Stimulants overdose/toxicity

SAFETY PROFILE A deadly human poison by an unspecified route. An experimental poison by ingestion, subcutaneous, intraperitoneal, and intravenous routes. Experimental reproductive effects. Mutation data reported. A central nervous system stimulant. Overdoses cause hyperactivity, restlessness, insomnia, rapid pulse, rise in blood pressure, dilated pupils, dryness of the throat. Combustible when exposed to heat, flame, or oxidizers. When heated to decomposition it emits toxic fumes of NO. To fight fire, use CO2, dry chemical, alcohol foam, water mist, fog. See other benzedrine entries. 

Treatment with imipramine, the most studied TCA, leaves 45% to 70% of patients panic free. Both desipramine and clomipramine have demonstrated effectiveness in PD as well. Despite their efficacy, TCAs are considered second- or third-line pharmacotherapy due to poorer tolerability and toxicity on overdose.48,49 TCAs are associated with a greater rate of discontinuation from treatment than SSRIs.53 PD patients taking TCAs may experience anticholinergic effects, orthostatic hypotension, sweating, sleep disturbances, dizziness, fatigue, sexual dysfunction, and weight gain. Stimulant-like side effects occur in up to 40% of patients.49... 

TABLE 11.4 Toxic Reactions to Stimulants Usually in Overdose and Occasionally at Low Doses... 

Item taken from the 2002 FDA-approved overdose section of the labels for Dexedrine, Adderall, and Adderall XR, but not Ritalin. The remainder was taken from the Ritalin label with some overlap. The Dexedrine and Adderall labels both state that individual patient responses to amphetamines vary widely and toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg. The Adderall XR label also states that patient responses vary widely and toxic symptoms may occur at low doses. Any of the symptoms can occur with any of the stimulants at routine clinical doses. 

Paracetamol is now sold in smaller packs to make it more difficult for suicidal people to acquire sufficient drug for an overdose. An understanding of why the drug is toxic has stimulated the development of other possibly less toxic analogues of this drug. 

Cocaine and other stimulant drugs are often taken in combination with other drugs, particularly alcohol and opiates. Laboratory studies in humans have shown that alcohol can enhance and prolong the subjective pleasure associated with cocaine, and this is likely the basis for their frequent association. Recent studies have revealed that when cocaine is taken with alcohol, a new compound called cocaethylene is formed in the body. Cocaethylene has pharmacological properties similar to cocaine, but it may be more toxic. Many cases of cocaine overdose may in fact involve cocaethylene toxicity caused by combining cocaine and alcohol (Raven, Necessary, Danluck, Ettenberg,... 

There is no antidote for azathioprine toxicity. Treatment for an overdose entails ipecac within 30 min or lavage within 1 h, followed by activated charcoal. Side effects may be minimized with adequate monitoring of peripheral blood count and liver enzymes. Asymptomatic leucopenia, as well as most other side effects, may be treated with dose reduction or drug cessation (and changing to 6-MP) however, a life-threatening leucopenic episode may require administration of granulocyte colony-stimulating factor as well as other supportive care. 

Hypertension and tachycardia are the primary toxic manifestations of pseudoephedrine overdose. An amount of more than three or four times the maximum daily dosage for adults or children may produce symptoms of jS-adrenergic stimulation. In severe poisonings, cardiac dysrhythmias and cerebral hemorrhage due to hypertensive crisis may occur. Anxiety, muscle tremor, and seizures may result from CNS stimulation. Hallucinations, drowsiness, and/or irritability are more common symptoms exhibited by children. Hypokalemia and hyperglycemia may be noted. Acute renal failure and rhabdomyolysis have occurred in rare instances with large overdoses. 

The most common side effect of clonidine is dose-dependent sedation that usually subsides after 2 to 3 weeks of therapy. Of concern are reports of bradycardia, rebound hypertension, heart block, and sudden death. Four children have died on the combination of methylphenidate and clonidine however, complicating factors make it impossible to link the drug combination directly with the cause of death. Of 10,060 children exposed to clonidine and assessed by a poison control center over a 7-year period, moderate (19%) to major (2%) toxic effects (bradycardia, hypotension, and respiratory depression) including one death were reported. Overdoses, concurrent clonidine and stimulant administration, as well as missed doses of clonidine aU add to the risk of adverse cardiovascular events. Similar adverse-effect concerns apply to treatment with guanfacine, although its U2a selectivity may result in less sedation and hypotension than clonidine. ... 

Cannabinoid agonists are especially advantageous in pain management due to a relative lack of toxicity, with reported deaths from overdose rare to nonexistent. This is attributable to their low potential for respiratory depression because of the lack of CB receptors in the respiratory center of the brainstem. When used adjunctively, they are opioid-sparing and thereby reduce the risk of respiratory depression by opioids. In addition, A -THC stimulates beta endorphin production, delays development of tolerance to opioids, and limits withdrawal symptoms from opioids. 

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