Phenothiazines interaction with other drugs

A study in one healthy subject found that attapulgite-pectin reduced the absorption of a single 50-mg dose of promazine by about 25%, possibly due to adsorption of the phenothiazine onto the attapulgite. The clinical importance of this interaction and whether other phenothiazines behave similarly does not appear to have been studied. If a problem does occur, separating administration as much as possible (2 hours or more) to avoid admixture in the gut has been shown to minimise the effects of this type of interaction with other drugs. 

Hypersensitivity to the drug or any other component of the product (cross-sensitivity between phenothiazines may occur) comatose or greatly depressed states caused by CNS depressants or from any other cause (phenothiazines, clozapine, loxapine, molindone, pimozide, haloperidol) coadministration with other drugs that prolong the QT interval and in patients with congenital long QT syndrome or history of cardiac arrhythmias (mesoridazine, thioridazine, pimozide, ziprasidone see Drug..Interactions). 

In contrast, acute alcohol use can inhibit metabolism of other drugs because of decreased enzyme activity or decreased liver blood flow. Phenothiazines, tricyclic antidepressants, and sedative-hypnotic drugs are the most important drugs that interact with alcohol by this pharmacokinetic mechanism. 

Most of the drugs form micelles at concentrations that they do not attain in vivo. It is therefore their surface activity, rather than their self-association tendency which is more important biologically. Surface-active drugs will tend to bind hydrophobically to proteins and other macromolecules and to associate with other amphipathic substances such as bile salts, phospholipids, and receptors. As with other surface-active agents, surface-active drugs may interact directly with biological membranes. The possible biological implications of surface activity is discussed by Attwood and Florence " in relation to the phenothiazine tranquillisers and local anesthetics. 

A patient taking chlorpromazine who was given nifedipine [dosage not stated] for 2 days before snidery, developed marked hypotension during surgery, which was eventually controlled with noradrenaline (norepinephrine). Other phenothiazines and calcium-channel blockers may interact similarly, see Antihypertensives + Other drugs that affect blood pressure , p.880. 

The concurrent use of MAOIs and phenothiazines is usually safe and effective. However, rarely, cases of possible neuroleptic malignant syndrome or hyperpyrexia have been reported with MAOIs and chlorpromazine, levomepromazine or trifluoperazine. Some of these cases were fatal Chiorpromazine has been successfully used for treatment of the serotonin syndrome occurring with MAOIs and other drugs. Moclobemide has been used with various phenothiazines without problem, but one case of fatal overdose is attributed to an interaction between moclobemide and perazine. 

The interactions of TDZ (6) with model membranes composed of different phospholipids were also studied by the same group [78]. Calorimetric studies demonstrated that TDZ (6) altered the thermotropic properties of negatively charged DMPC membranes to a larger extent than of zwitterionic phospholipids (PC and PE). The character of the drug-induced changes of the transition parameters of all studied lipids indicated that TDZ (6), similarly to other phenothiazine derivatives, was likely to be localized close to the po-lar/apolar interface of the bilayers. Experiments in which fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was employed revealed that TDZ (6) reduced the mobility of lipid molecules in a concentration-dependent manner and thus decreased membrane fluidity. The influence of TDZ (6) on isolated... 

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