Mechanism of Action
What specific intracellular signaling molecule is increased by nitrates to promote vasodilation?
Cyclic guanosine monophosphate (cGMP).
Why are nitrates effective in both stable and variant angina?
They reduce myocardial oxygen demand and also relieve coronary artery spasm.
Why do nitrates frequently cause headaches as a side effect?
Due to cerebral vasodilation increasing blood flow in the meninges.
Why do β-blockers reduce myocardial oxygen demand without directly affecting coronary perfusion?
They lower myocardial workload by reducing heart rate, contractility, and systolic blood pressure (double product).
Why are short-acting calcium channel blockers like nifedipine avoided in unstable angina management?
They can cause reflex tachycardia, increasing myocardial oxygen demand and worsening ischemia.
What is the most dangerous consequence of combining nitrates with phosphodiesterase inhibitors like sildenafil?
Severe hypotension due to exaggerated cGMP accumulation causing profound vasodilation.
How do calcium channel blockers reduce both myocardial oxygen demand and increase oxygen supply?
By reducing myocardial contractility and heart rate while causing coronary vasodilation, increasing perfusion.
In which type of angina are calcium channel blockers considered first-line therapy, and why?
Vasospastic (Prinzmetal's) angina, as they relieve coronary artery spasm directly.
Why can β-blockers worsen symptoms in patients with severe peripheral vascular disease?
β-blockers reduce cardiac output and block β2-mediated vasodilation, potentially worsening limb ischemia.
Which β-blocker property makes drugs like metoprolol preferable for angina compared to propranolol?
Cardioselectivity (β1-selective blockade).
Explain the rationale behind using β-blockers in post-myocardial infarction patients with angina.
β-blockers reduce the risk of further ischemic events by decreasing myocardial workload and preventing arrhythmias.
What is a unique side effect of verapamil not commonly seen with other calcium channel blockers like nifedipine?
Constipation due to inhibition of smooth muscle contraction in the GI tract.
Explain the step-by-step cellular mechanism of how nitrates relax vascular smooth muscle starting from nitrate conversion.
Nitrates convert to nitric oxide → activate guanylate cyclase → increase cGMP → dephosphorylation of myosin light chain → smooth muscle relaxation
Why should long-acting nitrates be combined with nitrate-free intervals?
To prevent the development of nitrate tolerance, which reduces their efficacy over time.
Explain the physiological reason why β-blockers should not be discontinued abruptly in angina patients.
Chronic β-blockade leads to upregulation of β1 receptors, so abrupt withdrawal can cause rebound tachycardia and increased myocardial oxygen demand, risking myocardial infarction.