Angina and CAD Flashcards
Amlodipine besylate
Drug class: pharmacologic class—dihydropyridine calcium entry blocker; therapeutic class– antihypertensive, antianginal (classical and variant) •
Pharmacodynamics: reduces BP by inhibiting influx of calcium through “slow channels”, thereby dilating peripheral arterioles; also, produces negative inotropic effect as well in myocardial cells; for angina, reduces afterload, thus decreasing oxygen consumption; also, inhibits spasm of coronary arteries in vasospastic angina •
Pharmacokinetics: F 64-90%; peak effects 6-12 hours post dose; duration 24 hours; extensively metabolized in liver 90% excreted in urine as inactive metabolites •
Toxicity: hypotension, AV block, worsening of CHF, bradycardia, headache, edema; watch out in patients with aortic stenosis, heart failure, severe liver disease •
Interactions: additive effects with most other antihypertensives; additive toxic effects on heart when given with beta-blockers (negative inotropic and dromotropic effects) •
Special considerations: shorter-acting nifedipine (and similar CEBs) can increase risk of MI (unclear why); Pregnancy C; less cardiac impact than older verapamil and diltiazem •
Indications and dose/route: 2.5 up to 10 mg daily •
Monitor: weight, edema, BP
Atenolol/Tenormin™
Drug class: pharmacologic class— “specific” β1-adrenoceptor blocker; therapeutic class–antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti- anginal •
Pharmacodynamics: binds directly to β1-receptors, with a preference for beta-1 over beta-2, leading to lower blood pressure via several potential mechanisms (less cardiac output, less activation of the RAA system); recent evidence suggests less effective in preventing strokes than other drugs used as monotherapy for HTN •
Pharmacokinetics: available po or iv; variable oral F; onset 1-2 hours h, duration 12-24 h; can be given once per day; renally excreted (longer half-life); metoprolol has hepatic metabolism (and shorter half-life) •
Toxicity: excessive hypotension; bradycardia; heart block; can worsen severe CHF (but indicated for mild to moderate and stable CHF); worsen bronchospasm in severe asthmatics •
Interactions: additive effects with most other anti-hypertensives; additive AV block with CEB’s •
Special considerations: may be especially useful in HTN patients with exertional angina, MI, atrial fibrillation; watch out for abrupt withdrawal; may no longer be “first line” drug for essential HTN unless other indications exist (recent data); metoprolol (needs to be taken several times per day) has more data for use in patients s/p MI •
Indications and dose/route: for treatment of hypertension, 25-100 mg per day, in one or two doses •
Monitoring: BP, HR, exercise tolerance
Nitroglycerin
Drug class: pharmacologic class: organic nitrate; therapeutic class: antianginal, vasodilator, venodilator •
Pharmacodynamics: reacts directly with nitrate receptor on SM cell; sulfhydryl groups in receptor reduce organic nitrate (R-ONO2) to NO2 and then NO; NO crosses into SM cells, activates guanylate cyclase, leading to production of cGMP from GTP; cGMP acts to relax SM cells (probably by dephosphorylation of myosin light chains, making them less likely to react with Actin); then produces venodilation and vasodilation •
Pharmacokinetics: well absorbed po, but very high first pass effect; prompt onset (1-2 min) when taken as SL tablet or spray; also can be given transdermally or iv •
Toxicity: excessive hypotension, esp if patient is volume depleted; throbbing headache; flushing •
Interactions: excessive hypotension with other vasodilators; severe hypotension if taken with Viagra™ (sildenafil); Why is that??? •
Special considerations: remove transdermal patch before defibrillation; use only fresh TNG tablets; tolerance can develop quickly (give 8 h holiday each night) •
Indications and dose/route: For angina, 0.15-0.3-0.4-0.6 mg SL tablets, take one tablet every 5 minutes up to three; also available as transdermal paste, IV solution
Aspirin
DRUG CLASS: Pharm class–salicylate; therapeutic class–analgesic, anti-inflammatory, antiplatelet, antipyretic, prevention of MI •
PHARMACODYNAMICS: at low doses (<325 mg/day), tends to irreversibly inhibit COX-1 in platelets, leading to decreased formation of TBX A2 (vasocontrictor, platelet aggregator), and transiently inhibit COX-2 in endothelium, leading to transient decreased formation of prostacyclin (PGI2) (vasodilator, inhibitor of platelet aggregation) •
PHARMACOKINETICS: F~60%, Tmax variable (e.g. AlkaSeltzer), metabolized to salicylate, half-life 3-4 h, duration of action 4-24+ h, 90% excreted as salicylate metabolites in urine •
TOXICITY: especially at high doses can cause ulceration of GI tract, bleeding disorders, tinnitus •
INTERACTIONS: inhibit tubular secretion of methotrexate, potentiate bleeding from warfarin •
SPECIAL CONSIDERATIONS: avoid in patients with nasal polyps and asthma; regular, buffered, enteric coated •
INDICATIONS AND DOSE: for antiplatelet effects, 81-325 mg per day; for arthritis, 2.4-3.6 g/day in divided doses
Clopidogrel (Plavix™)
Drug Class: pharmacologic class—inhibitor of ADP-induced platelet aggregation; therapeutic class—antiplatelet agent •
Pharmacodynamics: After metabolism to active metabolite by CYP 2C19, Blocks P2Y12 platelet ADP receptors irreversibly, which then helps prevent aggregation mediated by ADP released by an activated platelet from recruiting other platelets via GP IIb/IIIa; useful in primary or secondary prevention of TIA, stroke, angina, MI; angioplasty, stent placement, ACS, etc; note: parent drug is not active, but one metabolite is pharmacologically active •
Pharmacokinetics: well absorbed, onset 1-2 h after oral dose, hepatic metabolism, half-life ~8h •
Toxicity: hemorrhage at virtually any site; extensive skin bruising and discoloration •
Interactions: may inhibit CYP 3A; increased risk of bleeding when given with aspirin (but also increased efficacy) •
Special considerations: Careful risk/benefit assessment in each patient, AND it’s quite expensive • Used in conjunction with aspirin after recent stent or angioplasty
Indications and dose: for ACS, LD 300-600 mg up front, then 75 mg once daily (in conjunction with ASA 81-325 mg daily)
Abciximab, eptifibatide
• Drug class: pharmacologic class–Fab fragment chimeric monoclonal antibody; therapeutic class: adjunct to PCI to prevent ischemic complications; treatment of MI •
Pharmacodynamics:noncompetitive inhibitor of the GP IIb/IIIa receptor, prevents binding of fibrinogen, vWF, and other adhesive ligands to the receptor on activated platelets. Need to block >80% of these receptors to maximially inhibit platelet •
Pharmacokinetics: IV bolus followed by IV infusion; half-life about 30 min. Bleeding time declines to <12 min within 12 h of stopping infusion •
Toxicity: contraindicated in presence of aneurysm, AV malformation, bleeding, coagulopathy, GI bleed, intracranial mass, retinal bleeding, stroke, surgery, low platelets, trauma, vasculitis •
Interactions: Additive effects with aspirin, clopidogrel, heparin, low dose t-PA •
Special considerations: Exact role is still being defined, and evolves over time; cost is a big factor •
Indications and dose: when PCI is planned to treat ACS, 0.25 mg/kg bolus (e.g. 20 mg) followed by 10 mcg/min for 18-24 h
Ranolazine
• Approved by the FDA in 2006 to treat chronic angina •
May be used concomitantly with more common drugs – Beta-blockers – Nitrates – Calcium entry blockers – Antiplatelet drugs – Statins – ACEI or ARB •
MOA appears to be: inhibiting the late inward sodium current in heart muscle, leading to reduction in elevated intracellular calcium levels, leading to reduced wall tension, leading to reduced oxygen requirement in heart muscle (less oxygen demand) •
May prolong QTc interval; dizziness and constipation both occur around 11% of patients
