Central nervous system delayed effects

Figure 13-3 Potential adverse effects of Hi antihistamines through central nervous system and effect on various receptors and through ion channels. (Igr = rapid component of the delayed rectifier potassium current.) (Adapted with permission from Simons PER.Advances in Hi-antihistamines. N Engl J Med 2004 351 2204.)...

B. Pharmacokinetics. Lithium is completely absorbed within 6-8 hours of ingestion. The initial volume of distribution (Vd) is about 0.5 L/kg, with slow entry into tissues and a final Vd of 0.7-0.9 L/kg. Entry into the brain is slow, which explains the delay between peak blood levels and central nervous system (ONS) effects after an acute overdose. Elimination is virtually entirely by the kidney, with a half-life of 14-30 hours. 

The substance is irritating to the eyes, the skin and the respiratory tract. The substance may cause effects on the central nervous system, resulting in impaired functions. Exposure may result in death. The effects may be delayed. Medical observation is indicated. 

The antidotal action of the barbiturates is probably limited to the effects of chlordan on the nervous system. They most likely have no beneficial antagonistic action against the delayed parenchymatous degenerative changes produced by chlordan (4). Therefore, they are primarily only of possible value in acute poisoning in which severe stimulation of the central nervous system may be the primary cause of death. 

The precise mechanism of dimethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute effects of dimethylhydrazine exposure may involve the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Back and Thomas (1963) noted that the deaths probably involve respiratory arrest and cardiovascular collapse. The central nervous system as a target is consistent with the delayed latency in response reported for dimethylhydrazine (Back and Thomas 1963). There is some evidence that 1,1-dimethylhydrazine may act as an inhibitor of glutamic acid decarboxylase, thereby adversely affecting the aminobutyric acid shunt, and could explain the latency of central-nervous-system effects (Back and Thomas 1963). Furthermore, vitamin B6 analogues that act as coenzymes in the aminobutyric acid shunt have been shown to be effective antagonists to 1,1-dimethylhydrazine toxicity (reviewed in Back and Thomas 1963). 

Cumulative toxic effects occurred in various animal species receiving repeated small doses of decaborane by oral, intraperitoneal, or cutaneous routes. The rate of recovery was markedly delayed in some animal species surviving repeated doses compared with those that had received a single, large dose. In dogs repeatedly given oral doses of 3mg/kg, the effects on the central nervous system were not pronounced but there was damage to the liver and kidneys. 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

Drug interactions Proleukin may affect central nervous system function. Therefore interactions could occur following concomitant administration of psychotropic drugs. Concurrent administration of drugs possessing nephrotoxic, myelotoxic, cardiotoxic, or hepatotoxic effects with Proleukin may increase toxicity in these organ systems. Reduced kidney and liver function secondary to Proleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. Beta-blockers and other antihypertensives may potentiate the hypotension seen with Proleukin. 

Changes in drug effects are often delayed in relation to changes in plasma concentration. This delay may reflect the time required for the drug to distribute from plasma to the site of action. This will be the case for almost all drugs. The delay due to distribution is a pharmacokinetic phenomenon that can account for delays of a few minutes. This distributional delay can account for the lag of effects after rapid intravenous injection of central nervous system (CNS)-active agents such as thiopental. 

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