Amphetamine Toxicity

AM Report

8/10/09

Mike Contarino

Learning Points

1. Hyperthermia has a broad differential, and drugs of abuse should be kept in mind.

2. Watch for rhabdomyolysis, DIC, and multiorgan failure after hyperpyrexia.

3. Amphetamines result in dopamine, NE, and serotonin release, catecholamine surge!

Hyperthermia Differential

Sepsis Encephalitis Meningitis/Brain Abscess NMS Malignant hyperthermia Pheochromocytoma Thyroid storm Tetanus EtOH/Benzo withdrawal

Salicylate/Li toxicity Sympathomimetic toxicity Serotonin syndrome Anticholinergic Toxicity Hypothalamic Stroke/

Cerebral hemorrhage Status Epilepticus Typhoid fever Catatonia

Amphetamines

Used and abused since 1930’s after reports of enhanced intellectual performance.

Schedule I: MDMA (ecstasy), MDA, MDEA Schedule II: Adderall, Ritalin, etc. OTC: Ma Huang (ephedra), Sudafed

Amphetamines

Mechanism: Enter neurons via serotonin/dopamine transporters, displace storage vesicles leading to NE, serotonin, and dopamine efflux.

Catacholamine release leads to tachycardia, inc SVR, mydriasis, and hyperthermia.

Amphetamine increases the concentration of dopamine in the synaptic cleft in 3 ways: (1) bind to the pre-synaptic membrane of dopaminergic neurones and induce the release of dopamine from

the nerve terminal (2) interact with dopamine containing synaptic vesicles, releasing free dopamine into the nerve terminal (3) bind to the dopamine re-uptake transporter, causing it to act in reverse and transport free dopamine out

of the nerve terminal. Amphetamine can also cause an increased release of noradrenaline into the synaptic cleft.

Acute Toxicity

May present w/ AMS, agitation, seizures, palpatations, chest pain, n/v/d.

Severe Hyperpyrexia Hyponatremia Secondary Conditions:

Rhabdomyolysis DIC Renal Failure Hepatic Necrosis GI Bleeding Diarrhea

Acute Toxicity

Thermoregulatory: up to 43 deg, which leads to rhabdo, DIC, multiorgan failure

CV: tachy, inc SVR, HTN, dysrhythmia, late- hypotension

Neuro: stimulant effects to coma Electrolyte: Severe hyponatremia, acidosis and

rhabdo changes GI: Hepatotoxicity and GI Bleeding MSK: rhabdomyolysis Renal: ARF from rhabdo, DIC, shock Heme: DIC

Chronic Toxicity

Risk of vasculitis Neuropsychiatric abnormalities

Damage to dopaminergic and serotonergic neurons

Cardiomyopathy

Learning Points

1. Hyperthermia has a broad differential, and drugs of abuse should be kept in mind.

2. Watch for rhabdomyolysis, DIC, and multiorgan failure after hyperpyrexia.

3. Amphetamines result in dopamine, NE, and serotonin release, catecholamine surge!

Sources

White, S. Amphetamine Toxicity. Seminars in Resp & Critical Care Medicine Vol 23, 2002.

Lanken, PN. UpToDate. Hyperthermia. 2008. Stahl S. Drugs of abuse. Essential Psychopharmacology –

neuroscientific basis and practical applications. Cambridge University Press: Cambridge. 1996:332–366.

THANKS!!