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 .