Pharmacology 12 - Drugs and the Vasculature Flashcards
Which equation is important in the physiology of hypertension?
Blood pressure = cardiac output x total peripheral resistance
Describe the pathophysiology of hypertension
- Consistantly above 140/90mmHg
- Single most important risk factor for stoke, causing 50% ischaemic strokes
- Accounts for 25% heart failure cases, increases to 70% in the elderly
- Risk factor for MI and chronic kidney disease
What stimulates the renin angiotensin system?
- Decreased renal Na+ reabsorption
- Decreased renal perfusion pressure
- Increased SNS
How do ACE inhibitors work, and when are they used?
- Inhibit the somatic form of ACE, preventing conversion of angiotensin I to angiotensin II
- Used in hypertension, heart failure, post MI, diabetic nephropathy, progressive renal insufficiency, and in patietns at risk of CVD
Give an example of an ACE inhibitor
Enalapril - usually drugs ending in -pril
How do angiotensin receptor blockers work?
- Antagonists of type 1 receptors for angiotensin II, preventing the renal and vascular actions of angiotensin II (reduced vasoconstriction, salt and water reteion, and aldosterone secretion)
- Used in hypertension and heart failure
Give an example of an angiotensin receptor blocker
Losartan
List the possible side effects of ACE inhibitors and angiotensin receptor blockers
- Generally well tolerated
- Cough (ACE inhibitors due to bradykinin increase - as ACE inhibitors breakdown bradykinin)
- Hypotension (both)
- Hyperkalaemia (both by interfering with sodium reuptake)
- Renal failure in patients with renal artery stenosis (both due to inability to constrict the efferent arteriole and regulate the GFR)
How do calcium channel blockers work?
- Dihydropyridines are more selective for blood vessels. Amiodipine causes no negative ionotropy. Licensed for prophylaxis of angina
- Non-DHPs such as verapamil have a large negative ionotropic effect
- Dihydropyridines are mainly used, as they inhibit calcium entry to vascular smooth muscle and decrease TPR
How is peripheral resistance influenced?
- By factors causing vasoconstriction and vasodilation
- Eg. antiotensin II, noradrenaline, ATP, bradykinin, nitric oxide, prostaglandins (can cause contraction or relaxation)
What is the consequence of peripheral resistance increasing?
Increased arterial pressure
- Radius decreases
- Increased resistance
- Decreased blood flow
How does angiotensin II increase blood pressure?
- Increase thirst
- Increase vasoconstriction
- Activate SNS
- Increase salt and water retention
- Increase aldosterone secretion (salt and water retention)
How do ACE inhibitors reduce hypertension and heart failure?
- Hypertension via reducing vasoconstriction, reducing water intake and water and salt retention
- Heart failure via vasodilation (decreased afterload) and decreased volume being returned to the heart due to decreased water retention (decreased venous return)
Describe the process of smooth muscle contraction
- Membrane depolarisation opens VGCCs
- Calcium enters and binds to calmodulin
- Calcium calmodulin complex binds to and activates myosin light chain kinase
- Myosin light chain kinase mediated phosphorylation results in smooth muscle contraction
Why are people over 55 and afro-caribbeans given CCBs or thizide type diuretics?
- Hypertension is more likely to be due to atherosclerosis
- Therefore ACE inhibitors and ARBs do not work
- Afro-caribbeans have a low plasma renin activity genetically
Compare the mortality in RAS drugs and CCBs
- RAS inhibitors decrease heart failure
- RAS inhibitors increase stroke
Compare mortality in RAS and thiazides
RAS inhibitors increase heart failure and stroke
Compare mortality in RAS and beta blocker drugs
RAS inhibitors decrease CV events and stroke
Why are a1 adrenoceptor antagonists used as anti-hypertensives?
- Blockade of vasoconstriction
- Improves TPR and hypertension
