Pharmacology of hypertension

Question 1

What drugs treat hypertension?

Answer 1

• Angiotensin converting enzyme inhibitors
• Calcium channel blockers
• Thiazide or thiazide-like diuretics
• Angiotensin receptor blockers

Question 2

What are examples of ACEis?

Answer 2

Ramipril

Lisinopril

Perindopril

Question 3

What is the drug target of ACEis?

Answer 3

Angiotensin converting enzyme

Question 4

What is the primary mechanism of action of ACEis?

Answer 4

Inhibit the angiotensin converting enzyme

Prevent the conversion of angiotensin I -> angiotensin II by ACE

Question 5

What are the side effects of ACEis?

Answer 5

• 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 6

What is required for ACEis to be active?

Answer 6

Hepatic activation to generate the active metabolites required for therapeutic effects

Question 7

What must be monitored with ACEis?

Answer 7

eGFR and serum potassium

Question 8

What are examples of calcium channel blockers?

Answer 8

Amlodipine

Felodipine

Question 9

What is the primary target of calcium channel blockers?

Answer 9

L-type-calcium channel

Question 10

What is the primary mechanism of action of calcium channel blockers?

Answer 10

Block L-type calcium channels (vascular smooth muscle). Decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation -> vasodilation reduces peripheral resistance

Question 11

What are the side effects of CCBs?

Answer 11

Ankle oedema

Constipation

Palpitations

Flushing/Headaches



Question 12

Which drugs show a higher degree of vascular selectivity?

Answer 12

Dihydropyridine type calcium channel blockers

Question 13

What is the primary target of thiazide or thiazide-like diuretics?

Answer 13

Sodium/chloride cotransporter



Question 14

What is the primary mechanism of action of thiazide?

Answer 14

They block the Na+, Cl- co-transporter (early DCT)

Therefore Na+ and Cl- reabsorption is inhibited.

Osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct.

Question 15

What are the side effects of thiazide?

Answer 15

Hypokalemia

Hyponatremia.

Metabolic alkalosis (increased hydrogen ion excretion)

Hypercalcemia.

Hyperglycemia (hyperpolarised pancreatic beta cells).

Hyperuricemia.

Question 16

What are examples of ARBs?

Answer 16

Losartan

Irbesartan

Candesartan

Question 17

What is the primary target of ARBs?

Answer 17

Angiotensin receptors

Question 18

What is the primary mechanism of action of ARBs?

Answer 18

These agents act antagonists at AT1 receptor (found on kidneys and vasculature)

Question 19

What are the side effects of ARBs?

Answer 19

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 20

What are examples of thiazide diuretics?

Answer 20

Bendro-flumethiazide (thiazide)

Indapamide (thiazide-like)

Question 21

Most ACEis are pro-drug, which are not?

Answer 21

Lisinopril

Question 22

What must be monitored with ACEis?

Answer 22

eGFR and serum potassium must be regularly monitored when prescribing ACE inhibitors.

Question 23

What happens to thiazide/ thiazide like diuretics?

Answer 23

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)

Question 24

Which angiontensin receptor blockers require hepatic portal activation?

Answer 24

Losartan

Candesartan

Question 25

Are ARBs more effective than ACEis?

Answer 25

Most trials suggest no