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Benzodiazepines


The first benzodiazepine, Chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available by 1960 by Hoffmann-La Roche. Following Chlordiazepoxide, Diazepam was synthesized in 1959 and marketed by Hoffmann La Roche under the brand name Valium in 1963. Oxazepam was synthesized in 1961, Nitrazepam in 1962, and Temazepam and Nimetazepam in 1964. In 1965, Flurazepam and Nordazepam were introduced into the market. The introduction of benzodiazepines led to a decrease in barbiturate use, and by the 1970s they had largely replaced them.

Classifications


Internationally, benzodiazepines are classified as Schedule IV controlled drugs by the International Narcotics Control Board; Flunitrazepam, Nimetazepam, and Temazepam are Schedule III drugs under the Convention On Psychotropic Substances. In the United Kingdom, Midazolam and Temazepam are Schedule III controlled drugs. Benzodiazepines are categorized as either short-, intermediate- or long-acting. Short- and intermediate-acting benzodiazepines are used for the treatment of insomnia, and longer-acting benzodiazepines are used for the treatment of anxiety.

Uses


Benzodiazepines have sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant, and amnesic actions, and are used in treating anxiety, insomnia, agitation; seizures, muscle spasms, alcohol withdrawal, and as a premedication for medical or dental procedures. Most are administered orally; however, they can also be given intravenously, intramuscularly, or rectally.
Due to their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are often used to treat the anxiety associated with panic disorder. Benzodiazepines are highly effective in the short-term management of generalized anxiety disorder (GAD); they can be useful for short-term treatment of insomnia; prolonged convulsive epilectic seizures can usually be dealt with effectively by administering fast-acting benzodiazepines, which are strong anticonvulsants. Chlordiazepoxide is the most widely used benzodiazepine for alcohol detoxification and the management of alcohol withdrawal syndrome, in particular, for the prevention and treatment of the dangerous complication of seizures and in subduing severe delirium.

Effects


Physical effects of benzodiazepines include drowsiness, dizziness, and decreased alertness and concentration. Decreased libido, sexual dysfunction, and depression are also a common side effect. Hypotension and suppressed breathing may be encountered with intravenous use. Less common side effects include nausea and changes in appetite, blurred vision, confusion; euphoria, depersonalization and nightmares. Cases of liver toxicity have been reported, but are very rare.

Paradoxical reactions, such as increased seizures in epileptics, aggression, violence; impulsivity, irritability, and suicidal behavior can occur. Paradoxical effects may also manifest after chronic use of benzodiazepines.

The short-term use of benzodiazepines adversely affects cognition, the formation and consolidation of new memories, and can potentially induce complete anterograde amnesia.

The long-term adverse effects of benzodiazepine use include a general deterioration in physical and mental health, which tend to increase with time. Feelings of turmoil, difficulty in thinking constructively, loss of sex-drive; agoraphobia and social phobia, increasing anxiety and depression, loss of interest in leisure pursuits and interests, and an inability to experience or express feelings can also occur. Additionally, an altered perception of self, environment and relationships can be side effects.

Similar Drugs


Drugs in the category of benzodiazepines include:

Drugs with similar effects to those of benzodiazepines include:


Addiction Information


Chronic use of benzodiazepines can lead to the development of tolerance and dependence because the drug has a high potential for abuse. Tolerance to anti-anxiety effects develops more slowly with little evidence of continued effectiveness beyond four to six months of continued use.

Benzodiazepine addiction causes anxiety, panic attacks, odd sensations, feelings of being "outside" the body; feelings of unreality, or confusion. Sometimes the withdrawal symptoms are similar to the original anxiety symptoms.

Physical symptoms include sweating, sleeplessness, headache; tremor, tinnitus, feeling sick; palpitations, muscle spasms, and being oversensitive to light, sound and touch. Sudden withdrawal after high doses can cause fits.

Withdrawal


The most frequent symptoms of withdrawal from benzodiazepines are insomnia, gastric problems, tremors; agitation, fearfulness, and muscle spasms.

The less frequent effects are irritability, sweating, depersonalization; derealization, hypersensitivity to stimuli, depression; suicidal behavior, psychosis, seizures and delirium tremens.

Severe symptoms usually occur as a result of abrupt or over-rapid withdrawal. Abrupt withdrawal can be dangerous, therefore gradual reduction of the drug is recommended. Approximately 10% of users experience a notable withdrawal syndrome, which can persist for many months or in some cases a year or longer.

Overdose


Benzodiazepines can be taken in excessive amounts, causing overdoses, and can cause dangerous deep unconsciousness. However, they are much less toxic than barbiturates, and death rarely results when a benzodiazepine is the only drug taken. In combination with other central nervous system depressants, such as alcohol and opiates, the potential for toxicity increases exponentially. Taken alone, benzodiazepines rarely cause severe complications in overdoses; statistics in England showed that benzodiazepines were responsible for 3.8% of all deaths by poisoning. The symptoms of a benzodiazepine overdose may include drowsiness, slurred speech, nystagmus; hypotension, ataxia, coma; respiratory depression and cardiorespiratory arrest.


 

 
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