts and this can cause a protein anaphylaxis reaction. There is a significant chance for fever, chills, etc…
IF there are two steps to hemostasis and blocking pathway, so if I give drugs that block platelet aggregation then pt is at much higher risk. Careful of anti-platelet and heparin. They have no way to coagulate anything. Aspirin/heparin, etc…
Monistering. Difficult to preduct how much is enough. APTT: Activated Partial trothomboplastin time. Typically this is 40%. Don’t memorize how to give it daily. Also moniter platelets.
Low molecular weight heparin: smaller molecules
-still has chain
-same activated site where it binds to ant thrombin.
-With short arms, low molecular weight heparin cannot activate thrombin. But it CAN activate factor 10A. It’s arms are too short. Like a T-rex!! It is still as effective as heparin at anticoagulation.
-Adverse effects: bleeding, thrombocytopenia, hypersensitivity. Less risk of all of these, except the risk for bleeding is the same. The differences between unfractionated heparins and low moleuclear weight are thse…
-does not bind indiscriminately to all proteins. Measure by body weight, give dose, and you know how much will be in their plasma. So you don’t need to moniter at all. It doesn’t bind so non-specifically. Much more specific molecule. Much more predictable kinetic profile so you know what you’re gonna get. You can give it on a fixed dose schedule and for heparin, it must be adjusted more or less depending on APTT. Has a longer halflife, so you can give it 1 or 2 times daily. It is sub Q, still not PO, and less likely to cause thrombocytopenia.
Low molecular weight heparin is much more expensive, though. However, pts can be given this and be sent home, and the hospitalization cost of monitoring pts with heparin treatment. So actually, how molecular weight heparin is still cheaper.
KNOW: Advantages of Lowmoleuclar weight heparin over heprain.
Direct Thrombin Inhibitors:
-Don’t need to know the name.
-(Heparin is the indirect thrombin inhibitor, because it must bind to ant thrombin first and then activate thrombin. Also, heparin can only act on Free Thrombin.)
-However, Direct thrombin inhibitors can directly act on free thrombin floating around in blood stream as well as thrombin that’s in a clot.
-Largely used for angioplasty, iv stuff in cardiology unit. Critical Care kind of drug. Extremely expensive. Not more effective than heparin.
-Adverse effects: backpain, decreased BP,
So those are the three types of anticoagulants given IV, SubQ or both.
One PO anticoagulant……
Warfarin:
-Cattle ate some spoiled clover and had a bleeding reaction. WARF came up with a synthetic form of spoiled clover and gave it to animals which caused hemorrhaging there too. Used in rat poison. In early 1950s a guy tried to commit suicide and took allot of rat posion, but didn’t die. But they did find out it had an anticoagulant effect.
-Mechanism of warfarin action is very different from heparin, low moleuclear wight heparin, or direct thombin inhibitors….
*Draws on board* Inactive factor becomes another factor…etc… Vitamin K is necessary to biosynthesize these inactivated factors. So it blocks biosynthesis. That’s a very different mechanism. Warfarin works on one side, and Heparin works on another side of the cascade:
From the intrinsic pathway, once it gets started there are inactive protiens witing to be activated and that activated factor activates another inactivated factor. This is the cascade effect. So one of the components of these factors, in order to be built by body they need vitamin K. Warfarin blocsk this biosynthesis, but warfarin blocsk Vitamin K so these can be synthesized.
-Effects of warfarin are not immediate.
-Once a factor is made and is circulating in the body, warfarin can’t do anything to it. Warfarin only affects factors that are BEING synthesized. So halflife of typical factor is a day or two. So you have to wait for old ones to die to see any effect. Allot of pts you have on Heparin and you have to switch to PO warfarin to get that going. You can gradually wean off the heparin to coumadin, but you can’t just send them out the door because there’s not a peak until several days have passed. Likewise, if a pt is finished taking warfarin, it will be several days until coagulation pathway is back to normal. Wait several days while the body is makin gnew factor. Still at risk for bleeding.
-Adverse effects: Bleeding is #1 problem/ antidote is Vitamin K: overcomes the inhibition of vitamin K from warfarin. Pts who are on warfarin are out in society and they must be advised to use a medical alert bracelet, in case they are in an accident and have a bleeding problem. Also causes birth defects like fetal hemorrhage, central birth defects, etc…because it passes right through the placenta.
-Must moniter the PT:
-prothrombin time. Average pt is 12 seconds. This was normalized to INR. (but you don’t need to know these specifics, like what the INR would be of pt.)
-Moniter also IR: the lab would giv eyou a figure of the Pts prothrombin time vs. the control’s prothrombin time. So institutions have normalized it as INR: normalized prothrombin time. Unanticoagulated blood as an INR of 1. A pt on warfarin you are shooting for 2-3. Some pts should be more than that. If the INR is too high, like 4, you need to cut back on warfarin.
-At home kits are available for pts so they don’t need to come in and get prothrombin time tests at doctor’s.
- Dependent on Cytochrome P450 mechanism.
-Hepatically metabolized.
-99% protein bound, so drug interactions are a major issue
-Non polar: easily absorbed through GI and Placenta. So for OB pts, it is better to give heparin.
-DVT or PE: use
-Every drug that a pt takes in addition must be okayed bythe doctor.
-Nursing considerations:
-Surgury, Peptic ulcer disease, moniter IV sites, moniter platelts, if warfarin moniter INR, educate them to look for bleeding and medical alert bracelets and pregnancy.
*now we draw a little table comparing heparin and warfarin*
HEPARIN
WARFARIN
MOA
Route
Onset
_________________________________________________________________________________
Only works on 10A.
Low moleculular weight heparin.
Know why these LMWH are more convenient and why they are the choice: don’t need to moniter, pts can go home on this drug, has a predicable plasma concentration. Longer halflife. Side effects are same as heparin. Thrombocytopenia which is less than heparin. Direc thrombin inhibitors.
Direct thrombin inhbitors: used in acute care setting
-inactivate thrombin both free and inbedded within.
-Don’t need to know Direct thrombin inhibitors specifically
Warfarin is a biggie. Number one adverse effect is bleeding. Know this drug.
Antiplatlet drugs:
-Aspirin.
-Know which mechanism and its side effect.
EPP
-Receptor antagonists and how those work and glycoprotein II and IIIa and how they work.
Other antipathetic drugs.
Thrombolytics: Don’t know any specifically like names but know what they do and where they are used.
-not in notes
-in anticoagulants worksheet.
-promote conversion of plasminogen to plasmin and that enzyme chews up clots. So if she gives this thormbolyticl ike streptokinase they are clot busters. Zbut you don’t need to know the names of any specifics. Given to babies with clots in their extremities.
Will make a study guide again.
Anemias: read about several. #2 most common and deadly disease in the world. Extremely common. Like iron deficiency. Common in underdeveloped countries. Can affect mortality and morbidity, particularly in vulnerable pts. Renal disease, congestive heart failure, cancer, etc… Can make quality of life awful. For the normal person who has had trauma and lost blood they can get over the hump and be healthy again.
What is anemia?
-The reduction in number of RBCs, size of RBCs or hemoglobin content of RBCs. Normal hemoglobin is 13 for men and 12 for women. Can be due to blood loss, hemolytic, bone marrow disfunciton. Deficincy anemais,
1. Iron
2. B12
3. Folic Acid.
There are two types of deficiency:
1. Microcytic
2. Macrocytic
Iron deficiency is a microcrystal anemia. Low hemoglobin you can’t carry oxygen well to the tissues. Most of the iron the body absorbs goes into the bone marrow. Osme goes to myoglobin and a tiny bit goes to make other enzymes that have iron in them. If a patients iron stores are low the amount of iron their body takes up will be high. IF the stores are high, uptake will be low. If you give allot of iron to a pt who has high iron store, they will not take up much of it. The iron cycle is this:
Iron from your diet binds with ferratin in the small intestine mucosal cells and sometimes it gets stored there. But sometimes it passes through and binds with transferrinand makes complex.
1. About 80% can go to the bone marrow. Then it can go to the bone marrow to make RBCs,
2. can go to the liver for storage for later, Liver is a high iron tissue,
3. it can go tot hmsucles to make myoglobin and
4 it goes to tissues to make enzymes.
Body loses some iron everyday, but very little. When The liver was discovered that it was iron rich. In early 1920s, Minot was working with iron deficint dogs and fed them raw liver. Minot did the same experiment with people. Both cured.
So when a pt has not a whole lot of iron, the RBCs lack enough iron and they tend to be small, thusmicrocytic anemia. Tend also to be hypo chromic or pale. Changes depending on what the body’s stores are. Most common causes of poisoning are iron poisining. But generally if stores are high the uptake will not be high. What you need to know is adverse effects:
Nausia, vomiting, diarrhea, constipation: will make people non-adherent. Constipation is a big deal. Heartburn, bloating, etc… Tricks to get pts around this issue: GI are not dangerous and become more tolerated over time. Iron supplements wont be taken if it makes them feel awful. Taken with food, and the risk is lower. Not the same adverse effects. Problem is that aborption goes down as well. If they take iron between meals, absorption goes up but also with adverse effects. Start taking drug with meals initially and then after a week take it between meals and that way hopefully the body will have grown accustomed and the side effects wont be quite so bad. Given in eavenly spaced daily doses because the body needs a steady continuous amount. Taken morning, noon, evening. Give moms vitron C. Ascoprbic acid boosts absorption and side effects. Also antacids. Tums or Prilosec and Zantac…that increases PH in stomach, acid content is reduced and iron is not well absorbed. Last one is tetracyclines, which we don’t need to know.
Depending on severity of anemia and causes, recover will take several weeks to several months. Next drug is parenteral. This is a dangerous medication of anyphylaxis. Encourages pts to take the drug Po. And if a pt cannto take po iron because of malabosprtion then they need something parenteral. When blood loss has been huge they can get iron detrate though IV. Po iron should be the best because of anyphylaxis. Can be fatal even when treated.
Vitamin B12 anemia: treating pts with raw liver in 1920s and minot has a student who studied pernicious anemia. Was a fatal disease. Lived 1-3 years. Noticed that pts don thave gastric acid. Pts who received gastric juices and raw hamburger survived.
So humans are dependent on getting B12 from soil, microorganisms, etc.. Anmials that eat the soil and microorganisms get it, and we get it from the animals we eat. Sometimes they live on legumes, etc.. or on leafy vegetables. And allot of strict vegetarians take vitamin supplements anyways. So we need vitamin B12 in order to synthesize dna. Rapidly growing cells are most effective: bone marrow, erythrocytes, plaetelets , wbcs and gi tracts. Rapidly growing cells are most effective.
Mechanism is this: Folic acid is inactive and it needs to become activated and that’s done by vitamin B12. So without, we don’t get active folic acid. And without active folic acid, we can’t synthesize DNA. There is an alternate pathway. This is the marjor and inor pathway. So you can bypass it but not enough to survive. What you need is for vitamin B12 to bind with intrinsic factor and that’s whats in gastric jucie. So vitamin B12 binds with intrinsic factor in the stomach and it can be transported through tissues that way. But if pts do not have any intrinsic factor ad you give them enough b12 youcan get them to absorb it. Elimination of B12 is very slow, so its developed slowly over months. The causes of B12 deficiency are reduced stomach acid, intrinsic factor, diseases like celiac disease which can contibute. Consequece; affects the high growth tissues, oral ulcerations, and bone marrow disfunction and what happens is the dnA replicates and the cell can’t multiply so you have these big cells called macrocytes.
IM, SubQ, pO, and intranasal gel.
Pain: didn’t read chpter 28. But read it before Wed class. On opiods.
What we did read for today, start on pg 54 of notes and down to section of opoids and skip pg. 59. Pain is a huge issue in the hospital. Affects millions of people. Know that pain is very subjective.
IF in doubt, remember rule number 1. If a pt claims pain, you must believe them. Most common pain is lower back pain. Gate controlled theory. Best explanation so far. Go up through the spinal cord and into the brain. Perception and stimulation. Stimulation of the nose receptors causes stimulation in the CNS. Chemicals called
bradykinens
prostoglandins
cytokines
substance P
CGRP
But there are lots of others. A complicated molecular system. After stimulation you’ve got transmission. Pain stimulus travels though spinal cord up into the brain. Third stage is perception.
Ouch that hurts that’s pain perception which happens nthe brain. Laswt is modulation. And what happens ist he brain siulates other nurons which release chemical inhiitorslike norpinephrine, seratonin and endogenous opoids. And those suppress the pain. A or C fibers. Just there for your interest. When you are assessing someones pain, its called the PQRST. P is for palliation, what causes your pain,
Q is quality
R is radiation
S is severity
T is for temporal. What happens over time.
Switch to pg 59.
Nsaids
Acetopmenophen is not an Nsaid. It is not.
Cyclooxygenaseinhibitors. The body take sarachadonic acid and two types of same enzyme. Cox 1 and Cox 2 synthesizes prostoglandins and thromboxine. Prostoglandins one of their functinos is increasing sensitivity to pain. So if we inhibit this enzyme we inhibit prostoglandin s ynthesis and indoing that youreduce the action of prostoglandins and suppress our sensitivity to pain. That’s the though process behind cox inhibitors. Cox 1 is presnt in almost all tissues thoughout the body and it is responbile for housekeeping chores of the body and it has a significan taction in the gastric mucosa and cox 1 is responsible for producing prostoglandins and thomboxanes.
Prostoglandins
-act on the gastric mucusa and increase bicoarbonate secreation, which is a base.
-And in doing sothey decreaes the acid content in the stomach which is protective.
-Also stimulates the rlease of mucus inth stomach which protects the stomach.
-Also decrease acid production
-increase gastric blood flow, perfusion of the stomach.
Cox 1
-Increase renal blood flow.
-Synthesizes trhomboxane which acauses platlet aggregation.
Cox 2’s prostoglandins
-Tissue injury
-Increased sensitivity to pain and inflammation.
-Affects set point for thermogregulation so those prostoglandins cause fever.
-Presnt in the kidneys and the prostoglanin synthesized from those Cox 2 increase renal blood flow.
NSAIDs.
-Aspirin: only one we need to know
-blocks cox 1 and cox 2
-well absorbed kinetically. Converted to an active metabolite. Elimination is dependent on ph. Aspirn is a weak acid and if you want to get rid of aspirn quickly youcan mekt he urin more basic and that will help get rid of aspirin. If aspirn blocks cox 1 then it would have a role in thromboxine synthesis blocking it, reducing platlet aggregation. Used prophylacitcally. Antiinflammation. Also bocks prostoglanin synthesisis at tissue site reducing pain. Sensitivity reducing paiat injury site and perception of pain in the CNS. Also works since cox two is presntinthe brain it also works as a fever reducer. We do not use aspirn in children at all anymore. Reyes syndrom/.
Dysmennorrea. Reduces pain in smooth muscle of uterous;
____________________________________________________________________
October 8 Wednesday
Lung Cancer and Breast Cancer
Types of Breast cancer: ductal and globular
Ductal Carcinoma in Situ DCIS
-others are being more selective in pt population
Ductal Breast Cancer
-more invasive. Insitu means it hasn’t started to invade the basement membrane. Ductal then has become invasive once its called breast cancer. Large nucleated cells filling the ducts. Once it becomes more advanced moving well beyond the ducts. More advanced. Subcategories of ductal breast cancer. Globular
Carcinoma in situ. Before it penetrates the basement membrane.
-No one treats this as a benign condition.
Infiltrating lobular
Pagets disease
-Description of the nipple. Ductal carcinoma that involves the areaola itself. Itching and oozing a common problem.
Inflammatory Breast cancer:
-Worst possible diagnosis
-Aggressive/Invasive
-Orange-peel skin overlying the tumor.
Half of women will be dead already by the time they reach 85. Chance getting it by 85 is 1:7. Live to age 79, risk is 1:15. Percent of women to die of breast cancer is 2.8% which is similar to chance of dying from a hip fracture. Risk of death by breast cancer decreases when you’re old, but only because you’ll probably die of something else first. May be more on our mind, since it affects younger people and its more on our mind.
Risk factors on pg. 106
Spending more time on genetics than anything else. Age is a risk factor and family history is certiantly a risk, even without knowing anything else about genetics. Definable genetical mutation, which is inherited. Mutation of the BRCA gene #1.
BRCA=breast cancer gene. This particular mutation is not one mutation, there are at least 17 mutations that can affect this gene. Another word is polymorphism. MOre and more when you look at the literature it means that a gene has many many possible mutations. Only a few mutations confer a significant enough risk for breast cancer. There’s a mutation and in different people it means different risks. If you look at BRCA mutation in general which is located on chromosome #17, and found in 1 in 500 women, you have a 40% risk in your lifetime of ovarian cancer.
Options include more frequent screening, diet and exercise, avoiding fatty foods, prophylactice removal of the breasts (both) which is the only kind of surgery where you don’t do anything with the lymph nodes. Gives you a 98% reduction in risk. But this person is also at risk for ovarian cancer, which could be a oopherectomy. Removed primary source of growth factor for breast cancer.
So
-double simple prophylactic mastectomy (cosmetic and breastfeeding issues)
- oopherectomy (no children, osteoperosis, and hot flashes…needing HRT)
-more frequent screening
BRCA 2 is a different gene.
-much higher risk for breast cancer
-not as high a risk for ovarian cancer
-men get this mutation
-increases risk for other cancers too, though.
Indications for Genetic screening in Breast cancer.
-90% is sporadic, rather than inherited. These mutations would be called aquired.
-Know that P53 is a significant risk.
-Women who inheret a BCRA, must be homozygous. Women who don’t inherent these mutations much less commonly aquire one. When you inheret a mutation of a gene you can be vulnerable to other mutations.
What cells in the body are going to have an inherited mutation? ….
Every cell ijn the body. You inheret the same DNA in every cell which makes the same perosn. You find an aquired mutation only in the tumor itself.
Methylation Problems
Early menarche or late menopause, high circulating levels of serum estradial or HRT. Estrogen is a growth factor for tumors. When we are talking about HRT we are talking about stimulating a cancer that was already there and making it grow faster. Lifetime exposure cause some carcinogenic effects over a lifetime. High levels of estrogen for 40 years, that may actually be a carcinogenic exposure over that many years. But if a women goes through menopause at age 52, its highly unlikely that estrogen caused the mutations, it was simply a growth factor. Birth control pills have finally been laid to rest as a risk factor for bresat cancer. If anything, the current forms of birth control are protected reducing the risk of breast cancer. With HRT we are stimulating a tumor that’s aready there.
Mitogenesis
-increases cell divisions
Mutogenesis
-of oxidative damage to the DNA.
WHI results: statistics can be a little misleading. If you have tumors and you take estrogens that cause tumor to grow over next few years. Look at the hazard ratio for breast cancer in year five.
No risk with abortions. Oral contraceptive use, and decreased risk of breat cancer with breastfeeding and pregnancy.
…
Pg. 108: Progressive cellular and tissue changes.
Why does pregnancy help prevent? Where the cells are most ready to divide. Cells that are most vulnerable are places where cells are ready to divide anyways. That’s true in the breast also. The portion of the total breast tissue hwere there is the most cell division is Lob 1. Active undifferentiated part of breast with high proliferation rates. Present in geastest amounts between onset of puberty and first child making this the most vulnerable time. Allows the cells to differentiate further into more mature cell types called Lob 2 and Lob 3.
Increased risk in breast cancer is called proliferate breast disease: Fibroadenoma also known as a cyst. Many women have fibro adenomas and cysts int heir breast and this is why…
However if the cyst if full of cells even if they are not cancerous yet they are called atypical hyperplasia this is a significant breast cancer. Women come sin the clinic feeling alump, and mamogram looks funny. They might do a digital mamogram and then an ultrasound. If the lump is full of fluid, they say it’s a cyst don’t worry about it, but if its solid on ultrasound, they are going to biopsy it. That’s how we get clinical evaluation of breats cancer. Past history of breast cancer increases risk for another one.
Gale model: one way women can type in their personal info and get some indication of what hteir risk factors are.
Mutations:
-Formation of oncogenes and mutation of sumor suppressor genes
_Aquired p53 mutation
-BRCA inheritance
-other gene mutations.
Bottom of page. 108: Atypical hyperplasia CIS eventually leading to invasive carcinoma.
Concept of the growth factors in a little bit more detail.
The most important growth factor in breast cancer is estrogen. Required for normal breast cell function. Activation of breast cells at puberty. In neoplastic cells, estrogen stimulation results in over stimulation of growth factor reduction resulting in uncontrolled proliferation.
Estrogen receptor positive…normal cells have estrogen receptors, but if the tumor hast retained its estrogen recetpors it is at least in that way more normal. A better chacne of controlling gtumor, slower growth, and we can block the cancer with Tomoxafin and blocking estrogen synthesiis then those tumors will not progress. That implies about ….
ER negative: Autocrine sitmulation. Don’t need estrogen and don’t care about oopherectomy, tomoxifin or drugs that block estrogen synthesis. That’s when we talk about ER positive and ER negative. Progesterone receptors…tumors are more responsive and slower growing. Insulin-like growth factors don’t have much to do with insulin. All called IGFs. Alpha, beta, gamma, and play a variety in diseases.
Epidermal growth factor: Her2/neu. Treated with HERCEPTIN which blocks the Her receptors and prevents the growth promoting effects of epidermal growth factor. You will see women who are on herceptin for breast cancer.
What we do in looking at brast cancer…usually occurs in upper, outer quadrant. Retaracting and making the breast look asymmetric. Mostly will be found when it’s a little lump. Second most common place is upper, inner. If you look closely you can see that the skin is starting to look different. Regional spread is to the axillary nodes. The amount spread to the nodes is related to how big the primary tumor is. Divided into three regions that help predict prognosis. If you don’t feel nodes, that doesn’t mean that there isn’t cancer there. You have to sample the nodes to make sure they are negative for cnacer.
Sentinal node: injecting dye and watcing for it go to into the sentinal node. If the node is negative, then you are fine. Spreads to lungs, bones, brain, adrenal glands, etc…
MRI better in mammography.
Excisional biopsy
Sentinal node
PET scanning
TNM tumor nodes metastises.
Pharm: Angina , Afterload, Coronary system, specific drugs
Angina stretch that the ventrical feels. What determines the stretch of the heart? Preload.
Preload higher increases oxygen demand as well as contractility and heart rate.
At what condition does the heart need to push arder in order to get the heart to empty.. If you have high afterlaod with allot of arteriolar peressure then the heart needs to use some extra force to get the blood out of the heart. So that’s how heart rate, contractility, after load and preload affect demand. The only t hing we know that increases oxygen suppyly to the heart is to dialate the coronayr arteries. With every heartbeat the blood that gets delivered ot your heart most of your oxygen gets taken right out of there. The only way the heart can’t takey anymore oxygen out of the bloodi s to take as much asyou can?
So how does the heart rate increaes coronary blood flow? A faster heart beat deliveres more blood to the heart that increases coronary blood flow. So when you exercise and the heart needs lots of blood the demand is high so you decrease your heart rate and the coronary blood supply jumps up several times. If you increase b lood flow to the heart you increase oxygen supply. The blood has oxygen in it so you increase its supply.
Now, lets move on. We are going to try to put all of these thigns together. Does heart rate increase supply and demand? Yes.
Afterload and demand. If you hae a narrow aorta then the force to get it into the periphery is much higher. That is after load. So as after load goes up the heart has to use more force and a stronger contraction in order to get the blood out.
Why is it necessary to treat hypertension? Lead sto heart disease. Renal disesase. Stroke. Want to present kidney disease.
Equations:
AP =PR x CO
CO = HR x SV
AP=PR x (Sv x HR)
So we will target all of these things.
Vasodilators reduce peripheral resiistance
Heart rate
Stroke volume
How our bodies regulate our bp.
-bar receptor reflex in the corodit sinus and in the aortic arch there are little pressure sensors. If the BP goe s down we send a signal to the brain stem. The brainstem increases sympathetic outflow. Sympathetic outflow works on beta 1 receptors hre. WE know what sympathetic outflow on vessels does. IT restricts them to reduce preload and after load and bp. WE know what increasing sympathetic outflow. So after that happens the BP goes up and the baro receptors stops firing and stops sending messages. The whoel feedback system.
The baro receptors funcing on that high set point notice that it’s difference. That’s a bioreactor thign.
Second way is through the renin angiogenesis aldosterone system. How sodium and water retuntion workw ith kidneys and diruetics to control bp.
Drugs we can use to regulate bp. So first we have the drugs we use in the brianstem. Claunodine. That’s the alpha II agonist. Remember that mechanism. Alpha II receptors are on the rpresynatpic membrane when you turn those on you turn the presynaptic cell off and reduce the brainstem outflow.
Resurpine:
When presynaptic neuron is stimulated thare is nothing to put in the synapse it dissipates into tnohign . Less beta 1 less alpha 1 less peripheral resistance and less HR. The side effects of Resurpine that make it not our favorite: Depression and awful diarrhea.
Beta blockers:
Propranolol:
-nonselective beta blockers and beta blockers. Work on beta 1 and beta 2. That’s propranolol. Blcoks beta 1 receptors: decreased HR, decreased force of contraction, slows down conduction for the av node. Beta blaockers slow conduction for the AV node so all of thos ethree effects cause slowind down of cardiac muscle. Lower heart rate, less stroke volume (because force of contraction is lowered with less volume being pumped o ut). We’’ve done nothing with peripheral resistance. Renin restriction.
-And when you block beta 2 receptors: bronchconstriction. Looking at lungs and liver. Inhibit gycogenolysis. Lowered ability to create glucose. This class of drugs does not affect alpha receptors.
- Kinestica: highly lipid soluble, gets into the CNS easily. Use these drugs for hypertension, angina, dysrythmias due to AV slowing, and used in pts with MI as well.
Side effects: blocking beta 1 receptors: decreased HR or bradycardia. AV heart block. Some pts are more prone than others. Pts who already have AV block should not receive beta blockers or be very cautious when giving them. Bronchoconstirciotn: not a huge effect, but be careful with asthmatics and COPD.
-Inhibition of glycogenolysis: not a big deal. Be very cautious with Ivs. Problem with hyperglycemia? Not a good thing.
-If glucose gets slow the body doenst have an ability to pump up the glucose level. Another thing is one of the sgns nd symptoms of hypoglycemia: anxiety and sweating. Pts with diabetes are on the alert for that. So their glucose may get very slow since their hear rates won’t go up and they wont’ feel jittery.
-CNS affects; insomnia, nightmares, hallucinations… uncommon but pts with depression are much more at risk.
Drug interactions:
Calcium channel blockers
Insulin
There are many nonselective and selectives. Properanolol and metropolis.
No beta two for metrololol
Decreased HR for ce of contraction , AV node
NO broncho constriciton.
Adverse: bradycardia, av block.
If pts been on for a hwile and dr says they can stop beta blockers there is a risk of reobund hypertension. All beta blockers need to be tapered slowly over a week or two. Don’t stop immediately. Propranolol used allot for stage fright or migrane headache. Metropolol are used for.
Stage fright: heart rate doesn’t go up and you don’t have that anxious feeling. Propranalol not used in pts with CHF. But metropolol does.
Moving on to Reducing BP:
Alpha 1 blockers: Crazinsin?
Don’t act on alpha one receptor but on vascular smooth msucel: Hydralazine and metnostazil. Menoxazzil increased potassium, vasodialation.
Decreaed peripheral resistance. Problemw ith alpha one blockers and hydrolyzing causing vasodialation is stimulating bacro receotr. The side effect of all of those is reflex tachycardia. Know side effects of crazasin. Reflex tachycardia for a ll three
Nitropresside: turns into NO and that dilates the vessels. Used in hypertensive crises in ER. Titrated quickly. Given IV. Side effects: cyanide poisoning with thyosianate toxicity.
Calcium channel blockers:
Nifedipine: works only on vascular smooth msucle
Work on vascular smooth msucle AND the heart itself.
Vorapimil -shorter duration of action.
Viltiazim.
Contractino of cell causing constriction. Influx of calcum in the myocardium itself increases contractility. Influx of calcium into the SA node, the palce maker increaes the pacemaking activity. Also increased calcium in the AV node increases conduction velocity.
Dixoxin: favorite on NCLEX
Suppresses AV conduction
Preload higher increases oxygen demand as well as contractility and heart rate.
At what condition does the heart need to push arder in order to get the heart to empty.. If you have high afterlaod with allot of arteriolar peressure then the heart needs to use some extra force to get the blood out of the heart. So that’s how heart rate, contractility, after load and preload affect demand. The only t hing we know that increases oxygen suppyly to the heart is to dialate the coronayr arteries. With every heartbeat the blood that gets delivered ot your heart most of your oxygen gets taken right out of there. The only way the heart can’t takey anymore oxygen out of the bloodi s to take as much asyou can?
So how does the heart rate increaes coronary blood flow? A faster heart beat deliveres more blood to the heart that increases coronary blood flow. So when you exercise and the heart needs lots of blood the demand is high so you decrease your heart rate and the coronary blood supply jumps up several times. If you increase b lood flow to the heart you increase oxygen supply. The blood has oxygen in it so you increase its supply.
Now, lets move on. We are going to try to put all of these thigns together. Does heart rate increase supply and demand? Yes.
Afterload and demand. If you hae a narrow aorta then the force to get it into the periphery is much higher. That is after load. So as after load goes up the heart has to use more force and a stronger contraction in order to get the blood out.
Why is it necessary to treat hypertension? Lead sto heart disease. Renal disesase. Stroke. Want to present kidney disease.
Equations:
AP =PR x CO
CO = HR x SV
AP=PR x (Sv x HR)
So we will target all of these things.
Vasodilators reduce peripheral resiistance
Heart rate
Stroke volume
How our bodies regulate our bp.
-bar receptor reflex in the corodit sinus and in the aortic arch there are little pressure sensors. If the BP goe s down we send a signal to the brain stem. The brainstem increases sympathetic outflow. Sympathetic outflow works on beta 1 receptors hre. WE know what sympathetic outflow on vessels does. IT restricts them to reduce preload and after load and bp. WE know what increasing sympathetic outflow. So after that happens the BP goes up and the baro receptors stops firing and stops sending messages. The whoel feedback system.
The baro receptors funcing on that high set point notice that it’s difference. That’s a bioreactor thign.
Second way is through the renin angiogenesis aldosterone system. How sodium and water retuntion workw ith kidneys and diruetics to control bp.
Drugs we can use to regulate bp. So first we have the drugs we use in the brianstem. Claunodine. That’s the alpha II agonist. Remember that mechanism. Alpha II receptors are on the rpresynatpic membrane when you turn those on you turn the presynaptic cell off and reduce the brainstem outflow.
Resurpine:
When presynaptic neuron is stimulated thare is nothing to put in the synapse it dissipates into tnohign . Less beta 1 less alpha 1 less peripheral resistance and less HR. The side effects of Resurpine that make it not our favorite: Depression and awful diarrhea.
Beta blockers:
Propranolol:
-nonselective beta blockers and beta blockers. Work on beta 1 and beta 2. That’s propranolol. Blcoks beta 1 receptors: decreased HR, decreased force of contraction, slows down conduction for the av node. Beta blaockers slow conduction for the AV node so all of thos ethree effects cause slowind down of cardiac muscle. Lower heart rate, less stroke volume (because force of contraction is lowered with less volume being pumped o ut). We’’ve done nothing with peripheral resistance. Renin restriction.
-And when you block beta 2 receptors: bronchconstriction. Looking at lungs and liver. Inhibit gycogenolysis. Lowered ability to create glucose. This class of drugs does not affect alpha receptors.
- Kinestica: highly lipid soluble, gets into the CNS easily. Use these drugs for hypertension, angina, dysrythmias due to AV slowing, and used in pts with MI as well.
Side effects: blocking beta 1 receptors: decreased HR or bradycardia. AV heart block. Some pts are more prone than others. Pts who already have AV block should not receive beta blockers or be very cautious when giving them. Bronchoconstirciotn: not a huge effect, but be careful with asthmatics and COPD.
-Inhibition of glycogenolysis: not a big deal. Be very cautious with Ivs. Problem with hyperglycemia? Not a good thing.
-If glucose gets slow the body doenst have an ability to pump up the glucose level. Another thing is one of the sgns nd symptoms of hypoglycemia: anxiety and sweating. Pts with diabetes are on the alert for that. So their glucose may get very slow since their hear rates won’t go up and they wont’ feel jittery.
-CNS affects; insomnia, nightmares, hallucinations… uncommon but pts with depression are much more at risk.
Drug interactions:
Calcium channel blockers
Insulin
There are many nonselective and selectives. Properanolol and metropolis.
No beta two for metrololol
Decreased HR for ce of contraction , AV node
NO broncho constriciton.
Adverse: bradycardia, av block.
If pts been on for a hwile and dr says they can stop beta blockers there is a risk of reobund hypertension. All beta blockers need to be tapered slowly over a week or two. Don’t stop immediately. Propranolol used allot for stage fright or migrane headache. Metropolol are used for.
Stage fright: heart rate doesn’t go up and you don’t have that anxious feeling. Propranalol not used in pts with CHF. But metropolol does.
Moving on to Reducing BP:
Alpha 1 blockers: Crazinsin?
Don’t act on alpha one receptor but on vascular smooth msucel: Hydralazine and metnostazil. Menoxazzil increased potassium, vasodialation.
Decreaed peripheral resistance. Problemw ith alpha one blockers and hydrolyzing causing vasodialation is stimulating bacro receotr. The side effect of all of those is reflex tachycardia. Know side effects of crazasin. Reflex tachycardia for a ll three
Nitropresside: turns into NO and that dilates the vessels. Used in hypertensive crises in ER. Titrated quickly. Given IV. Side effects: cyanide poisoning with thyosianate toxicity.
Calcium channel blockers:
Nifedipine: works only on vascular smooth msucle
Work on vascular smooth msucle AND the heart itself.
Vorapimil -shorter duration of action.
Viltiazim.
Contractino of cell causing constriction. Influx of calcum in the myocardium itself increases contractility. Influx of calcium into the SA node, the palce maker increaes the pacemaking activity. Also increased calcium in the AV node increases conduction velocity.
Dixoxin: favorite on NCLEX
Suppresses AV conduction
Vasodialators, Ace I inhibitors, renal failure
Finishing up with blood vessel drugs, specifically vasodialators. Review of angiogenesis aldosterone system. There is angiotensinogen that is converted to angiogenesis one via renin and renin is released dehydration, low blood pressure, decreased sodium. Angiotensin I is inactive. Once it is formed it is rapily formed to angiogenesis II. Put these up on collab so we can download them.
Angiotensin II actions. Changes in periphera resistance. Causes vasoconstriction.
CAPTICRIK: used in treatment of hypertension and heart failure. Thsee drugs are good in treatment of heart failure for several reasons like dilating the arteries which promotes after load so the heart doesn’t have to work so hard and is pushing against a high pressur esytem it does also act on veins so if you dialte the veous sytem you are decreaing preload so there is less cardiac return and the heart’s cardiac output can go down so its good on both sides. Less pressur ethat the heart has to work against. Less venous returna nd volume for the heart to pump out. That’s good for a diseased heart. Also since it causes dilation of the renal arteries it increases glomerular filtrationa and allows the body to get rid of sodium and water. Important for pts with heart fialure. Used in treamtent fo rpts with MI’s. Post MI’s.
Ace I inhibitor Side Effects:
There are also pts with nephropathy. Diabetic or not. Dilate the renal vasculature and lessen the pressure for glomerular apparation apparatus. Prevention of stroke and MI. Research on that si still ongoing. Ace inhibitors have a couple of adverse affects. First dose hypotension. Soon after you give an ACE inhiitors youg et a significant effect with the first dose. So how might we treat that? How might we avoid having htem fall on the floor? Don’t start with full dose. Have them lying down. Measure BP before and af ter they take it. Now, cough is the annoying side effect of ace inhibitors. Can occur within days or months. Anytime it’s a persistant non productive cough. Not contagious.
Cough is caused by bradykinen effect. So if you blick bradykinen brakedown, you have an excess of it.
Hyperkalemia is an increase of potassium Sodium water and potassium are all regulated and go together so when you have sodium and water retention you have a buildup of potassium. So there is a tendency for pts to get hyperkalemia. Salt substitutes is potassium instead of sodium. So there are allot of pts who are told to reduce their salt intake and instead of taking stalk they take No-salt. When you have high potassium you are at a risk of serous dysrhythmias. Potassium levels os ace inhibits polus those diuretics the pts who are not taking those diuretics. Hyperaklemia is generally not a problem. You don’t want or need to avise them not to eat banannas, etc….
Renal failure: can be a problem in a small population. In those with renal bilateral stenoss. So here sthe golmerulus. AN affferent arteriole. Goes in there and ef feerent blood comes out. This apparatus is very carefully regulated as far as pressure. The pressur ethat goes though tis glamorous is carefully regulated. And if the afferent arteriole constricts then the efferent constricts. Pts who have athrosclerosis. Paque forms here. O in the normal situation without an ace inhibitor the plaque reduces blood flow to the glamorous. Consitrct in order to normalzie that pressure. If you give an ace inhbitor you will cause vasodilation of the efferent and woul d of the afferent but youc an’t because its got all kinds of plaque in it. So tohe blood though going to afferent doesn not change. But efferent changes cause its got a n ace inhiitor. So the pressure within the glamorous the pressure I goes right down and the pressur echanges dramatically. So for pts with bilateral plaque formation in both kidneys. Bilateral renal artery stenosis, that can be dangerous. That can cause serious kidney disfunction failure, etc….
Another aadverse effect is fental injury. Pregnant women need to stop taking it. The second couple of trimester makes it bad for fetus, not so much the first.
Angioedema is a life threatening side effect where the epiglottis and the tonge because really swelled and cut off the air supply.
Vasodialtion from the ace inhibitors that promostes water loss can be a good interaction for those inheart failure. Some people need that, but some people’s pressures would drop through the floor. So it all depends.
Ace inhibitors are very highly effective good for pts with cardiac disease.
___________
A new class is ANGIOTENSIN II RECEPTOR BLOCKERS.
Less evidence tha they reduce mortality. They are not irst iline agents because they are not less effective, but hteir reduction in mortality has not been shown yet. These do not lock the enzyme ase at all. They block angiotensin II receptors. They don’t have a bradykinen effect. That kinase II effect is not at play here. O thse are n used primarily for the same things as inhibitors. Storke provention. HTN, CHF, DM neuropathy, MI, etc… blocking the angiotensin . Vasodialation, preripharal and renal. Blockage of aldosterone release. Same as ace inhibitors. Just a different mechanism. The current kinetics are all available Po. Increasing number of drugs with every passing year. Often used with diuretics. Just like ace inhibitors. Angioedema is still a risk but it is even more rare with ace inhibitors. Angioedema on an ace inhibitor they can be put on an R but there is still a risk of angioedema with those pts. 8 to 10 % do have cross sensitivity to angioedema. Worth the risk. Rare to begin with then the rare pts can take an R but you do need to watch them a little bit. Not like its 90%. Bilateral renal artery stenosis. No cough, no bradykinen effect. Pts who cannot taolerate if they need to be switched from Ace inhibitor to R because of cough then that’s okay. Another class is calcium cahannel blockers. Ther are two types. Only talk aobut one today.
VSM is vascular smooth muscle. Nifedipine works only on VSM. Verapamil and diltiazem work on both vascular smooth muscle and on the heart. Mechanism of action is that it blcoks Ca channels. SO the role of calcium channels is that they sit in the plasma membrane when a cardiac or vascular smooth muscle cell the calium chennel moves open and pores into the cell. So if you block the calcium channel then you don’t get the clium influx or cell excitation. Block sthe action of calcium channels. The effect is to cause constriction. So if you block calcium influx you cause dilation. That happens in the arterioles of the whole body and of the smooth muscles of the arteries not on the heart msucle themselves. If the vasculature is dilated, what reflex is there to compensate for dropping BP? With these drugs, reflex tachycardia is an issue. A drop in BP by dilating the vasculature stimulates the bar receptor reflex. That’s true for niphedipine. Not for other two.
Calcium channel blockers are used for pts with hypertension and angina? The kinetics are that there are two types of formuls. The rapid actin fomrualt is likey to ause a quicker onset of action so that large vasoedilation that happens kind of quickly with cause the bar receptor ot take over. Slower actin formuales, sustaine drelease act a bit slower and cause a more gradual dcrease. Reflex tachycardia is not such as issue but it still can occur the effect alances out ove rtime. Dverse effects include flushing dissiness and heaache. Suually well tolerated. Nifedipine is often given with a beta blocker, and we have beta receptors in the heart and lugs. If you stimulate beta I you get an increase in heart rate so if you block beta I you block heart rate increase. So youc an block the reflex tachycardia.
This drug , Hydralazine. Makes less calcium inside the cell. Selective for arterioles rather than veins so if you dilate the arteries you cause a decreased after load and therefore a decreased blood pressure bu rtyou do get a reflext tachycardia. Remember hwo in the beginning the arteriol es and arteris don’t hav ea ahuge stretch factors. The venous system has a huge stretch capability. Dilating ateriole side doesn’t caus the same t yep of postural hypotension as dialting veins does because ther is only so far theey can stretch. When you dilate the arteriole sid e the postural hypotension does not occur so much. Hydralazine. Can be given Po or IV. PO works in 30 to 45 minutes. Acts for 5 or 6 hours. Can be used IV like in hypertensive crises to reduce rapidly. Shoter duration of activity when its given IV. Can be used PO for pts with hypertensino. Hypertensive crisis. Adverse effects include reflex tachycardia. Baro reflext. Also sodium and water retention. When the vasculature dilates the decrease in BP makes the body think there isn’t enough blood volume. Sodium and water are retained like that. So allot of times they are given with a diuretic type drug. SLES: system lupus elytrous syendorme? Symptomes like lupus. Joint pain, fever, etc… reversible after the drug is gone.
So because eof this water and sodium rentention we give the drug with a diruetic because of reflextacchycardia and contractility we ive a beta blocker. Other hypertensives can be additive which can be a goo thing or additive which also be a bad thing. You will see Hydrolazine usedin hopsital setting.
Mechanism of mInoxidil
-increases intracellular potassium which hyperpolarizes the cell which releaes the cell. Increased potassium hyper polarizes the cel which causes the cell to relax. Selective for arterioles. Used in pts iwht hyeprtension. Used in arteriolar dilation. Sodium and water retention like hydrolyzing. And hypertrichosis. Minoxadil is rogaine used topically for hair growth. Drug designed to treat hypertension. Side effect is a potentially money making sceme.
Nitroprusside. Sodium ad ron.. And Cyanide.
Nitropressid eis converted to Nitric oxide and cyanide. Nitric oxide is a powerful vaso dialtor. Metabolized . Cyanide is converted in the liver to thiocyanate. Thiocyanate is excreted by kidneys so if a pt has liver disease they have a risk of accumulating cyanide. Those pts have to be monitored for t heir cyanaide toxicity. Pts with renal diseae are tat risk for accumulating cyandide. Either one or both of thse is a send out lab. Extremely effective. Rapidly active. You can titrate it very carefuly minute to minute. You risk all kind of reprofusion. You can to pull it down a little bit at a time. Nitropresside can be handled very farully. Used in hypertensive crisies. Cyanide poisoning
Angina; Sudden chest pain. Athrosclerosis or vasospasms. Mycoardialoxygen supply and demand. Demand increases wen heart is beating fast. It needs more oxygen that’s the same thing is having incread oxygen mean. A stronger more forceful contraction also increases oxygen demand. And wall tension has to do with preload and after load. The more the heart is stretched the cardiav filling the heart needs more oxygen to get that blood out an if th ehart is beting aginst allot of pressure it needs more oxygen to push aginst the heigh pressur eystem. So things that increase cardia oxygen demand are heart rate, contractility, preoload , and after load. Typically with each hear tbeat, two things> the coronary arteries prefuse the heart during diastole only. During sytole the coronary arteries are squeezed tight. Whenblood is relaxed, blood goes through the heart. So whenthe heart is beating, the arteries come up though the base of the aorta. Nt a whole lot goes thorugh the contrary arteries and perfuse the heart.
Second, on a normal cardia ccycla all the oxygen divlered to the heart during diasole al of ithe oxygen is e tracted by the heart. With every diastol the blood thg goes through the art all gets used. So the only way to increae t oxygen supply to the myocardium is o dialte the vessels t get more blood flow so myocardial oxygen supply by dilating the arteries and increasing the blood flow. Wo types of angina. This is a vaso spams. This is called a vasospastic angina. So it can happen anytime night or day. Tnohing to do with exrcise. On the other and it is much more common in this country where there is athrosclerosis somewhere alllont here. Angina occurs when the heart nees t wokand needs more oxyg And so the heart needs more blood but the arteirs can’t diate to compensate.
So this type of angina is tgenrally a demand t ype of angina. So if the pts sits and rests the ainga goes away. The heart doesn’t need all tat oxygen when the pt is resitn ghte agina goes away. This istable. This is a demand type angina and this is a supply type agina. So if the cornary artery is not spasming it could idlate but when its spasming the supply to the heart goes don. This is a supply type, t his is a dmeand type. One of the drugs we use to treat aginina is
Nitroglycerine
Converted to nitric oxide the powerful vasodialtor by chemicals that have sufichdric groups? There are only so many sulfhydryl groups that can cause this reaction. Once they are depleted you ca n’t ge th e reaction anymore and so primarily the nitritogyceirne acts that he side at the veins and it ialso acts on cocnary ateries. Does not have a n action on arteriole peripheral system It mostly venous. So if you dilate the viens ou reduce the prelodad. And does preload play a role in oxygen demand? Yes it does. Heart rate ,c ontactility, preload and after load. IF you dilate veins you reduce your prelod. Nitrolgycerine alo acts on contrary lbood flow on the ateries an that incrteas the suppl yso this aspect of ntiroglyerine can affect the stable parts. vs. treating the vasospasm types. Good fore both types.
A few thigns about kinetics. Please go bak and read chatper fifty in your tex book on angina and nitroglycerine. Make sur eyou hav eit cold befor eyou take the NCLEXX. Need to know lot sof htings about nitroglyceirne. Kinetics. EXAM will be asked a Kinetics quesitno about tnitrogyueirne. Goest though tissues easily. HUGe first pass mechanism. Only a tiny fraction actually gets where it needs to go wo we tend to get the drug through sublingual buccal or Tran lingual spray it gets aborbed directly thorugh the aulature which drain it into the heart and that’s eactlywhere we ant it o go. Also have ointments and patches and pasts and sustained release formulas po. So a pt who has hastbe angina and mows his lawn and gets aninga will needs something that will act rapidly. So does tht peron need to be waring a pathc” no they need sublingual which will work fast. Or a buccal spray.
So lipid soluble that if you get past on your finger syou will get systemic vasodilation. You could always were glvoes th efirst sign of it is a headache. So if you’re working with nitro past wash it off as soon as it youcan. Tolerance. Remmeber hwo tnitroglycerine requires sulfhydral groups in order to be converted to nitrix oxyide: in tehsapan of 24 hours pt s deplete their sulhyrl gropus anymore. So pts who hav particularly vasospasitc ned a restorativ etoime to resutore their sulhydryl groups. If they need an attack in the night they can do it but they shouldn’t wear the patch all night. Only take it when you have symmptioms. So
Pts with stable angina who get it rin resposne to exercise they should tak eit when they are symptomatic. So they have a nitrate free time as well. When we tal about heart drugs we’ll pull this back in and tlakabout guidelines aobut when to giv ethe drug.
NTG
Side effects adverse> headache, orthostatic hypotension, reflex tachycardia,
Drug interactions” hypertensive agents, MDE5 inhibitors.
NTG to NO to cGMP (increase in Cyclic GMP )wich cuases vasodilaation.
PDE5 I are erectile dysfunction drugs. This is not to be used for pts with nitroglycerine. Phosophodiestriase breaks down cyclic GMP. The inhibiotr blocks that. If you give nitroglyceirne and bump the amount of lcycicl GMP youc an cause vasodiatio and if you give a phosphodisterize inhbiot then you have Tooons of cyclic GMP and tooons of vasodilationand a huuuge drup on blood pressure .
Angiotensin II actions. Changes in periphera resistance. Causes vasoconstriction.
CAPTICRIK: used in treatment of hypertension and heart failure. Thsee drugs are good in treatment of heart failure for several reasons like dilating the arteries which promotes after load so the heart doesn’t have to work so hard and is pushing against a high pressur esytem it does also act on veins so if you dialte the veous sytem you are decreaing preload so there is less cardiac return and the heart’s cardiac output can go down so its good on both sides. Less pressur ethat the heart has to work against. Less venous returna nd volume for the heart to pump out. That’s good for a diseased heart. Also since it causes dilation of the renal arteries it increases glomerular filtrationa and allows the body to get rid of sodium and water. Important for pts with heart fialure. Used in treamtent fo rpts with MI’s. Post MI’s.
Ace I inhibitor Side Effects:
There are also pts with nephropathy. Diabetic or not. Dilate the renal vasculature and lessen the pressure for glomerular apparation apparatus. Prevention of stroke and MI. Research on that si still ongoing. Ace inhibitors have a couple of adverse affects. First dose hypotension. Soon after you give an ACE inhiitors youg et a significant effect with the first dose. So how might we treat that? How might we avoid having htem fall on the floor? Don’t start with full dose. Have them lying down. Measure BP before and af ter they take it. Now, cough is the annoying side effect of ace inhibitors. Can occur within days or months. Anytime it’s a persistant non productive cough. Not contagious.
Cough is caused by bradykinen effect. So if you blick bradykinen brakedown, you have an excess of it.
Hyperkalemia is an increase of potassium Sodium water and potassium are all regulated and go together so when you have sodium and water retention you have a buildup of potassium. So there is a tendency for pts to get hyperkalemia. Salt substitutes is potassium instead of sodium. So there are allot of pts who are told to reduce their salt intake and instead of taking stalk they take No-salt. When you have high potassium you are at a risk of serous dysrhythmias. Potassium levels os ace inhibits polus those diuretics the pts who are not taking those diuretics. Hyperaklemia is generally not a problem. You don’t want or need to avise them not to eat banannas, etc….
Renal failure: can be a problem in a small population. In those with renal bilateral stenoss. So here sthe golmerulus. AN affferent arteriole. Goes in there and ef feerent blood comes out. This apparatus is very carefully regulated as far as pressure. The pressur ethat goes though tis glamorous is carefully regulated. And if the afferent arteriole constricts then the efferent constricts. Pts who have athrosclerosis. Paque forms here. O in the normal situation without an ace inhibitor the plaque reduces blood flow to the glamorous. Consitrct in order to normalzie that pressure. If you give an ace inhbitor you will cause vasodilation of the efferent and woul d of the afferent but youc an’t because its got all kinds of plaque in it. So tohe blood though going to afferent doesn not change. But efferent changes cause its got a n ace inhiitor. So the pressure within the glamorous the pressure I goes right down and the pressur echanges dramatically. So for pts with bilateral plaque formation in both kidneys. Bilateral renal artery stenosis, that can be dangerous. That can cause serious kidney disfunction failure, etc….
Another aadverse effect is fental injury. Pregnant women need to stop taking it. The second couple of trimester makes it bad for fetus, not so much the first.
Angioedema is a life threatening side effect where the epiglottis and the tonge because really swelled and cut off the air supply.
Vasodialtion from the ace inhibitors that promostes water loss can be a good interaction for those inheart failure. Some people need that, but some people’s pressures would drop through the floor. So it all depends.
Ace inhibitors are very highly effective good for pts with cardiac disease.
___________
A new class is ANGIOTENSIN II RECEPTOR BLOCKERS.
Less evidence tha they reduce mortality. They are not irst iline agents because they are not less effective, but hteir reduction in mortality has not been shown yet. These do not lock the enzyme ase at all. They block angiotensin II receptors. They don’t have a bradykinen effect. That kinase II effect is not at play here. O thse are n used primarily for the same things as inhibitors. Storke provention. HTN, CHF, DM neuropathy, MI, etc… blocking the angiotensin . Vasodialation, preripharal and renal. Blockage of aldosterone release. Same as ace inhibitors. Just a different mechanism. The current kinetics are all available Po. Increasing number of drugs with every passing year. Often used with diuretics. Just like ace inhibitors. Angioedema is still a risk but it is even more rare with ace inhibitors. Angioedema on an ace inhibitor they can be put on an R but there is still a risk of angioedema with those pts. 8 to 10 % do have cross sensitivity to angioedema. Worth the risk. Rare to begin with then the rare pts can take an R but you do need to watch them a little bit. Not like its 90%. Bilateral renal artery stenosis. No cough, no bradykinen effect. Pts who cannot taolerate if they need to be switched from Ace inhibitor to R because of cough then that’s okay. Another class is calcium cahannel blockers. Ther are two types. Only talk aobut one today.
VSM is vascular smooth muscle. Nifedipine works only on VSM. Verapamil and diltiazem work on both vascular smooth muscle and on the heart. Mechanism of action is that it blcoks Ca channels. SO the role of calcium channels is that they sit in the plasma membrane when a cardiac or vascular smooth muscle cell the calium chennel moves open and pores into the cell. So if you block the calcium channel then you don’t get the clium influx or cell excitation. Block sthe action of calcium channels. The effect is to cause constriction. So if you block calcium influx you cause dilation. That happens in the arterioles of the whole body and of the smooth muscles of the arteries not on the heart msucle themselves. If the vasculature is dilated, what reflex is there to compensate for dropping BP? With these drugs, reflex tachycardia is an issue. A drop in BP by dilating the vasculature stimulates the bar receptor reflex. That’s true for niphedipine. Not for other two.
Calcium channel blockers are used for pts with hypertension and angina? The kinetics are that there are two types of formuls. The rapid actin fomrualt is likey to ause a quicker onset of action so that large vasoedilation that happens kind of quickly with cause the bar receptor ot take over. Slower actin formuales, sustaine drelease act a bit slower and cause a more gradual dcrease. Reflex tachycardia is not such as issue but it still can occur the effect alances out ove rtime. Dverse effects include flushing dissiness and heaache. Suually well tolerated. Nifedipine is often given with a beta blocker, and we have beta receptors in the heart and lugs. If you stimulate beta I you get an increase in heart rate so if you block beta I you block heart rate increase. So youc an block the reflex tachycardia.
This drug , Hydralazine. Makes less calcium inside the cell. Selective for arterioles rather than veins so if you dilate the arteries you cause a decreased after load and therefore a decreased blood pressure bu rtyou do get a reflext tachycardia. Remember hwo in the beginning the arteriol es and arteris don’t hav ea ahuge stretch factors. The venous system has a huge stretch capability. Dilating ateriole side doesn’t caus the same t yep of postural hypotension as dialting veins does because ther is only so far theey can stretch. When you dilate the arteriole sid e the postural hypotension does not occur so much. Hydralazine. Can be given Po or IV. PO works in 30 to 45 minutes. Acts for 5 or 6 hours. Can be used IV like in hypertensive crises to reduce rapidly. Shoter duration of activity when its given IV. Can be used PO for pts with hypertensino. Hypertensive crisis. Adverse effects include reflex tachycardia. Baro reflext. Also sodium and water retention. When the vasculature dilates the decrease in BP makes the body think there isn’t enough blood volume. Sodium and water are retained like that. So allot of times they are given with a diuretic type drug. SLES: system lupus elytrous syendorme? Symptomes like lupus. Joint pain, fever, etc… reversible after the drug is gone.
So because eof this water and sodium rentention we give the drug with a diruetic because of reflextacchycardia and contractility we ive a beta blocker. Other hypertensives can be additive which can be a goo thing or additive which also be a bad thing. You will see Hydrolazine usedin hopsital setting.
Mechanism of mInoxidil
-increases intracellular potassium which hyperpolarizes the cell which releaes the cell. Increased potassium hyper polarizes the cel which causes the cell to relax. Selective for arterioles. Used in pts iwht hyeprtension. Used in arteriolar dilation. Sodium and water retention like hydrolyzing. And hypertrichosis. Minoxadil is rogaine used topically for hair growth. Drug designed to treat hypertension. Side effect is a potentially money making sceme.
Nitroprusside. Sodium ad ron.. And Cyanide.
Nitropressid eis converted to Nitric oxide and cyanide. Nitric oxide is a powerful vaso dialtor. Metabolized . Cyanide is converted in the liver to thiocyanate. Thiocyanate is excreted by kidneys so if a pt has liver disease they have a risk of accumulating cyanide. Those pts have to be monitored for t heir cyanaide toxicity. Pts with renal diseae are tat risk for accumulating cyandide. Either one or both of thse is a send out lab. Extremely effective. Rapidly active. You can titrate it very carefuly minute to minute. You risk all kind of reprofusion. You can to pull it down a little bit at a time. Nitropresside can be handled very farully. Used in hypertensive crisies. Cyanide poisoning
Angina; Sudden chest pain. Athrosclerosis or vasospasms. Mycoardialoxygen supply and demand. Demand increases wen heart is beating fast. It needs more oxygen that’s the same thing is having incread oxygen mean. A stronger more forceful contraction also increases oxygen demand. And wall tension has to do with preload and after load. The more the heart is stretched the cardiav filling the heart needs more oxygen to get that blood out an if th ehart is beting aginst allot of pressure it needs more oxygen to push aginst the heigh pressur eystem. So things that increase cardia oxygen demand are heart rate, contractility, preoload , and after load. Typically with each hear tbeat, two things> the coronary arteries prefuse the heart during diastole only. During sytole the coronary arteries are squeezed tight. Whenblood is relaxed, blood goes through the heart. So whenthe heart is beating, the arteries come up though the base of the aorta. Nt a whole lot goes thorugh the contrary arteries and perfuse the heart.
Second, on a normal cardia ccycla all the oxygen divlered to the heart during diasole al of ithe oxygen is e tracted by the heart. With every diastol the blood thg goes through the art all gets used. So the only way to increae t oxygen supply to the myocardium is o dialte the vessels t get more blood flow so myocardial oxygen supply by dilating the arteries and increasing the blood flow. Wo types of angina. This is a vaso spams. This is called a vasospastic angina. So it can happen anytime night or day. Tnohing to do with exrcise. On the other and it is much more common in this country where there is athrosclerosis somewhere alllont here. Angina occurs when the heart nees t wokand needs more oxyg And so the heart needs more blood but the arteirs can’t diate to compensate.
So this type of angina is tgenrally a demand t ype of angina. So if the pts sits and rests the ainga goes away. The heart doesn’t need all tat oxygen when the pt is resitn ghte agina goes away. This istable. This is a demand type angina and this is a supply type agina. So if the cornary artery is not spasming it could idlate but when its spasming the supply to the heart goes don. This is a supply type, t his is a dmeand type. One of the drugs we use to treat aginina is
Nitroglycerine
Converted to nitric oxide the powerful vasodialtor by chemicals that have sufichdric groups? There are only so many sulfhydryl groups that can cause this reaction. Once they are depleted you ca n’t ge th e reaction anymore and so primarily the nitritogyceirne acts that he side at the veins and it ialso acts on cocnary ateries. Does not have a n action on arteriole peripheral system It mostly venous. So if you dilate the viens ou reduce the prelodad. And does preload play a role in oxygen demand? Yes it does. Heart rate ,c ontactility, preload and after load. IF you dilate veins you reduce your prelod. Nitrolgycerine alo acts on contrary lbood flow on the ateries an that incrteas the suppl yso this aspect of ntiroglyerine can affect the stable parts. vs. treating the vasospasm types. Good fore both types.
A few thigns about kinetics. Please go bak and read chatper fifty in your tex book on angina and nitroglycerine. Make sur eyou hav eit cold befor eyou take the NCLEXX. Need to know lot sof htings about nitroglyceirne. Kinetics. EXAM will be asked a Kinetics quesitno about tnitrogyueirne. Goest though tissues easily. HUGe first pass mechanism. Only a tiny fraction actually gets where it needs to go wo we tend to get the drug through sublingual buccal or Tran lingual spray it gets aborbed directly thorugh the aulature which drain it into the heart and that’s eactlywhere we ant it o go. Also have ointments and patches and pasts and sustained release formulas po. So a pt who has hastbe angina and mows his lawn and gets aninga will needs something that will act rapidly. So does tht peron need to be waring a pathc” no they need sublingual which will work fast. Or a buccal spray.
So lipid soluble that if you get past on your finger syou will get systemic vasodilation. You could always were glvoes th efirst sign of it is a headache. So if you’re working with nitro past wash it off as soon as it youcan. Tolerance. Remmeber hwo tnitroglycerine requires sulfhydral groups in order to be converted to nitrix oxyide: in tehsapan of 24 hours pt s deplete their sulhyrl gropus anymore. So pts who hav particularly vasospasitc ned a restorativ etoime to resutore their sulhydryl groups. If they need an attack in the night they can do it but they shouldn’t wear the patch all night. Only take it when you have symmptioms. So
Pts with stable angina who get it rin resposne to exercise they should tak eit when they are symptomatic. So they have a nitrate free time as well. When we tal about heart drugs we’ll pull this back in and tlakabout guidelines aobut when to giv ethe drug.
NTG
Side effects adverse> headache, orthostatic hypotension, reflex tachycardia,
Drug interactions” hypertensive agents, MDE5 inhibitors.
NTG to NO to cGMP (increase in Cyclic GMP )wich cuases vasodilaation.
PDE5 I are erectile dysfunction drugs. This is not to be used for pts with nitroglycerine. Phosophodiestriase breaks down cyclic GMP. The inhibiotr blocks that. If you give nitroglyceirne and bump the amount of lcycicl GMP youc an cause vasodiatio and if you give a phosphodisterize inhbiot then you have Tooons of cyclic GMP and tooons of vasodilationand a huuuge drup on blood pressure .
Cardioenzymes, pathologic changes in MI
Other pathologic myocardial changes with MI
Stunning - ischemic but not infracted cells may take time to recover even after reperfusion. Avoiding this stunned period might save their lives. Cooling people off to reduce inflammation and anti oxidants are being used.
Hibernating- some cells remain ischemic and nonfunctional. Cells that are getting a little bit of collateral flow. Their main blood supply is cut off, but they shut down. Learn to live without as much oxygen and sugar. Restore perfusion to these cells. Maybe by bypassing to a collateral vessels or gene therapies, lasers, etc…
Remodeling. Myocyte changes that lead to decreased contractility, mianly mediated by RAA but also role for SNS. Biggest strides are being made. This is about the heart itself. Some of the heart muscle itself tries to compensate in ways that aren’t good. Everybody who has an MI gets directly with the RAA, ace inhibitors and blocking the SNS, beta blockers. Very significantly reduce mortality after MI.
Non stemie can have st depression
Stemie has a characteristic big Q qave and big elevation in ST elevation.
Cardioisoenzymes, serieal every 4 hours
TROPONIN,
CPXMB
Arrythmia,
PVCs.
Vtac
Vfib
Acute congestive heart failure
Shock - 80% mortality.
Ventricular aneurism- clotting is a problem
Pericarditis
Everyone with chest pain should chew an aspirin.
In a pt with stemie: use emergency thrombolitic therapy and PCI (put a catheter in, open the vessel, and stent) all kinds of different ways to do it. Give ace inhibitors, beta blockers, and statins because of their anti-inflammatory effects.
Pt education/rehab. Allot of psychological issues. Pg. 150. Talking about MI.
Non stemie_
Unstable plaque rupture with prolonged obstruction by clot, some tissues infaction but clot solves before all of the at rik myocardium is ckilled
Infarction is confined to area just insie the endocardium.
Cardiac is enzymes ar elevated Troponin and CPK MB
Severe prolonged chest pain and heart failure.
ST elevation.
Manage with asprin, thrombolytics or PCI and later adde ACE inhibitors and Beta blockers.
More likey to be complicated by arrhythmias, CHF, shock, or rupture of valve or heart wall.
ECG with pain: st depression. When they stop having pain, return to normal. No increase in iso enzymes. So just ask when the pain came on?
Chest pain, nausia, st depression. Cardiac is enzymes
Prolonged severe, crackles, ECG shoes ST elevation. Interventions for all acute coronary syndromes try to rpevent clot formation. Antithrombootics and thrhombolytics. MI: add beta blockers and ace inhibitors. Stable angina. Immediately to thrombolytics and PCI. Stress stesting
Heart failure: pathological condition where the heart can’t generate adequate cardiac output. Second half: 40-60% have diastolic filling pressur eof the left ventrical thus that pulmonary capillilariy pressures are increased. If you can’t pump the blood out, you have more blood left in so the and is not the problem. It’s the or that’s the problem. Non-compliant. Even a n ormal amount of blood creates pressure. Systolic heart failure. Then diastolic failure. Refers to primary dysfunciton of the left ventrical. LV.
May be systolic, diastolic or both. Most common reason for elderly to be admitted to the hospital.
Cardio Myo Pathy: disease of the heart muscle.
Leucotropy; ability to relax normally.
Systolic Heart failure:
Decreased centrality
Increased after load: increased resistance to LV ejection. Usually due to increased peripheral vascular resistance (HTN) can olso occur with aortic outlet obstruction and aortic stenosis. Resulsts in myocardial hypertrophy. Increased LV muscle mass and increased oxygen demand.
Increased preload.
LDEDV: optimally, ejection fraction is optimized and volume is euvolemia .
Too much volume: decreases ejection fraction. Increaes in vlume can occur ecause you work t he heart too har or you have fluid overload because of renal falilure or too many iv fluids.
What did hypertension do to the ventricular muscle? Made it thick, and then remodeled it. This is scarring. Think of two balloons before this idea. When a ventrical is hypertrophied and scarred it’s the baloon that’s stiff and hard to blow up. So if a heart is supposed to be a little bit strenchy and you take one breathe to blow into it vs. the really stiff balloon . One breath won’t go so far. Not a problem of increasd LVEDV. Even a normal amount of problem clauses a presssure problem. Increased in LVEDP. Even a normal amount of volume put into a stiff ventrical means you have increased pressure.
After MI sometime the heart muscle gets so scarred this is a problem. The one we should remember is hypertension. The most common cause of diastolic heart failure. Another bullet with algorhythm.
Increases in HR makes this worse.
Very clinical test questions:
When you have a thick stiff ventrical forcing that last bit of blood into ti it made a knocking sound. Tennessee. Tennessee. Was the S4.
S3 is Kentucky. Kentucky.
Pt: dyspnea on exertion. Clear lung fields and an S4. That pt has diastolic heart failure. Doesn not get treated.
Another pt. Hist of HTN. Crackles in lungs. Evidence of lfuid overload. S3: pt has systolic heart faiure.
Exact question on exam.
JVD: bet that drawing done. Forward and backward. Heart fialure was in the Left ventrical. To the right of the most important organ in the body. Pressure backing up, it goes first to the left atrium in the lungs. Pulmonary edema. Pt will be tachypnic. And tachycardia . We’ve
Fetal edema. JVD ut this car is how we used to do coronary artery byb pass grafting. Beif aside: very particular we’re supposed to do it. Pt at 45 degrees measure from seconmd intercostal space. Ruler, etc… It’s one of those things were people sometimes try to quiantitate it so you make it up. You see big neck veins or you don’t.
One main take home: can aperson be in heart failure and have an MI? Yes. MI caused heart failure. So if they come in with heart failure, ask if they are having a life threatening MI. Are they in renal fialure? Are they having a HTN crises? Heart failure is a result form something else. If you are just reating heart fialure you might have them die.
Ace inhibitos and beta blockers. Ifyou look under treatment under acute CHF under 3a n the midle. It’s 4 that she wants to talk about.
VMP: Vatriuretic neuron? Peeing salt. In heart failure the ody tries as hear da s in can to be its own diuretic bu tit can’t do it is you’re nto perfusing ht ekidneys properly so the hear keeps tyring othe bmp is not causing heart failure. It’s trying ot respond and it can’t. We give people even more BMP to help them pee even more salt. So two points we ant to make. We measure BMP as a way to quantify the severity of heart fialure. And we give VMP IV to help the person pee more salt. If the perosn’s already got a BMP through the roof, then it won’t help. Same thing as giving more insulin to insulin resistanc DM. You can put in a balloon pump helping with after load. PCI of osme sort. Same things: use diuretics may use digoxin, ace inhiitors, and beta blockers as well. Instead of just using lasiks, you may put them on more than one diuretic. So summarizing, and then take questions. We’re going to almost certiantly get a pt who ahs had an ischemic heart. Maybe in the past or maybe right now, and then you’re also going to get a pt with bad hypertnesion. So I might get you ap t who is acutely having hcest pain. ST elevation and tropon tin gh the foof and stmeie so to be mangin gtha tyou are goig to be thining aobut aspirn oxygen thonobotiic or PCI and don the road we oook at ace inhibotrs and et a blcoker but hat the same time they ar complaining of severe hsortness of brehat lots of cracles and S 3 systolic hear falure os at the ame you’re reaitng hteir stmei you are also thinning about what kidn ofintervnetions> Oxygen. Idreetics. Ace inhitors. Beta lbockers. And baye dopamine. Or dpoutamie to try to support the hreat. Because that’s rthe real world.
She will give us a pt like that and we nneed the pathophyiologic of heart failure and ischemic heart dieseaes.
Then definitely a more chronic HTN pt starts out with diastolic disfunciotn and ending up with systolic disfunciton. We should explain it out loud. Think of what pt might complian of. You can reason it out.
Stunning - ischemic but not infracted cells may take time to recover even after reperfusion. Avoiding this stunned period might save their lives. Cooling people off to reduce inflammation and anti oxidants are being used.
Hibernating- some cells remain ischemic and nonfunctional. Cells that are getting a little bit of collateral flow. Their main blood supply is cut off, but they shut down. Learn to live without as much oxygen and sugar. Restore perfusion to these cells. Maybe by bypassing to a collateral vessels or gene therapies, lasers, etc…
Remodeling. Myocyte changes that lead to decreased contractility, mianly mediated by RAA but also role for SNS. Biggest strides are being made. This is about the heart itself. Some of the heart muscle itself tries to compensate in ways that aren’t good. Everybody who has an MI gets directly with the RAA, ace inhibitors and blocking the SNS, beta blockers. Very significantly reduce mortality after MI.
Non stemie can have st depression
Stemie has a characteristic big Q qave and big elevation in ST elevation.
Cardioisoenzymes, serieal every 4 hours
TROPONIN,
CPXMB
Arrythmia,
PVCs.
Vtac
Vfib
Acute congestive heart failure
Shock - 80% mortality.
Ventricular aneurism- clotting is a problem
Pericarditis
Everyone with chest pain should chew an aspirin.
In a pt with stemie: use emergency thrombolitic therapy and PCI (put a catheter in, open the vessel, and stent) all kinds of different ways to do it. Give ace inhibitors, beta blockers, and statins because of their anti-inflammatory effects.
Pt education/rehab. Allot of psychological issues. Pg. 150. Talking about MI.
Non stemie_
Unstable plaque rupture with prolonged obstruction by clot, some tissues infaction but clot solves before all of the at rik myocardium is ckilled
Infarction is confined to area just insie the endocardium.
Cardiac is enzymes ar elevated Troponin and CPK MB
Severe prolonged chest pain and heart failure.
ST elevation.
Manage with asprin, thrombolytics or PCI and later adde ACE inhibitors and Beta blockers.
More likey to be complicated by arrhythmias, CHF, shock, or rupture of valve or heart wall.
ECG with pain: st depression. When they stop having pain, return to normal. No increase in iso enzymes. So just ask when the pain came on?
Chest pain, nausia, st depression. Cardiac is enzymes
Prolonged severe, crackles, ECG shoes ST elevation. Interventions for all acute coronary syndromes try to rpevent clot formation. Antithrombootics and thrhombolytics. MI: add beta blockers and ace inhibitors. Stable angina. Immediately to thrombolytics and PCI. Stress stesting
Heart failure: pathological condition where the heart can’t generate adequate cardiac output. Second half: 40-60% have diastolic filling pressur eof the left ventrical thus that pulmonary capillilariy pressures are increased. If you can’t pump the blood out, you have more blood left in so the and is not the problem. It’s the or that’s the problem. Non-compliant. Even a n ormal amount of blood creates pressure. Systolic heart failure. Then diastolic failure. Refers to primary dysfunciton of the left ventrical. LV.
May be systolic, diastolic or both. Most common reason for elderly to be admitted to the hospital.
Cardio Myo Pathy: disease of the heart muscle.
Leucotropy; ability to relax normally.
Systolic Heart failure:
Decreased centrality
Increased after load: increased resistance to LV ejection. Usually due to increased peripheral vascular resistance (HTN) can olso occur with aortic outlet obstruction and aortic stenosis. Resulsts in myocardial hypertrophy. Increased LV muscle mass and increased oxygen demand.
Increased preload.
LDEDV: optimally, ejection fraction is optimized and volume is euvolemia .
Too much volume: decreases ejection fraction. Increaes in vlume can occur ecause you work t he heart too har or you have fluid overload because of renal falilure or too many iv fluids.
What did hypertension do to the ventricular muscle? Made it thick, and then remodeled it. This is scarring. Think of two balloons before this idea. When a ventrical is hypertrophied and scarred it’s the baloon that’s stiff and hard to blow up. So if a heart is supposed to be a little bit strenchy and you take one breathe to blow into it vs. the really stiff balloon . One breath won’t go so far. Not a problem of increasd LVEDV. Even a normal amount of problem clauses a presssure problem. Increased in LVEDP. Even a normal amount of volume put into a stiff ventrical means you have increased pressure.
After MI sometime the heart muscle gets so scarred this is a problem. The one we should remember is hypertension. The most common cause of diastolic heart failure. Another bullet with algorhythm.
Increases in HR makes this worse.
Very clinical test questions:
When you have a thick stiff ventrical forcing that last bit of blood into ti it made a knocking sound. Tennessee. Tennessee. Was the S4.
S3 is Kentucky. Kentucky.
Pt: dyspnea on exertion. Clear lung fields and an S4. That pt has diastolic heart failure. Doesn not get treated.
Another pt. Hist of HTN. Crackles in lungs. Evidence of lfuid overload. S3: pt has systolic heart faiure.
Exact question on exam.
JVD: bet that drawing done. Forward and backward. Heart fialure was in the Left ventrical. To the right of the most important organ in the body. Pressure backing up, it goes first to the left atrium in the lungs. Pulmonary edema. Pt will be tachypnic. And tachycardia . We’ve
Fetal edema. JVD ut this car is how we used to do coronary artery byb pass grafting. Beif aside: very particular we’re supposed to do it. Pt at 45 degrees measure from seconmd intercostal space. Ruler, etc… It’s one of those things were people sometimes try to quiantitate it so you make it up. You see big neck veins or you don’t.
One main take home: can aperson be in heart failure and have an MI? Yes. MI caused heart failure. So if they come in with heart failure, ask if they are having a life threatening MI. Are they in renal fialure? Are they having a HTN crises? Heart failure is a result form something else. If you are just reating heart fialure you might have them die.
Ace inhibitos and beta blockers. Ifyou look under treatment under acute CHF under 3a n the midle. It’s 4 that she wants to talk about.
VMP: Vatriuretic neuron? Peeing salt. In heart failure the ody tries as hear da s in can to be its own diuretic bu tit can’t do it is you’re nto perfusing ht ekidneys properly so the hear keeps tyring othe bmp is not causing heart failure. It’s trying ot respond and it can’t. We give people even more BMP to help them pee even more salt. So two points we ant to make. We measure BMP as a way to quantify the severity of heart fialure. And we give VMP IV to help the person pee more salt. If the perosn’s already got a BMP through the roof, then it won’t help. Same thing as giving more insulin to insulin resistanc DM. You can put in a balloon pump helping with after load. PCI of osme sort. Same things: use diuretics may use digoxin, ace inhiitors, and beta blockers as well. Instead of just using lasiks, you may put them on more than one diuretic. So summarizing, and then take questions. We’re going to almost certiantly get a pt who ahs had an ischemic heart. Maybe in the past or maybe right now, and then you’re also going to get a pt with bad hypertnesion. So I might get you ap t who is acutely having hcest pain. ST elevation and tropon tin gh the foof and stmeie so to be mangin gtha tyou are goig to be thining aobut aspirn oxygen thonobotiic or PCI and don the road we oook at ace inhibotrs and et a blcoker but hat the same time they ar complaining of severe hsortness of brehat lots of cracles and S 3 systolic hear falure os at the ame you’re reaitng hteir stmei you are also thinning about what kidn ofintervnetions> Oxygen. Idreetics. Ace inhitors. Beta lbockers. And baye dopamine. Or dpoutamie to try to support the hreat. Because that’s rthe real world.
She will give us a pt like that and we nneed the pathophyiologic of heart failure and ischemic heart dieseaes.
Then definitely a more chronic HTN pt starts out with diastolic disfunciotn and ending up with systolic disfunciton. We should explain it out loud. Think of what pt might complian of. You can reason it out.
Heart: RAA,
Implications of short stay on 4E. Short.
Endothelial lining of heart.
Critical role for nursing.
Valves
1. Tricuspid
2. Plutonic
3. Aortic
4.
Superior inferior vena cava out plutonic to pulmonary artery to lungs.
Left corroded/ left subclavians. Which get more blood flow? Subclavians do the arms and are pretty active, also the brain which is the most needy organ in the body. So if you have a problem in your heart.
Brachiocephalic.
Coronary circulation. First branches off the aorta. Right off the aortic valve. Two main arteries: L branches into l anterior descending and L circumflex. LAD= left antioer decending, Left Cirq, RCA= right circulating artery,
Athroschlerosis: coronary arteries of particular concern. Starts at SA node.
WILL NOT HAVE TO LEARN ABOUT ACTION POTENTIALS. Automoticity= will beat on its own. Major two influences on heart rate with relation to the nervous system. Driven by the autonomic nervous system. Three major hormnes of the autonomic : epinephrine, norephinephrine, and Ach. Speed up will epi/norepi. AcH will slow the heart down.
Marjor cause of death in heart disease: dysrhythmias. May have end state heart disease, valvular disease, but that last even that happens one day is usually a dysrythmia. ECG is relied on. Won’t show us picture on exam, but we should be able to recognize the verbal description.
S1: blood ejected through pumonic and ventricular ejection: systole.
When 2/3 ejected mitral and tricuscpid open and that’s S2, dubb.
Then blood flows from atria into ventriacals called diastole, and when the ventrals are full again, that’s SI again.
Early diastolic filiing: high volume, high rate
Gallop: S3, a gallopy knocking noise. Early in diastoly and indicated ventricular dialation. Heart failure. Kentrucky.
Atrium contracts to get last bit of blood out of antriam an dinto ventrical. IF walls are stiff then atrial ejectio will make a very succato sound called an S4. Hypertrophy. Bigger cells, thicker muscle. S4. Tennesee.
Other thing that’s key is murmers.
Bruie: peripheral artery swishing noise, turbulent blood flow.
Murmer: turbulent bloof flow in the heart. Adults: muermers almost always caused by valvular heart disease.
Systole: ventricular ejection. Ventrical is contracting.
Stenosis: valve is too small. Which valve being steno tic is going to giv eyou a systolic murmer. Ventricular ejection Pushing blood through aortic valve. Systeolic ejection murmer due to stenosis is ogiong to be aortic stenosis
Mitral stenosis: blood mvoes through during diastole.
Regurgitation.
Systolic murmer due to narrowing of aortic valve.
Loud systolic murmer to second intercostal space radiating to neck you would thin aortic stenosis.
Slow rumibing during diastole heard beat at base: mitrl stenosis.
Think about where blood is moving.
Pge 28. Cardiac output. Extremely important.
Heart rate times stroke volume Number of berats per minute times the amount of blood per beat. So you come out with liters per minute.
Contractility: how good is the muscle.
Myocardial infartion: #1 way to mess with contractiiity.
What is peripheral resistance swhcih increaes our blood pressure. If vessels are really clamped down pushing it into a smaller container that’s called after load. Third component has todo with how much blood it has to work with when it starts contracting.
Preload: determines how hard it can pump. Not enough blood with which to work before contraction, like if the blood is not in the cardiovascular system but on the floor
Too mch fluid: heart stretched tooo big. Give them too much volume or kidneys don’t work.
Vaso dialators: beta blockers, calcium channel inhibitors
EF: ejection fraction
LVEDV: preload;
Veins dialate and accept volume.
Arteries are much stiffer; low compliance and low capacitance much higher pressure system. Can constrict.
Pressure in whole system related to how much volume.
Increase blood volume to increase BP or resistance.
Diuretics and vasodialtors: manage high BP
Sympathetic nervus system/ renin-angiotensin.
Pulse pressure: difference between systolic and diastolic. Higher in elderly people. Indicate stif fvessels.
Peripheral resistance:
Ace inhibitors:
Kidney: decided its in charge of BP. Sense renal blood flow t hrough JGA Juxa glomerular apparatus. Tells CVS to increae blood pressure. Renin: interacts with angiotensinin to make angiogenesis 1 Goes to lungs, where there is an enzyme called ACE: Angiotensin converting enzyme from 1 to 2, which is a powerful vasco constrtictoer of arteriorles. Stimulates adrenal cortext to make aldosterone which tell sthe kidney to hang ont o salt and water. So ace inhibitor is vasodialtor and a diuretic becase it prevents salt and water retention Improves ability to get rid of it if youdind’t have mechanism having you hang onto it.
RAA:
-bock ace
-block angiotensin receptors
-block aldosterone
This is more or less the endocrine system: effects all over the body, acting like hormones. Paracrine system in our tissues. The cardiovascular tissues themselves make angiotensin II. Endothelial and myocardial cells can do this. A growth factor and vascoconstirctor.
Remodeling.
-scarring. Not just from fibroblasts but growth of certain tissues. Disruption of norma tisssue sctrcuture. Angiotensin II constributes ot myocardial and vascular remodeling. Funcional problems of basco cnstriction and long term s structural problems that actually damage bood vesses.
Statins, Ace inhibitors: nmot ony prevenitn g but reversing. Ischemic heart disease and heart fialure. Must use ace inhibitors for people With DM, etc… more expensive.
Popurri of pt evaluations:
Pg. 130. Chest pain of heart diesease tends to be substernal and tends to be dull vs. sharp . Innervation that tells you that your heart hurts runs through the vagus nerve and the sympathetic as well. Also runs through arm and jaw. Classic symptom of heart diesase: dyspnea and dethrone (when laying down). PND
Pt; sense of impending doom. Tachycardia, tachypnea, BP elevated, murmers, gallops, Ralls, edema
Pg. 145:
ST depression or elevation: myocardial ischema.
This will become my friend:
Physiologic drawing:
L ventrical not enough blood getting out. Increase in LEVDV? Which will stretch the heart
Endothelial lining of heart.
Critical role for nursing.
Valves
1. Tricuspid
2. Plutonic
3. Aortic
4.
Superior inferior vena cava out plutonic to pulmonary artery to lungs.
Left corroded/ left subclavians. Which get more blood flow? Subclavians do the arms and are pretty active, also the brain which is the most needy organ in the body. So if you have a problem in your heart.
Brachiocephalic.
Coronary circulation. First branches off the aorta. Right off the aortic valve. Two main arteries: L branches into l anterior descending and L circumflex. LAD= left antioer decending, Left Cirq, RCA= right circulating artery,
Athroschlerosis: coronary arteries of particular concern. Starts at SA node.
WILL NOT HAVE TO LEARN ABOUT ACTION POTENTIALS. Automoticity= will beat on its own. Major two influences on heart rate with relation to the nervous system. Driven by the autonomic nervous system. Three major hormnes of the autonomic : epinephrine, norephinephrine, and Ach. Speed up will epi/norepi. AcH will slow the heart down.
Marjor cause of death in heart disease: dysrhythmias. May have end state heart disease, valvular disease, but that last even that happens one day is usually a dysrythmia. ECG is relied on. Won’t show us picture on exam, but we should be able to recognize the verbal description.
S1: blood ejected through pumonic and ventricular ejection: systole.
When 2/3 ejected mitral and tricuscpid open and that’s S2, dubb.
Then blood flows from atria into ventriacals called diastole, and when the ventrals are full again, that’s SI again.
Early diastolic filiing: high volume, high rate
Gallop: S3, a gallopy knocking noise. Early in diastoly and indicated ventricular dialation. Heart failure. Kentrucky.
Atrium contracts to get last bit of blood out of antriam an dinto ventrical. IF walls are stiff then atrial ejectio will make a very succato sound called an S4. Hypertrophy. Bigger cells, thicker muscle. S4. Tennesee.
Other thing that’s key is murmers.
Bruie: peripheral artery swishing noise, turbulent blood flow.
Murmer: turbulent bloof flow in the heart. Adults: muermers almost always caused by valvular heart disease.
Systole: ventricular ejection. Ventrical is contracting.
Stenosis: valve is too small. Which valve being steno tic is going to giv eyou a systolic murmer. Ventricular ejection Pushing blood through aortic valve. Systeolic ejection murmer due to stenosis is ogiong to be aortic stenosis
Mitral stenosis: blood mvoes through during diastole.
Regurgitation.
Systolic murmer due to narrowing of aortic valve.
Loud systolic murmer to second intercostal space radiating to neck you would thin aortic stenosis.
Slow rumibing during diastole heard beat at base: mitrl stenosis.
Think about where blood is moving.
Pge 28. Cardiac output. Extremely important.
Heart rate times stroke volume Number of berats per minute times the amount of blood per beat. So you come out with liters per minute.
Contractility: how good is the muscle.
Myocardial infartion: #1 way to mess with contractiiity.
What is peripheral resistance swhcih increaes our blood pressure. If vessels are really clamped down pushing it into a smaller container that’s called after load. Third component has todo with how much blood it has to work with when it starts contracting.
Preload: determines how hard it can pump. Not enough blood with which to work before contraction, like if the blood is not in the cardiovascular system but on the floor
Too mch fluid: heart stretched tooo big. Give them too much volume or kidneys don’t work.
Vaso dialators: beta blockers, calcium channel inhibitors
EF: ejection fraction
LVEDV: preload;
Veins dialate and accept volume.
Arteries are much stiffer; low compliance and low capacitance much higher pressure system. Can constrict.
Pressure in whole system related to how much volume.
Increase blood volume to increase BP or resistance.
Diuretics and vasodialtors: manage high BP
Sympathetic nervus system/ renin-angiotensin.
Pulse pressure: difference between systolic and diastolic. Higher in elderly people. Indicate stif fvessels.
Peripheral resistance:
Ace inhibitors:
Kidney: decided its in charge of BP. Sense renal blood flow t hrough JGA Juxa glomerular apparatus. Tells CVS to increae blood pressure. Renin: interacts with angiotensinin to make angiogenesis 1 Goes to lungs, where there is an enzyme called ACE: Angiotensin converting enzyme from 1 to 2, which is a powerful vasco constrtictoer of arteriorles. Stimulates adrenal cortext to make aldosterone which tell sthe kidney to hang ont o salt and water. So ace inhibitor is vasodialtor and a diuretic becase it prevents salt and water retention Improves ability to get rid of it if youdind’t have mechanism having you hang onto it.
RAA:
-bock ace
-block angiotensin receptors
-block aldosterone
This is more or less the endocrine system: effects all over the body, acting like hormones. Paracrine system in our tissues. The cardiovascular tissues themselves make angiotensin II. Endothelial and myocardial cells can do this. A growth factor and vascoconstirctor.
Remodeling.
-scarring. Not just from fibroblasts but growth of certain tissues. Disruption of norma tisssue sctrcuture. Angiotensin II constributes ot myocardial and vascular remodeling. Funcional problems of basco cnstriction and long term s structural problems that actually damage bood vesses.
Statins, Ace inhibitors: nmot ony prevenitn g but reversing. Ischemic heart disease and heart fialure. Must use ace inhibitors for people With DM, etc… more expensive.
Popurri of pt evaluations:
Pg. 130. Chest pain of heart diesease tends to be substernal and tends to be dull vs. sharp . Innervation that tells you that your heart hurts runs through the vagus nerve and the sympathetic as well. Also runs through arm and jaw. Classic symptom of heart diesase: dyspnea and dethrone (when laying down). PND
Pt; sense of impending doom. Tachycardia, tachypnea, BP elevated, murmers, gallops, Ralls, edema
Pg. 145:
ST depression or elevation: myocardial ischema.
This will become my friend:
Physiologic drawing:
L ventrical not enough blood getting out. Increase in LEVDV? Which will stretch the heart
Ischemic syndromes
Wednesday, November 19, 2008
Ischemic syndromes
Stable angina vs. unstable
Stemi vs. nonstemi
A stemi, plaque rupture rapid thrombus formation through the whole wall. A much bigger infarcton. This is something you have on page 146.
They all relate to atherosclerotic plaque
If it’s stable, it sticks way out into the vessel
Unstable plaques tho, might be completely flat. Pts may have no symptoms at all until they rupture. We go to acute coronary syndromes. If it’s sustained it leads to MI which is stemi and nonstemi. Page 143. We are only looking at part of this picture. Left main divides into the LAD and left cirq.
Right coronary comes off the aortic valves and perfuses the right ventrical and the nodes and wraps around in the inferior part of the heart. SA nodes. Responsible as the pacemaker of the heart and controlling conduction in the heart. IF you had an infarction that damaged your nodes you might not generate an adequate heart rate. Right coronary disease can cause bradycardia. And if conduction can’t go from the av node you call it heart block. Obstruction to right coronary artery affects the inferior heart and is associated with bradycardia and heart block.
The left coronary artery perfuses the major heart muscle which is required for normal ventricular function. When you have an infarction involving the distributino of the LAD you worry about tachyrhythmias. Morelikely to result in heart fialure.
In men of middle age, the symptoms of ischemic heart disease are extremely predictable. Nausia diaphorses, anxiety, substantial pain chest pain radiating to arm and neck, dypnea.
Women often present with atypical symptoms most commonly the sudden onset of extreme fatigue. Elderly pts and pts with diabetes frequently have silent ischemia. Just know they feel bad. The absence of classis symptoms does not rule out someone having a heart attack.
Stable plaque partially obstructs flow. Increase demand by some form of exercise. Pain is predictable and relieved with rest. Measuring something called cardiac iso enzymes. Troponin. CPKMB. Not elevated during stable angina. ST depression which returns to normal with cessation of pain. Treat with antithrombitcs like aspirin and treating risk factors like statins and PCI or CABBG.
Changes on the ECG.
Lactic acidoses stimulates the autonomic nervous system and the sympathetic nerves enter thes pine in the same place as the arm and the jaw. Arm is getting enough flow, its just a cross stimulation of nerves.
Krebs cycle requires oxygen and sugar to make ATP and if you don’t have nough it releases lactate which is an acid and an acidic environment is bad for tissue function and it hurts.
Coronary stenting. You probably don’t have just one problem. You must deal with it systemically. Get nitrates to deal with vasospasms. May be beta blockers and calcium channel blockers. And Every one with atherosclerotic heart disease will get STATINS. They help to stabalize plaques.
Coronary Artery bipass graph: used to be more common than anything. Pypass the obstruction.
Acute Coronary Syndromes: all characterized by the rupture of an unstable plaque. How long did that clot stick there? If they have ST elevaation, we know what they have. ST depression of ischemia with exercise. Lesion may not obstruct the vessel very much. Thin cap and vulnerable to rupture. IF that clot is big enough and stays a long time, we see ST elevation and stemie. So we just did stable plaque and stable angina. Alteration of rupture. Sustained ischemia infarction. Fabulus artists rendition.
The plaque ruptures. Stress and Cold weather, so it may have to do with SNS. Also more in moring when theres a busrt of cortical. Unstable angina often occurs at rest. So the thing just ruptures and once it rupture it exposes all this damaged tissue and we see them stick until they obstruct the vessel. If we have spontaneous dissolution of this clot, which does happen, then less than 20 mins perfusion is restored and we have unstable angina. If it was to stay there more than 20 minutes then we would see noontime or stemie depending on whow long it stuck there./
\
Next step. Understnaidng anatomy of coronary perfusion. Whqat we have is across section of the ventricle. Clot forms an area of ischemia. If clot dissolves in more than 20 minutes then is this unstable angina a prescursor to ? No heart damage to eleveation fo cardiac is enzymes. If a clot stays longer, you get infarction. Yellow part is infarction. Because of anatomy of coronary vessels. Infarction stays near the . Sub endocardial MI = non stemie.
Watching desperate housewives and gets tremendous chest pain. Rushes to Er and gets there in 20 minutes. ST deprssion and no elevation of cardiac is enzymes: Unstable angina
ST depression and cardiac enzymes elevated. If didn’t get there till 40 minutes…
Later…transmural
And when that occurs we see .
Chest pain at rest, ECG shoes transient changes relieved with rest: unstable angina.
Review thse stemie things.
Ischemic syndromes
Stable angina vs. unstable
Stemi vs. nonstemi
A stemi, plaque rupture rapid thrombus formation through the whole wall. A much bigger infarcton. This is something you have on page 146.
They all relate to atherosclerotic plaque
If it’s stable, it sticks way out into the vessel
Unstable plaques tho, might be completely flat. Pts may have no symptoms at all until they rupture. We go to acute coronary syndromes. If it’s sustained it leads to MI which is stemi and nonstemi. Page 143. We are only looking at part of this picture. Left main divides into the LAD and left cirq.
Right coronary comes off the aortic valves and perfuses the right ventrical and the nodes and wraps around in the inferior part of the heart. SA nodes. Responsible as the pacemaker of the heart and controlling conduction in the heart. IF you had an infarction that damaged your nodes you might not generate an adequate heart rate. Right coronary disease can cause bradycardia. And if conduction can’t go from the av node you call it heart block. Obstruction to right coronary artery affects the inferior heart and is associated with bradycardia and heart block.
The left coronary artery perfuses the major heart muscle which is required for normal ventricular function. When you have an infarction involving the distributino of the LAD you worry about tachyrhythmias. Morelikely to result in heart fialure.
In men of middle age, the symptoms of ischemic heart disease are extremely predictable. Nausia diaphorses, anxiety, substantial pain chest pain radiating to arm and neck, dypnea.
Women often present with atypical symptoms most commonly the sudden onset of extreme fatigue. Elderly pts and pts with diabetes frequently have silent ischemia. Just know they feel bad. The absence of classis symptoms does not rule out someone having a heart attack.
Stable plaque partially obstructs flow. Increase demand by some form of exercise. Pain is predictable and relieved with rest. Measuring something called cardiac iso enzymes. Troponin. CPKMB. Not elevated during stable angina. ST depression which returns to normal with cessation of pain. Treat with antithrombitcs like aspirin and treating risk factors like statins and PCI or CABBG.
Changes on the ECG.
Lactic acidoses stimulates the autonomic nervous system and the sympathetic nerves enter thes pine in the same place as the arm and the jaw. Arm is getting enough flow, its just a cross stimulation of nerves.
Krebs cycle requires oxygen and sugar to make ATP and if you don’t have nough it releases lactate which is an acid and an acidic environment is bad for tissue function and it hurts.
Coronary stenting. You probably don’t have just one problem. You must deal with it systemically. Get nitrates to deal with vasospasms. May be beta blockers and calcium channel blockers. And Every one with atherosclerotic heart disease will get STATINS. They help to stabalize plaques.
Coronary Artery bipass graph: used to be more common than anything. Pypass the obstruction.
Acute Coronary Syndromes: all characterized by the rupture of an unstable plaque. How long did that clot stick there? If they have ST elevaation, we know what they have. ST depression of ischemia with exercise. Lesion may not obstruct the vessel very much. Thin cap and vulnerable to rupture. IF that clot is big enough and stays a long time, we see ST elevation and stemie. So we just did stable plaque and stable angina. Alteration of rupture. Sustained ischemia infarction. Fabulus artists rendition.
The plaque ruptures. Stress and Cold weather, so it may have to do with SNS. Also more in moring when theres a busrt of cortical. Unstable angina often occurs at rest. So the thing just ruptures and once it rupture it exposes all this damaged tissue and we see them stick until they obstruct the vessel. If we have spontaneous dissolution of this clot, which does happen, then less than 20 mins perfusion is restored and we have unstable angina. If it was to stay there more than 20 minutes then we would see noontime or stemie depending on whow long it stuck there./
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Next step. Understnaidng anatomy of coronary perfusion. Whqat we have is across section of the ventricle. Clot forms an area of ischemia. If clot dissolves in more than 20 minutes then is this unstable angina a prescursor to ? No heart damage to eleveation fo cardiac is enzymes. If a clot stays longer, you get infarction. Yellow part is infarction. Because of anatomy of coronary vessels. Infarction stays near the . Sub endocardial MI = non stemie.
Watching desperate housewives and gets tremendous chest pain. Rushes to Er and gets there in 20 minutes. ST deprssion and no elevation of cardiac is enzymes: Unstable angina
ST depression and cardiac enzymes elevated. If didn’t get there till 40 minutes…
Later…transmural
And when that occurs we see .
Chest pain at rest, ECG shoes transient changes relieved with rest: unstable angina.
Review thse stemie things.
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