INDEX overdose

Tricyclic antidepressants are cardiotoxic, inducing tachycardias and an increased tendency for ventricular arrhythmias with high doses. This dose dependent cardiotoxicity gives these agents a low therapeutic index. Overdoses are characterized by cardiac conduction disturbances, hyperpyrexia, hypertension, confusion, hallucinations, seizures and coma and there is a high mortality rate in suicide attempts. Depressed patients should therefore not be given more than one week supply of these drugs. 

Secondary amines are more noradrenergic Clomipramine is primarily serotonergic Narrow therapeutic index Overdoses can be fatal Anticholinergic (dry mouth, constipation, blurred vision)... 

Monoamine oxidase inhibitors have a low therapeutic index. Adverse effects include orthostatic hypotension, impotence and insomnia. Overdoses become manifest by symptoms of agitation, hyper-reflexia followed by convulsions. Rare but serious cases of hepatotoxicity have been associated with the use of isocarboxazid and of phenelzine. 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

Mirtazapine like the other new antidepressants has a wide therapeutic index and is generally safe in overdose ( 470). Twelve overdoses occurred during the clinical development program with mirtazapine. The largest amount ingested in such an acute overdose was 975 mg per day, which is more than 20 times the maximal... 

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. 

Overdoses of paracetamol can be very dangerous, as the drug has a narrow therapeutic index and may cause hepatic and renal necrosis. Nausea, vomiting, lethargy, and sweating are the early overdose symptoms. Paracetamol must be given with caution in alcoholics and patients with liver and kidney damage. 

Because digitoxin has a very low therapeutic index, toxicity occurs rather routinely and can be fatal patients must be monitored closely. Moderate overdoses can be picked up by GI or CNS complaints however, more serious toxicity on cardiac rhythm is more difficult to distinguish from the effects of heart disease. Digitalis antibody fragments are available for serious toxicity, i.e., when cardiac arrest is imminent. The fragments bind the drug and are excreted by the kidneys. 

It has a narrow therapeutic index and is associated with nephrotoxicity and cognitive impairment in overdose, There is less potential for interactions when it is administered topically,... 

Several drugs, including salicylate (in overdose), alcohol, and possibly some hydrazines and other drugs which are metabolised by acetylation, have saturable elimination kinetics, but the only significant clinical example is phenytoin. With this drug, capacity-limited elimination is complicated further by its low therapeutic index. A 50% increase in the dose of phenytoin can result in a 600% increase in the steady-state blood concentration, and thus expose the patient to potential toxicity. Capacity-limited pathways of elimination lead to plasma concentrations of drugs which can be described by a form of the Michaelis-Menten equation. In such cases, the plasma concentration at steady state is given by... 

Overdose. Benzodiazepines are remarkably safe in acute overdose and the therapeutic dose x 10 induces sleep from which the subject is easily aroused. It is said that there is no reliably recorded case of death from a benzodiazepine taken alone by a person in good physical (particularly respiratory) health, which is a remarkable tribute to their safety (high therapeutic index) even if the statement is not absolutely true, death must be extremely rare. But deaths have occurred in combination with alcohol (which combination is quite usual in those seeking to end their own lives) and from complications of prolonged unconsciousness. Flumazenil selectively reverses benzodiazepine effects and is useful in diagnosis and in treatment (see below). 

Barbiturates have a low therapeutic index, i.e. relatively small overdose may endanger life they also cause dependence and have been popular drugs of abuse. The use of intermediate-acting drugs... 

Glucagon has a positive cardiac inotropic effect by stimulating adenylyl cyclase it appears to have value in acute overdose of p-adrenoceptor blockers (see Index). 

Theophylline has a narrow therapeutic index, with 12-25% of overdose patients developing serious or life-threatening symptoms. Age >60 years and chronic use are risk factors for increased morbidity and mortality. 

Toxic dose. The noncyclio antidepressants generally have a wide therapeutic index, with doses in excess of 10 times the usual therapeutic dose tolerated without serious toxicity. Bupropion can cause seizures in some patients with moderate overdose or even in therapeutic doses. 

Poison hemlock has been used as a sedative and for its antispasmodic properties. It was also used by Greek and Persian physicians for a variety of problems, such as arthritis. It was not always effective, however, as the difference between a therapeutic and a toxic amount (the therapeutic index) is very slight. Overdoses can produce paralysis and loss of speech, followed by depression of the respiratory function, and then death. 

Overdose Easy, since narrow therapeutic index Synptoms sweating, dizziness, blurred vision, hot/cold flushes, memory lapses, agitation, IHR, IBP, coma Respiratory depression and death (especially combined with alcohol/benzodiazepines)... 

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