UNDER REVIEW (September 2016)
Mechanism of Action:
Diazepam is a benzodiazepine that binds to specific benzodiazepine-receptors, which are part of the GABAa-receptor complex. On binding it causes an increase in the inhibitory effects on GABA. The effect of diazepam does not last long, partly because it is fairly quickly redistributed into tissues and fat deposits, and partly because of the adaptation of benzodiazepine receptors
Lecture and CAL materials:
Drug specifics
| Alternative drug name | Valium® |
| Effects | Diazepam is used to relieve anxiety and occasionally as a hypnotic (the related drug temazepam is more commonly used). Because of the problems with dependence the CSM advises that: (a) benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness. (b) The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate and unsuitable. (c) Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress. Diazepam is used primarily for anxiety, alcohol withdrawal, muscle relaxation and as an anti-epileptic. OTHER DRUGS USED FOR ANXIETY. Lorazepam is a shorter-acting benzodiazepine. Buspirone is thought to act at specific serotonin (5HT1A) receptors and is sometimes used to alleviate withdrawal from benzodiazepines. Beta-blockers (e.g. propranolol) do not affect psychological symptoms, such as worry, tension, and fear, but they do reduce autonomic symptoms, such as palpitations and tremor; they do not reduce non-autonomic symptoms, such as muscle tension. |
| Adverse actions | Typical benzodiazepine side effects are drowsiness and lightheadedness the next day; confusion and ataxia (especially in the elderly); amnesia; dependence; paradoxical increase in aggression; muscle weakness; occasionally: headache, vertigo, hypotension, salivation changes, gastro-intestinal disturbances, visual disturbances, dysarthria, tremor, changes in libido, incontinence, urinary retention; blood disorders and jaundice reported; skin reactions; on intravenous injection, pain, thrombophlebitis, and rarely apnoea. |
| Dose | For anxiety 2mg tds by mouth. Can also be given IM, IV and by rectum. |
| Interactions | Interacts with other CNS depressants including alcohol. See BNF. |
| Contraindications | not specified |
| Comments | Most anxiolytics (‘sedatives’) will induce sleep when given at night and most hypnotics will sedate when given during the day. Prescribing of these drugs is widespread but dependence (both physical and psychological) and tolerance occurs. This may lead to difficulty in withdrawing the drug after the patient has been taking it regularly for more than a few weeks. Hypnotics and anxiolytics should therefore be reserved for short courses to alleviate acute conditions after causal factors have been established. Benzodiazepines are the most commonly used anxiolytics and hypnotics; they act at benzodiazepine receptors which are associated with gamma-aminobutyric acid (GABA) receptors. Older drugs such as meprobamate and barbiturates are not recommended—they have more side-effects and interactions than benzodiazepines and are much more dangerous in overdosage. A paradoxical increase in hostility and aggression may be reported by patients taking benzodiazepines. The effects range from talkativeness and excitement, to aggressive and antisocial acts. Adjustment of the dose (up or down) usually attenuates the impulses. Increased anxiety and perceptual disorders are other paradoxical effects. Increased hostility and aggression after barbiturates and alcohol usually indicates intoxication. Hypnotics and anxiolytics may impair judgement and increase reaction time, and so affect ability to drive or operate machinery; they increase the effects of alcohol. Moreover the hangover effects of a night dose may impair driving on the following day. Withdrawal of a benzodiazepine should be gradual because abrupt withdrawal may produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal of a barbiturate is even more likely to have serious effects. The benzodiazepine withdrawal syndrome may develop at any time up to 3 weeks after stopping a long-acting benzodiazepine, but may occur within a few hours in the case of a short-acting one. It is characterised by insomnia, anxiety, loss of appetite and of body-weight, tremor, perspiration, tinnitus, and perceptual disturbances. These symptoms may be similar to the original complaint and encourage further prescribing; some symptoms may continue for weeks or months after stopping benzodiazepines. A benzodiazepine can be withdrawn in steps of about one-eighth (range one-tenth to one-quarter) of the daily dose every fortnight. OTHER BENZODIAZEPINES. Lorazepam is shorter acting and used for anxiety or agitation. Temazepam is used as a hypnotic (10mg nocte). Nitrazepam is also a hypnotic but has a longer duration of action with greater likelihood of carryover effects. Chlordiazepoxide (proprietary name Librium)is a benzodiazepine used for treating anxiety and may also be used for treating alcoholism or other drug abuse. |
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