Guanethidine Chlorpromazine

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.)... 

May increase the effects of antihypertensive drugs except for guanethidine, whose antihypertensive actions chlorpromazine may antagonize... 

Large doses of chlorpromazine may reduce or even abolish the antihypertensive effects of guanethidine, although in some patients the inherent hypotensive effects of the chlorpromazine may possibly predominate. Case reports surest that haloperidol and tiotixene may interact similarly. Molindone is reported not to interact with guanethidine, and a single-dose of prochlorperazine also did not interact with guanethidine. 

Chlorpromazine prevents the entry of guanethidine into the adrenergic neurones of the sympathetie nervous system resulting in a loss of its blood pressure-lowering effeets. The other interacting antipsychotics probably have similar effeets. This is essentially the same mechanism of interaction as that seen with the trieyelie antidepressants , (p.888). 

Farm WE, Janow DS, Davis JM, Oates JA Chlorpromazine reversal of the antihypertensive action of guanethidine. Lancet (1971) ii, 436-7. 

Janowsky DS, El-Yousef MK, Davis JM, Fann WE Antagcmi of guanethidine by chlorpromazine. Am J Psychiatry 9Ti) 130,808-12. 

N-Oxidation, e.g. 2>acetylaminofluorene, nicotinamide trimethylamine, guanethidine, chlorpromazine, in pramine. 

In the presence of NADPH and oxygen, hepatic microsomal enzymes convert the following substrates to the corresponding N-oxides chlorpromazine, chlor-qrclizine. imipramine. nicotinamide, guanethidine, and trimethylamine. Based on limited data, it was sug sted that the formation of N-oxides might be an intermediate step in all microsomal N-dealkylations. It is now clear that although N-oxides are formed by liver microsomes, they are not obligatory intermediates in all N-dealky-lation reactions. 

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