Drugs and the cardiovascular system: the vasculature Flashcards
List examples of vasoconstictors
- angiotensin II
- noradrenaline
- ATP
List examples of vasodilators
- NO
- PGI2
- C-type natriuretic peptide
What happens to pressure with increased sympathetic discharge to arterioles?
- increased arteriolar constriction
- increased peripheral resistance
What happens if arterioles contract?
- reduced radius, increased resistance, decreased blood flow
What happens if arterioles relax?
- increased radius, decreased resistance, increased blood flow
What defines hypertension?
- constant BP above 140/90 mmHg
What is the most important risk factor for stroke?
hypertension
What diseases is hypertension a major risk factor for?
- myocardial infarction
- chronic kidney disease
What is the first step of hypertension treatment?
- ACE inhibitor or angiotensin receptor blocker (ARB) for under 55s
- calcium channel blocker (CCB) or thiazide-type diuretic for over 55s or AfroCaribbeans
What is the second step of hypertension treatment?
- ACE inhibitor and calcium channel blocker
- ACE inhibitor and thiazide type diuretic
ARB preferred to ACE for AfroCaribbean
What is the third step of hypertension treatment?
-combination of ACE inhibitor/ARB with CCB and thiazide-like diuretic
What is the fourth step of hypertension treatment?
-diagnosed as resistant hypertension
- consider low dose spironolactone
- consider beta-blocker or alpha blocker
Outline how the renin angiotensin-system works
- Angiotensinogen is produced by the liver
- reduced renal Na+ reabsorption, reduced renal perfusion pressure and increase sympathetic activation leads to the release of renin
- renin converts angiotensinogen into angiotensin I
- ACE converts angiotensin I into angiotensin II and bradykinin into inactive metabolites
-angiotensin II stimulates: thirst/SNS activation, vasoconstriction, salt and water retention and aldosterone secretion
How does ACEi work?
-inhibit ACE from converting angiotensin I to angiotensin II
What are the uses of ACEi?
- hypertension
- heart failure
- post- MI
- diabetic neuropathy
- progressive renal insufficiency
- patients at high risk of cardiovascular disease
Give an example of an ACEi
enalapril
How does ACEi help hypertension?
inhibits vasoconstriction of vessels, reducing TPR directly leading to reduced BP
-it also contributes to decreased venous return and hence CO
How does ACEi help heart failure?
- inhibits vasoconstriction, meaning there is a decrease in afterload and hence cardiac work
- this also reduces the chance of oedema due to long term venous return
How do ARB work?
They prevent the renal and vascular actions of ANG II
-inhibits vasoconstriction, salt and water retention and aldosterone secretion
Give an example of ARB
losartan
What are the main side effects of ACEi and ARB
- cough (ACEi)
- hypotension
- hyperkalaemia (less sodium reuptake and potassium excretion) - care with K supplements
- renal failure in patients with renal artery stenosis
What is the mechanism for smooth muscle contraction?
- membrane depolarisation opens voltage-gated calcium channels
- Ca++ enters and binds to calmodulin (CaM)
- Ca++ CaM complex binds to and activates myosin light chain kinase
- MLCK mediated phosphorylation leads to smooth muscle contraction
What are the two types of CCB?
-dihydropyridines
more selective for blood vessels
-non-DHPs (non-rate limiting)
Give examples of each type of CCB
-dihydropyridine- amlodipine (doesn’t cause any negative inotropy)
licensed for prophylaxis of angina
-non- DHPs - verapamil (large inotropic effect)
