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bretylium (Bretylol, Ornido)

Tradename: Bretylol. Class III antiarrhythmic agent. Indications: - formerly used as second line agent for treatment of life-threatening ventricular arrhythmias NOT responding to lidocaine (no longer used in ACLS protocols) Contraindications: - digitalis-induced arrhythmias Dosage: 1) initial dose 5 mg/kg IV. 2) repeat dose 10 mg/kg, max 35 mg. 3) infusion 500 mg in 50 mL D5W (10 mg/mL) at 1-3 mg/min (7-21 mL/hr) Injection: 50 mg/mL (10 mL). Dosage adjustment in renal failure: creatinine clearance dosage 10-50 mL/min 25-50% of dose < 10 mL avoid use Pharmacokinetics: 1) onset of action is 5-10 minutes 2) may be delayed up to 20-60 minutes 3) duration of action: 6-12 hours Adverse effects: 1) common (> 10%) - hypotension, orthostatic & supine 2) less common (1-10%) - nausea/vomiting (associated with rapid infusion) 3) uncommon (< 1%) - transient hypertension, PVCs, bradycardia, flushing, nasal congestion, vertigo, syncope, confusion, rash, diarrhea, abdominal pain, muscle atrophy & necrosis with repeated IM injections at the same site, conjunctivitis, renal impairment, hyperthermia, hiccups, respiratory depression, angina 4) other - parotid pain & swelling - emotional liability - proarrhythmic affects resulting from initial elaboration of catecholamines Drug interactions: 1) enhances pressor effects of catecholamines 2) may aggravate digoxin-induced tachyarrhythmias 3) tricyclic antidepressants (TCA) may inhibit bretylium uptake by the myocardium Laboratory: 1) specimen: a) serum, plasma (EDTA, heparin) 2) methods: GLC 3) NO correlation of serum levels with cardiac effect Mechanism of action: 1) inhibits catecholamine release resulting in catecholamine depletion 2) results in initial increase in blood pressure, heart rate & myocardial contractility, followed by hypotension 3) blocks K+ channels 3) prolongs action potential duration 4) increases refractory period in Purkinje fibers & ventricular muscle

Interactions

drug interactions drug adverse effects of antiarrhythmic agent, Group III

General

antiarrhythmic agent, Group III

Properties

MISC-INFO: elimination route KIDNEY 80% LIVER 20% 1/2life 9 +/- 2 HOURS protein-binding 0-8% elimination by hemodialysis + pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
  3. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 161
  4. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  5. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  6. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995