Toxic substances overdosing

The most commonly used emetics are ipecac and apo-morphine. Induced emesis is the preferred means of emptying the stomach in awake patients who have ingested a toxic substance or have recently taken a drug overdose. Emesis should not be induced if the patient has central nervous system depression or has ingested certain volatile hydrocarbons and caustic substances. 

Many drug users die from toxic substances that are used to dilute illegal narcotics and from overdoses when drugs are more po tent than represented. Government control on the production of these drugs could make certain they were pure and standardize them so that their strength would not be in question. 

Although atropine is a known antidote against several toxic substances, its overdose can cause severe poisoning. As with other tropane alkaloids, atropine competitively blocks muscarinic acetylcholine receptor sites. This results in dilation of the pupil of the eye (mydriatic effect), dryness of the mucous membranes, especially of the mouth, and inhibition of activity of sweat glands (parasympatholytic action). At toxic doses, it causes palpitation, speech disturbance. 

Cases when comprehensive-exact-rapid-repeatable systems for toxic substance analysis in (suspected) overdose cases are urgent for decision making ... 

Drug (trade name) Toxic/Overdosed substance... 

Direct organ toxicity. Some substances may directly damage cells of a particular organ or system, either because they or their metabolites are specifically toxic to these cells, or because they are concentrated in one area, e.g. the renal fluoride ion toxicity of methoxyflurane, or the liver damage that occurs in paracetamol overdose because of a toxic intermediate product binding to hepatocytes. Secondary effects. Some effects are only indirectly related to the action of the drug, e.g. vitamin deficiency in patients whose gut flora have been modified by broad-spectrum antibiotics. 

The exact mechanism of action of most volatile substances remains unknown. Altered function of ionotropic receptors and ion channels throughout the central nervous system has been demonstrated for a few. Nitrous oxide, for example, binds to NMDA receptors and fuel additives enhance GABAa receptor function. Most inhalants produce euphoria increased excitability of the VTA has been documented for toluene and may underlie its addiction risk. Other substances, such as amyl nitrite ("poppers"), primarily produce smooth muscle relaxation and enhance erection, but are not addictive. With chronic exposure to the aromatic hydrocarbons (eg, benzene, toluene), toxic effects can be observed in many organs, including white matter lesions in the central nervous system. Management of overdose remains supportive. 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

Drugs or other substances that come in contact with the skin are readily absorbed as the skin is well hydrated and the stratum corneum is thin overdose toxicity may result, e.g. with hexachlorophane used in dusting powders and emulsions to prevent infection. 

Frequently, diazepam overdoses are adequately managed with clinical observation and supportive care. However, coingestion of ethanol and other CNS depressants which may exacerbate toxicity are common and warrant investigation in the patient history. Flumazenil, a benzodiazepine antagonist, effectively reverses symptoms of CNS toxicity, but is hazardous with the coingestion of other substances such as antidepressants. Therefore, it should not be used routinely. 

Toxic Effects of Acute Overdoses Acute poisoning with tricyclic antidepressants or MAO inhibitors is potentially hfe-threatening. Fatalities are much less common since modern antidepressants have widely replaced these drugs however, suicide rates have not declined consistently as clinical usage of modern antidepressants has increased. Deaths have been reported with acute doses of 2 g of imipramine, and severe intoxication can be expected at doses >1 g, or about a week s supply. If a patient is severely depressed, potentially suicidal, impulsive, or has a history of substance abuse, prescribing a relatively safe antidepressant agent with close clinical follow-up is appropriate. If a potentially lethal agent is prescribed, it is best dispensed in small, sublethal quantities, with the risk that sustained adherence to recommended treatment may be compromised. 

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