Antianginal Flashcards
Nitroglycerin: class
organic nitrate
Antianginal, vasodilator, venodilator
Nitroglycerin: PD
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
Nitroglycerin: PK
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
Nitroglycerin: tox
excessive hypotension, esp if patient is volume depleted; throbbing headache; flushing
Nitroglycerin: special issues
remove transdermal patch before defibrillation; use only fresh TNG tablets; tolerance can develop quickly (give 8 h holiday each night)
Nitroglycerin: interactions
excessive hypotension with other vasodilators; severe hypotension if taken with Viagra™ (sildenafil)[why is that???]
Nitroglycerin: indications
angina
Isosorbide dinitrate: class
organic nitrate, Venous vasodilator
Antianginal, CHF, antihypertensive
Isosorbide dinitrate: PD
same as nitroglycerin?:
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
Isosorbide dinitrate: PK
same as nitroglycerin?:
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
Isosorbide dinitrate: tox
same as nitroglycerin?:
excessive hypotension, esp if patient is volume depleted; throbbing headache; flushing
Isosorbide dinitrate: special issues
same as nitroglycerin?:
remove transdermal patch before defibrillation; use only fresh TNG tablets; tolerance can develop quickly (give 8 h holiday each night)
Isosorbide dinitrate: interactions
same as nitroglycerin?:
excessive hypotension with other vasodilators; severe hypotension if taken with Viagra™ (sildenafil)[why is that???]
Isosorbide dinitrate: indications
angina
Atenolol: class
Beta blocker (relatively beta1 specific) Antihypertensive, antianginal, antiarrhythmic, anti-MI
Atenolol: PD
binds directly to beta-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 via reduced renin release); recent evidence suggests less effective in preventing strokes than other drugs
Atenolol: PK
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)
Atenolol: tox
excessive hypotension; bradycardia; heart block can worsen severe CHF (but indicated for mild to moderate CHF); worsen bronchospasm in severe asthmatics (bc not perfectly B1 selective, will block 10% of B2s)
Atenolol: special issues
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 unless other indications exist (recent data)
Atenolol: interactions
additive effects with most other antihypertensives, additive AV block with CEB’s
Atenolol: indication
HTN
Atenolol: monitor
BP, HR, exercise tolerance. You cannot stop this drug cold turkey: you will have rebound angina/rearrythmias.
Metoprolol: class
Beta blocker (relatively beta1 specific) Antihypertensive, antianginal, antiarrhythmic, CHF
Metoprolol: PD
binds directly to beta-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 via reduced renin release); recent evidence suggests less effective in preventing strokes than other drugs
Metoprolol: PK
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: tox
excessive hypotension; bradycardia; heart block can worsen severe CHF (but indicated for mild to moderate CHF); worsen bronchospasm in severe asthmatics (bc not perfectly B1 selective, will block 10% of B2s)
Metoprolol: special issues
may be especially useful in HTN patients with exertional angina, MI, atrial fibrillation; watch out for abrupt withdrawal
from lect: pts have to be compliant with taking it 3x/day OR take a more expensive brand name
Metoprolol: interactions
additive effects with most other antihypertensives, additive AV block with CEB’s
Metoprolol: indication
HTN
Metoprolol: monitor
BP, HR, exercise tolerance. You cannot stop this drug cold turkey: you will have rebound angina/rearrythmias.
Verapamil: class
pharmacologic class–calcium entry blocker; therapeutic class– antihypertensive, antianginal, antiarrhythmic CLASS IV
Verapamil: PD
reduces BP by inhibiting influx of calcium through “slow channels”, thereby dilating peripheral arterioles; produces negative inotropic effect as well; for angina, reduces afterload, thus decreasing oxygen consumption; also, inhibits spasm of coronary arteries in vasospastic angina; blocks reentry paths through AV nodes in paroxysmal SVT.
From Rang/Dale: Blocks Ca2+ channels in both cardiac and smooth muscle so has negative inotropic and smooth muscle relaxant actions. prolongs plateau in action potential.
Verapamil: PK
absorbed rapidly, but F ~30%; also available in SR tablets; cleared by kidney and liver (produces active metabolites); onset 2 h po, 1-5 min iv; half-life 6-12 h; may be given po or iv
Verapamil: tox
hypotension, AV block (because slows action potential in SA and AV nodes), worsening of CHF, bradycardia
Verapamil: interactions
additive effects with most other antihypertensives; additive toxic effects on heart when given with beta-blockers
Verapamil: special
use reduced doses in patients with both renal and hepatic disease; short-acting nifedipine (and similar CEBs) can increase risk of MI (unclear why); Pregnancy C
Verapamil: monitor
weight, edema, BP
Diltiazem: class
Ca entry blocker
Antihypertensive, antianginal, antiarrhythmic
Diltiazem: class representative?
Verapamil
Aspirin: class
Pharm class–salicylate, COX inhibitor
Therapeutic class–analgesic, anti-inflammatory, antiplatelet, antipyretic, prevention of MI
Aspirin: PD
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)
Aspirin: PK
F~60%, Tmax variable (e.g. AlkaSeltzer), metabolized to salicylate, half-life 3-4 h, duration 4-24+ h, 90% excreted as salicylate metabolites in urine
Aspirin: tox
especially at high doses can cause ulceration of GI tract, bleeding disorders, tinnitus
Aspirin: interactions
inhibit tubular secretion of methotrexate, potentiate bleeding from warfarin
Aspirin: special
avoid in patients with nasal polyps and asthma; regular, buffered, enteric coated
Aspirin: indications
antiplatelet, arthritis
Clopidogrel: class
pharmacologic; ADP receptor blocker
therapeutic class–platelet aggregation inhibitor
Clopidogrel: PD
Inhibits platelet aggregation by irreversibly blocking ADP receptors. Inhibits fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen.
useful in primary or secondary prevention of TIA, stroke, angina, MI, angioplasty, stent placement, ACS, etc
Clopidogrel: PK
well absorbed, onset 1-2 h after oral dose, hepatic metabolism, half-life ~8h
bc irreversible, effects last several days until platelets are replaced
Clopidogrel: tox
hemorrhage at virtually any site;
Clopidogrel: special
Careful risk/benefit assessment in each patient, AND it’s quite expensive
Clopidogrel: interactions
may inhibit CYP 3A4
Clopidogrel: indications
ACS. often given with aspirin
Abciximab: class
pharmacologic class–Fab fragment chimeric monoclonal antibody, IIb-IIIa inhibitor
therapeutic class: adjunct to PCI to prevent ischemic complications; treatment of MI; Antiplatelet
Abciximab: PD
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
Abciximab: PK
IV bolus followed by IV infusion; half-life about 30 min. Bleeding time declines to <12 min within 12 h of stopping infusion
Abciximab: tox
contraindicated in presence of aneurysm, AV malformation, bleeding, coagulopathy, GI bleed, intracranial mass, retinal bleeding, stroke, surgery, low platelets, trauma, vasculitis
Abciximab: special
Exact role is still being defined, and evolves over time; cost is a big factor
Abciximab: interactions
Additive effects with aspirin, clopidogrel, heparin, low dose t-PA
Abciximab: indication
when PCI is planned to treat ACS
Tirofinab: class
IIb-IIIa inhibitor
Antiplatelet
Tirofinab: class rep
Abciximab
Eptifibatide: class
IIb-IIIa inhibitor
Antiplatelet
Eptifibatide: class rep
Abciximab
