Vasodilators

Question 1

Describe the mechanism of action of the ACE inhibitors

Answer 1

Inhibits the conversion from angiotensin I to angiotensin II
Decrease angiotensin II and aldosterone which decreases :
- Vasoconstriction (including renal efferent arteriole)
- myocardial fibrosis
- sodium and water retention
- SNS tone
- bradykinin degradation —> natural vasodilator, stimulates synthesis of PGI2/NO

Question 2

What are the indications of ACE inhibitors.

Answer 2

Congestive heart failure —> increases survival and quality of live
Asymptomatic DCM —> increase in survival
At age B2 chronic degenerative valve disease —> conflicting evidence
Systemic hypertension —> small decrease only (10 mmHg)

Question 3

What are the side effects of ACE inhibitors

Answer 3

Hypotension
Anorexia
Decrease renal blood flow and GFR —> risk of azotemia and AKI.
Decreased effects with NSAIDs —> interfere with bardykinin —> inhibits formation of prostaglandins.

Question 4

Describe the mechanism of action of nitrates

Answer 4

Nitrates -> nitroprusside and nitroglycerine

Pro-drug for nitric oxyde (NO) —> second messenger for cGMP —> interacts with myosin light chain kinase in vascular muscle —> causes vasodilation.

Question 5

What are the indication of nitrates

Answer 5

Acute fulminant CHF in hospital

Question 6

What are the side effects of nitrates

Answer 6

Hypotension

Cyanide toxicity with nitroprusside.
Tolerance after 24 hours —> nitroglyceride

Question 7

What is the mechanism of action of amlodipine

Answer 7

Calcium channel blocker —> dihydropyridine : vessel specific.
Block inward calcium movement in the voltage-gated channels which results in vasodilation

Question 8

What are the indication of amlodipine

Answer 8

Systemic hypertension

Question 9

What are the side effects of amlodipine

Answer 9

Hypotension and RAAs system activation

Question 10

What is the mechanism of action of sildenafil

Answer 10

PDE-V inhibitor (if you are thinking PDE-III it’s pimobendan)
Inhibits the breakdown of cGMP —> interactions with myosin light chain kinase in vascular smooth muscle —> will cause vasodilation.

Question 11

What is the indication of sildenafil ?

Answer 11

Pulmonary hypertension
(And relaxation of the LES)

Question 12

What are the side effects of sildenafil

Answer 12

Hypotension —> very rare

Question 13

Usage of sildenafil is contra-indicated when used with which other medication

Answer 13

Nitrates —> increases the risk of hypotension.