Sedative-hypnotic drugs toxicity

Buspirone Mechanism uncertain Partial agonist at 5-HT receptors but affinity for D2 receptors also possible Slow onset (1-2 weeks) of anxiolytic effects t minimal psychomotor impairment—no additive CNS depression with sedative-hypnotic drugs Generalized anxiety states Oral activity forms active metabolite short half-life Toxicity Tachycardia paresthesias t gastrointestinal distress Interactions CYP3A4 inducers and inhibitors... 

Toxicity The sedation produced by diazepam is significant but milder than that produced by other sedative-hypnotic drugs at doses that induce equivalent muscle relaxation. Baclofen produces less sedation than diazepam. Dantrolene causes significant muscle weakness but less sedation than either diazepam or baclofen. Tizanidine may cause drowsiness and hypotension. 

Older medications, such as the barbiturates, are used as sedative-hypnotics, but toxicity limits their widespread use. For example, they can cause significant central nervous system (CNS) depression, physical dependence, and tolerance. Additionally, they are potent inducers of liver enzymes, which can lead to clinically significant drug interactions when these medications are administered with other drugs extensively metabolized by the liver. 

Uni 1ke other drugs of abuse, the diagnosis of PCP intoxication is often difficult because of the wide spectrum of clinical findings that occurs with this drug. PCP toxicity sometimes can be mistaken for delirium tremens, acute psychiatric illness, sedative/ hypnotic overdosage, amphetamine intoxication, or sedative/ hypnotic withdrawal syndromes. 

Sedation is an intermediate degree of CNS depression, while hypnosis is a degree of CNS depression similar to natural sleep. From the chemical point of view, soporific, sedative, and hypnotic drugs are classified as barbiturates, benzodiazepine hypnotics, and so on. Except for a few rare exceptions, any one of these compounds can be used for acquiring a sedative effect or state of sleep. Presently, the less toxic benzodiazepines are edging out the class of barbiturates more and more because of the possibility of chronic dependence associated with the use of barbiturates. Drugs of both classes are primarily CNS depressants, and a few of their effects, if not all, are evidently linked to action on the GABA-receptor complex. 

Historically the first sedative hypnotics to be introduced were the bromides in the mid 19th century, shortly followed by chloral hydrate, paraldehyde and urethane. It was not until the early years of this century that the first barbiturate, sodium barbitone, was developed and this was shortly followed by over 50 analogues, all with essentially similar pharmacological properties. The major breakthrough in the development of selective, relatively non-toxic sedative hypnotics followed the introduction of chlordiazepoxide in 1961. Most of the benzodiazepines in current use have been selected for their high anxiolytic potency relative to their central depressant effects. Because of their considerable safety, the benzodiazepines have now largely replaced the barbiturates and the alcohols, such as chloral hydrate and trichloroethanol, as the drugs of choice in the treatment of insomnia. 

Sedative and hypnotic drugs, such as benzodiazepines and barbiturates, increase the half-life from 50% to 150% in patients between 30 and 70 years of age. The most alarming toxicity is ataxia, which must be considered to avoid accidents. Ataxia is an alarming effect hence the patient is advised not to drive if taking these drugs. Elderly patients are found to be more sensitive to opioids and should use them with caution. 

FIGURE 5—4 Frequency distribution curves and quantal concentration-effect and dose-effect curves. A. Frequency distribution curves. An experiment was performed on 100 subjects, and the effective plasma concentration that produced a quantal response was determined for each individual. The number of subjects who required each dose is plotted, giving a log-normal frequency distribution (colored bars). The gray bars demonstrate that the normal frequency distribution, when summated, yields the cumulative frequency distribution—a sigmoidal curve that is a quantal concentration-effect curve. B. Quantal dose-effect curves. Animals were injected with varying doses of sedative-hypnotic, and the responses were determined and plotted. The calculation of the therapeutic index, the ratio of the to the ED q, is an indication of how selective a drug is in producing its desired effects relative to its toxicity. (See text for additional explanation.)... 

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... 

Aspirin, sympathomimetics, agents with muscarinic blocking actions, and drugs that cause muscle rigidity or seizures are all likely to cause hyperthermia at toxic doses. Hypothermia is more typical of overdoses with opioids or sedative-hypnotics. The answer is (C). 

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