Atropine overdose

Mackenzie AL, Pigott JFG (1971) Atropine overdose in three children. Br J Anaesth 43 1088-1090... 

Only six of 36 children who took overdoses of co-phenotrope had signs of atropine overdose (central nervous system excitement, hypertension, fever, flushed dry skin) (1). Opioid overdose (central nervous system and respiratory depression with miosis) predominated or occurred without any signs of atropine toxicity in 33 cases (92%). Diphenoxylate-induced hjrpoxia was the major problem and was associated with slow or fast respiration, hypotonia or rigidity, cardiac arrest, and in three cases cerebral edema and death. Respiratory depression recurred 13-24 hours after the ingestion in seven cases and was probably due to accumulation of difenoxine, an active metabolite of diphenoxylate. Recommended treatment is an intravenous bolus dose of naloxone, followed by a continuous intravenous infusion, prompt gastric lavage, repeated administration of activated charcoal, and close monitoring for 24 hours. 

Another condition that could be confused with botulism is nerve agent and/or atropine poisoning (28). Unlike botulinum toxin, which results in decreased secretions, nerve agent poisoning (see Chap. 3) causes patients to develop copious respiratory secretions and miotic pupils. As compared to the clear sensorium of botulism patients, atropine overdose causes nervous system excitation, including hallucinations and delirium, even though the mucous membranes are dry and patients have mydriasis (see Chap. 3). 

Physostigmine Tertiary amine (enters CNS) Rx—glaucoma antidote in atropine overdose... 

From 18 January to 28 February 1991, 39 Iraqi-modified SCUD missiles reached Israel.4 Although many were off target or malfunctioned, some of them landed in and around Tel Aviv. Approximately 1,000 people were treated as a result of missile attacks, but only 2 died. Anxiety was listed as the reason for admitting 544 patients and atropine overdose for hospitalization of 230 patients. Clearly, these conventionally armed SCUDs were not effective mass casualty weapons, yet they caused significant disruption to the population of Tel Aviv. Approximately 75% of the casualties resulted from inappropriate actions or reactions on the part of the victims. Had one of the warheads contained a chemical or biological agent that killed or intoxicated a few people, the terror effect would have been even greater. 

The answer is local anesthetic properties it can block the initiation or conduction of a nerve impulse. It is biotransformed by plasma esterases to inactive products. In addition, cocaine blocks the reuptake of norepinephrine. This action produces CNS stimulant effects including euphoria, excitement, and restlessness Peripherally, cocaine produces sympathomimetic effects including tachycardia and vasoconstriction. Death from acute overdose can be from respiratory depression or cardiac failure Cocaine is an ester of benzoic acid and is closely related to the structure of atropine. 

Muscarine, an alkaloid from certain species of mushrooms, is a muscarinic receptor agonist. The compound has toxicologic importance muscarine poisoning will produce all of the effects that are associated with an overdose of ACh (e.g., bronchocon strict ion, bradycardia, hypotension, excessive salivary and respiratory secretion, and sweating). Poisoning by muscarine is treated with atropine. 

Accidental overdose (usually Atropine sulfate is recommended antidote double-dosed), 60 mg/kg BW LABORATORY WHITE RAT, Rattus sp. Dermal Single application, mg/kg BW 23... 

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. 

Accidental overdoses were especially common. Of 576 cases of atropine intoxication, almost half were due to oral ingestion of plant material, particularly by children below the age of five. Opthalmological, liquid medicinal, parenteral and percutaneous overdoses made up the remainder. Significant differences in the source of the drug occurred among age groups, however. Individuals above the age of 61, for example, were inclined to encounter overdosage from eye drops or medicinal plasters. 

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. 

A number of drugs in addition to atropine and scopolamine have antimuscarinic properties. Tbese include tricyclic antidepressants, phenothiazines, and antihistamines. Physostigmine has been used in the treatment of acute toxicity produced by these compounds. However, physostigmine can produce cardiac arrhythmias and other serious toxic effects of its own, and therefore, it should be considered as an antidote only in life-threatening cases of anticholinergic drug overdose. 

Atropine is used as an antidote in poisoning by an overdose of a cholinesterase inhibitor (see Chapter 14). It also is used in cases of poisoning from species of mushroom that contain high concentrations of muscarine and related alkaloids (e.g., Clitocybe dealbata). 

C. Atropine will not directly paralyze the respiratory muscles. However, it can prevent the detection of early signs of an overdose of neostigmine, which can quickly progress to a depolarizing block of skeletal muscle and paralysis of the respiratory muscles. Dry mouth, ocular disturbances, and tachycardia are common side effects of atropine given alone, but these effects are less likely to occur with competition between atropine and the increase in the synaptic ACh produced by inhibition of AChE by neostigmine. 

Overdose may result in cholinergic crisis, characterized by severe nausea, increased salivation, diaphoresis, bradycardia, hypotension, flushed skin, abdominal pain, respiratory depression, seizures, and cardiorespiratory collapse, increasing muscle weakness may result in death if respiratory muscles are involved. The antidote is 1 -2 mg IV atropine sulfate with subsequent doses based on therapeutic response. 

Parenteral overdose produces a cholinergic crisis manifested as abdominal discomfort or cramps, nausea, vomiting, diarrhea, flushing, facial warmth, excessive salivation, diaphoresis, urinary urgency, and blurred vision. If overdose occurs, stop all anticholinergic drugs and immediately administer 0.6-1.2 mg atropine sulfate IM or IV. 

Overdose can cause cholinergic crisis, marked by increased salivation, lacrimation, bradycardia, respiratory depression, hypotension, and increased muscle weakness. Treatment usually consists of supportive measures and an anticholinergic such as atropine. 

Accidental overdose (usually Atropine sulfate Is recommended antidote 23... 

The overdose toxicity occurs when the high dose of drug is required for the specific treatment or the drug is taken accidentally or with the intention of suicide. The effects are predictable and dose related. For example delirium by the use of atropine and respiratory failure by morphine occur due to their overdoses. The well known antitubercular drug, streptomycin causes vestibular damage and deafness on prolonged use. 

Unfortunately, children, especially infants, are very sensitive to the hyperthermic effects of atropine. Although accidental administration of over 400 mg has been followed by recovery, deaths have followed doses as small as 2 mg. Therefore, atropine should be considered a highly dangerous drug when overdose occurs in infants or children. 

Constriction of the pupils is seen with virtually all opioid agonists. Miosis is a pharmacologic action to which little or no tolerance develops (Table 31-3) thus, it is valuable in the diagnosis of opioid overdose. Even in highly tolerant addicts, miosis is seen. This action, which can be blocked by opioid antagonists, is mediated by parasympathetic pathways, which, in turn, can be blocked by atropine. 

For many drugs, at least part of the toxic effect may be different from the therapeutic action. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures the body s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, 13 blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and any other drugs that may be given. 

Physostigmine Suggested for antimuscarinic anticholinergic agents not for tricyclic antidepressants Adult dose is 0.5-1 mg IV slowly. The effects are transient (30-60 minutes), and the lowest effective dose may be repeated when symptoms return. May cause bradycardia, increased bronchial secretions, seizures. Have atropine ready to reverse excess effects. Do not use for tricyclic antidepressant overdose. 

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