Benzodiazepines

Benzodiazepines

Benzodiazepines produce many therapeutic effects, including:

• sedation before anesthesia
• sleep inducement
• relief of anxiety and tension
• skeletal muscle relaxation
• anticonvulsant activity.

Keep your eye on the hypnotic ones

Benzodiazepines are used in various clinical situations and exert either a primary or a secondary sedative or hypnotic effect. Benzodiazepines used primarily for their sedative or hypnotic effects include:

• estazolam
• flurazepam
• lorazepam
• quazepam
• temazepam
• triazolam.

When some calm is needed

Benzodiazepines used primarily for the treatment of anxiety include:

• alprazolam
• chlordiazepoxide
• clonazepam
• clorazepate
• diazepam
• lorazepam
• oxazepam.

Pharmacokinetics (how drugs circulate)

Benzodiazepines are absorbed rapidly and completely from the GI tract and are distributed widely in the body. Penetration into the brain also occurs rapidly. Some benzodiazepines, such as diaze-pam and lorazepam, may also be given parenterally.

How fast?

The rate of absorption determines how quickly the drug will work; flurazepam and triazolam have the fastest onset.

How long?

The duration of effect is determined by the extent of distribution. Triazolam binds quickly to fat and is widely distributed; therefore, it has a short duration of action.

Metabolism and excretion

All benzodiazepines are metabolized in the liver and excreted primarily in urine. Some benzodiazepines have active metabolites, which may give these drugs a longer period of action.

Pharmacodynamics (how drugs act)

Researchers believe that benzodiazepines work by stimulating gamma-aminobutyric acid (GABA) receptors in the ascending reticular activating system (RAS) of the brain. The RAS is associated with wakefulness and attention and includes the cerebral cortex and limbic, thalamic, and hypothalamic levels of the central nervous system (CNS). 

Low will ease your mind

At low dosages, benzodiazepines decrease anxiety by acting on the limbic system and other areas of the brain that help regulate emotional activity. The drugs can usually calm or sedate the patient without causing drowsiness.

High will ease you into sleep

At higher dosages, benzodiazepines induce sleep, probably because they depress the RAS of the brain.

Zzzzzzzzzzzz…

Benzodiazepines increase total sleep time and reduce the number of awakenings. In most cases, benzodiazepines don’t decrease the time spent in rapid-eye-movement (REM) sleep, the state of sleep in which brain activity resembles the activity it shows when awake; the body’s muscles relax, and the eyes move rapidly. Because benzodiazepines don’t decrease the duration of REM sleep, they have a significant advantage over barbiturates.

 

During each sleep cycle the sleeping person progresses from stage 1, which is drowsiness, to stages 3 and 4, which are deep-sleep stages. Benzodiazepines reduce the amount of time spent in stages 3 and 4. The decrease in stage 4 sleep is accompanied by a reduction in nightmares.

Pharmacotherapeutics (how drugs are used)

Clinical indications for benzodiazepines include:

• relaxing the patient during the day of or before surgery
• treating insomnia
• producing I.V. anesthesia
• treating alcohol withdrawal symptoms
• treating anxiety and seizure disorders
• producing skeletal muscle relaxation.

Now I get it!

How benzodiazepines work

These illustrations show how benzodiazepines work at the cellular level.

Speed and passage

The speed of impulses from a presynaptic neuron across a synapse is influenced by the number of chloride ions in the postsynaptic neuron. The passage of chloride ions into the postsynaptic neuron depends on the inhibitory neurotransmitter called gamma-aminobutyric acid, or GABA.

It binds

When GABA is released from the presynaptic neuron, it travels across the synapse and binds to GABA receptors on the postsynaptic neuron. This binding opens the chloride channels, allowing chloride ions to flow into the postsynaptic neuron and causing the nerve impulses to slow down.

The result is another kind of depression

Benzodiazepines bind to receptors on or near the GABA receptor, enhancing the effect of GABA and allowing more chloride ions to flow into the post-synaptic neuron. This depresses the nerve impulses, causing them to slow down or stop.

Drug interactions

Except for other CNS depressants such as alcohol, few drugs interact with benzodiazepines.

Deep sleep

When benzodiazepines are taken with other CNS depressants (including alcohol and anticonvulsants), the result is enhanced sedative and CNS depressant effects, including reduced level of consciousness, reduced muscle coordination, respiratory depression, and death.

Possible problems with the pill

Hormonal contraceptives may reduce the metabolism of fluraze pam hydrochloride, increasing the risk of toxicity.

Triazolam may be affected by inhibitors of the CYP3A system (such as erythromycin and ketoconazole). 

Warning!

Adverse reactions to benzodiazepines

Benzodiazepines may cause:

• amnesia
• fatigue
• muscle weakness
• mouth dryness
• nausea and vomiting
• dizziness
• ataxia (impaired ability to coordinate movement).

Getting groggy

Unintentional daytime sedation, hangover effect (residual drowsiness and impaired reaction time on awakening), and rebound insomnia may also occur.

One more may be one too many

These drugs have a potential for abuse, tolerance, and physical dependence. Benzodiazepines with a long half-life or active metabolites may accumulate and cause adverse effects in elderly patients. In general, lower starting doses, with gradual dosage increases, should be used in elderly patients who are taking benzodiazepines.