Therapeutic overdose

Hazard (Gaseous) Moderate fire risk as oxidizing agent therapeutic overdoses can cause convulsions. (Liquid) May explode on contact with heat or oxidizable materials. Irritant to skin and tissue. 

A. Acute single overdose is usually a result of a suicide attempt or accidental childhood ingestion but may also be caused by accidental or iatrogenic misuse (therapeutic overdose). 

Gold poisoning is not common and occurs practically only as a result of therapeutic overdoses and as a side effect of chrysotherapy (gold therapy). Inhalation does not hurt the respiratory tracts. Levels of tolerance for the toxic effects of gold are not reported. Neither threshold limit values nor maximum permissible concentrations in the workplace are available [4]. 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

Clinical Particulars (therapeutic indications, administration, contraindications, special warnings and precautions, interaction with other drugs, use in pregnancy or lactation, effects on driving, undesirable effects, overdose)... 

The adverse side-effects of the TCAs, coupled with their toxicity in overdose, provoked a search for compounds which retained their monoamine uptake blocking activity but which lacked the side-effects arising from interactions with Hj, aj-adreno-ceptors and muscarinic receptors. One of the first compounds to emerge from this effort was iprindole, which has an indole nucleus (Fig. 20.3). This turned out to be an interesting compound because it has no apparent effects on monoamine uptake and is not a MAO inhibitor. This, together with its relatively minor antimuscarinic effects, led to it commonly being described as an atypical antidepressant. Mechanisms that could underlie its therapeutic actions have still not been identified but, in any case, this drug has now been withdrawn in the UK. 

Gold is used therapeutically in chronic inflammations as rheumatic arthritis (Ishida and Orimo 1994). The dose is given in the form ofa gold complex, such as gold sodium thiomalate and Auranofin toxic effects due to overdoses may appear. The most common method to monitor the therapeutic dose in serum or urine is GF-AAS. 

May be observed with therapeutic doses or overdoses. 

Many antipsychotics show great interindividual variation in plasma levels and so analysis of therapeutic levels can be important clinically as well as in the research laboratory. In addition, nonresponse to the drugs may actually be due to excessive levels of neuroleptics, a paradoxical situation that requires analysis to identify (Rockland, 1986). Several methods using FID were cited in the previous edition of the Handbook of Neurochemistry but ECD and NPD have both shown utility for the typically low therapeutic levels (Cooper, 1988). GC-FID has been used to analyze levels of clozapine in blood, gastric, and urine samples in fatal cases of overdose with this drug (Ferslew et al., 1998), and olanzapine has been measured in blood and urine samples by GC-NPD in overdoses (Stephens et al., 1998). 4-(4-Chlorophenyl)-4-hydroxypiperidine, a metabolite of haloperidol, was analyzed in urine, plasma, brain, and liver from haloperidol-treated rats by GC-ECD, after derivatization with PFBC under aqueous conditions (Fang et al., 1996). 

Physicians have, of course, used atropine for many centuries as treatment for a variety of conditions. Therapeutic doses generally range from 0.5 to 2.0 mg. At doses above 10 mg, atropine causes profound mental changes. Following massive overdose (above 100 mg), the outcome can be lethal. 

These statistics tends to belie the notion that children and the elderly, although somewhat more vulnerable, are extremely more likely to succumb to overdose. None of these data clearly establish the LD50 however, which is required to estimate the therapeutic ratio (LD50/ID50) for atropine. This ratio is an important key to making reasonable estimates of lethality for the other belladonnoids, since there are no BZ deaths (for example) from known dosage on which to base such estimates. 

The side effects of barbiturates include sedation, poor physical coordination, and impaired mental performance. They also potentiate the intoxicating effects of alcohol. Barbiturates can be extremely dangerous in overdose, causing anesthesia, coma, and even death. In addition, barbiturates can cause dangerous suppression of breathing in patients with sleep apnea or other respiratory disorders. With repeated use over just a few weeks, physical dependence and tolerance to their effects can develop, leading to increasing doses to maintain the desired therapeutic effect. If a... 

HT) into the nerve terminal, the desmethylated metabolites show selectivity as noradrenaline uptake inhibitors. Thus no TCA can be considered to be selective in inhibiting the uptake of either of these biogenic amines. In the case of TCA overdose, the normal oxidative pathways in the liver are probably saturated, which leads to a disproportionately high concentration of the desmethylated metabolite. The practical consequence of this finding is that toxic plasma concentrations of a TCA are very likely to occur if the dose of the drug is increased in those patients who fail to respond to normal therapeutic doses of the drug. Such a transition to toxic doses could occur suddenly. 

Analeptics are drugs that have a stimulatory effect on the respiratory and vasomotor centers of the medulla. Analeptics are primarily used as antagonists in depressant drug overdose (hypnotics, narcotics). Having a relatively small range of therapeutic action, they can stimulate other parts of the CNS even in minor overdoses, causing a number of undesirable side effects such as stimulation of the cardiovascular system, hyperreflexia, vomiting, and seizures. 

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