Pharmacology
Benzodiapenes
The most common agent that we use are the benzodiazapines. They are sedative hypnotics, inhibitory agents that provide calming, drowsiness and sleep. The benzodiazapine receptors are closely related to the GABA receptor. GABA stands for gamma-aminobutyric acid, which is an inhibitory neurotransmitter. When it binds to a GABA receptor it causes rapid changes in chlorite/iron permeability, and it plays important roles in seizure protection, sleep and anxiety reduction. Benzodiazapines increase GABA binding by causing the same changes in chloride/iron permeability. Thus, they play similar roles as GABA, providing seizure protection, as well as sleep and anxiety reduction.
Diazepam (Valium)
Diazepam is the gold standard of the benzodiazapines. It is sedating, hypnotic, and provides anterograde amnesia, but not retrograde amnesia. There are very few cardiovascular effects, and, of course, it may be a respiratory depressant, so the patient's airway needs to be monitored. Diazepam or valium is water insoluble, which leads to a burning sensation upon injection; it should not be injected into the small veins of the mouth, as they are very highly protein bound. It also has a very long half-life due to the high activity of the metabolites are active.
Common effects of diazepam include the following:
- Skeletal muscle relaxation (it is an anticonvulsant, and is used as an emergency drug used in patients with prolonged seizures)
- Anterograde amnesia
Contraindications to diazepam are rare and few,
- allergy (very rare)
- acute angleglaucoma
- pregnancy (especially in the first trimester)
Side effects include:
- Hiccough
- Confusion
- Phlebitis of the small vessels, especially of the hand (because diazepam is insoluble in water, and is actually dissolved in solution in propylene-glycol, which is similar to antifreeze)
- Apnea (especially in the elderly and the debilitated)
- Change in libido
- Agitation (occasionally in patients with liver disease)
- Nausea (rare)
Precautions:
- Use a decreased dose in elderly patients.
- Use a decreased dose in patients with renal disease.
- Potential effects when used with narcotics and barbiturates.
Dosage: 2 to 20 mg IV by titration. You should titrate this drug to affect. Oral dosages come in 2 mg, 5 mg, and 10 mg tablets. (Though it can also be administered via intramuscular injection, remember that it does burn.)
Midazolam
Midazolam is a fairly new benzodiazapam that has been available on the market for approximately 15 years. It has become the new standard due to several advantages it has over diazepam. First of all, it is water soluble, and therefore doesn't burn on injection. In addition, it doesn't predispose the patient to phlebitis, and the metabolites are inactive, therefore making the half-life is relatively short (about two hours). Like diazepam it is also highly protein bound.
Midazolam is three times as potent as diazepam, so it is important to titrate carefully. 5 mg of diazepam is equivalent to approximately 15 mg of midazolam, so one must use additional caution when administering this drug. It is also important to remember that, like diazepam, midazolam will also cause respiratory depression.
Dosage: approx. one to 7 mg titrated slowly.