Diphenhydramine toxicity/interactions

Diphenhydramine Competitive antagonism at Hi receptors Reduces or prevents histamine effects on smooth muscle, immune cells also blocks muscarinic and adrenoceptors highly sedative IgE immediate allergies, especially hay fever, urticaria some use as a sedative, antiemetic, and antimotion sickness drug Oral and parenteral t duration 4-6 h Toxicity Sedation when used in hay fever, muscarinic blockade symptoms, orthostatic hypotension Interactions Additive sedation with other sedatives, including alcohol some inhibition of CYP2D6, may prolong action of some 13 blockers... 

Elevations of TCA levels may occur when combined with CYP2D6 inhibitors or from constitutional factors. About 7% of the Caucasian population in the USA has a CYP2D6 polymorphism that is associated with slow metabolism of TCAs and other 2D6 substrates. Combination of a known CYP2D6 inhibitor and a TCA in a patient who is a slow metabolizer may result in additive effects. Such an interaction has been implicated, though rarely, in cases of TCA toxicity. There may also be additive TCA effects such as anticholinergic or antihistamine effects when combined with other agents that share these properties such as benztropine or diphenhydramine. Similarly, antihypertensive drugs may exacerbate the orthostatic hypotension induced by TCAs. 

D. Toxicity and Interactions Sedation is common, especially with diphenhydramine, doxylamine, and promethazine. It is much less common with second-generation agents, which do not enter the CNS readily. Antimuscarinic effects such as dry mouth and blurred vision occur with some first-generation drugs in some patients. Alpha-blocking actions may cause orthostatic hypotension. 

Propantheline reduced the rate, but not the extent, of paracetamol absorption. This would be expected to reduce the rate of onset of analgesia. Other antimuscarinic drugs that delay gastric emptying would be expected to interact similarly. In one case, the diphenhydramine component of a paracetamol product delayed paracetamol absorption after an overdose, and complicated the evaluation of the risk of toxicity. 

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