Hypertension Flashcards
Name 4 classes of drug used to treat hypertension
- ACE inhibitors
- Calcium channel blockers
- Thiazide or thiazide-like diuretics
- Angiotensin receptor blockers
Give some examples of ACE inhibitors
- Ramipril
- Lisinopril
- Perindopril
Give some examples of calcium channel blockers
- Amlodipine
- Felodipine
Give some examples of thiazide or thiazide-like diuretics
- Bendro-flumethiazide (thiazide)
- Indapamide (thiazide-like)
Give some examples of angiotensin receptor blockers
- Losartan
- Irbesartan
- Candesartan
What is the mechanism of action of ACE inhibitors?
- Inhibits ACE to prevent it converting
angiotensin I to angiotensin II (which raises BP by vasoconstriction, sympathetic NS stim and increased ADH and aldosterone) - Vasodilates efferent renal arteriole
What is the mechanism of action of calcium channel blockers?
- Block L-type calcium channels mainly on vascular smooth muscle causing a decrease in calcium influx w/ downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation
- The resultant vasodilation reduces peripheral resistance
What is the mechanism of action of thiazide/thiazide-like diuretics?
- They block the Na+/Cl- co-transporter in the early DCT so Na+ and Cl- reabsorption is inhibited
- Thus the osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct
What is the mechanism of action of angiotensin receptor blockers?
These agents act as insurmountable/non-competitive antagonists at AT1 (angiotensin II type 1) receptors which are found on the kidneys and vasculature
Which anti-hypertensives are pro-drugs?
- Most ACE inhibitors (not lisinopril)
- Losartan
- Candesartan
What are pro-drugs?
Drugs that req hepatic activation to generate the active metabolites needed for therapeutic effects
Are angiotensin receptor blockers or ACE inhibitors more effective anti-hypertensives?
ACE inhibitors are more effective anti-hypertensives
What are some side effects of ACE inhibitors?
- Cough - due to increased bradykinins
- Hypotension - Hyperkalaemia - K+ moves out of blood when aldosterone gen. (care w/ K+ supplements or K+ sparing diuretics)
- Foetal injury (avoid in pregnancy)
- Renal failure (in patients w/ renal artery stenosis)
- Urticaria/angioedema
What are some side effects of calcium channel blockers?
- Ankle oedema
- Constipation - relax smooth muscles in blood vessels incl. those in gut muscles
- Palpitations (reflex tachycardia w/ felodipine as CCBs slow HR)
- Flushing/headaches
What are some side effects of thiazide/thiazide-like diuretics?
- Hypokalaemia
- Hyponatremia
- Metabolic alkalosis (increased hydrogen ion excretion)
- Hypercalcemia
- Hyperglycaemia (hyperpolarised pancreatic beta cells)
- Hyperuricemia
What are some side effects of angiotensin receptor blockers?
- Hypotension
- Hyperkalaemia - K+ moves out of blood when aldosterone gen. (care w/ K+ supplements or K+ sparing diuretics)
- Foetal injury (avoid in pregnancy)
- Renal failure (in patients w/ renal artery stenosis)
Why are ACE inhibitors and angiotensin receptor blockers contraindicated in renal artery stenosis?
Because these drugs prevent ang II gen and this is the main thing that causes efferent renal arteriole vasoconstriction and so maintains GFR when renal perfusion is low e.g. in renal artery stenosis so if used these drugs would cause acute renal failure
What happens when thiazide/thiazide-like diuretics are taken?
- Diuretic effect only lasts for 1-2 wks as kidney becomes tolerant and there is rebound activation of RAAS system which counteracts diuretic effect due to increasing Na+ reabsorption
- Anti-hypertensive effect continues though due to thiazide vasodilating action
