CVS - Angiotensin Antagonists, CCBs, Vasodilators - Drugs affecting vascular tone

Question 1

Classes of angiotensin antagonists & examples

Answer 1

1. ACE Inhibitors - Captopril, Enalipril
2. AT1 Receptor Antagonists - Losartan, Valsartan
3. Renin Inhibitors - Aliskiren

Question 2

Actions of angiotensin II (5)

Answer 2

1. Arteriolar vasoconstriction - increases bp
2. NaCl reabsorption, K+ excretion, H2O retention
3. Increased sympathetic activity
4. Post pit - ADH secretion - CD H2O absorption
5. Aldosterone secretion

Question 3

Mechanism of action of ACEI

Answer 3

1. Inhibits converting enzyme peptidyl dipeptidase (ATI to ATII) - inhibits RAAS - hypotension
2. Inhibits bradykinin (potent vasodilator) degradation - stimulation of kallikrein-kinin system - hypotension

Question 4

Uses of ACEI (3)

Answer 4

1. Hypertension - by decreasing PVR, CO & HR unchanged
2. Chronic Renal Failure - diminish proteinuria, stabilize fn
3. Heart Failure, after MI

Question 5

Toxicity of ACEI (4) + Contraindications (1)

Answer 5

1. Severe Hypotension
2. Acute Renal Failure - esp in bilat renal stenosis
3. Hyperkalemia - esp in renal insufficiency/diabetes
4. Dry Cough +/- wheezing & angioedema - due to bradykinin & substance P
5. Pregnancy - 1st trimester - increased teratogenicity, 2nd/3rd trimester - fetal hypotension, anuria, renal failure

Question 6

Mechanism of action of AT1R antagonist

Answer 6

1. Antagonizes angiotensin II type 1 receptors - no effect on bradykinin, more selective, more complete effects
2. Prolonged inhibition of AT1 - disinhibits renin secretion + increases circulating AII - increases ATIIR activation (vasodilation)

Question 7

Mechanism of action of renin inhibitors

Answer 7

1. Inhibits renin - involved in the rate limiting step for AII production
2. Produces dose dependent reduction in plasma renin activity, AI, AII and aldosterone concentrations

Question 8

Uses of renin inhibitors (2)

Answer 8

1. Reduces BP - similar to ACEI/diuretics in safety, tolerability
2. Prevents rise in renin activity - produced by ACEI/ARBs/diuretics

Question 9

Compare Verapamil, Diltiazem, Nifedipine
(A) Lowering BP
(B) Vasodilator
(C) Cardiac Depressant

Answer 9

(A) V = D = N
(B) N > D > V
(C) V > D > N

Question 10

Mechanism of action of CCBs

Answer 10

• L-type channel blockers, predominant type in cardiac/smooth muscle
• Blocks Ca channels on the inner side of membrane (binds more effectively to open and inactivated channels) - decreases frequency of opening in response to depolarization - reduced transmembrane calcium current

Question 11

Uses of CCBs (4)

Answer 11

1. Anti-HTN - sustained relaxation in smooth muscle - decreasd muscle tone - reduced bp
2. Anti-angina - reduced cardiac contractility - decreases O2 requirements in patients with angina
3. Anti-arrhythmia - slowed/blocked SAN & AVN conduction (Verapamil, Diltiazem)
4. Cerebral Vasospasm following subarachnoid hemorrhage (Nimodipine)

Question 12

Toxicity of CCBs (2) + Contraindications (1)

Answer 12

1. Cardiac Depression (cardiac arrest, bradycardia, AV block, heart failure) - due to excessive inhibition of Ca influx - but rare
2. Minor effects - flushing, dizziness, nausea, constipation (esp verapamil), peripheral edema
3. Congestive Heart Failure

Question 13

Mechanism of α-1 blockers

Answer 13

Prazosin, terazosin, doxazosin

Selectively blocks α-1 receptors in arterioles & venules - dilates both resistance & capacitance vessels - anti-HTN

Question 14

Uses of α-1 blockers (3)

Answer 14

1. Hypertension
2. Prostate Hyperplasia
3. Bladder Obstruction (urinary hesitancy)

Question 15

Considerations when using α-1 blockers (3)

Answer 15

1. Has 1st dose effect - marked postural hypotension - Give small first dose at bedtime
2. Increased salt/water retention - Use with diuretics/β-blockers
3. Mild, infrequent toxicities - dizziness, palpitations, headache, lassitude

Question 16

Mechanism of hydralazine

Answer 16

1. Increases cGMP + is a NO donor

2. leading to smooth muscle dilation (arterioles, not veins)

Question 17

Uses of hydralazine (2)

Answer 17

1. Hypertension - combination therapy, 2nd line with diuretics/β-blockers
2. Heart Failure - in combination with nitrates

Question 18

Toxicity of hydralazine (2)

Answer 18

1. Headaches, nausea, anorexia, palpitations, sweating, flushing
2. In IHD: reflex tachycardia & sympathetic stimulation may provoke angina/ischemia arrhythmias

Question 19

Mechanism of minoxidil

Answer 19

Opens K+ channels in smooth muscle stabilizing membranes - makes contractions less likely - dilates arterioles, not veins

Question 20

Uses of minoxidil (2)

Answer 20

1. Hypertension associated with reflex sympathetic stimulation & Na/fluid retention, use with loop diuretic/β-blocker
2. Stimulant for hair growth in male pattern baldness (topical)

Question 21

Toxicity of minoxidil (3)

Answer 21

1. Sweating
2. Hypertrichosis
3. With inadequate diuretics/β-blockers - tachycardia, palpitations, angina, edema

Question 22

Mechanism of smooth muscle relaxants

Answer 22

Sildenafil, Tadalafil, Vardenafil

Increases cGMP by inhibiting PDE5 breakdown (primarily in arterial walls of smooth muscle of lungs, penis)

Question 23

Uses of smooth muscle relaxants (2)

Answer 23

1. Erectile Dysfunction - relaxes intimal cushions in helicine arteries - vasodilation + increases blood flow to corpus cavernosum
2. Pulmonary Hypertension - relaxes pulmonary arteries - reduces PR & workload of right ventricle

Question 24

Toxicity of smooth muscle relaxants + Contraindications (3+4)

Answer 24

1. Headache
2. Flushing
3. Nasal congestion
4. If taking nitrates
5. Hepatic impairment
6. Renal dysfunction
7. Hypotension