Phenothiazines Guanethidine

Drugs that may be affected by phenothiazines include anticholinergics, beta-blockers, guanethidine, meperidine, oral anticoagulants, phenytoin, thiazide diuretics, and dofetilide. 

The tricyclic antidepressants (e.g., desipramine and amitriptyline) and some phenothiazines block the sympathetic neuronal amine uptake system they thereby would also block the uptake of guanethidine and thus reduce its hypotensive effectiveness. Conversely, guanethidine competitively inhibits the uptake of drugs that are substrates for neuronal uptake, such as the indirectly acting adrenomimetics, or sympathomimetics (see Chapter 10). 

Because neuronal uptake is necessary for the hypotensive activity of guanethidine, drugs that block the catecholamine uptake process or displace amines from the nerve terminal (see Chapter 6) block its effects. These include cocaine, amphetamine, tricyclic antidepressants, phenothiazines, and phenoxybenzamine. 

Phenothiazines may inhibit the hypotensive action of guanethidine (624). This antagonism does not occur with molindone (622). 

ADRENERGIC NEURONE BLOCKERS PHENOTHIAZINES Variable effect some cases of t hypotensive effect other cases where hypotensive effects 1 by higher doses (> 100 mg) of chlorpromazine Additive hypotensive effect. Phenothiazines cause vasodilatation however, chlorpromazine blocks uptake of guanethidine into adrenergic neurones Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

Indications Psychosis, manic-depressive disorders Category Antipsychotic, phenothiazine Muscarinic antagonist Half-life initial 2 hours terminal 30 hours Clinically important, potentially hazardous interactions with alcohol, antihistamines, arsenic, chlorpheniramine, dofetilide, epinephrine, evening primrose, guanethidine, mivacurium, quinolones, sparfloxacin... 

Tricyclic antidepressants and some phenothiazines block the uptake of guanethidine into adrenergic neurons and, thus, prevent the hypotensive activity of guanethidine. Orthostatic hypotension may be increased by concomitant administration of alcohol with guanethidine, and patients receiving guanethidine should be cautioned to limit alcohol... 

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