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