Pharmacokogy Of Hypertension

Question 1

Angiotensin converting enzyme inhibitor examples

Answer 1

Angiotensin converting
enzyme inhibitors

Examples:
Ramipril
Lisinopril
Perindopril

Question 2

ACEi mechanism of action

Answer 2

Inhibit the angiotensin converting
enzyme.
Prevent the conversion of
angiotensin I to angiotensin II
by ACE.

Question 3

Drug target of ACEi

Answer 3

Angiotensin converting enzyme

Question 4

Main side effects of ACEi

Answer 4

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 5

Extra info on ACEi

Answer 5

Most ACE inhibitors (not lisinopril) are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects. Reducesvasoconstriction and salt water retention and aldosterone secretion

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

In 2020, ramipril was the 7th, lisinopril the 42nd and perindopril the 51st most commonly prescribed drugs in the West London area

Question 6

Calcium channel blocker examples

Answer 6

Calcium channel blockers

Examples:
Amlodipine
Felodipine

Question 7

Mechanism if action of calcium channel blockers

Answer 7

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.
Also causes reduced cardiac contraction and cardiac output reduces causing reduced bp

Question 8

Drug target of calcium channel blockers

Answer 8

L type calcium channel

Question 9

Side effects of calcium channel blockers

Answer 9

Ankle oedema
Constipation
Palpitations
Flushing/Headaches

Question 10

Extra info of calcium channel blockers

Answer 10

Dihydropyridine type calcium channel blockers demonstrate a higher degree of vascular selectivity

In 2020, amlodipine was the 2nd and felodipine the 98th most commonly prescribed drugs in the West London area

Question 11

Thiazide or thiazide-like diuretics example

Answer 11

Thiazide or thiazide-like diuretics

Examples:
Bendro-flumethiazide (thiazide)
Indapamide (thiazide-like)

Question 12

Mechanism of action of thiazide

Answer 12

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.
Decreasing blood volume,venous return,cardiac output

Question 13

Drug target of thiazide

Answer 13

Sodium/chloride
cotransporter

Question 14

Side effects of thiazide

Answer 14

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

Question 15

Extra info of thiazide

Answer 15

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)
Excreted unchanged in urine as it needs to be transported from the blood to the basolateral side then apocalyptic side then sodium chloride transporter

In 2020, bendro-flumethiazide was the 38th and indapamide the 46th most commonly prescribed drugs in the West London area

Question 16

Angiotensin receptors blockers examples

Answer 16

Angiotensin receptor blockers

Examples:
Losartan
Irbesartan
Candesartan

Question 17

Mechanism of action of angiotensin receptor blockers

Answer 17

These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)
. Angiotensin II isn’t made so less vasoconstriction occurs and aldosterone inhibited so less water an salt reabsorption

Question 18

Angiotensin receptor blockers target

Answer 18

Angiotensin receptor

Question 19

Side effects of angiotensin receptor blockers

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

Extra info on angiotensin receptor blockers

Answer 20

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.

In 2020, losartan was the 13th, irbesartan the 57th and candesartan the 80th most commonly prescribed drugs in the West London area

Question 21

Time to peak plasma levels

Answer 21

Time to peak concentration is the time required for a drug to reach a peak concentration in plasma. The faster the absorption rate rhe lower the time to peak plasma concentrations

Question 22

Felodopine vs amlodipine

Answer 22

Felodipine resulte in dose dependent decades in bp and reflex increase in heart rate

Amlodipine has a slow onset and much longer half life. Slow onset mitigates effect of tachycardia

Question 23

ACEi or ARB

Answer 23

AECi used before ARB as chef effective and its more effective drug
ARB used in patients of African or Caribbean descent