Pharm 23 - Anti-Arrhythmics Flashcards
MOA Moderate block of voltage-gated Na+ channels; block K+ channels in ventricular myocytes (decreased phase 0 upstroke velocity, prolongs depolarization) and SA nodal cells (shifts threshold to more positive potentials and decreases slope of phase 4 depolarization)
Class IA
Class IA Drugs (3)
Quinidine, Procainamide, Disopyramide
Also Blocks K+ channels that are opened upon vagal stimulation of muscarinic receptors in the AV node (vagolytic effect)
Quinidine
Clinical applications Conversion of atrial flutter/fibrillation; maintenance of normal sinus rhythm; paroxysmal SVT; Premature atrial/ventricular contractions; paroxysmal AV junctional rhythm or atrial/ventricular tachycardia
Quinidine
Clinical applications Symptomatic premature ventricular contractions (PVCs); life-threatening ventricular tachycardia; maintenance of normal sinus rhythm after conversion of atrial flutter; MALIGNANT HYPERTHERMIA
Procainamide
Clinical applications PVCs; Ventricular tachycardia; Conversion of atrial fibrillation/flutter and paroxysmal atrial tachycardia to normal sinus rhythm
Disopyramide
Adverse effects Torsades de pointes ( & syncope w/ quinidine), complete AV block, ventricular tachycardia, agranulocytosis, thrombocytopenia, hepatotoxicity, acute asthma attack, respiratory arrest, angioedema, SLE; also fatigue, headache, lightheadedness, widening of QRS, lengthening of QT and PR, hypotension, PVCs, tachycardia, diarrhea, cinchonism (More SLE and less anticholinergic w/ Procainamide; More anticholinergic and less GI w/ Disopyramide)
Class IA
Contraindications Hx of torsades de points, Hx of prolonged QT interval, concurrent use of drugs that prolong QT interval (thioridazine, ziprasidone), Conduction defects, Myasthenia gravis; also SLE for Procainamide
Class IA
Therapeutic considerations - Inhibits conversion of codeine to morphine -> reduced analgesic effect
- Digoxin toxicity
- Amiodarone, amprenavir, azole antifungals, cimetidine, and ritonavir increase quinidine levels
- Avoid co-administration with anticholinergics b/c increases anticholinergic effects
- Agent that slows AV conduction (beta blocker/CCB) should be used w/ quinidine in pts w/ atrial flutter to prevent too rapid ventricular response
Quinidine
Therapeutic considerations - Does not alter plasma levels of digoxin
- Consider pre-treatment w/ cardiac glycoside to prevent accelerated ventricular rate due to vagolytic effects on AV node
- Take baseline ANA and monitor during therapy for development of lupus-like syndrome
Procainamide
Therapeutic considerations - Rifampins impair efficacy
- Consider pre-treatment w/ cardiac glycoside to prevent accelerated ventricular rate due to vagolytic effects on AV node
Disopyramide
MOA Use-dependent block of voltage gated Na+ channels in ventricular myocytes (decreased phase 0 upstroke velocity), may shorten REpolarization
Class IB
Class IB Drugs (3)
Lidocaine, Mexiletine (oral analog of lidocaine), Phenytoin
Clinical applications Ventricular arrhythmias when they occur w/ MI, cardiac manipulation, or cardiac glycosides; status epilepticus; Local anesthesia of skin/mucus membranes; pain, burning, itching; Postherpetic neuralgia
Lidocaine/Mexiletine
Adverse effects Seizures, asystole/cardiac arrest, new/worse arrhythmias, bradycardia, respiratory depression, anaphylaxis, status asthmaticus; also restlessness, stupor, tremor, hypotension, diplopia/blurred vision, tinnitus
Lidocaine/Mexiletine
Contraindications Stokes-Adams syndrome; Wolff-Parkinson-White syndrome; severe conduction blocks; don’t give spinal/epidural block w/ inflammation, infection, septicemia, severe HTN, spinal deformities, neuro disorders
Lidocaine/Mexiletine
Dose adjustment if coadministered w/ CYP450 inhibitors (cimetidine) or inducers (barbiturates, phenytoin, rifampin); In severely-ill pts, seizures are 1st sign of toxicity; IM injection of lidocaine can greatly increase serum CK
Lidocaine/Mexiletine
Clinical applications Generalized tonic-clonic seizures, status epilepticus, non-epileptic seizures, eclampsia seizures; Neuralgia, Ventricular arrhythmias that don’t respond to lidocaine/procainamide, Arrhythmias induced by cardiac glycosides
Phenytoin
Adverse effects Agranulocytosis, leukopenia, pancytopenia, thrombocytopenia, hepatitis, Stevens-Johnson syndrome, TOXIC EPIDERMAL NECROLYSIS; also ataxia, confusion, slurred speech, diplopia, nystagmus, gingival hyperplasia, hirsutism, N/V
Phenytoin
Contraindications Hydantoin (whatever THAT is) hypersensitivity, Sinus bradycardia, SA block, 2nd/3rd degree AV block, Stokes-Adams syndrom
Phenytoin
Therapeutic considerations Metabolized by P450 2C9/10 and 2C19 - coadministration w/ other drugs metabolized by same enzymes can increase plasma phenytoin; Can induce P450 3A4 - increased metabolism of oral contraceptives, etc.
Phenytoin
MOA Block of voltage gated Na+ channels in ventricular myocytes (decreased phase 0 upstroke velocity)
Class IC
Class IC Drugs (4)
Encainide; Flecainide; Moricizine; Propafenone
Clinical applications Last resort-type drug for sustained ventricular tachycardia, paroxysmal SVT, and paroxysmal atrial fibrillation
Class IC