Linger - Anti-anginal Agents Flashcards
Do organic nitrates preferentially act on arteries or veins?
Primarily venodilators, reducing preload
Where do calcium channel blockers primarily act?
Primarily act on arterioles, decreasing smooth muscle contractility and therefore reducing afterload
What is the mechanism of action of organic nitrates?
Organic nitrates converted to nitric oxide (NO) > NO upregulates guanylyl cyclase activity > GTP converted to cGMP > cGMP promotes activty of enzyme that dephosphorylates myosin > desphosphorylation of myosin leads to increased time muscle spends in relaxed state > in vasculature, this results in vasodilation
What is the mechanism of action of calcium channel blockers?
CCBs prevent calcium from entering myocytes, reducing activation of myosin light chain kinase, which prevents phosphorylation of myosin and therefore reduces smooth muscle activity. In vasculature, this results in vasodilation
What is the mechanism of action of β-blockers in the heart?
Block β receptors coupled to Gs proteins, preventing the activation of adenylyl cyclase and therefore reducing the amount of intracellular cAMP. This decreases activation of PKA, resulting in less Ca being released from the sarcoplasmic reticulum of myocardiocyctes, and thus reducing contractility.
Describe the concept of nitrate tolerance and a potential complication
The body rapidly acclimates to the increased presence of nitrates. Thus, nitrate efficacy over a period of time decreases with repeated dosing. Pts who use NTG patches are instructed to remove the patch for 8-12 hours per day to reduce the tolerance their bodies will develop to the drug. Over time, these pts report increasing anginal episodes during off-patch hours, and these patches can increase the risk for silent MI.
What is the role of β blockers in angina?
Reduces myocardial O2 demand
What type of angina are β blockers not indicated in?
Variant (Prinzemetal) angina resulting from vasospasm
Describe the concept of β blocker withdrawal
Pts who take β blockers have upregulation of β receptors on their cell surfaces; when the pt comes off the β blocker too fast, there will be increased adrenergic activity from the increased number of receptors. This effect is not observed in pts who take a partial agonist, as the cells are still receiving some stimulation and therefore do not upregulate their β receptor expression.
What is the difference between dihydropyridine and non-dihydropyridine CCBs?
DHPs mainly act on arteriolar smooth mm to induce vasodilation; non-DHPs have significant effects in cardiac tissue
How are reflex cardiac effects addressed when considering a calcium channel blocker?
DHPs with long half lives are preferred agents to minimize risk of reflex cardiac responses
What is an adverse effect associated with verapamil that the USMLE/COMLEX likes to test on?
Constipation, although this effect is no more common with verapamil than diltiazem
What is ranolazine?
Relatively new anti-anginal drug that works via late sodium channel blockade. Used in pts with angina refractory to tx with β blockers, CaCh blockers, and nitrates.
