NMDA receptor antagonism
- Inhibits excitatory signaling within CNS
- Also inhibits noradrenaline reuptake in sympathetic nerve terminals

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

CNS: Causes dissociative anaesthesia
- Hallucinations
- Emergence delirium

CVS: Indirect sympathomimetic
chronotropy, inotrophy and Hypertension
Direct cardiodepressant
 if depletion of NA  hypotension
Resp - Bronchodilation

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

A: 20% oral bioavailability

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

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

25%

Approximately 96% protein-bound in plasma.

highly protein bound (95%)

95%

3l/kg

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

small-mod Vd = 1-2 L/kg
high lipid sol crosses BBB

1-2 L/kg

Hepatic metabolism with active
norketamine metabolite

hepatic via CYP3A4, and glucuronidation
active metabolite

Renal elimination

excreted in urine (as glucuronide conjugated metabolites)

T1/2a 15 mins, T1/2b
2~3 hours, CSHT 40mins at 5 hours

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

Increased salivation - Upper airway reflexes intact  laryngospasm - Hypotension if given in shock states - Emergence delirium

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

Respiratory depression and excessive sedation with overdosage
Same CYP as alfentanil (increases e¬ffect)

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

Sedative/hypnotic with non-opioid analgesic properties.

Non-Opiate Analgesic

Sedative / Hypnotic

Anticonvulsant Sedative-Hypnotic

Anticonvulsant
Sedative-Hypnotic

Sedative / Hypnotic

Induction of anaesthesia
- Procedural sedation
- Analgesia
- ?Role in management of depression. - Recreational

Sedative, amnesic+ anxiolytic,
antiepileptic

Phencyclidine (remember the street drug name PCP) derivative that
produces dissociative anesthesia

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

Level 1

Level 1

10, 50 or 100mg/ml

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

- 1mg/kg induction dose
- 10~20mg analgesia

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