Medication-Induced Dry Mouth

Abstract

A wide range of medications have been found to be associated with xerostomia, the subjective symptom of dry mouth. The assessment of medication-induced xerostomia (MIX) is usually made through a subject’s responses to relevant questions or the use of visual analogue scales whereby the subject is asked to rate the severity of their oral dryness. It is uncertain how much MIX is accompanied or can be ascribed to medication-induced salivary gland hypofunction and reduced secretion of saliva. MIX in older age groups is associated with the number of medications being taken and is higher than seen in the younger subjects. Many medications cause xerostomia as a side effect, but some of these, for example, selective serotonin reuptake inhibitors, do not appear to cause salivary gland hypofunction. However, there have been relatively few studies assessing objective changes in salivary flow in response to medications. The salivary reflex has peripheral and central components which can be the targets of medications, leading to interruption of the reflex and medication-induced salivary gland dysfunction (MISGD) characterized by reduced production of saliva. The principal peripheral target is the cholinergic muscarinic (M3) receptor of salivary gland acinar cells which is blocked by antimuscarinic drugs used in the treatment of, for example, irritable bladder and chronic obstructive pulmonary disease. Tricyclic antidepressants not only have targets in the central nervous system but interact with and block muscarinic receptors in the periphery. Sympathetic nerve- mediated stimuli enhance salivary secretion, and there is no peripheral inhibition. Although adrenergic antagonists cause MIX, there is no evidence that they reduce salivary secretion. However, antihypertensive β-adrenoceptor blockers such as propranolol reduce the protein concentration of saliva which may impact on ‘mouthfeel’. The main target for the central action of drugs causing MISGD is α2 adrenoceptors, and antihypertensive drugs that stimulate these receptors such as clonidine cause MIX and MISGD. Mixed serotonin and noradrenaline reuptake inhibitors (SNRIs) used in the treatment of depression, such as venlafaxine, cause significant MIX and MISGD. It may be that the mechanism of action involves activation of α2 adrenoceptors due to central accumulation of noradrenaline. Opioids such as tramadol that cause MIX and MISGD may have a similar mechanism of action. Gum chewing has been demonstrated to be effective for increasing salivary secretion in subjects with dry mouth and has been used to alleviate MIX. Parasympathomimetics might be appropriate for relieving xerostomia and salivary hypofunction resulting from non-anticholinergic xerogenic medications. Saliva substitutes with lubricative properties may also be appropriate.