Respiratory depression cocaine

Other nonreceptor site of action interactions include MAOIs - pethidine (acute dystonias), ethanol - benzodiazepines (synergisitic sedation and respiratory depression), cocaine - amphetamines (hypertensive crisis) and dihydrocodeine -morphine (the former is a partial agonist and reduces the efficacy of the full agonist). 

The treatment goals for acute intoxication of ethanol, cocaine/amphetamines, and opioids include (1) management of psychological manifestations of intoxication, such as aggression, hostility, or psychosis, and (2) management of medical manifestations of intoxication such as respiratory depression, hyperthermia, hypertension, cardiac arrhythmias, or stroke. 

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. 

Action on CNS Local anaesthetics stimulate CNS and produce restlessness, tremor, mental confusion, convulsion. In toxic doses, it causes respiratory depression, coma and death. Cocaine is a powerful stimulant while procaine and other agents produce less CNS stimulant effect. 

Addicts use cocaine intravenously or by snorting the powder. After intravenous injections, coma and respiratory depression can occur rapidly. It has been reported that fatalities associated with snorting usually occur shortly after the abrupt onset of major motor seizures, which may develop within minutes to an hour after several nasal ingestions. Similar results occur if the substance is taken by mouth Treatment is directed toward ventilatory support and control of seizures—although in many instances a victim may not be discovered in time to prevent death. It is interesting to note that cocaine smugglers, who have placed cocaine-filled condoms in their rectum or alimentary tract, have died (Suarez et al.. 1977). The structural formula of cocaine is given in Fig 1. 

At higher doses, cocaine can produce undesirable effects, including tremor, emotional lability, restlessness, irritability, paranoia, panic, and repetitive stereotyped behavior. At even higher doses, it can induce intense anxiety, paranoia, and hallucinations, along with hypertension, tachycardia, ventricular irritability, hyperthermia, and respiratory depression. In overdose, cocaine can cause acute heart failure, stroke, and seizures. Acute intoxication with cocaine produces these various clinical effects, depending on the dose these effects are mediated by inhibition of the dopamine transporter and in turn by the effects of excessive dopamine activity in dopamine synapses, as well as by norepinephrine and serotonin in their respective synapses. 

Overdoses of cocaine are often rapidly fatal, victims dying within minutes from arrhythmias, seizures, or respiratory depression. Those who survive for 3 hours usually recover fully. Intravenous administration of diazepam, propranolol, or calcium channel-blocking drugs may be the best... 

Some people have an exaggerated reaction to cocaine and overdose on small amounts. Chronic users become more sensitive to the toxic effects of the drug, and may experi ence serious problems after taking their accustomed dose. Seizures, elevated blood pressure, respiratory depression, coma, and death can follow. 

In a retrospective study of the case notes of patients who had been admitted to hospital with acute attacks of asthma, there was a high prevalence of heroin use—15 % had used only heroin and another 16% had used both heroin and cocaine (9). Heroin users had been intubated more often than non-drug users (17% versus 2.3%). Similarly, more heroin users were admitted to ICU than non-users (21% versus 12%). However, they did not spend more time receiving mechanical ventilation or being in hospital. These findings suggest that heroin induced some degree of bronchoconstriction and respiratory depression, which worsened the initial presentation of asthma. 

Besides its effects on the higher centers, cocaine depresses the respiratory center when it is applied in a mixture with gelatin on the floor of the fourth ventricle (137). Aducco (138) observed a respiratory depression when cocaine was mixed with vaseline and put in direct contact with the respiratory center. Mosso (139) stated that cocaine, administered to the animal in small doses, stimulates the respiration. 

Cocaine has been shown to inhibit the reuptake of norepinephrine in the sympathomimetic nerve terminal. Local anesthesia probably results from a membrane effect. Small doses cause an increase in respiratory rate whereas large amounts lead to death from respiratory depression or cardiac arrest. 

Cocaine. This lias a bitter taste, is mydriatic, produces local anaesthesia and is toxic. After absorption, or when taken internally, it acts chiefly by stimulation of the central nervous system, succeeded by depression. Since the two phases may be present in different areas simultaneously, a mixed result may ensue. With large doses the chief symptoms are those of medullary depression. Death is due to paralysis of the respiratory centre. The main use of cocaine in medicine is as a local anaesthetic. 

Large or quickly repeating doses over a period of hours can led to extreme anxiety, paranoia and even hallucinations. These effects usually disappear as the drug is eliminated from the body. The after-effects of cocaine and crack use may include fatigue and depression as people come down from the high. Excessive doses can cause death from respiratory or heart failure but this is rare. 

Death from cocaine often occurs within 2-3 minutes, suggesting direct cardiac toxicity, fatal dysrhythmias, and depression of medullary respiratory centers as common causes of death (11,12). Thus, cocaine s local anesthetic properties can contribute additional hazards when high doses are used, reminiscent of deaths reported in the era when it was used as a mucous membrane paste for nasopharyngeal surgery (13). 

Cocaine has a spectrum of pharmacological effects. It initially causes excitement and euphoria later, with higher doses, lower centers become involved, producing reduced coordination, tremors, hyper-reflexia, increased respiratory rate, and at times nausea, vomiting, and convulsions. These symptoms are eventually followed by CNS depression. 

The other group of cocaine poisonings is characterized by delirium, increased reflexes, more or less violent convulsions, the pulse usually being rapid and fairly strong but later may become weak, and syncope and cyanosis may intervene. The delirium is frequently associated with hallucinations and at times the patient may develop a violent mania of even homicidal character, as in a case reported by Mattison. In fatal cases death is usually due to respiratory failure although the circulation is also depressed. 

Zachowski (104a) confirmed the reality of this respiratory stimulation in the cat, the mouse, and the rabbit. The cytisine is capable of ameliorating respiration depressed by morphine and acts reflexly via the carotid body. This author stated also that cocaine reinforces the circulatory effects of cytisine whereas ergotamine and yohimbine reduce them, thus proving the part played by the adrenergic stimulation. 

B. Toxicodynamics Toxicodynamics is a term used to denote the injurious effects of toxins, ie, their pharmacodynamics. A knowledge of toxicodynamics can be useful in the diagnosis and management of poisoning. For example, hypertension and tachycardia are typically seen in overdoses with amphetamines, cocaine, and antimuscarinic drugs. Hypotension with bradycardia occurs with overdoses of calcium channel blockers, beta-blockers, and sedative-hypnotics. Hypotension with tachycardia occurs with tricyclic antidepressants, phenothiazines, and theophylline. Hyperthermia is most frequently a result of overdose of drugs with antimuscarinic actions, the salicylates, or sympathomimetics. Hypothermia is more likely to occur with toxic doses of ethanol and other CNS depressants. Increased respiratory rate is often a feature of... 

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