BUPROPION

A. ACTIVATED CHARCOAL

1. CHARCOAL ADMINISTRATION

a. Consider administration of activated charcoal after a potentially toxic ingestion (Chyka & Seger, 1997). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2. CHARCOAL DOSE

a. Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years; and 1 gram/kilogram in infants up to 1 year old (USP DI, 2000; Chyka & Seger, 1997).

(1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (Barceloux et al, 1997).

b. ADVERSE EFFECTS/CONTRAINDICATIONS

(1) Complications: emesis, aspiration (Chyka & Seger, 1997). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
(2) Contraindications: unprotected airway, gastrointestinal tract not anatomically intact, therapy may increase the risk or severity of aspiration; ingestion of most hydrocarbons (Chyka & Seger, 1997).

B. GASTRIC LAVAGE

1. INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).

a. Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

2. PRECAUTIONS:

a. SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b. AIRWAY PROTECTION: Alert patients - place in Trendelenburg and left lateral decubitus position, with suction available. Obtunded or unconscious patients - cuffed endotracheal intubation.

3. LAVAGE FLUID:

a. Use small aliquots of liquid. Lavage with 150 to 200 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in children over 5 or adults) and 10 milliliters/kilogram body weight of normal saline in young children. Continue until lavage return is clear.
b. The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c. CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

4. COMPLICATIONS:

a. Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications.
b. Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).

5. CONTRAINDICATIONS:

a. Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.

C. WHOLE BOWEL IRRIGATION

1. Consider the use of whole bowel irrigation after ingestion of sustained release products.
2. CONTRAINDICATIONS - This procedure should not be used in patients who are currently or are at risk for rapidly becoming obtunded, comatose, or seizing until the airway is secured by endotracheal intubation. Whole bowel irrigation should not be used in patients with bowel obstruction, bowel perforation, megacolon, or toxic colitis.
3. DOSE - Polyethylene glycol solution (e.g. GoLYTELY(R)) is taken orally or infused by nasogastric tube at a rate of 500 milliliters/hour in children (alternatively 20 milliliters/kilogram/hour) or 2 liters/hour in adults or adolescents until the rectal effluent is clear.
4. ADVERSE EFFECTS - Include nausea, vomiting, abdominal cramping and bloating. Fluid and electrolyte status should be monitored, although significant fluid and electrolyte abnormalities have not been reported. Prolonged periods of irrigation may produce a mild metabolic acidosis.

6.5.3 TREATMENT

A. SEIZURES

1. SUMMARY

a. Attempt initial control with a benzodiazepine (diazepam or lorazepam). If seizures persist or recur administer phenobarbital. Benzodiazepines and barbiturates are generally preferred over phenytoin for the control of overdose or withdrawal related seizures.
b. Monitor for respiratory depression, hypotension, dysrhythmias, and the need for endotracheal intubation.
c. Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or treat with intravenous dextrose ADULT: 50 milliliters IV, CHILD: 2 milliliters/kilogram 25% dextrose).

2. DIAZEPAM

a. MAXIMUM RATE: Administer diazepam intravenously over 2 to 3 minutes (maximum rate = 5 milligrams/minute).
b. ADULT DIAZEPAM DOSE: 5 to 10 milligrams initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
c. PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 milligram per kilogram repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
d. RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (generally use twice the usual initial dose because of decreased absorption), or lorazepam may be given intramuscularly.
e. MIDAZOLAM: has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. PEDIATRIC MIDAZOLAM DOSE: INTRAMUSCULAR: 0.2 milligram/kilogram (maximum 7 milligrams) (Chamberlain et al, 1997); INTRANASAL: 0.2 milligram/kilogram (Lahat et al, 2000). Buccal midazolam, 10 milligrams, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

3. LORAZEPAM

a. MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 milligrams/minute (Prod Info Ativan(R), 1999).
b. ADULT LORAZEPAM DOSE: 2 to 8 milligrams intravenously. Initial doses may be repeated in 10 to 15 minutes if seizures persist (Prod Info, Ativan(R), 1999; AMA, 1991).
c. PEDIATRIC LORAZEPAM DOSE: 0.05 to 0.1 milligram/kilogram intravenously, (maximum 4 milligrams/dose) repeated twice at intervals of 10 to 15 minutes (Benitz & Tatro, 1995).

4. PHENOBARBITAL

a. ADULT PHENOBARBITAL LOADING DOSE: 600 to 1200 milligrams of phenobarbital intravenously initially (10 to 20 milligrams per kilogram) diluted in 60 milliliters of 0.9 percent saline given at 25 to 50 milligrams per minute.
b. ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 milligrams may be given every 20 minutes.
c. MAXIMUM SAFE ADULT PHENOBARBITAL DOSE: No maximum safe dose has been established. Patients in status epilepticus have received as much as 100 milligrams/minute until seizure control was achieved.
d. PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 milligrams per kilogram of phenobarbital intravenously at a rate of 25 to 50 milligrams per minute.
e. PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 milligrams per kilogram may be given every 20 minutes.
f. MAXIMUM SAFE PEDIATRIC PHENOBARBITAL DOSE: No maximum safe dose has been established. Children in status epilepticus have received doses of 30 to 120 milligrams/kilogram within 24 hours. Vasopressors and mechanical ventilation were needed in some patients receiving these doses.
g. MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation.
h. NEONATAL PHENOBARBITAL LOADING DOSE: 20 to 30 milligrams/kilogram intravenously at a rate of no more than 1 milligram/kilogram per minute in patients with no preexisting phenobarbital serum levels.
i. NEONATAL PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 2.5 milligrams/kilogram every 12 hours may be given; adjust dosage to maintain serum levels of 20 to 40 micrograms/milliliter.
j. MAXIMUM SAFE NEONATAL PHENOBARBITAL DOSE: Doses of up to 20 milligrams/kilogram/minute up to a total of 30 milligrams/kilogram have been tolerated in neonates.
k. CAUTIONS: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.
l. SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (20 to 40 micrograms per milliliter).

5. PHENYTOIN/FOSPHENYTOIN

a. Benzodiazepines and/or barbiturates are generally preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures.
b. PHENYTOIN

(1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION: Manufacturer does not recommend intravenous infusions due to lack of solubility and resultant precipitation, however infusions are commonly used.

(a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 milligrams per milliliter solution in 50 to 100 milliliters of 0.9 percent saline.

(2) PHENYTOIN ADMINISTRATION RATE: Rate of administration by either method should not exceed 0.5 milligram per kilogram per minute or 50 milligrams per minute.
(3) ADULT PHENYTOIN LOADING DOSE: 15 to 18 milligrams per kilogram of phenytoin initially. Rate of administration by very slow intravenous push or diluted to 50 milligrams per milliliter should not exceed 0.5 milligram per kilogram per minute or 50 milligrams per minute.
(4) ADULT PHENYTOIN MAINTENANCE DOSE: Manufacturers recommend a maintenance dose of 100 milligrams orally or intravenously every 6 to 8 hours. The goal is to maintain a serum concentration between 10 to 20 micrograms/milliliter.
(5) PEDIATRIC PHENYTOIN LOADING DOSE: 15 to 20 milligrams per kilogram or 250 milligrams/square meter of phenytoin. Rate of intravenous administration should not exceed 0.5 to 1.5 milligrams per kilogram per minute.
(6) PEDIATRIC PHENYTOIN MAINTENANCE DOSE: Repeat doses of 1.5 milligrams per kilogram may be given every 30 minutes to a maximum daily dose of 20 milligrams per kilogram.
(7) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if arrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle.
(8) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (10 to 20 micrograms per milliliter).

c. FOSPHENYTOIN

(1) ADULT DOSAGE AND ADMINISTRATION: The dose, concentration in dosing solutions, and infusion rate of fosphenytoin are expressed as phenytoin sodium equivalents.
(2) ADULT LOADING DOSE FOSPHENYTOIN: 15 to 20 milligrams/kilogram of phenytoin sodium equivalents at a rate of 100 to 150 milligrams phenytoin equivalent/minute.
(3) Fosphenytoin should not be infused at rates greater than 150 milligrams phenytoin equivalent/minute because of the risk of hypotension.
(4) CAUTIONS: Perform continuous monitoring of respiratory function, cardiac rhythm, and blood pressure throughout infusion and for at least 30 minutes thereafter.
(5) ADULT MAINTENANCE DOSING: 4 to 6 milligrams phenytoin equivalents/kilogram/day. Rate of administration should not exceed 150 milligrams phenytoin equivalent/minute.
(6) SERUM LEVEL MONITORING: Monitor serum phenytoin levels over the next 12 to 24 hours; therapeutic levels 10 to 20 microgram/milliliter. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin.

B. MONITORING PARAMETERS

1. Monitor cardiac rhythm and vital signs. Although bupropion has not demonstrated significant cardiac effects, experience is limited and monitoring is recommended in substantial overdoses. QRS and QTc prolongation have been reported. Although Torsades de Pointes has not been reported with bupropion, multidrug ingestions with agents such as tricyclic antidepressants may predispose to this.

a. Complete resolution of QRS and QTc prolongation on serial ECGs has been reported even in the absence of drug therapy following bupropion overdoses (Shrier et al, 2000; Fresh et al, 1999).

2. It is suggested to monitor EEG for the first 48 hours following large overdoses (Prod Info Wellbutrin(R), 1999).

C. TORSADE DE POINTES

1. SUMMARY

a. Withdraw the causative agent. Hemodynamically unstable patients require electrical cardioversion. Emergent treatment with magnesium, isoproterenol, or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (hypomagnesemia, hypokalemia, hypocalcemia) (Smith & Gallagher, 1980; Keren et al, 1981; AHA, 2000).

2. MAGNESIUM SULFATE

a. ADULT DOSE: No clearly established guidelines exist. Administer 2 grams (16 mEq) mixed in 50 to 100 milliliters D5W intravenously over 5 minutes, followed if needed by a second 2 gram bolus and infusion of 3 to 50 milligrams/minute in patients not responding to the initial bolus or with recurrence of dysrhythmias (AHA, 2000; Perticone et al, 1997).
b. PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes.
c. PRECAUTIONS: Use with caution in patients with renal insufficiency.
d. MAJOR ADVERSE EFFECTS: High doses may cause respiratory depression, weakness, neuromuscular blockade, and hypotension.
e. MONITORING PARAMETERS: Heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium.

3. ISOPROTERENOL

a. DOSE: 2 to 10 micrograms/minute (children: 0.1 to 1 microgram/kilogram/minute) by continuous monitored intravenous infusion; titrate to heart rate and rhythm response. A 2-microgram/milliliter solution may be prepared by mixing 1 milligram isoproterenol hydrochloride in 500 milliliters of dextrose 5 percent in water.
b. AVAILABLE FORMS: Isuprel(R) (parenteral solution) 1:100,000; 1:50,000; 1:5000
c. PRECAUTIONS: Correct hypovolemia before using; do not administer simultaneously with epinephrine; contraindicated in patients with acute cardiac ischemia; may precipitate fatal ventricular fibrillation if the rhythm is not torsade de pointes.

(1) Use caution in patients with coronary insufficiency, diabetes, hyperthyroidism, or sensitivity to sympathomimetics; contraindicated in patients with pre-existing dysrhythmias.

d. MAJOR ADVERSE EFFECTS: Cardiac dysrhythmias, dizziness, nervousness, tremor.
e. MONITORING PARAMETERS: Heart rate and rhythm, blood pressure, central venous pressure

4. OVERDRIVE PACING

a. Institute overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated.

5. PHENYTOIN

a. ADULT DOSE: 15 milligrams/kilogram intravenous infusion at a rate not exceeding 50 milligrams/minute.
b. PEDIATRIC DOSE: 15 to 20 milligrams/kilogram by intravenous infusion at a rate not exceeding 1 to 3 milligrams/kilogram/minute to a maximum of 50 milligrams/minute.
c. PRECAUTIONS: Too rapid infusion may induce hypotension and dysrhythmias. Extravasation may cause significant tissue injury.
d. MAJOR ADVERSE EFFECTS: Hypotension and dysrhythmias may develop with too rapid infusion. Mild central nervous system depression, nystagmus, and ataxia are common.
e. MONITORING PARAMETERS: Heart rate and rhythm, blood pressure

6. AMIODARONE

a. Despite its prolongation of the QT interval, amiodarone has been reported to be effective in both treating acute episodes of torsades de pointes and preventing recurrences (Mattioni et al, 1989; Lazzara, 1989).

7. OTHER DRUGS

a. Lidocaine, mexiletine, verapamil, bretylium, propranolol, and labetalol have also been used to treat torsade de pointes, but results have been inconsistent.

8. AVOID

a. Avoid class Ia antiarrhythmics (quinidine, disopyramide, procainamide, aprindine) and most class III antiarrhythmics (N- acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with torsade de pointes.

D. ANXIETY/AGITATION

1. Benzodiazepines may be used to control tremulousness, anxiety and agitation (Weiner et al, 1998).

E. SEROTONIN SYNDROME

1. Serotonin syndrome following bupropion therapy or overdoses has not been reported to date. Bupropion has dopamine agonist properties, but does not affect serotonin and does not inhibit monoamine oxidase. Isolated cases of serotonin syndrome occurring with some drugs with dopamine agonist effects (reviewed in Sporer, 1995) have been reported, and could possibly occur with bupropion, particularly if taken in conjunction with drugs that affect serotonergic neurotransmission.

Refer to "SEROTONIN SYNDROME" management for further information.

7.0 RANGE OF TOXICITY

7.1 SUMMARY

A. Therapeutic adult doses are 300 to 450 mg/day. Seizures have been reported with doses of 600 to 900 mg. Overdoses of 9 grams in adults, resulting in seizures, have been survived.
B. In 12 of 13 overdoses reported during clinical trials, patients ingested 850 to 4200 mg and recovered without significant sequelae.

7.2 THERAPEUTIC DOSE

7.2.1 ADULT

A. GENERAL

1. The manufacturer recommends 300 to 450 milligrams/day given in 3 divided doses. Each dose is not to exceed 150 milligrams, and the maximum dose is 450 milligrams/day (Prod Info Wellbutrin(R), 1999). The target dose for sustained-release preparations is 300 milligrams/day (150 milligrams twice daily) (Prod Info Wellbutrin(R), 1999).

7.3 MINIMUM LETHAL EXPOSURE

A. ADULT

1. Deaths following overdoses of bupropion, with no concurrent drugs, are rare. Deaths that have been reported are preceded by multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest (Prod Info Wellbutrin(R), 1999).

7.4 MAXIMUM TOLERATED EXPOSURE

A. CASE REPORTS

1. An overdose of 9000 milligrams in an 18-year-old, with no other co-ingestants, resulted in tonic-clonic seizures within approximately 7 hours. Sinus tachycardia, lasting 48 hours, was also reported in this patient (Storrow, 1994). Gittelman & Kirby (1993) reported seizures in a 39-year-old several hours following ingestion of 1000 to 2000 milligrams.
2. An overdose of up to 3000 milligrams in a 14-year-old, with no other co-ingestants and no history of seizures, resulted in 2 tonic-clonic seizures of short duration (up to 45 seconds) requiring no pharmacological intervention. Spontaneous emesis, transient tachycardia, confusion and somnolence were also reported. The patient was hospitalized for 72 hours (Ayers & Tobias, 2001).
3. A retrospective analysis of 58 bupropion overdoses revealed a range of 575 to 6000 milligrams (mean 3078 milligrams) bupropion in those patients experiencing seizures. Patients that did not exhibit seizures ingested from 200 up to 6300 milligrams (mean 2148 milligrams) bupropion (Spiller et al, 1994).
4. In a review of manufacturer's records on 37 cases of seizures, there was a greater incidence in patients receiving doses of greater than 450 milligrams/day. The mean dose in patients experiencing seizures was 8.3 +/- 3.3 milligrams/kilogram/day. In 9 of 34 cases (excluding 2 with polydrug overdose and 1 with cerebral palsy), the dose exceeded 10 milligrams/kilogram (Davidson, 1989).

7.5 SERUM/PLASMA/BLOOD CONCENTRATIONS

7.5.1 THERAPEUTIC CONCENTRATIONS

A. GENERAL

1. Therapeutic levels were associated with 4-hour levels of 150 to 200 nanograms/milliliter and trough levels of 50 to 100 nanograms/milliliter (Preskorn, 1983).
2. The mean plasma level of bupropion in patients who experienced seizures was 170.4 nanograms/milliliter, obtained 0.25 to 12.5 hours after the seizure. The mean hydroxybupropion level was 1022.5 nanograms/milliliter (Davidson, 1989). In unpublished studies in animals, this metabolite was associated with seizures (Davidson, 1989).

7.5.2 TOXIC CONCENTRATIONS

A. CASE REPORTS

1. An 18-year-old woman had a bupropion level of 400 nanograms/milliliter 7 hours after ingesting 9,000 milligrams (Storrow, 1994). Clinical effects included confusion, tachycardia and seizures.
2. A post mortem blood bupropion level of 0.7 milligrams/liter was reported in a 38-year-old woman after a mixed ingestion of bupropion and ethanol (Ramcharitar et al, 1992).
3. A four hour serum bupropion level was reported as 220 nanograms/milliliter following an ingestion of 4500 milligrams sustained-release bupropion in a 19-year-old female. Clinical effects included vomiting, tremulousness and tachycardia; symptoms improved following intravenous lorazepam (Weiner et al, 1998).
4. A 16-hour serum bupropion level was reported as 0.44 milligrams/liter (therapeutic 0.025-0.2 milligrams/liter) in a 36-year-old female who ingested 4.5 grams of bupropion (Fresh et al, 1999).

7.7 LD50/LC50

A. ANIMAL DATA

§ LD50 - (ORAL) MOUSE: 575 mg/kg (Budavari, 1996)

§ LD50 - (IP) MOUSE: 230 mg/kg (Budavari, 1996)

§ LD50 - (ORAL) RAT: 600 mg/kg (Budavari, 1996)

§ LD50 - (IP) RAT: 210 mg/kg (Budavari, 1996)

§ LD50 - (ORAL) MOUSE: 544 mg/kg (RTECS, 2001)

8.0 KINETICS

8.1 ABSORPTION

A. ORAL

1. Well absorbed orally, with peak plasma levels within 2 hours.

8.2 DISTRIBUTION

8.2.1 DISTRIBUTION SITES

A. PROTEIN BINDING

1. 85%

B. TISSUE/FLUID SITES

1. Bupropion and its metabolites have been detected post-mortem in the blood, heart, bile, kidney, liver, stomach and urine (Ramcharitar et al, 1992).

8.2.2 DISTRIBUTION KINETICS

A. VOLUME OF DISTRIBUTION

1. 19.8 to 47 liters/kg (Laizure et al, 1985).

B. DISTRIBUTION HALF-LIFE

1. 1.5 hours

8.3 METABOLISM

8.3.1 METABOLISM SITES AND KINETICS

A. GENERAL

1. 99% of the dose is metabolized

8.3.2 METABOLITES

A. GENERAL

1. M-chlorohippuric acid is a major metabolite.
2. Other metabolites include (Davidson, 1989):

a. hydroxybupropion
b. erythrohydrobupropion
c. threohydrobupropion

3. The major urinary metabolite is reported to be the threoamino alcohol metabolite (Ramcharitar et al, 1992).

8.4 EXCRETION

8.4.1 KIDNEY

A. 87% of the dose is excreted in the urine, mostly as metabolites.

8.4.2 FECES

A. 10% excreted in the feces as metabolites.

8.5 ELIMINATION HALF-LIFE

8.5.1 PARENT COMPOUND

A. GENERAL

1. 13.1 to 20.9 hours (Lai and Schroeder, 1983).
2. The bupropion half-life ranged from 3.8 to 23 hours in 6 subjects receiving 200 mg (Laizure et al, 1985).

8.5.2 METABOLITE

A. GENERAL

1. HYDROXY METABOLITE - 15.4 to 30.8 hours
2. ERYTHROAMINO ALCOHOL METABOLITE - 20.5 to 43.4 hours.
3. THREOAMINO ALCOHOL METABOLITE - 9 to 27.5 hours (Laizure et al, 1985).

9.0 PHARMACOLOGY/TOXICOLOGY

9.1 PHARMACOLOGIC MECHANISM

A. The precise neurochemical mechanism of the antidepressant effect of bupropion is unknown. Bupropion does not inhibit monoamine oxidase. Compared to traditional tricyclic antidepressants, it is a weak blocker of the neuronal uptake of serotonin and norepinephrine; it also directly inhibits the neuronal re-uptake of dopamine to a lesser extent. Bupropion is reported to produce dose-related central nervous system stimulant effects in animals (Prod Info Wellbutrin(R), 1999; Shrier et al, 2000).

10.0 PHYSICOCHEMICAL

10.1 PHYSICAL CHARACTERISTICS

A. This compound possesses a bitter anesthetizing taste (Budavari, 1996).

10.3 MOLECULAR WEIGHT

A. 276.2 (Budavari, 1996)

12.0 REFERENCES

12.2 GENERAL BIBLIOGRAPHY
1. AMA Department of Drugs: Drug Evaluation Subscription. American Medical Association, Chicago, IL, 1991.
2. American Heart Association & International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation, 2000; suppl 8:1-383.
3. Ames D, Wirshing WC & Szuba MP: Organic mental disorders associated with bupropion in three patients. J Clin Psychiatr 1992; 53:53-55.
4. Ayers S & JD: Bupropion overdose in an adolescent. Ped Emerg Care 2001; 17:104-106.
5. Balon R: Bupropion and nightmares (letter). Am J Psychiatry 1996; 153(4):579.
6. Barceloux D, McGuigan M, Hartigan-Go K: Position statement: cathartics. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Clin Toxicol 1997; 35:743-752.