## Antipsychotics and Alpha-1 Adrenergic Blockade **Key Point:** Orthostatic hypotension is a direct consequence of α1-adrenergic receptor antagonism in blood vessels, causing vasodilation and reduced peripheral vascular resistance. ### Mechanism of Orthostatic Hypotension Alpha-1 adrenergic receptors on vascular smooth muscle maintain vascular tone. Blockade of these receptors leads to: 1. Peripheral vasodilation 2. Reduced systemic vascular resistance 3. Decreased venous return when supine → standing 4. Orthostatic drop in blood pressure ### Antipsychotic Potency for α1 Blockade | Antipsychotic | α1-Blockade Potency | Orthostatic Risk | Class | | --- | --- | --- | --- | | Chlorpromazine | **High** | **High** | First-generation (typical) | | Thioridazine | Very high | Very high | First-generation (typical) | | Haloperidol | Low | Low | First-generation (typical) | | Clozapine | High | High | Second-generation (atypical) | | Aripiprazole | Low | Low | Second-generation (atypical) | | Paliperidone | Low | Low | Second-generation (atypical) | **High-Yield:** Chlorpromazine is a **low-potency typical antipsychotic** with strong anticholinergic, antihistaminic, and α1-blocking properties — making it the classic cause of orthostatic hypotension among antipsychotics. **Clinical Pearl:** Orthostatic hypotension with chlorpromazine is most pronounced in the first few days of treatment and when rising from a supine position. Elderly patients and those on concurrent antihypertensives are at highest risk. **Tip:** Remember: **low-potency typicals** (chlorpromazine, thioridazine) cause more autonomic side effects; **high-potency typicals** (haloperidol, fluphenazine) cause more extrapyramidal side effects.
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