Pharmacology of Hypertension

Question 1

How do ACE inhibitors work? Provide examples

Answer 1

Inhibit the angiotensin converting enzyme. Prevent the conversion of angiotensin I to angiotensin II by ACE. Examples: Ramipril, Lisinopril, Perindopril

Question 2

What is the drug target of ACE inhibitors?

Answer 2

Angiotensin converting enzyme

Question 3

What are the main side effects of ACE inhibitors?

Answer 3

Cough, Hypotension, Hyperkalaemia (care with K+ supplements or K+-sparing diuretics), Foetal Injury (AVOID IN PREGNANT WOMEN), Renal failure (in patients with renal artery stenosis), Urticaria/Angioedema


Question 4

What are 4 facts about ACE inhibitors?

Answer 4

1. Most ACE inhibitors (not lisinopril) are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.
2. eGFR and serum potassium must be regularly monitored when prescribing ACE inhibitors.
3. Most trials indicate that angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors.
4. Losartan and candesartan are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.

Question 5

How do calcium channel blockers work?

Answer 5

Block L-type calcium channels – predominantly on vascular smooth muscle. This results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation. The resultant vasodilation reduces peripheral resistance.

Question 6

What is the drug target of calcium channel blockers?

Answer 6

L-type calcium channel

Question 7

What are the main side effects of calcium channel blockers?

Answer 7

Ankle oedema, Constipation, Palpitations, Flushing/Headaches

Question 8

What is an important fact about calcium channel blockers? Provide examples

Answer 8

Dihydropyridine type calcium channel blockers demonstrate a higher degree of vascular selectivity. Examples: Amlodipine, Felodipine

Question 9

How do thiazide/thiazide-like diuretics work?

Answer 9

They block the Na+, Cl- co-transporter in the early DCT. Therefore Na+ and Cl- reabsorption is inhibited. As a result the osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct.

Question 10

What drug targets do thiazide/thiazide-like diuretics act on?

Answer 10

Sodium/chloride cotransporter

Question 11

What are side effects of thiazide/thiazide-like diuretics?

Answer 11

Hypokalemia. Hyponatremia. Metabolic alkalosis (increased hydrogen ion excretion). Hypercalcemia. Hyperglycemia (hyperpolarised pancreatic beta cells). Hyperuricemia.

Question 12

What is a fact about thiazide/thiazide-like diuretics? Provide examples

Answer 12

Thiazide and thiazide-like diuretics both lose their diuretic effects within 1-2 weeks of treatment. Continuing anti-hypertensive action appears to be due to vasodilating properties (these are more pronounced for the thiazide-like diuretics).
Bendro-flumethiazide (thiazide), Indapamide (thiazide-like)

Question 13

How do angiotensin-receptor blockers work?

Answer 13

These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)

Question 14

What is the drug target of angiotensin receptor blockers?

Answer 14

Angiotensin receptor

Question 15

What are side effects of using angiotensin receptor blockers?

Answer 15

Hypotension, Hyperkalaemia (care with K+ supplements or K+-sparing diuretics), Foetal Injury (AVOID IN PREGNANT WOMEN), Renal failure (in patients with renal artery stenosis)

Question 16

What are 2 facts about angiotensin receptor blockers? Provide examples

Answer 16

Most trials indicate that angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors.
Losartan and candesartan are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.
Examples: Losartan, Irbesartan, Candesartan