Antiarrhythmic agents include-

Group I -  Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin,

               Tocainide,  Mexiletine, Flecanide,  Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine

Interacting drugs- summary

Bretylium +

Catecholamines 
 the pressor effects of catecholamines(eg dopamine, norepinephrine)
  are enhanced by bretylium. Use dilute solutions and monitor blood
   pressure

Digoxin   
  digitalis toxicity may be aggrevated by the initial release of
   norephinephrine caused by bretylium. When a life-threatening cardiac
   arrhythmias occurs, use bretylium only if the etiology of the arrhythmia
    does not appear to be digitalis toxicity. Avoid simulaneous initiation of
    therapy
              

Prophylaxis and therapy for ventricular fibrilation

Antiarrhythmic agents include-

Group I -  Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin,

                Tocainide,  Mexiletine, Flecanide,  Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine

Drug relationship not clearly established-

Renal dysfunction, diarrhea, abdominal pain, hiccoughs, erythematous macular rash, flushing, hyperthermia, confusion, paranoid psychosis, emotional lability, lethargy, generalised tenderness, anxiety, shortness of breath, diaphoresis, nasal stuffness, mild conjunctivitis.

Cardiovascular-

Hypotension and postural hypotension( most frequent) , bradycardia, increased premature ventricular contractions, transcient hypertension, initial increase in arrhythmias precipitation of angina, sensation of substrenal pressure.

GI-

Nausea, vomiting, vertigo, lightheadedness.

CNS-

Vertogo, dizziness, lightheadedness, syncope

None known

Special precautions:

Hypotension, transcient hypertension and increased frequency of arrhythmias, renal function impairment,Pregnancy,Children

Warnings-

• Limit- use to intensive care units,coronary care units or other facilities with equipment and personnel for constant cardiac and blood pressure monitoring.

• Hypotension- (postural) occurs in about 50% of the patients while they are supine ,manifested by dizziness, lightheadedness, vertigo or faintness. Keep patients supine until tolerance has developed.

• Transcient hypertension and increased frequency of arrhythmias- may occur due to initail release of norephinphrine from adrenergic postgangionic nerve terminals.

• Fixed cardiac output- avoid use with fixed cardiac output (ie severe aortic stenosis or severe pulmonary hypertension) since severe hypertension may result from a fall in peripheal resistence without a compensatory increase in cardiac output.

• Renal function impairment- since the drug is excreted principally via the kidney. increase the dosage interval in patients with impaired renal function.

• Pregnancy- give to a pregnant women only if clearly required.

• Children- safety and efficacy for use in children have not ben esatblished.

Indications:

Prophylaxis and therapy for ventricular fibrilation

Dosage:

For short term use only. Immediate life threatening arrthythmias- dilute before admin- administer 5 to 10 mg/kg by IV over 8 minutes.

Maintenance- administer the diluted solution at dosage of 1 to 2mg/minute

Overdosage- Symptoms -

With life-threatening arrhythmias underdosing with bretylium probaly presents a greater risk to the parient than potential overdosage. One case of accidental overdosage resulted in marked hypotension followed by refracted hypotension The patient died 18 hrs after in asytole, complicated renal failure and aspiration pneumonia.

Treatment

1. If bretylium is overdosed and symptoms of toxicity develop give nitropruside or consider another short acting IV hypertensive agent.

2. Do not use long acting drugs that might potentiate subsequent hypotensive effects of bretylium.

3.Treat hypotensiuon with appropiate fliud therapy and pressor agents such as dopamine or norepinephrine.

4.Dialysis isprobably not useful in treating bretylium overdosage.

Missed dose- 

1. If you miss a dose of this medicine, and remember within 6 hours of take it as soon as possible unless the dose is less than 4 hours.

2. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Pharmacology:

Bretylium tosylate inhibits norepinephrine release by depressing adrenergic nerve terminal excitability, inducing a chemical sympathoectomy- like state

Pharmacokinetics:

Peak plasma concentration and peak hypotensive effects are seen within 1 hour of IM administration. The terrminal half-life ranges from 6.9 to 8.1 hours. approximately 70 to 80% of an IM dose is excreted in the urine in the first 24 hours

Pregnancy:

Give to a pregnant woman only if clearly indicated.

Children:

Safety and efficacy for use in children have not been established.