Agents acting on Renin-angiotensin system

Question 1

List the angiotensin II receptor blockers

Answer 1

Candesartan
Irbesartan
Losartan*
Telmisartan
Valsartan

Question 2

List the ACE inhibitors in class I

Answer 2

Captopril

Question 3

List the ACE inhibitors in class II

Answer 3

Enalapril*
Perindopril
Quinapril
Ramipril
Trandolapril

Question 4

List the drugs that are ACE inhibitors that are in class III

Answer 4

Lisinopril

Question 5

the ACE inhibitors MoA

Answer 5

Inhibit ACE1
Act preferentially on angiotensinsensitive
vascular beds including
kidney, heart and brain.

Question 6

Antihypertensive effectiveness increased by?

Answer 6

• Low salt diet
• Enhanced renin secretion (patients
  on diuretics)

Question 7

Explain the indications of ACEIs
12 marks

Answer 7

Indications:
* Hypertension (enhanced by low salt diet) – in Black patients they are
less effective in the absence of diuretics
* Reduce mortality in patients with heart failure
* Prevent post-infarct heart failure
* Reduce cardiovascular outcomes in patient at high risk of IHD
* Renoprotective in patients with diabetes mellitus (diabetic
nephropathy) and renal disease with proteinuria
* Prevent progression of chronic kidney disease

Question 8

explain why ACEIs are preferred in patients with DM

Answer 8

• Lack negative effects on glucose tolerance and blood lipids
• Reduce microalbuminuria

Question 9

Explain why the ACEIs are preferred in congestive heart failure

Answer 9

• Counteract overall metabolic-hormonal abnormalities
• Indirect diuretic effect via inhibition of aldosterone production

Question 10

List the 5 contra-indications of ACEIs

Answer 10

Contraindications:
* Pregnancy - teratogenic
* History of angioedema and hyperkalaemia
* Bilateral renal artery stenosis or stenosis of an artery to a dominant/single kidney
* Aortic valve stenosis
* Severe renal impairment (eGFR <30ml/min) – unless specialist dose-adjusted

Question 11

Explain the general caution of ACEIs

Answer 11

General cautions:
* Angioedema rare, but important adverse effect (caused by inhibition of
bradykinin degradation) – more common in Black patients and those with history
of allergy
* Combination with ARBs should be avoided

Question 12

List the adverse effects of ACEIs

Answer 12

Adverse effects:
* Dry cough
* Angioedema
* Hyperkalaemia (due to reduced
aldosterone secretion)
* Hypotension
* In patients with bilateral renal artery
stenosis: precipitate renal failure,
because AT2 usually constrict
efferent arterioles and maintains
pressure in the glomerulus for
filtration

Question 13

Explain the pharmacokinetics for ACEIs

Answer 13

Pharmacokinetics
* Administer orally (bioavailability ranges from 25%-75%)
* Varying degrees of first pass hepatic metabolism, several has active
metabolites

Question 14

Explain the pharmacokinetics of Enalapril

Answer 14

Pharmacokinetics:
Excreted predominantly in the urine as enalaprilat (active metabolite)
and unchanged drug

Question 15

List the adverse effects of enalapril

Answer 15

Adverse effects:
* Dry cough most common usually happen in early phase of tx (can
happen after many years on tx)
* Angioedema (can happen after many years on tx)
* Hyperkalaemia

Question 16

List Contra-indications of Enalpril

Answer 16

Contraindications:
Bilateral renal artery stenosis, hyperkalaemia, pregnancy

Question 17

List the Drug interactions of Enalpril

Answer 17

Drug interactions:
* Other antihypertensives (hypotension)
* Potassium-sparing diuretics / potassium supplements
* ARBs
* High-dose aspirin & all NSAIDs
* Digoxin & lithium
* Trimethoprim

Question 18

List the contraindication of Losartan

Answer 18

Contraindications:
* Bilateral renal artery stenosis, hyperkalaemia, pregnancy

Question 19

Cautions of Losartan

Answer 19

Cautions:
* Unilateral renal artery stenosis, pre-existing renal insufficiency,
hypersensitivity (angioedema) to ACEIs

Question 20

List the adverse effects of Losartan

Answer 20

Adverse effects:
* Dizziness, dose-related orthostatic hypotension
* Hyperkalaemia, raised liver enzymes