Midazolam is a sleep-inducing agent characterized by a rapid onset and short duration of action. It also exerts an anxiolytic, anticonvulsant and muscle-relaxant effect.

Pharmacology

The actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the central nervous system. Benzodiazepines increase the activity of GABA, thereby producing a sedating effect, relaxing skeletal muscles, and inducing sleep, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening. These receptors have been identified in different body tissues including the heart and skeletal muscle, although mainly appear to be present in the central nervous system.

Midazolam is indicated in-

• Short-term treatment of insomnia.
• Sedation in premedication before surgical or diagnostic procedures.

Oral dosage:

• For adults: 7.5-15 mg daily.
• In elderly and debilitated patients: The recommended dose is 7.5 mg.
• In premedication: 15 mg of Midazolam should be given 30-60 minutes before the procedure.

Intravenous administration:

• Endoscopic or Cardiovascular Procedures: In healthy adults, the initial dose is approximately 2.5 mg. In cases of severe illness and in elderly patients, the initial dose must be reduced to 1 to 1.5 mg.
• Induction of Anesthesia: The dose is 10-15 mg.

Intramuscular administration:

• Adult: 0.07-0.1 mg/kg body weight. The usual dose is about 5 mg.
• Children: 0.15-0.20 mg/kg
• Elderly and debilitated patients: 0.025-0.05 mg/kg

Rectal administration in children:

• For preoperative sedation: Rectal administration of the ampoule solution (0.35-0.45 mg/kg) 20-30 min. before induction of general anesthesia.

Midazolam must not be given to patients with severe respiratory insufficiency, severe hepatic insufficiency, myasthenia gravis, sleep apnea syndrome and with known hypersensitivity to benzodiazepines or to any component of the product

At the start of therapy, drowsiness during daytime, confusion, fatigue, headache and muscle weakness may occur which usually disappear with repeated administration. Following parenteral (IV or IM) administration of Midazolam, fluctuations in vital signs have been noted including respiratory depression, apnea, variations in blood pressure and pulse rate.

Overdose Effects

Extreme overdosage may lead to coma, areflexia, cardiorespiratory depression and apnea. The effects of overdosage can be controlled with benzodiazepine antagonist flumazenil.

Midazolam IV should be administered very slowly.

Pregnancy & Lactation

Midazolam should be avoided during pregnancy unless there is no safer alternative. Since Midazolam passes into breast milk, it should not be administered to breast-feeding mothers.