Drug management of Angina Flashcards
To what drug class does Nitroglycerin belong?
Pharmacologic class: organic nitrate
Therapeutic class: antianginal, vasodilator, venodilator
*Nitroglycerin (TNG/NitroStat™ $4 per month)
Describe the pharmacodynamics of 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 => produces venodilation and vasodilation
Describe the pharmacokinetics of Nitroglycerin.
- Well absorbed po, but very high first pass effect
- Prompt onset (1-2 min) when taken as sublingual tablet or spray
- Can be given transdermally or iv
What toxicity is associated with Nitroglycerin?
- Excessive hypotension (esp if patient is volume depleted)
- Throbbing headache
- Flushing
What drug-drug reactions should be considered with patients on Nitroglycerin?
- Excessive hypotension with other vasodilators
- Severe hypotension if taken with Viagra™ (because it blocks phosphodiesterase type V => increase nitroglycerin effects)
What special considerations should be made for patients on Nitroglycerin?
- Remove transdermal patch before defibrillation
- Use only fresh TNG tablets
- Tolerance can develop quickly (don’t take at night/don’t leave patch on at night)
What are the indications/dose/route for Nitroglycerin?
For angina => 0.15-0.3-0.4-0.6 mg sublingual tablets
- Take one tablet every 5 minutes up to three
- Also available as transdermal paste, IV solution
What are the major actions of beta blockers?
All Beta blockers serve to decrease HR, contractility, CO, BP (afterload), and wall tension => thereby reducing oxygen demand
What are 3 major Beta blockers?
Propranolol, metoprolol, atenolol
Why should abrupt withdrawal of a beta blocker be avoided?
Abrupt withdrawal of a beta blocker can be very dangerous, since the abrupt increase in HR, BP, contractility, etc can lead to abrupt increase in agina, or even MI
What other drugs can be used for angina (apart from beta blockers)?
- Verapamil and Diltiazem => exertional angina
- Nifedipine (of the dihydropyridine class) => used less due to decreased clinical benefit
What drugs are used in the treatment of vasospastic angina?
- Nitrates and Calcium entry blocker
* Beta blockers are CONTRAindicated
How should unstable angina be treated?
Unstable angina should be treated via suppression of platelet adhesion and platelet aggregation
To what drug class does Aspirin (Bayer™, Ascriptin™, Halfprin™) belong?
Pharmacologic class => salicylate
Therapeutic class => analgesic, anti-inflammatory, antiplatelet, antipyretic, prevention of MI
Describe the pharmacodynamics of aspirin.
- At low doses ( vasodilator/inhibitor of platelet aggregation
- Tends to irreversibly inhibit COX (1) in platelets
- Decreased formation of TBX A2 (vasocontrictor, platelet aggregator)
- Transiently inhibit COX(2) in endothelium
- Transient decreased formation of prostacyclin (PGI2)
Describe the pharmacokinetics of aspirin.
- 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
What toxicity is associated with aspirin?
At high doses => can cause ulceration of GI tract, bleeding disorders, tinnitus
What drug-drug interactions should be considered for patients on aspirin?
- Inhibit tubular secretion of methotrexate
- Potentiate bleeding from warfarin
What special considerations should be made for patients on aspirin?
- Avoid in patients with nasal polyps and asthma
- Regular, buffered, enteric coated
What is the indication/dose/route for aspirin?
- For anti platelet effects
- 81-325 mg per day
- For arthritis
- 2.4-3.6 g/day in divided doses
To what drug class does Clopidogrel (Plavix™) belong?
Pharmacologic => thienopyridine
Therapeutic class=> platelet aggregation inhibitor
- very expensive
Describe the pharmacodynamics of clopidogrel.
- Blocks ADP receptors => prevent aggregation mediated by ADP released by an activated platelet
- Prevents recruitment of other platelets
- Useful in primary or secondary prevention of TIA, stroke, angina, MI, angioplasty, stent placement, ACS, etc
Describe the pharmacokinetics of clopidogrel.
- Well absorbed
- Onset 1-2 h after oral dose
- Hepatic metabolism
- Half-life ~8h
What toxicity is associated with clopidogrel?
Hemorrhage at virtually any site
What interactions should be considered with patients on clopidogrel?
May inhibit CYP 3A4
What is the indication/dose/route for clopidogrel?
- For acute coronary syndrome
- LD 300 mg up front, then 75 mg once daily (in conjunction with ASA 81-325 mg daily)
To what drug class does Abciximab/ReoPro™ (also tirofiban/Aggrastat™, eptifibatide/Integrilin™) belong?
Pharmacologic class => Fab fragment chimeric monoclonal antibody
Therapeutic class => adjunct to PCI to prevent ischemic complications; treatment of MI
- Expensive
Describe the pharmacodynamics of Abciximab.
- Noncompetitive inhibitor of the GP IIb/IIIa receptor
- Prevents binding of fibrinogen, vWF, etc to the receptor on activated platelets.
- Need to block >80% of these receptors to maximially inhibit platelet
Describe the pharmacokinetics of Abciximab.
- IV bolus followed by IV infusion
- Half-life about 30 min.
- Bleeding time declines to <12 min within 12 h of stopping infusion
What toxicity is associated with Abciximab?
- Contraindicated in presence of aneurysm
- AV malformation
- Bleeding, coagulopathy, GI bleed, intracranial mass, retinal bleeding
- Stroke, surgery, low platelets, trauma, vasculitis
What drug-drug interactions should be considered with patients on Abciximab?
Additive effects with aspirin, clopidogrel, heparin, low dose t-PA
What are the indications/dose/route for Abxicimab?
- 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
What is NO (nitric oxide)?
NO is an endothelium derived relaxing factor that inhibits platelet aggregation, phagocytosis, and excitatory neurotransmission in CNS
