K2iv / 14B21: Haloperidol v Diazepam

14B21: Exam Report

Compare and contrast the pharmacology of haloperidol and diazepam.

50% of candidates passed this question.

These are both commonly used agents and a tabulated format worked well. Subheadings covering the “general” pharmacology approach ensured core areas were addressed. Vague terms such as “good” or “moderate” did not allow a detailed comparison between the agents. Repetition of facts between sections such as uses, pharmacodynamics, effects and adverse
effects did not gain further marks.

K2iv / 14B21: Compare and contrast the pharmacology of Haloperidol and Diazepam

Drug

Haloperidol

Diazepam

Use

Haloperidol

  1. Delirium & agitation in ICU
  2. Schizophrenia
  3. N&V

Diazepam

  1. Anxiety
  2. AWS
  3. Epilepsy
  4. Sedation
  5. Premed

Both used for agitation in ICU setting

Diazepam has a more robust profile especially for patients with Hx ETOH XS

Route

Haloperidol

PO/IV/IM

Diazepam

PO, IV, PR, IM (erratic absorption, muscle necrosis)

Similar routes of admin

MoA

Haloperidol

Central dopaminergic blockade

Post synaptic GABA antagonism

Diazepam

Binds BZD receptor – closely linked with GABA receptor

Facilitates GABA-ergic transmission

↑frequency of Cl– channel opening

Different MoAs

PD

Haloperidol

CNS

  • ↓motor activity
  • Anxiolysis
  • ↑seizure threshold
  • Indifference to external environment

 CVS – ↓BP (some α1 antagonism)

 GI – antiemesis (powerful) by ↑vomiting threshold @ CTZ

Diazepam

CNS – sedation, amnesia, anticonvulsant, anxiolysis

 CVS – transient ↓BP + CO, ↓myocardial O2 consumption, ↓sensitivity of BaroR

 Resp – Resp D 2° ↓VT, ↓response to ↑PaCO2, occasional apnoea

 MSK – ↓skeletal m. tone

Both cause similar neuro effects

BP effects of Haloperidol less marked

Significant respiratory SE of Diazepam

BZD well known for reducing sk m tone if this is desired also

Haloperidol well established as an antiemetic

PK

Haloperidol

A

OBA 60%

D

90% PPB

VD 9 – 20L/kg

M

Liver glucuronidation then reduction

(some) active metabolites

E

Metabolites via urine

15% faeces

t ½ B 10 – 45hrs

Diazepam

A

85% OBA

D

99% PPB

V­­D 1.5L/kg → large because deposits itself in fat

∴ prolonged DoA in elderly & women (↑fat content)

M

Liver OXIDATION

2 active metabolites

E

Desmethyldiazepam is oxidised & metabolites excreted in urine

Diaz has rapid oral absorption and onset w prolonged activity

Both metabolised in the liver

Diazepam has a prolonged DoA owed to its active metabolites

Adverse Effects

Haloperidol

  • Hypotension
  • Abnormal LFTs
  • GI & haematopoietic disturbances

EXTRAPYRAMIDAL → NMS

Diazepam

  • Tolerance
  • Dependence
  • Ataxia
  • Headache
  • GI upset
  • Rashes

IV = highly irritant to veins

Diazepam a drug of abuse

Risk of extrapyramidal se w haloperidol and requires monitoring of bloods