Overdoses pharmacokinetics

To date, all antidepressants appear to be similarly effective for treating major depression, but individual patients may respond preferentially to one agent or another. In addition, these medications are significantly different from one another with regard to side effects, lethality in overdose, pharmacokinetics, and the abihty to treat co-morbid disorders. 

Hantson P, Vandenplas O, Mahieu P, Wallemacq P, Hassoun A. Repeated doses of activated charcoal and cholestyramine for digitoxin overdose pharmacokinetic data and urinary elimination. J Toxicol Clin Exp 1991 ll(7-8) 401-5. 

The determination of these compounds in biological fluids is crucial for several reasons such as investigating overdosing (toxicological monitoring), conducting pharmacokinetic and bioavailability studies, and measuring compliance. 

The excellent clinical efficacy of the TCAs has been well documented and the pharmacokinetic profiles are favourable. The most serious disadvantage of the TCAs lies in their cardiotoxicity. Thus, with the exception of lofepramine, all the tricyclic antidepressants, including maprotiline, block the fast sodium channels in the heart which can lead to heart block and death. Approximately 15% of all patients with major depression die by suicide and a high proportion of these (up to 25%) do so by taking an overdose of TCAs. Such a dose can be as low as 5-10 times the recommended daily dose. 

What the body does to the drugs which enter the system may be referred to as pharmacokinetics. During a drug overdose and subsequent intoxication, the various parameters for pharmacokinetics are altered, and these will include changes in elimination half-lives, protein binding, saturation kinetics and excretion. These deviations from the normal pharmacokinetics may be referred to as toxicokinetics. 

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

Pharmacokinetics Onset of action is about 10 min and duration of action is 7 hr or more. Absorption occurs from the nasal mucosa and can produce systemic effects, primarily following overdose or excessive use. Excreted mostly in the urine as well as the feces. Half-life 5-8 hr. 

The concept of clearance is useful in pharmacokinetics because clearance is usually constant over a wide range of concentrations, provided that ehmination processes are not saturated. Saturation of biotransformation and excretory processes may occur in overdose and toxic okinetic effects should be considered. If a constant fraction of drug is eliminated per unit time, the elimination follows first-order kinetics. However, if a constant amount of drug is eliminated per unit time, the elimination is described by zero-order kinetics. Some drugs, for example, ethanol, exhibit zero-order kinetics at normal or non-intoxicating concentrations. However, for any drug that exhibits first-order kinetics at therapeutic or nontoxic concentrations, once the mechanisms for elimination become saturated, the kinetics become zero order and clearance becomes variable.3... 

Arem R, Zoghbi W. Insulin overdose in eight patients insulin pharmacokinetics and review of the literature. Medicine (Baltimore) 1985 64(5) 323-32. 

Clonidine is one of the most widely used sedating medications in pediatric and child psychiatry practice, particularly in children with sleep onset delay and ADHD. It is a central alpha2 agonist. Pharmacokinetics show rapid absorption, with an onset action within 1 h, peak effects at 2-4 h and a half-life 6-24 h. Effects on sleep architecture are fairly minimal but may include decreased REM, so that discontinuation can lead to REM rebound. Clonidine has a narrow therapeutic index, and there has been a recent dramatic increase in reports of overdose with this medication. Potentially significant side effects including hypotension, bradycardia, anticholinergic effects, irritability, and dysphoria rebound hypertension may occur on abrupt discontinuation. Tolerance often develops, necessitating increases in dose. 

Overdose of drugs with a narrow therapeutic range and/or unfavorable pharmacokinetics (e.g., phenprocoumon or warfarin, which exert their action in a delayed and indirect manner by inhibition of vitamin K biosynthesis). 

This suggests that even modest overdoses of citalopram can cause QTC prolongation and that cardiac monitoring should be considered. Based on the pharmacokinetic profile of citalopram and the temporal pattern of QTC change, the authors suggested that the effect of citalopram on the QTC interval was mediated by one of its metabolites, dimethylcitalopram. 

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