Drugs and vasculature Flashcards
(31 cards)
Where is ACE found?
in endothelial cells, lung capillaries, kidney epithelial cells
Where does angiotensin 2 act?
AT1 receptor
What are some VSM mediators that stimulate VSM contraction?
- Ang2
- PGG2, PGH2
- ET1
What are some endothelial cell agonists that cause relaxation?
- NO
- CNP –C-Type Naturietic Peptide
- PGI2
- EDHF –Endothelial Hypopolarising Factor
What are the vessels with the greatest influence on BP?
arterioles - they have partial tone normally
What is hypertension?
more than 140/90
What is the single most important risk factor for stroke and important in MI and CKD?
hypertension
What is the treatment overview for hypertension?
- Single therapy - for under 55s give ACEi or ARB, over 55 or afro caribbean give CCB or thiazide diuretic
- Dual therapy - ACEi and CCB or ACEi and thiazide diuretic
- Triple therapy - ACEi, CCB and thiazide diuretic
- Symptomatic relief - low dose spironolactone (aldosterone receptor antagonist so diuretic effects) and B blocker or alpha blocker
What should first be considered for hypertensive patients?
lifestyle modifications, then pharmacology
Why are patients over 55 not given RAS targetting drugs?
Low renin/low renin sensitivity over that age so less responsive to the drugs hence other drugs are needed
What stimulates the RAS?
- low renal sodium reabsorption
- low renal perfusion
- high sns activation
What do ACEi do?
Decrease Ang2 production and increase bradykinin
What are the uses of ACEi?
- hypertension
- heart failure
- post MI
- diabetic nephropathy
- progressive renal insufficiency
- high CVS disease risk patients
How do ACEi work in treating hypertension?
- Reduce TPR–more bradykinin & less AngII -> reduces TPR via less AT1R-mediated vasoconstriction so less BP and more bradykinin vasodilation
- Sodium retention –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 –less SNS activation of thirst in the brain via AT1R
How do ACEi work in heart failure?
- Reduce TPR –less vasoconstriction via AT1R in the peripheral vasculature so less TPR so less afterloadon the heartso ionotropic effects of the heart decrease.
- Reduce preload –venodilation (bradykinin?) means less preload
What do ACEi end in?
-ipril
What are ARBs and their uses?
- angiotensin receptor blockers
- used in hypertension and heart failure
Give an example of an ARB
losartan
What are the side effects of ARBs and ACEi?
Cough –ACEi
Urticaria/angioedema –ACEi rarely
Hypotension –ACEi, ARBs
Hyperkalaemia – ACEi, ARBs
Care with K+ supplements or K+-sparing diuretics. Aldosterone promotes K+loss so aldosterone inhibitors (ACEi, ARBs) produce a hyperkalaemia
Foetal injury –ACEi, ARBs
Renal failure (in patients with renal artery stenosis) –ACEi, ARBs Glomerular filtration is maintained by AngII so you need to be careful in renal failure patients
Give examples of calcium channel blockers
amlodipine, verapamil
What normally happens in smooth muscle contraction?
Membrane depolarisation opens VGCC -> Ca2+enters and binds calmodulin (CaM) -> Ca2+-CaM complex activates MLCK -> MLCK mediated phosphorylation -> VSM contraction
Why is amlodipine used to treat hypertension?
Doesn’t have an inotropic effect on the heart
What do dihydropyridines act on and what are they used for??
- Affect smooth muscle only
- More selective for blood vessels
- Amlodipine does not cause any negative inotropy
- Also licensed for prophylaxis of angina
- These are the drugs used to treat hypertension, because they are effective on the vasculature
What do non-DHPs act on?
- Cardiac and smooth muscle
- Verapamil has a large negative chronotropic effect
