11 General introduction, aim and outline of the thesis Figure 1: Overview of salivary functions, modified from Vila et al. [13]. Aetiologies of salivary dysfunction Under various conditions the salivary gland function can be partially or totally impaired, resulting in a quantitative and/or qualitative change in the output of saliva (salivary gland dysfunction) [15]. This can be attributed to various aetiologies. The most common aetiology is the intake of multiple medications (polypharmacy), especially of (combinations of) antidepressants, anxiolytics, opiates, antihypertensives, diuretics and antihistamines [15]. Over 500 medications are known to cause or increase oral dryness as a side-effect [11]. These medications affect the salivary secretory mechanisms in various ways; some have anticholinergic or sympathomimetic actions that affect the neural control of salivary glands. Others have a cytotoxic effect on the salivary glands, or they have a diuretic effect that depletes body fluids, or damage the ion-transport pathways in the acinar cells [16, 17]. It has been suggested that the number of medications administered is more significant in the aetiology of oral dryness than specific types of medication [11]. Also, numerous diseases and medical conditions are associated with salivary gland dysfunction (Table 1) [16, 18]. These conditions can result in e.g. dysfunctions in neurotransmitter receptors, destruction of glandular parenchyma, immune dysregulations that may interfere with the secretion process or alterations in fluid composition and electrolytes [16]. One of the disorders with a very high association with salivary dysfunction is Sjögren’s syndrome, an autoimmune disease that affects the integrity of exocrine glands, mainly the salivary and lacrimal glands. Also, endocrine disorders (such as diabetes mellitus), neurologic disorders (such as depression), genetic disorders 1
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