Indications

• Allergic Conditions
  • xxxx
• Anti-Emetic (see Nausea and Vomiting, [[Nausea and Vomiting]])
• Migraines (see Migraines, [[Migraines]])
• Motion Sickness
• Pruritus (see Pruritus, [[Pruritus]])
• Psychosis (see Psychosis, [[Psychosis]]): weak anti-psychotic effects
• Need for Sedation

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Pharmacology

Chemical Structure

• Phenothiazine Derivative

Pharmacologic Actions

• First Generation Antihistamine (H1-Histamine Receptor Antagonist) (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])
• Dopamine D2 Receptor Antagonist
• Moderate Muscarinic Receptor Antagonist (Anti-Cholinergic): likely accounts for anti-emetic effect
• 5-HT2A Receptor Antagonist
• 5-HT2C Receptor Antagonist
• Alpha-1 Adrenergic Receptor Antagonist

Metabolism

• Hepatic: CYP2D6 (hydroxylation) and CYP2B6 (N-demethylation)
  • Significant first-pass effect

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Administration

• IV (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN
  • Onset of Action: 5 min
  • Duration of Action: 4-6 hrs (up to 12 hrs)
• IM (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN
  • Onset of Action: 20 min
• PO (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN
• PR (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN

Dose Adjustment

• Hepatic: none
• Renal: none

Risk of Extravasation Injury

• Pain/Burning
• Thrombophlebitis
• Tissue Necrosis/Gangrene

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Adverse Effects

Cardiovascular Adverse Effects

• Orthostatic Hypotension (see Hypotension, [[Hypotension]])
• QT Prolongation without Definite Association with Torsade (see Torsade, [[Torsade]])

Dermatologic Adverse Effects

• Photosensitivity

Gastrointestinal Adverse Effects

• Constipation (see Constipation, [[Constipation]]): due to anti-cholinergic effects

Neurologic Adverse Effects

Extrapyramidal Symptoms (see Extrapyramidal Symptoms, [[Extrapyramidal Symptoms]])

• Akathisia (see Akathisia, [[Akathisia]]): motor restlessness
• Dystonia (see Dystonia, [[Dystonia]])): continuous spasms and muscle contractions
• Parkinsonism (see Parkinson’s Disease, [[Parkinsons Disease]]): rigidity, bradykinesia, tremor
• Tardive Dyskinesia (see Tardive Dyskinesia, [[Tardive Dyskinesia]]): irregular, jerky movements

Other Neurologic Adverse Effects

• Confusion/Delirium (see Delirium, [[Delirium]])
• Dizziness (see Dizziness, [[Dizziness]])
• Euphoria: rare (except with high intravenous doses or co-administration with opiates or central nervous system depressants)
• Exacerbation of Myasthenia Gravis (see Myasthenia Gravis, [[Myasthenia Gravis]]): due to anti-cholinergic effects
• Fatigue (see Fatigue, [[Fatigue]])
• Irritability
• Sedation (see Obtundation-Coma, [[Obtundation-Coma]]): common
• Seizures (see Seizures, [[Seizures]]): rare

Ophthalmologic Adverse Effects

• Blurred Vision (see Blurred Vision, [[Blurred Vision]]): due to anti-cholinergic effects

Otolaryngologic Adverse Effetcs

• Dry Mouth (Xerostomia): due to anti-cholinergic effects

Pulmonary Adverse Effects

• Respiratory Depression: may occur in children <2 y/o

Renal Adverse Effects

• Urinary Retention (see Urinary Retention, [[Urinary Retention]]): due to anti-cholinergic effects

Other Adverse Effects

• Neuroleptic Malignant Syndrome (see Neuroleptic Malignant Syndrome, [[Neuroleptic Malignant Syndrome]]): rare

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References

• Influence of promethazine on cardiac repolarisation: a double-blind, midazolam-controlled study. Anaesthesia. 2009 Jun;64(6):609-14. doi: 10.1111/j.1365-2044.2009.05890.x [MEDLINE]