Drugs and the vasculature Flashcards
What do the varicosities along the length of the sympathetic nerve do primarily?
Release NA to stimulate vasoconstriction
What are examples of VSM mediators that increase Ca2+ and stimulate a VSM contraction?
Angiotensin 2 -> AT1r
PGG2, PGH2 -> TP (T prostanoid receptor)
ET1 -> ET A/B
What are examples of endothelial cell agonists that stimulate a relaxation from the increase in Ca2+?
NO
CNP - C type naturietic peptide
PGI2
EDHR - endothelial hypopolarising factor
What is blood pressure generally mediated by?
CO and TPR
What’s the vascular tone like in hypertensive patients?
Raised base vascular tone leading to more TPR leading to a higher BP
What type of vessel contributes the most to blood pressure regulation?
Arterioles
What blood pressure is considered hypertensive
140/90mmHg
What is the first step of hypertension treatment?
Single therapy:
If under 55 give ACEi or ARD (angiotensin receptor blocker) but if over 55 or afro caribbean of any age then give CCB or thiazide diuretic
What is the second step of hypertension treatment?
Dual therapy using either ACEi and CCB or ACEi and thiazide diuretic
What is the third step of hypertension treatment?
Give ACEi, CCB and thiazide diuretic
What is the 4th and final step of hypertension treatment
Just giving symptomatic relief using a low dose spironolactone (diuretic therapy) and a beta blockade or alpha blockade
Give an example of an ACE inhibitor drug (ACEi)
Enalapril (they often have ‘-ipril’ endings)
What stimulates the renin angiotensin system?
LOW renal Na+ reabsorption
LOW renal perfusion pressure
HIGH SNS activation
What does ACEi do?
It decreases angiotensin II production and increases bradykinin
What are the uses of an ACe inhibitor?
Hypertension Heart failure Post MI Diabetic nephropathy Progressive renal insufficiency High CVS disease risk patients
How do ACE inhibitors treat hypertension?
- They reduce TPR by more bradykinin and less AngII. Lower TPR due to less AT1R mediated vasoconstriction leading to less BP and more bradykinin vasodilation.
- There is sodium retention due to less Na+ retention in the kidneys via blocked actions of AngII on the AT1R in the kidneys and less aldosterone secretion as blocked AT1R in the adrenal medulla
- Thirst drive due to less SNS activation of thirst in the brain via AT1R
How do ACE inhibitors treat heart failure?
- Reduce TPR - less vasoconstriction via AT1R in the peripheral vasculature so less TPR so less afterload on the heart so ionotropic effects of the heart decrease
- Reduce preload - venodilation by bradykinin
What is an example of an angiotensin receptor blocker drug
Losartan
What does an angiotensin receptor blocker drug do?
Prevent binding of Angiotensin ii to AT1 receptors
What are angiotensin receptor blocker drugs used for
Hypertension and heart failure
What are side effects of ARBs ?
Hypotension, Hyperkalaemia, Foetal injury, Renal failure in patients with renal artery stenosis
What are side effects of ACEis?
Cough, Urticaria/angiodema (rarely), Hypotension, Hyperkalaemia, Foetal injury, Renal failure in patients with renal artery stenosis
Why do ARBs and ACEis cause hyperkalaemia?
Aldosterone promotes K+ loss so aldosterone inhibitors produce a hyperkalaemia
How do ARBs and ACEis cause renal failure in patients with renal artery stenosis?
Glomerular filtration is maintained by AngII
Give examples of calcium channel blockers?
Amlodipine, verapamil
How are smooth muscle contractions caused? How do they happen?
Membrane depolarisation opens VGCC, Ca2+ enters and binds to calmodulin (CaM), and the Ca2+-CaM complex activates MLCK, MLCK mediated phosphorylation causes VSM contraction
What are the two different types of calcium channel blocker?
Dihydropyridines - non rate limiting and non-DHPs which are
Why is amlodipine used to treat hypertension
a calcium channel blocker that doesn’t have a ionotropic effect on the heart
What do DHPs do to decrease BP?
They inhibit Ca2+ entry into the VSMCs so less contraction of the cells so less TPR so less BP
How can a powerful vasodilation lead to increased myocardial O2 demand
Powerful vasodilation -> reflex tachycardia -> increased ionotropy -> increased myocardial oxygen demand
Why are ACE and ARB first line treatments for hypertension in patients under 55?
Because there is good patient adherence which is linked to less side effects and there is not much difference between the amoutn ACEi and ARB decrease BP
Why are CCB and thiazide diuretics first line treatments for hypertension in patients over 55 and in afro caribbean patients??
This group of people have a different drug schedule due to low plasma renin activity so ACEi doesn’t work as well
What are examples of alpha blocker drugs?
Prazosin and phentolamine
What type of drug is prazosin
An alpha 1 antagonist
What type of drug is phentolamine? How does this work?
An alpha1/alpha 2 antagonist.
The alpha 2 blocking leads to neg feedback of NA release so there is an enhanced NA release and SNS response leading to increased HR
