eMedicine Specialties > Emergency Medicine > Toxicology
Toxicity, Amphetamine: Treatment & Medication
Updated: Oct 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
Prehospital care of patients with amphetamine intoxication often requires physical and chemical restraint of the patient and treatment of complications of intoxication, including seizures, loss of competent airway, cardiac dysrhythmias, and trauma.
Emergency Department Care
- Patients with amphetamine intoxication who present with no life-threatening signs or symptoms may be treated with sedation and observation.
- Complications may require the physician to perform procedures to establish airway management or fluid resuscitation or to initiate vigorous cooling measures.
- In patients with acute oral ingestion, GI decontamination is performed by the administration of activated charcoal. Orogastric lavage often is not necessary but may be performed when the patient presents with immediately life-threatening intoxication shortly after ingestion. Whole-bowel irrigation may be indicated in suspected cases of body stuffing or body packing (large quantities of drugs in wrapping for international transport or drug hiding, respectively).
- Foley catheter placement may be useful to monitor urine output, particularly in situations in which diuretics are administered to manage pulmonary edema. Patients often have decreased urination due to the effects on bladder sphincter muscles to prevent passing urine. Other individuals may be dehydrated after recreational use in raves and club events. Quick assessment of bladder fullness can be performed with bedside ultrasonography or bladder palpation.
- Agitation or persisting seizures in patients with amphetamine toxicity requires generous titration of benzodiazepines and a calm soothing environment. Avoid physical restraints, if possible.
- Significant cardiac dysrhythmias may require cardioversion, defibrillation, and antidysrhythmics.
- Use benzodiazepine sedation (nonspecific sympatholysis) to initially manage hypertension, if present. Refractory cases or cases associated with significant end-organ toxicity (eg, cardiovascular accident [CVA], myocardial ischemia) can be managed with intravenous phentolamine, nitroprusside, or nitroglycerin.
- Avoid use of beta-blockers in order to prevent unopposed alpha effect (vasoconstriction).
- Cardiogenic pulmonary edema can be managed with nitroglycerin and diuretics.
- Aggressively cool hyperthermic patients with evaporative cooling, ice packs to the groin and axilla, and use of "ice-bath" (total body immersion in ice). Patients with severe hyperthermia (temperature >104°F) associated with psychomotor agitation may require immediate neuromuscular paralysis to rapidly decrease temperature. Temperature control should be achieved within 15-20 minutes upon presentation in order to prevent multiorgan failure and death.
- Haloperidol is controversial19 in the treatment of agitation in any patient with the potential to seize or develop hyperthermia because of associations with lowering the seizure threshold and altering thermoregulation.
- Of all neuroleptic drugs, however, haloperidol rarely is associated with seizures (minimal effects on seizure threshold). In addition, animal studies suggest that haloperidol can antagonize amphetamine-induced hyperthermia. Haloperidol can be considered as an adjunct to benzodiazepines for afebrile patients with normal vital signs and psychomotor agitation that requires chemical restraint.
- Look for and treat traumatic injuries in patients with amphetamine intoxication.
Consultations
- A medical toxicologist may be consulted for assistance in the management of amphetamine toxicity cases.
- Patients who demonstrate focal neural deficits or have CT scans of the head that indicate bleeding may need neurologic or neurosurgical consultations.
- Patients who show significant cardiac injury may require cardiologic consultation.
Medication
Medications available for amphetamine toxicity include gastric decontaminants (charcoal with or without sorbitol), sedatives to control CNS stimulation caused by amphetamines (benzodiazepines, antipsychotics), muscle relaxants (benzodiazepines, dantrolene), and several drugs to control possible hemodynamic cardiovascular disturbances (alpha-adrenergic blockers, nitrates, diuretics).
GI decontaminant
These agents are used to adsorb amphetamine after acute ingestion and to limit absorption into systemic circulation. Limited utility beyond 4 h of ingestion, unless the patient ingested sustained-release formulation or is suspected of being a body packer (ie, ingestion of a large amount of drug in a plastic bag or condom to smuggle or avoid arrest). Charcoal is not beneficial for other routes of exposure (eg, IV, inhalation or injection). Clinician should be aware of potential risk of charcoal aspiration and death due to aspiration pneumonia, especially in patients with altered mental status and/or having seizures. Prudent airway control is recommended in such population.
Activated charcoal
Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min of ingestion of poison. May administer as aqueous suspension or combine with cathartic (usually sorbitol 70%) in the presence of active bowel sounds.
Repeat dose, if necessary (without cathartic), to adsorb large pill masses or drug packages.
With superactivated forms, use of doses of 0.5 g/kg PO may be possible.
Adult
1 g/kg PO/NGT (with or without cathartic)
Pediatric
1 g/kg PO (omit cathartic if <2 y)
Effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases absorptive properties)
Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway; absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for presence of bowel sounds before administration to minimize risk of charcoal ileus (use aqueous solution to prevent bowel distention if bowel sounds are absent or diminished); not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administering; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black
Benzodiazepines
These agents are important for sedation counteracting the CNS and PNS excitation of amphetamines. A benzodiazepine is generally considered as the first agent of choice for hypertension and agitation, in addition to their utility for treating seizures.
Lorazepam (Ativan)
Beneficial for sedative and anticonvulsant effects. In addition, the calming effects may prove beneficial for the adverse cardiovascular effects (eg, hypertension, tachycardia) of amphetamines.
Adult
0.05 mg/kg (2-4 mg) IV, titrate to effect
Status epilepticus: 4 mg IV over 2-5 min; may repeat second dose in 10-15 min, if needed
Pediatric
Children: 0.05 mg/kg IV (range, 0.02-0.1 mg/kg)
Adolescents: Administer as in adults
Status epilepticus:
Neonates: 0.05 mg/kg over 2-5 min; may repeat in 10-15 min, if needed
Infants and children: 0.1 mg/kg over 2-5 min; second dose of 0.05 mg/kg IV at 10-15 min, if needed; maximum single dose 4 mg
Adolescents: 0.7 mg/kg IV slowly over 2-5 min; second dose in 10-15 min, if needed
Toxicity in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; contains benzyl alcohol, which may be toxic to infants in high doses
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Third-line agent for agitation or seizures because of shorter duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation.
Adult
5-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg
Pediatric
30 days to 5 years: 0.2-0.5 mg IV slowly q2-5min until symptoms resolve; not to exceed 5 mg
>5 years: 1 mg IV slowly q2-5min until symptoms resolve; not to exceed 10 mg
Increased toxicity in CNS with coadministration of phenothiazines, H1 blockers, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or renal and hepatic disease (may increase toxicity); monitor for respiratory depression with high or repeated doses
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to evaluate sedative effects fully before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.
Adult
0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV slowly over several min; may repeat q10-15min until adequate response achieved
Pediatric
<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min until seizures controlled
Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in patients with organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Neuroleptics
Antipsychotics are used to manage psychosis, agitation, and hyperthermia that may result from amphetamine use.
Haloperidol (Haldol)
DOC for patients with acute psychosis when no contraindications exist. Noted for high potency and low potential for causing orthostasis. Downside is the high potential for EPS (dystonia) and lowering the seizure threshold.
Use in acute amphetamine toxicity is controversial.19 If haloperidol is being considered, administer a benzodiazepine first. May then be used as adjunctive therapy to control agitation in afebrile patients with normal vital signs.
Parenteral dosage form may be admixed in syringe with 2 mg lorazepam for better anxiolytic effects.
Adult
5 mg IV/IM; titrate to effect; may double initial dose after 20-30 min
Pediatric
Not established
May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; coadministration with anticholinergics may increase intraocular pressure; encephalopathylike syndrome associated with concurrent administration with lithium
Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis; if IV/IM, watch for hypotension; caution in diagnosed CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue use)
Skeletal muscle relaxants
These agents are used to control or reverse hyperthermic effects. Most hyperthermia is mediated by neuromuscular agitation.
Dantrolene (Dantrium)
Has been used successfully in isolated case reports to control hyperthermia; however, efficacy has not been established for amphetamine-associated hyperthermia. Reverse of hyperthermic effects may take several hours. Because morbidity and mortality from hyperthermia is closely correlated with severity and duration of hyperthermia, aggressive cooling (eg, ice bath) and agents that work more readily to reverse hyperthermia are preferred over dantrolene.
Adult
0.8-3 mg/kg IV q6h
Pediatric
Administer as in adults
Toxicity may increase with the coadministration of clofibrate and warfarin; coadministration with estrogen may increase hepatotoxicity in women >35 y; hyperkalemia and bradycardia may occur with coadministration of verapamil
Documented hypersensitivity; active hepatic disease (hepatitis, cirrhosis)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause hepatotoxicity (use only for recommended indications); caution in impaired pulmonary function and severe cardiac insufficiency; may cause photosensitivity with exposure to sunlight
Cardiovascular agents
Alpha-adrenergic antagonists control peripheral vasoconstriction that results from sympathetic stimulation due to amphetamines. Treating with a beta-blocker to control the heart rate will leave unopposed alpha activity that causes vasoconstriction. Alpha-adrenergic antagonists specifically may be used to treat severe headache, SAH, cardiac ischemia, and hypertension associated with amphetamines. Use nitrates to control vasoconstriction and hypertensive emergency.
Phentolamine (Regitine)
Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on the alpha-adrenergic receptors.
Adult
1-2 mg IV initial, then 0.05 mg/kg IV; not to exceed 5 mg
Pediatric
0.1 mg/kg IV/IM; not to exceed 1 mg
Concurrent administration of epinephrine, phenylephrine, or ephedrine may decrease effects; ethanol increases toxicity
Documented hypersensitivity; coronary or cerebral arteriosclerosis; renal impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in tachycardia, non–drug-induced angina, coronary artery insufficiency, peptic ulcer, and gastritis; cerebrovascular occlusions and myocardial infarctions can occur following administration
Nitroprusside (Nitropress)
Produces vasodilation and increases inotropic activity of the heart. May exacerbate myocardial ischemia at higher doses by increasing heart rate.
Adult
0.1-8 mcg/kg/min IV; titrate to effect
Pediatric
Administer as in adults
Coadministration with DHE may decrease antianginal effects; coadministration with indomethacin may increase nitrate serum concentrations; sildenafil (Viagra) coadministration causes severe hypotension
Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis, atrial fibrillation, atrial flutter; hypovolemia; sildenafil (Viagra) use within 24 h
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; nitroprusside levels may increase in renal or hepatic insufficiency and can cause cyanide toxicity; monitor for thiocyanate and cyanide or limit use to <24 h (risk of cyanide toxicity is increased with infusions >2 mcg/kg/min); cyanide toxicity can be prevented with prolonged nitroprusside infusions by adding 1 g sodium thiosulfate to each 250-mL bag of nitroprusside for infusion; has ability to lower blood pressure, and, thus should be used only in patients with mean arterial pressures >70 mm Hg; not a first-line drug for use in pregnant women unless hypertensive emergency
Nitroglycerin (Deponit, Nitro-bid, Nitrostat)
Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. The result is a decrease in blood pressure. Valuable for controlling cardiac pain and pulmonary edema.
May administer bolus of 12.5-25 mcg or give a 400-mcg tab SL as a bolus before continuous infusion.
Initial infusion rate of 10-20 mcg/min may be increased 5-10 mcg/min q5-10min until desired clinical or hemodynamic response is achieved. Infusion rates of 500 mcg/min occasionally have been required.
Adult
400 mcg SL or 5 mcg/min IV; titrate to effect
Pediatric
Not established
Coadministration with DHE may decrease antianginal effects; coadministration with indomethacin may increase nitrate serum concentrations; sildenafil coadministration causes severe hypotension; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Documented hypersensitivity; severe anemia; shock; postural hypotension; head trauma; closed-angle glaucoma; cerebral hemorrhage; hypovolemia; constrictive pericarditis, pericardial effusion; hypertrophic cardiomyopathy; sildenafil (Viagra) use within 24 h
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in coronary artery disease, low systolic blood pressure, recent AMI, glaucoma, hepatic disease, and hyperthyroidism
Diuretics
These agents are used to control and treat pulmonary edema and could be beneficial in a hypertensive crisis.
Furosemide (Lasix)
Increases excretion of water by interfering with chloride-binding cotransport system that, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.
Adult
Pulmonary edema: 40 mg IV slowly over 1-2 min, repeat as 80 mg in 1 h, if needed, or sooner if no significant diuresis has occurred
Hypertensive crisis: 40-80 mg IV slowly over 1-2 min
Pulmonary edema and hypertensive crisis: 100-200 mg IV slowly over 1-2 min
Pediatric
1 mg/kg IV slowly over 1-2 min; may increase by 1 mg/kg at 2-h intervals prn; not to exceed 6 mg/kg
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication
Documented hypersensitivity; hepatic coma; anuria; severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter
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| Differential Diagnoses & Workup: Toxicity, Amphetamine |
 Treatment & Medication: Toxicity, Amphetamine |
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Further Reading
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