Chlorpromazine

H1 antagonism produces heavy sedation, particularly at initial doses and in elderly patients. Can be incapacitating. Tolerance often develops partially over time but sedation remains a limiting factor for many patients. This is the same H1-mediated sedation seen with quetiapine, mirtazapine, and hydroxyzine on the hub, but typically more intense.

Alpha-1 blockade produces vasodilation, causing syncope, falls, and cardiovascular compromise. Worst with IM administration and in volume-depleted or elderly patients. Reflex tachycardia often accompanies the blood pressure drop. Have patients lie down for 30 minutes after IM injection. This is the same alpha-1 mechanism that produces orthostasis with trazodone and quetiapine, but more pronounced with chlorpromazine.

Dry mouth, constipation, urinary retention, blurred vision, cognitive impairment, tachycardia. Adds to cumulative anticholinergic burden in polypharmacy patients. Connects to the anticholinergic teaching on the hydroxyzine and paroxetine pages. However, the muscarinic antagonism also partially protects against EPS (the same principle that makes benztropine an EPS treatment).

Chlorpromazine still causes extrapyramidal symptoms, particularly tardive dyskinesia with chronic use. The reduced acute EPS (compared to haloperidol) is due to intrinsic anticholinergic activity and some 5-HT2A antagonism. Students should not assume low-potency means EPS-free.

Patients sunburn easily. Counsel about sun protection. Chronic high-dose use can produce blue-gray skin discoloration in sun-exposed areas. This is specific to phenothiazines and does not occur with butyrophenones (haloperidol) or SGAs.

Corneal and lens pigmentary deposits with chronic high-dose use (classically several hundred mg/day for years). Usually not visually significant unless retinal involvement occurs (retinal toxicity more associated with thioridazine). Recommend ophthalmologic monitoring for patients on chronic chlorpromazine.

H1-mediated appetite effects. Generally less extreme than olanzapine but can be substantial, especially at higher chronic doses. Less studied than SGA metabolic effects due to the era in which chlorpromazine was primarily used.

D2 blockade in the tuberoinfundibular pathway. Less pronounced than haloperidol or risperidone but still clinically relevant with chronic use.

Monitor ECG, particularly at higher doses and with concurrent QTc-prolonging agents. Correct electrolytes (potassium, magnesium) before and during treatment.

Use caution in patients with seizure disorders. Chlorpromazine lowers the seizure threshold more than high-potency FGAs.

Recognition and management identical to haloperidol page. Fever + rigidity + altered mental status + autonomic instability = stop the drug. Mortality has decreased substantially with early recognition.