Benzodiazepines are a class of psychoactive drugs commonly used for their sedative, anxiolytic, muscle relaxant, and anticonvulsant properties.
They act by enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, which results in increased neuronal inhibition in the central nervous system (CNS).
Pharmacologically, benzodiazepines bind to specific sites on the GABA-A receptor, increasing the receptor’s affinity for GABA.
This interaction increases the frequency of chloride channel opening, potentiating the inhibitory effect of GABA in the CNS.
Benzodiazepines do not directly activate the GABA-A receptor but require the presence of GABA to exert their effects.
Benzodiazepines are classified based on their duration of action into short-, intermediate-, and long-acting agents.
Clinical use, which includes the treatment of anxiety, insomnia, seizures, muscle spasms, and alcohol withdrawal.
They are also used as premedication for medical procedures due to their sedative and amnestic properties.
The pharmacokinetics of benzodiazepines involve absorption, protein binding, and metabolism.
Benzodiazepines are metabolized primarily through glucuronide conjugation and microsomal oxidation.
Some benzodiazepines are directly metabolized by glucuronide conjugation, leading to shorter elimination half-lives.
Others undergo demethylation or oxidation before conjugation, resulting in longer half-lives and potential accumulation.They have sedative effects that can impair cognition, balance and cause daytime sleepiness.
Benzodiazepines augment the action of GABA, the major inhibitory neurotransmitter in the brain; effects usually begin to appear within minutes or hours.
In most patients, tolerance rapidly develops to the sedative effects of benzodiazepines, but not to the anxiolytic effects.
Use comprises 20-25% of the inappropriate prescriptions in the elderly.
Has a reported prevalence in the elderly ranging from 5-32% in community dwelling older adults.
Despite the recognition of the risk associated with these agents, almost 50% of physicians continue to renew prescriptions of this kind, citing patient dependence and benefits.
Side effects include daytime drowsiness and a hung-over feeling, which can increase the risk of automobile accidents.
Can worsen underlying breathing problems and can lead to falls in the elderly.
The mechanism of tolerance to benzodiazepines includes uncoupling of receptor sites, alterations in gene expression, down-regulation of receptor sites, and desensitisation of receptor sites to the effect of GABA.
About one-third of individuals who take benzodiazepines for longer than four weeks become dependent and experience withdrawal syndrome on cessation.
If taken during pregnancy may be associated with birth defects
Hazardous when used in combination with alcohol.
Overdoses rarely fatal.
Over time, these drugs may be less effective.
Withdrawal symptoms include insomnia, anxiety, and death.
As many as 30% of nursing home residents receive these agents.
Associated with increased risk of falls and fractures in nursing homes, although the findings in this regard have been inconsistent (Granek E, Mustard CA, Ray WA, Thapa PB).
Abrupt discontinuation of such agents may increase confusion, blood pressure and rarely cause seizure activity (Bambauer KZ, Uhelenhuyh LE Cantopher T).
Reduction in use of such agents did not result in a reduction in fracture risk in nursing homes (Briesacher BA).
Should be avoided in patients over 65 years of age.
Should also be avoided for generalized anxiety disorder and insomnia in the elderly.
More than 10% of women and 6% of men aged 65-80 years have at least one prescription for benzodiazepines in a year period and approximately one third receive these drugs for greater than 120 days in a year.
Widespread use of benzodiazepines in the elderly for which they are generally contraindicated has public health consequences of increased risk of dependence, cognitive defects, falls, motor vehicle accidents, and overall mortality.