1.8 - Pharmacology of hypertension (core drugs) Flashcards
(30 cards)
What are the main types of anti-hypertensive drugs? (4)
- angiotensin converting enzyme inhibitors
- calcium channel blockers
- thiazide / thiazide-like diuretics
- angiotensin receptor blockers
What are some examples of ACE inhibitors? (3)
- ramipril
- lisinopril
- perindopril
What is the primary mechanism of action of ACE inhibitors?
- inhibit ACE
- prevent conversion of angiotensin I –> angiotensin II
- angiotensin II increases BP
What is the drug target of ACE inhibitors?
ACE
What are the main side effects of ACE inhibitors?
- cough
- hypotension
- hyperkalaemia (care with K+ supplements or K+ sparing diuretics)
- foetal injury (AVOID IN PREGNANT WOMEN)
- renal failure (in renal artery stenosis patients)
- urticaria (hives) / angioedema (swelling under skin)
What is some extra information about ACE inhibitors?
- most (not lisonopril) are prodrugs so require hepatic activation to have an effect
- eGFR and serum K+ must be regularly monitored when prescribing ACE inhibitors
- typically used ahead of angiotensin II receptor blockers (cost and effectiveness)
What are some examples of calcium channel blockers?
- amlodipine
- felodipine
What is the primary mechanism of action of calcium channel blockers?
- block L-type calcium channels, predominantly on vascular smooth muscle
- results in decrease in calcium influx and downstream inhibition of myosin light chain kinase –> prevention of cross-bridge formation
- resultant vasodilation reduces peripheral resisatance
What is the drug target for calcium channel blockers?
L-type calcium channel
What are the main side effects of calcium channel blockers?
- ankle oedema
- constipation
- palpitations
- flushing/headache
What do dihydropyridine type calcium channel blockers do differently?
Demonstrate a higher degree of vascular sensitivity
What are some examples of thiazide or thiazide-like diuretics?
- bendro-flumethiazide (thiazide)
- indapamide (thiazide-like)
What is the primary mechanism of action of thiazide or thiazide-like diuretics?
- block Na+/Cl- cotransporter in early DCT
- therefore Na+ and Cl- reabsorption is inhibited
- as a result the osmolarity of the tubular fluid increases, decreasing osmotic gradient for water reabsorption in collecting duct
What is the drug target of thiazide or thiazide-like diuretics?
Sodium/chloride cotransporter
What are the main side effects of thiazide or thiazide-like diuretics?
- hypokalaemia
- hyponatraemia
- metabolic alkalosis (increased H+ excretion)
- hypercalcaemia
- hyperglycaemia (hyperpolarised pancreatic beta cells)
- hyperuricaemia
What is some extra information about thiazide or thiazide-like diuretics?
- these drugs lose diuretic effects in 1-2 weeks of treatment
- continuing anti-hypertensive action appears to be due to vasodilating properties (more pronounced for thiazide-like diuretics)
What are some examples of angiotensin receptor blockers (ARBs)?
- losartan
- irbesartan
- candesartan
What is the primary mechanism of action of ARBs?
These act as insurmountable (non-competitive) antagonists at angiotensin I receptor (found on kidneys and on vasculature)
(AT-II acts via both AT1 and AT2 receptors)
What is the drug target of ARBs?
Angiotensin receptor
What are the main side effects of ARBs?
- hypotension
- hyperkalaemia (care with K+ supplements and K+ sparing diuretics)
- foetal injury (AVOID IN PREGNANT WOMEN)
- renal failure (in patients with renal artery stenosis)
What is some extra information about ARBs?
- not as effective anti-hypertensives as ACEi (ACEi typically used first partly due to cost, partly due to effectiveness)
- losartan and candesartan are prodrugs so require hepatic activation to have effects
- ARBs for patients of African/Caribbean descent
What would you do if a patient had a BP of under 135/85, 135/85 to 149/94 and 150/95+?
- <135/85 = monitor at least every 5 years
- 135/85 to 149/94 = ABPM/HBPM offered, reduce CVD risk, start drug treatment if there is any of the following:
- target organ damage
- CVD
- renal disease
- diabetes
- 10 year CVD risk >10%
- > 150/95 = start drug treatment
What is drug clearance?
- clearance is the measure of the ability of the body to eliminate a drug
- clearance by means of various organs of elimination is additive
- elimination of drug may occur as a result of processes that occur in the liver, kidney and other organs
What is elimination half-life of a drug?
Elimination half-life is the length of time required for the concentration of a particular drug to decrease to half of its starting dose in the body
