Vasodilators & treatment of angina

Question 1

Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate

Answer 1

• MOA
• releases NO in smooth muscle→activates guanylyl cyclase, increases cGMP
• Effects
• smooth muscle relaxation, esp. in vessels
• vasodilation decreases venous return and heart size
• may increase coronary flow in some areas and in variant angina
• Clinical
• angina - sublingual for acute episodes, oral & transdermal for prophylaxis
• IV for ACS
• Kinetics, tox, int.
• high 1st pass effect - sublingual dose smaller than oral
• high lipid solubility - rapid absorption
• tox: orthostatic hypotension, tachycardia, headache
• int: synergistic hypotension with phosphodiesterase type 5 inhibitors (slidenafil)
• Isosorbide dinitrate
• similar to nitroglycerin but slightly longer duration of action
• Isosorbide mononitrate
• active metabolite of the dinitrate, used orally for prophylaxis

Question 2

Propranolol

Answer 2

• MOA
• nonselective competitive antagonist at β receptors
• Effects
• decreased heart rate, cardiac output, blood pressure
• decreases myocardial oxygen demand
• Clinical
• prophylaxis of angina (other indications mentioned in previous chapters)
• Kinetics, tox, int:
• oral & parenteral, 4-6h duration of action
• tox: asthma, AV-block, acute heart failure, sedation
• int: additive with all cardiac depressants

Question 3

Verapamil, diltiazem

Answer 3

• MOA
• nonselective block of L-type Ca²⁺​ channels in vessels and heart
• Effects
• reduced vascular resistance, cardiac rate, cardiac force - results in decreased oxygen demand
• Clinical
• prophylaxis of angina, hypertension, others
• Kinetics, tox, int:
• oral, IV, duration 4-8h
• tox: AV-block, acute heart failure, constipation, edema
• int: additive with other cardiac depressants and hypotensive drugs

Question 4

Nifedipine

Answer 4

• MOA
• block of vascular L-type Ca²⁺ channels more than cardiac channels
• Effects
• like verapamil and diltiazem but with less cardiac effect
• Clinical
• prophylaxis of angina and treatment of hypertension, but prompt release nifedipine is contraindicated
• Kinetics, tox, int.
• oral, duration 4-6h
• tox: excessive hypotension, baroreceptor reflex tachycardia
• int: additive with other vasodilators

Question 5

Ranolazine

Answer 5

• MOA
• inhibits late Na current in heart
• may modify fatty acid oxidation
• Effects
• reduces cardiac oxygen demand
• fatty acid oxidation modification may improve efficiency of cardiac oxygen utilization
• Clinical
• prophylaxis of angina
• Kinetics, tox, int.
• oral, duration 6-8h
• tox: QT-prolongation, nausea, constipation, dizziness
• int: concentration and duration increased by inhibitors of CYP3A