D2 receptor antagonism

Centrally acting D2 blockade and post-synaptic GABA antagonism

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

Diazepam has kappa-opioid agonist activity in vitro, which may explain the
mechanism of benzodiazepine-induced spinal analgesia

CVS: Minimal cardiovascular effects but has antagonistic effects at alpha adrenergic receptors that may cause hypotension in the presence of hypovolaemia

CNS: Induces neurolepsis, a state characterized by diminished motor activity, anxiolysis, and indifference to environment. Seizure threshold is raised

GIT: Powerful antiemetic

Metabolic/Other: Causes hyperprolactinaemia

CVS A transient decrease in the blood pressure and a slight decrease in
the cardiac output may occur, following the intravenous administration of
diazepam. The coronary blood flow is increased, secondary to coronary
arterial vasodilation; a decrease in myocardial oxygen consumption has also
been reported.
RS Large doses cause respiratory depression; hypoxic drive is depressed to
a greater degree than is hypercarbic drive.DIAzEPAM 101
CNS Diazepam is anxiolytic and decreases aggression, although paradoxical
excitement may occur. sedation, hypnosis, and anterograde amnesia occur
after the administration of diazepam. The drug has anticonvulsant and analgesic properties, and depresses spinal reflexes.

well absorbed orally with bioavailability of 60-80% orally

Diazepam is rapidly absorbed after oral administration; the bioavailability is 86–100%. Absorption after intramuscular administration is
slow and erratic.

92%

99%

18-30L/kg

0.8–1.4 l/kg

extensively hepatically metabolized

Hepatic to active metabolites.

Major metabolite is desmethyldiazepam (half life 100hrs). other metabolites are oxazepam
(which is further metabolized by glucuronidation) and temazepam.

mainly biliary, some urine

urine as oxidized and
glucuronide derivatives; <1% is excreted unchanged.

11ml/min/kg

elimination T1/2 is 10-38hours

elimination half-life is 20–40 hours.

1. Extrapyramidal Reactions
- Tardive dyskinesia occurs in 20% of patients taking the drug for >1 year. Women and elderly are more susceptible
- Acute dystonic reactions occur in 2% of patients in first 72 hour especially in young men. These include torticollis, oculogyric crisis and laryngospasm

2. Neuroleptic malignant syndrome
- Typically develops over 24-72 hours ad is characterized by hyperthermia, generalized hypertonicity, autonomic instability and fluctuating LOC
- Increased muscle tone may lead to chest wall rigidity and myonecrosis. Treatment includes dantrolene and bromocriptine

3. Cardiovascular
- May prolong QTc
- Hypotension in context of hypovolaemia but this is less pronounded in oral administration

4. Hyperprolactinaemia
- Galactorrhoea and gynaecomastia
- Hypothalamic effects may lead to increased weight gain

Depression of the CNs, including drowsiness,
ataxia, and headache, may complicate the use of diazepam. Rashes, gastrointestinal upsets, and urinary retention have also been reported. Tolerance
and dependence may occur with prolonged use of benzodiazepines; acute
withdrawal of benzodiazepines in these circumstances may produce insomnia, anxiety, confusion, psychosis, and perceptual disturbances. Intravenous
diazepam is highly irritant to veins; the oil-in-water preparation is less so.

First Generation Antipsychotics (D2-Antagonism)

Sedative / Hypnotic Benzodiazepine

Sedative / Hypnotic
Benzodiazepine

Sedative / Hypnotic

- Schizophrenia
- Nausea and vomiting
- Motor tics and hiccupping
- Acute confusional states and delirium in intensive care
- Premedication
- Palliative care

1. in the short-term treatment of anxiety
2. in the treatment of status epilepticus
3. for muscle spasm in tetanus and other spastic conditions
4. for alcohol withdrawal, and for
5. premedication and
6. sedation during endoscopy and procedures performed under local
anaesthesia.

Benzodiazepine

Level 3

Level 1

Oral tablets, syrup and clear colourless solution for injection

Solution: Clear, yellow solution and as a white oil-in-water emulsion for injection
containing 5 mg/ml.

Tab: 2/5/10 mg
Syrup: 0.4/1 mg/ml
Supp: 10 mg

The adult oral dose is 2–60 mg/day
in divided doses; the initial intravenous dose is 10–20 mg, increasing according to clinical effect.

- potentiates non-depolarizing muscle relaxants.
- adsorbed onto plastic
- not removed by dialysis.