Anticonvulsants overdose

SpiUer HA, Bosse GM. Management of anticonvulsant overdose. CNS Drugs 1996 6 113-29. 

RPC has found use in the analysis of barbiturates including the determination of drugs taken in an overdose (332). Thiopental was determined using a mobile phase comprised of methanol-0.1% sodium citrate buffer, pH 6.5 (45 55) (333). Hydantoins, along with other species which have anticonvulsant activity, have been determined with barbiturates. These include phenytoin in the presence of phenobarbital and primidone (334,335) and the related anticonvulsants ethosuximide and carbamazepine (336). 

Note It is a good general practice to avoid treating the symptoms of use, withdrawal and overdose with other drugs. General support and control are often adequate. On the other hand the use of anticonvulsants should be prompt and the use of other drug supports considered carefully, in relationship to the clinical, psychological and social situation. 

Solanine hydrochloride has been used as a commercial pesticide. It has sedative and anticonvulsant properties, and has sometimes been used for the treatment of asthma, as well as for cough and common cold. However, gastrointestinal and neurological disorders result from solanine poisoning. Symptoms include nausea, diarrhoea, vomiting, stomach cramps, burning of the throat, headaches and dizziness. Other adverse reactions, in more severe cases, include hallucinations, loss of sensation, paralysis, fever, jaundice, dilated pupils and hypothermia. Solanine overdose can be fatal. 

Phenobarbital, mephobarbital and metarbital are the only oral anticonvulsants which are effective at sub-hypnotic levels. Many barbiturates are classified as Schedule II, III, or IV due to their high potential for overdose and dependence. Abrupt withdrawal may cause seizures, restlessness, trembling, and insomnia and may be fatal. Phenobarbital is used as an anticonvulsant for the treatment of epilepsy and in some combination medications for the relief of irritable bowel syndrome. 

Other nervous system depressants that could trigger a GHB overdose reaction are benzodiazepines (mild tranquilizers such as Valium and Xanax), phenothiazines (potent tranquilizers like Thorazine and Stellazine), various painkillers (barbiturates and opiates), anticonvulsants (Dilantin and phenobarbital), and even many over-the-counter allergy and sleep remedies. 

In addition to sinus tachycardia and tremor, vomiting is common after overdose. Hypotension, tachycardia, hypokalemia, and hyperglycemia may occur, probably due to -adrenergic activation. The cause of this activation is not fully understood, but the effects can be ameliorated by the use of B-blockers (see below). Cardiac arrhythmias include atrial tachycardias, premature ventricular contractions, and ventricular tachycardia. In severe poisoning (eg, acute overdose with serum level > 100 mg/L), seizures often occur and are usually resistant to common anticonvulsants. Toxicity may be delayed in onset for many hours after ingestion of sustained-release tablet formulations. 

The manifestations of acute lamotrigine overdose can mimic the anticonvulsant hypersensitivity syndrome (68). 

Mylonakis E, Vittorio CC, HolUk DA, Rounds S. Lamotrigine overdose presenting as anticonvulsant hypersensitivity syndrome. Ann Pharmacother 1999 33(5) 557-9. 

Anticonvulsants Oversedation Confusion Incoordination Cardiac arrhythmia Severe overdoses oftentimes are fatal. Coma... 

Carbamazepine is both an important anticonvulsant in therapeutic doses and a powerful proconvulsant in overdose. The therapeutic anticonvulsant mechanism is primarily related to blockade of presynaptic voltage-gated sodium channels. Blockade of the sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. Carbamazepine is also a powerful inhibitor of the muscurinic and nicotinic acetylcholine receptors, N-methyl-D-aspartate (NMDA) receptors and the central nervous system (CNS) adenosine receptors. In addition, carbamazepine is structurally related to the cyclic antidepressant impramine and in massive overdose may affect cardiac sodium channels. 

Diazepam is used primarily in the treatment of mental anxiety. In addition, it acts as a muscle relaxant for a variety of medical conditions. It may also be used as a sedative-hypnotic and anticonvulsant (e.g., for status epilepticus and drug-induced seizures). Diazepam may also be used to alleviate some of the symptoms associated with the following cholinesterase poisoning, substance abuse withdrawal, antihistamine overdose. Black Widow spider envenomation, and chloroquine overdose. As an anesthetic, diazepam may be used alone or in combination with other drugs for conscious sedation. 

The most likely drug to be needed in an overdose due to this substance is an anticonvulsant, but beta-blockers are appropriate when cardiac arrhythmias are present... 

B. Adverse effects of chronic valproic acid therapy include hepatic failure (high-risk patients are less than 2 years of age, receiving multiple anticonvulsants, or have other long-term neurologic complications) and weight gain. Hepatitis is not dose related and Is not usually seen after an acute overdose. Pancreatitis is usually considered a non-dose-related effect. Alopecia, red cell aplasia, thrombocytopenia, and neutropenia have been associated with both acute and chronic valproic acid intoxication. 

B. Convulsions. All three drugs can be used for the treatment of acute seizure activity or status epilepticus resulting from idiopathic epilepsy or convulsant drug overdose. Midazolam and lorazepam have the advantage of rapid absorption after intramuscular injection. Lorazepam also has a longer duration of anticonvulsant action than the other two agents. 

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