Pharm 101: Midazolam

Class

Benzodiazepine

Pharmacodynamics

• Benzodiazepine drug:
  • Binds to GABA-A receptor in neuronal membranes in CNS (y subunit of the pentamer). This receptor is a chloride ion channel.
  • Enhances inhibitory effect of GABA through hyperpolarisation
  • This increases frequency of chloride channel opening

Pharmacokinetics

• Various routes of administration: PO, IV, IM, PR, IN, buccal
• Water soluble therefore intramuscular injection possible
• Poor oral bioavailability
• Crosses the blood brainer barrier easily at body pH
• Highly protein bound
• Hepatic metabolism and renal excretion (56%)
• Short elimination half-life of 1.5-2.5 hours

Clinical uses (and organ level effects)

• Sedative-hypnotic
• Anticonvulsant
• Anxiolytic
• Antiemetic
• Reduced sensitivity to CO2

Adverse effects

• Excess sedation
• Respiratory depression:
  • Can be profound even at therapeutic doses in patients with pulmonary disease
  • Effects are dose-related
  • Depression of medullary respiratory centre is usual cause of death in overdose
• Cardiovascular depression:
  • May occur at normal dose in hypovolaemic states and heart failure
  • Toxicity causes depression of both myocardial contractility and vascular tone leading to circulatory collapse

Precautions/contraindications

• As above, caution in patients with respiratory or cardiovascular disease due to depressant effects on these organ systems
• All benzodiazepines are liver metabolised and thus dose may need to be reduced in liver disease

Further Reading

• Guthrie K. Behavioural Emergency Management
• Nickson C. Status Epilepticus
• Long N. Flumazenil