Bretylium

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Dosage-adjustment-in-renal-failure 6 Pharmacokinetics 7 Adverse-effects 8 Drug-interactions 9 Laboratory 10 Mechanism-of-action 11 More General Terms 12 Internet Database 13 References

Introduction

• 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
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• initial dose 5 mg/kg IV.
• repeat dose 10 mg/kg, max 35 mg.
• 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

• onset of action is 5-10 minutes
• may be delayed up to 20-60 minutes
• duration of action: 6-12 hours
  

• elimination via kidney 80 %
• elimination via liver 20 %
• protein binding = 0-8 %
• elimination by hemodialysis = +

Adverse-effects

• common (> 10%)

• hypotension, orthostatic & supine

• less common (1-10%)

• nausea/vomiting (associated with rapid infusion)

• 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

• other

• parotid pain & swelling, emotional liability, proarrhythmic affects resulting from initial elaboration of catecholamines
  
• drug adverse effects of antiarrhythmic agent, Group III

Drug-interactions

• enhances pressor effects of catecholamines
• may aggravate digoxin-induced tachyarrhythmias
• tricyclic antidepressants ( TCA) may inhibit bretylium uptake by the myocardium
  
• drug interaction(s) of antiarrhythmic agents in combination with diuretics

Laboratory

• specimen:

• serum, plasma ( EDTA, heparin)

• methods: GLC
• NO correlation of serum levels with cardiac effect

Mechanism-of-action

• inhibits catecholamine release resulting in catecholamine depletion
• results in initial increase in blood pressure, heart rate & myocardial contractility, followed by hypotension
• blocks K+ channels
• prolongs action potential duration
• increases refractory period in Purkinje fibers & ventricular muscle

More General Terms

• antiarrhythmic agent, Group III

Internet Database

PubChem: 2431
PubChem: 6100
PubChem: 414642
PubChem: 18499

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

bretylium (Bretylol, Ornido)