Pharmacology Of Hypertension Flashcards
Give some examples of ACE inhibitors?
Ramipril
Lisinopril
Perindopril
What is the primary mechanism of action of ACEi?
Inhibit the angiotensin converting
enzyme preventing the conversion of
angiotensin I to angiotensin II
by ACE
What is the drug target of ACEi?
Angiotensin converting enzyme
What are the main side effects of ACEi?
Cough
Hypotension
Hyperkalaemia (take care with K+ supplements or K+-sparing diuretics)
Foetal Injury (avoid in pregnant women)
Renal failure (in patients with renal artery stenosis)
Urticaria/Angioedema
Why are ACEi contraindicated in patients with bilateral renal artery stenosis?
Ang II - determinant of efferent arteriole vasoconstriction
Helps maintain GFR when renal perfusion is low
Inhibiting Ang II may lead to acute renal failure
Why may ACEi cause hyperkalaemia?
Inhibit Angiotensin II production, preventing aldosterone secretion
Aldosterone causes potassium excretion
Is Lisinopril a pro-drug?
No, most ACEi are pro-drugs but Lisinopril is an exception
What is a pro-drug?
A drug that requires hepatic activation to generate the active metabolites required for therapeutic effects
What must be regularly monitored when taking ACEi?
eGFR and serum potassium
Give some examples of calcium channel blockers (CCBs)
Amlodipine
Felodipine
What is the primary mechanism of action of CCBs?
Block L-type calcium channels – predominantly on vascular smooth muscle
Results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation
Resultant vasodilation reduces peripheral resistance
What is the primary drug target for CCBs?
L-type calcium channel
What are the main side effects of CCBs?
Ankle oedema
Constipation
Palpitations
Flushing/headaches
What type of CCBs show a higher degree of vascular selectivity?
Dihydropyridine type calcium channel blockers
What side effect is commonly with Felodipine and not Amlodipine?
Reflex increase in heart rate (reflex tachycardia)
Amlodipine has a slow-onset and longer half-life (35-50hrs) mitigating reflex tachycardia
Give some examples of thiazide/thiazide-like diuretics
Bendro-flumethiazide (thiazide)
Indapamide (thiazide-like)
What is the primary mechanism of action of thiazide/thiazide-like diuretics?
They block the Na+, Cl- co-transporter in the early DCT
Inhibit Na+ and Cl- reabsorption
Osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct
What is the drug target of thiazide/thiazide-like diuretics?
Sodium/chloride co-transporter
What is the net effect of thiazide/thiazide-like diuretics?
Sodium and water loss
Decreased blood volume
Decreased venous return
Decreased cardiac output
What are the main side effect of thiazide/thiazide-like diuretics?
Hypokalemia
Hyponatremia
Metabolic alkalosis (increased hydrogen ion excretion)
Hypercalcemia
Hyperglycemia (hyperpolarised pancreatic beta cells)
Hyperuricemia
Are the diuretic effects of thiazide and thiazide-like diuretics long lasting?
No, they lose their diuretic effects within 1-2 weeks of treatment
Kidney becomes tolerant to the diuretics because there is a rebound activation of the renin angiotensin system which counteracts the diuretic effect by increasing sodium reabsorption
How comes the anti-hypertensive properties of thiazide/thiazide-like diuretics are more long-lasting?
Thought to be due to vasodilating properties
Why may thiazide/thiazide-like diuretics cause hypokalaemia?
Increase sodium delivery from early distal tubule to distal (distal) tubule causing increase in potassium loss
(Increase in distal tubular sodium concentration stimulates aldosterone-sensitive sodium pump to increase sodium reabsorption and potassium/H+ excretion)
Give some examples of Angiotensin receptor blockers?
Losartan
Irbesartan
Candesartan
What is the primary mechanism of action of ARBs?
Non-competitive antagonists of Ang II at AT1 receptor found on kidneys and on the vasculature
What is the drug target of ARBs?
Angiotensin receptor
What are the main side effects of ARBs?
Hypotension
Hyperkalaemia (take care with K+ supplements or K+-sparing diuretics)
Foetal Injury (avoid in pregnant women)
Renal failure (in patients with renal artery stenosis)
Most trials suggest which anti-hypertensives are more effective, ACEi or ARBs?
ACEi
Which ARBs are pro-drugs?
Losartan and Candesartan
