Term 1 Pharm - Angina Drugs Flashcards
What is Classical angina?
“classical” = “exertional” = “typical” angina
What is Variant angina?
“vasospastic” = “variant”= “Prinzmetal” angina
Nitrates are a key treatment!
CEB’s can also be useful, because of their direct vasodilating action
Beta-blockers are CONTRAINDICATED!
What is Unstable angina?
“unstable” = “pre-infarction” angina or ACS
Unstable angina, crescendo angina, preinfarction angina are all phrases describing angina that is rapidly worsening in terms of intensity of pain, frequency, timing, trigger (especially occurring at rest), duration, response to treatment, etc
Today it is often called ACS (acute coronary syndrome)
It most often involves a chronically narrowed coronary artery, WITH THE ACUTE DEVELOPMENT OF A RUPTURED PLAQUE
It is imperative that treatment also include suppression of platelet adhesion and aggregation
What are the Useful Drug Classes for angina?
Nitrates
- Trinitroglycerin (1)
Beta-blockers
- Atenolol, metoprolol (2,3)
Calcium entry blockers
- Verapamil, diltiazem, also amlodipine (4,5)
Antiplatelet agents
- Aspirin, clopidogrel (6,7)
Platelet Gp IIb/IIIa receptor blockers
- Abciximab (8), eptifibatide
Nitroglycerin
Drug class: pharmacologic class: organic nitrate;
Therapeutic class: antianginal, vasodilator (reduces afterload), venodilator (reduces preload)
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)
Beta-blockers for Angina (see earlier card for atenolol)
Propranolol, metoprolol, atenolol and others have all been extensively studied and used
ALL serve to produce decrease in HR, contractility, CO, BP (afterload), and wall tension, thereby reducing oxygen demand. Also, slower HR gives more time in diastole, thereby increasing diastolic perfusion of subendocardium
Differences between the three of these similar drugs
REMEMBER: abrupt withdrawal of a beta-blocker is very dangerous, since the abrupt increase in HR, BP, contractility, etc can lead to abrupt increase in agina, or even result in an acute MI!!!
NEVER use Beta blockers on vasospastic (variant angina)! It makes angina worse and is CONTRAINDICATIVE!
CEB’s for Angina
For EXERTIONAL ANGINA give Verapamil and Diltiazem (in many ways, act similarly to beta-blocker: reduce HR, B, contractility, wall tension, etc) – GIVE to pts w/ AFib (These are the two that most affect cardiac tissue as well as producing peripheral vasodilatation)
Amlodipine also approved for this indication - affects AV node less (DO NOT give to pts w/ Afib)
DO NOT ever give Nifedipine (makes angina more likely)
Aspirin
DRUG CLASS: Pharm class–salicylate; therapeutic class–analgesic, anti-inflammatory, antiplatelet, antipyretic, prevention of MI
PHARMACODYNAMICS: at low doses (
Clopidogrel (Plavix™)
Drug Class: pharmacologic class—inhibitor of ADP-induced platelet aggregation; therapeutic class—antiplatelet agent
Pharmacodynamics: Blocks 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 EXPENSIVE
- Use Abciximab for a cpl hours after surgery, Clopidogrel for 3-6 months, and then Aspirin for life
- You have to stop Clopidogrel b/c causes increase risk of bleeding (bruised hand/arm)
Abciximab/ReoPro™
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
What is NO
What is N2O
What is NO2
What is NO3
What is NO – Nitric oxide
What is N2O – Nitrogen oxide (laughing gas)
What is NO2 – nitrite
What is NO3 – nitrate
