Core pharmacology

Chemical Pharmaceutics

- Imidazole ring in its structure - Accounts for water solubility And rapid metabolism
- 2-3x potent Diazepam

Presentation

Clear solution pH 3.5 (IV/IM), Tablet
pKa 6.5 – 89% un-ionized

Mechanism of action

increases the sensitivity GABAA receptors which open (via GABA) and allow Cl influx
causing hyperpolarisation
- Influx of Cl- into nerve cell
- Hyperpolarised, preventing conduction

Physiological effects

CNS: Sedative, reduces epileptiform activity,
increases confusion and disorientation, amnesic properties more prominent than
sedative eff¬ects
CVS: minor hypotension has been reported

Resp: respiratory depression - synergistic with opioids

Absorption

A : IV,PO,In,IM
poor oral bioavailability 45%

Metabolism

hepatic via CYP3A4, and glucuronidation
active metabolite

Excretion

excreted in urine (as glucuronide conjugated metabolites)

Half-life

half life 1-4 hrs
prolonged in cirrhosis, CRF, CCF, obesity, elderly

Route And Dose

2-2.5mg initially then 1mg boluses to eff¬ect

Introduction

- Benzodiazepine
- Imidazole ring in its structure - Accounts for water solubility And rapid metabolism
- 2-3x potent Diazepam

Indications Uses

Sedative, amnesic+ anxiolytic,
antiepileptic

Distribution

lipid soluble at physiological pH (pKa 6.5).
high lipid sol crosses BBB

Class Group

Anticonvulsant Sedative-Hypnotic

Volume of distribution

Volume of distribution approximately 0.8-1.5 L/kg, increasing to about 3.1 L/kg in critically ill patients.

Protein binding

Approximately 96% protein-bound in plasma.

Adverse Effects Toxicity

Respiratory depression and excessive sedation with overdosage
Same CYP as alfentanil (increases effect)