THERAPEUTICS

Brands

• Phenadoz, Promethagan, Phenergan, Zipan, Remsed

Generic?

• Yes

Class

• Antiemetic, antihistamine

Commonly Prescribed for

(FDA approved in bold)

• Allergic conditions

• Analgesia

• Antiemetic

• Motion sickness

• Induce sedation

• Dermatographism

• Migraine (acute)

• Vertigo

• Nausea and vomiting of pregnancy

How the Drug Works

• It is a phenothiazine derivative acting as a strong histamine (H1) antagonist and moderate muscarinic cholinergic antagonist. In addition, it binds to dopaminergic, serotonergic, α-adrenergic, and NMDA receptors. It acts on voltagegated ion channels, ATPase, and mitochondrial transition pores. The high lipophilicity allows promethazine to penetrate the BBB and interact with many neural receptors leading to sedation and other CNS effects

How Long Until It Works

• IV: within 5–10 minutes

If It Works

• Use at lowest effective dose

• Continue to assess effect of the medication and if it is still needed

If It Doesn't Work

• Increase dose, or discontinue and change to another agent

• Migraine: change to another antiemetic (prochlorperazine, droperidol, chlorpromazine) or combine with other agents

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Migraine: often combined with NSAIDs, triptans, or ergots

Tests

• ECG prior to drug initiation

ADVERSE EVENTS (AEs)

How the Drug Causes AEs

• Anticholinergic and other CNS effects

Notable AEs

• Sedation, blurred vision, dry mouth, confusion, oculogyric crisis, tardive dyskinesia, tinnitus, akathisia, ataxia, tremor, hallucination, nightmare, agitation, photosensitivity, cholestatic jaundice, and orthostatic hypotension

Life-Threatening or Dangerous AEs

• Respiratory depression

• Neuroleptic malignant syndrome

• Neutropenia, thrombocytopenia

• Delirium

• Seizure

• Narrow-angle glaucoma

Weight Gain

• Common

Sedation

• Problematic

What to Do About AEs

• Excessive sedation: lower dose or use only as a rescue agent when patient can lie down or sleep

• Movement disorders: lower dose or stop

Best Augmenting Agents to Reduce AEs

• Most AEs do not respond to adding other medications. The most important