drugs and the vasculature

Question 1

What are the main agents that cause vasodilation and constriction?

Answer 1

contract-AngII-PG2, ET1
Dilate-NO, PG2, bradykinin

And remember contriction UP means TPR Up-increase arterial pressure
With arterioles-more constricted -more BP is high (and Lower blood flow to that tissue

Question 2

What is BP equal to? What is “too high”?

Answer 2

Hypertension-140/90 mmHg (most important risk factor for stroke-silent killer). Also cause CKD
So bring tension down

Question 3

What is the tier list for hypertension treatment?

Answer 3

Step 1:ACE inhibitors if under 55
Calcium channel blocker or thiazide diuretics if over 55
Step 2-combine them CCB +ACE
Step 3-combine them ALL
STEP 4-consider B-blockers, a-blockers, sprirolactone

Question 4

What is an ACE inhibitor, how does it work?

Answer 4

RAAS system-renin->angI->angII->contrition
Renin increased by Lower : Na reabsorb, renal perfusion pressure, SNS
ACE converts AngI to II, and decrease bradykinin (vasodilator)
AngII cause thirst, Vasocontriction, salt and water reabsorb (via aldosterone)
So overall increase BP

So ACEi-reduce ACE acitivty-decrease BP, etc
Enalapril- (pril endings tend to be ACE inhibitor)
Works well for heart failure-cause less work needed-lower TPR, and increase venous return-increase CO-

Well tolerated-but can cause cough cause stop bradykinin degrade-procough, hypotension

Question 5

What are Angiotensin Receptor blocker?

Answer 5

Does stop it from being produced, but stops it binding the receptors mediating its effects

So overall act very similar to ACEi-
eg.: Losartan

Very well tolerated-can cause excessive hypotension

Question 6

What are the side effects of ACEi and ARBs?

Answer 6

ACEi-Well tolerated-but can cause cough cause stop bradykinin degrade-procough, hypotension
ARB-Very well tolerated-can cause excessive hypotension

Can cause hyperkalemia-because not reabsorb Na as much-so not excrete K as much —be careful with K supplements or K sparing diuretics

Renal failure in patients with artery stenosis (both)
(Normally, AngII helps modulate GFR (via glomerular pressure)-increasing it when pressure low)-but in renal failure, blocking AngII means they can’t even do that to try and icrease GFR

Question 7

How do CCB helps deal with hypertension?

Answer 7

Membrane depolarisation opens VGCC’s- etc cause contraction
So if you block Ca in the SMC cause less contraction-vasodilate

More interested in NON rate affecting CCB-those with vasculature effects
Amilodipine (dihydropyridines)
Cause we don’t want to affect heart rate really

Question 8

So which drugs are best for hypertension? How do you decide?

Answer 8

Overall, ACE, ARB, CCB actually work pretty much the same on hypertension
But the adherence is different-ARBs and ACEi have higher than CCB-so thats why you go for them 1st line of treatment (except in older patient-CCB or thiazide-like—because they’re old and their BP are less sensitive)-afroamericans also take CCB/Thiazide because they see, to have lower plasma renin activity (maybe-,maybe?)

Question 9

How do co-morbidities change which drugs to give for hypertension?

Answer 9

CCB reduce the risks of stroke more than RASi
But RASi is better to reduce HR issues
Diuretics seem to be more effective vs both
B-blockers generally have worse overall death

But really overall the all-cause mortality seems to be the same everywhere (except B-blocker)

Question 10

Why can a-blockers be used as anti-hypertensive

Answer 10

Will block a-receptors (directly via Prasozin, or with phentolamine (a1block and a2 activation)-
A-receptor cause vasoconstriction in peripheral so blocking that dilates and reduce TPR -therefore BP