Sedative-hypnotics coma caused

Although the responses depicted in curves A, B, and C of Figure 2-15 approximate the shape of a simple Michaelis-Menten relation (transformed to a logarithmic plot), some clinical responses do not. Extremely steep dose-response curves (eg, curve D) may have important clinical consequences if the upper portion of the curve represents an undesirable extent of response (eg, coma caused by a sedative-hypnotic). Steep dose-response curves in patients can result from cooperative interactions of several different actions of a drug (eg, effects on brain, heart, and peripheral vessels, all contributing to lowering of blood pressure). 

An understanding of common mechanisms of death due to poisoning can help prepare the care-giver to treat patients effectively. Many toxins depress the central nervous system (CNS), resulting in obtundation or coma. Comatose patients frequently lose their airway protective reflexes and their respiratory drive. Thus, they may die as a result of airway obstruction by the flaccid tongue, aspiration of gastric contents into the tracheobronchial tree, or respiratory arrest. These are the most common causes of death due to overdoses of narcotics and sedative-hypnotic drugs (eg, barbiturates and alcohol). 

Patients with ethanol or sedative-hypnotic overdose may be euphoric and rowdy ("drunk") or in a state of stupor or coma ("dead drunk"). Comatose patients often have depressed respiratory drive. Depression of protective airway reflexes may result in aspiration of gastric contents. Hypothermia may be present because of environmental exposure and depressed shivering. Ethanol blood levels greater than 300 mg/dL usually cause deep coma, but regular users are often tolerant to the effects of ethanol and may be ambulatory despite even higher levels. Patients with GHB overdose are often deeply comatose for 3-4 hours and then awaken fully in a matter of minutes. 

At high doses, both the major and minor tranquilizers are severely toxic and may cause coma, respiratory arrest, convulsions, acute renal failure, speech impairment, or death. However, at therapeutic doses, the neuroleptics have been associated with more severe, longterm side effects than the sedative-hypnotics. 

The clinical effects of sedative-hypnotics include sedation and sleep. Sedative-hypnotic drugs depress the function of the CNS and in a dose-dependent fashion produce drowsiness (sedation). Several sedative-hypnotic drugs, especially the older ones, produce sedation, sleep, unconsciousness, surgical anesthesia, coma, and ultimately may cause fatal depression of respiration and cardiovascular regulation. 

Diphenoxylate is an opiate (schedule V) with antidiarrheal properties. It is usually dispensed with atropine and sold as Lomotil. The atropine is added to discourage the abuse of diphenoxylate by narcotic addicts who are tolerant to massive doses of narcotic but not to the CNS stimulant effects of atropine. Diphenoxylate shonld be used cautiously in patients with obstructive jaundice because of its potential for hepatic coma, and in patients with diarrhea cansed by pseudomembranous colitis because of its potential for toxic megacolon. In addition, it should be used cautiously in the treatment of diarrhea caused by poisoning or by infection by Shigella, Salmonella, and some strains of E. coli because expulsion of intestinal contents may be a protective mechanism. Diphenoxylate should be used with extreme caution in patients with impaired hepatic function, cirrhosis, advanced hepatorenal disease, or abnormal liver function test results, because the drug may precipitate hepatic coma. Because diphenoxylate is structurally related to meperidine, it may cause hypertension when combined with monoamine oxidase inhibitors. As a narcotic, it will augment the CNS depressant effects of alcohol, hypnotic-sedatives, and numerous other drugs, such as neuroleptics or antidepressants that cause sedation. 

Barbiturates are derivatives of barbituric acid. These substances were once used extensively in clinical practices as sedatives-hynotics. Because of their abuse and physical dependence, their therapeutic application has diminished considerably. The sedative effects of barbiturates are similar to those of alcohol. Higher dosage can cause hypnosis and anesthesia. An intake of barbiturates 10-15 times that of the hypnotic dose can be toxic. Coma and death can result from overdose. 

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