Benzodiazepine Pharmacology

Unlike barbiturates, where we aren’t sure how they work, we know benzodiazepines stimulate the GABA receptors.  GABA stands for Gamma-amino butyric acid.  GABA receptors are an inhibitory pathway.  So in this case, we’re going to stimulate a receptor in the brain to cause a slowing effect.  So if you stimulate inhibitory pathways in the brain, it’s going to cause sedation.

Advantages: What’s the advantage of the benzodiazepine over the barbiturate?

• They have a higher therapeutic index (aka therapeutic ratio) and therefore, safer.
  • Therapeutic Ratio = LD50 (Lethal dose) / ED50 (Effective Dose)
• No effect on hepatic metabolism
• No fatalities from overdose by itself, but when combined with another depressant, all bets are off.
• Minimal to no effect on REM sleep

Side effects: Drowsiness and sometimes, increased hostility.  A very unique and unusual side effect.  This tends to happen before a procedure.  When we give a patient a benzo in an operating room, instead of sedation, they may become fully alert, awake and hostile and you can’t control them.  It seems to be age-group specific as this tends to happen in the very young and old population.  In this case the procedure needs to be stopped and rescheduled.

Dependence: They can be dependent both physically and psychologically.

In any case, treatments are readily available should patients become dependent on the drug.

Withdrawal: Hyperexcitability. Tapering may take months to YEARS.

Therapeutic Use

• Sedative/Hypnotic
• Anticonvulsant
• Alcohol Withdrawal.  The most severe form of alcohol withdrawal involves deleterious tremors.  This is when a person stops drinking alcohol and as a result, in their brain they are having a seizure.  It’s basically an alcohol withdrawal seizure and a benzo is useful due to its anticonvulsant priorities.
• Premedication prior to procedure (as long as they don’t turn hostile).
• Muscle Relaxant

Benzodiazepine List

Tip: They generally end in -pam or -lam.  Two of them break that rule: Chlordiazepoxide and Chlorazepate which are both long-acting benzos.

Long Acting

• Chlordiazepoxide (Librium) – IV, p.o. – Chlordiazopoxide is usually used for alcohol treatment.
• Diazepam (Valium) – IV, p.o. – Diazepam is used as a sedative and as a muscle relaxant.  It is used prior to procedures to relax/sedate an individual but this would not be used for an ambulatory procedure cause it’s long acting and they won’t be able to get up and go home.  This could also be found in your crash carts for a very severe form of seizure known as Status epilepticus (SE) which are nonstop grand mal seizures.
• Clorazepate (Tranxene) – p.o. – Chlorazepate is usually found in drug treatment programs to help sedate an individual.

Short Acting:  These get out of your body within a matter of hours.

• Oxazepam (Serax) – p.o. – Used as a sedative.
• Lorazepam (Ativan) – inj., p.o. – Used as a hypnotic.  It could also be found in your crash carts for Status epilepticus more commonly than diazepam. (You may not find it in your crash cart, however, as it may be in the fridge of your unit cause you have to throw it out after 90 days if it’s not refrigerated).
• Midazolam (Versed) – inj. – Midazolam is usually utilized before a procedure.  This is commonly used for an ambulatory procedure.
• Alprazolam (Xanax) – p.o. – Alprazolam is one of the most commonly prescribed drugs used for anxiety/sedation.

Hypnotics: The drugs under this are approved by the FDA as a hypnotic.

• Flurazepam (Dalmane) – p.o. – Flurazepam makes the least sense as a hypnotic as this is a long acting drug that lasts for over 24 hours.  Although, a lot of nurses love to administer it to their patients for this reason.
• Temazepam (Restoril) – p.o. – Temazepam is a good sleep agent.
• Triazolam (Halcion) – p.o.  – Triazolam is a good sleep agent.

Reversal of Benzodiazepine Sedation

Flumazenil (Romazicon) – inj. – This blocks the GABA receptors.  We use it in the post-operative case in the recovery room because we want to wake them up afterwards.