Skip to main content
SpringerLink
Log in

Medication-Induced Dry Mouth

  • Chapter
  • First Online:
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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sreebny LM, Vissink A. Dry mouth. The malevolent symptom: a clinical guide. Ames: Wiley-Blackwell; 2010.

    Google Scholar 

  2. Sreebny LM, Valdini A. Xerostomia. 1. Relationship to other oral symptoms and salivary-gland hypofunction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1988;66(4):451–8.

    Article  Google Scholar 

  3. Nederfors T. Xerostomia and hyposalivation. Adv Dent Res. 2000;14:48–56.

    Article  PubMed  Google Scholar 

  4. Longman LP, et al. Salivary gland hypofunction in elderly patients attending a xerostomia clinic. Gerodontology. 1995;12(12):67–72.

    Article  PubMed  Google Scholar 

  5. Field EA, et al. The establishment of a xerostomia clinic: a prospective study. Br J Oral Maxillofac Surg. 1997;35(2):96–103.

    Article  PubMed  Google Scholar 

  6. Kaplan I, Zuk-Paz L, Wolff A. Association between salivary flow rates, oral symptoms, and oral mucosal status. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106(2):235–41.

    Article  PubMed  Google Scholar 

  7. Sreebny LM, Schwartz SS. A reference guide to drugs and dry mouth–2nd edition. Gerodontology. 1997;14(1):33–47.

    Article  PubMed  Google Scholar 

  8. Osailan S, et al. A validated clinical oral dryness score. Oral Dis. 2010;16(6):538.

    Google Scholar 

  9. Nederfors T, et al. Prevalence of perceived symptoms of dry mouth in an adult Swedish population – relation to age, sex and pharmacotherapy. Community Dent Oral Epidemiol. 1997;25(3):211–6.

    Article  PubMed  Google Scholar 

  10. Ship JA, Baum BJ. Old age in health and disease. Lessons from the oral cavity. Oral Surg Oral Med Oral Pathol. 1993;76(1):40–4.

    Article  PubMed  Google Scholar 

  11. Narhi TO, et al. Association between salivary flow rate and the use of systemic medication among 76-, 81-, and 86-year-old inhabitants in Helsinki, Finland. J Dent Res. 1992;71(12):1875–80.

    Article  PubMed  Google Scholar 

  12. Smidt D, et al. Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people. Community Dent Oral Epidemiol. 2010;38(5):422–35.

    Article  PubMed  Google Scholar 

  13. Sreebny LM. Salivary flow in health and disease. Compend Suppl. 1989;13:S461–9.

    PubMed  Google Scholar 

  14. Wu AJ, Ship JA. A characterization of major salivary gland flow rates in the presence of medications and systemic diseases. Oral Surg Oral Med Oral Pathol. 1993;76(3):301–6.

    Article  PubMed  Google Scholar 

  15. Sreebny LM, Valdini A, Yu A. Xerostomia. Part II. Relationship to nonoral symptoms, drugs, and diseases. Oral Surg Oral Med Oral Pathol. 1989;68(4):419–27.

    Article  PubMed  Google Scholar 

  16. Thomson WM, et al. The occurrence of xerostomia and salivary gland hypofunction in a population-based sample of older South Australians. Spec Care Dentist. 1999;19(1):20–3.

    Article  PubMed  Google Scholar 

  17. Ikebe K, et al. Perception of dry mouth in a sample of community-dwelling older adults in Japan. Spec Care Dentist. 2001;21(2):52–9.

    Article  PubMed  Google Scholar 

  18. Gallagher JC, et al. The effect of dose titration and dose tapering on the tolerability of desvenlafaxine in women with vasomotor symptoms associated with menopause. J Womens Health (Larchmt). 2012;21(2):188–98.

    Article  Google Scholar 

  19. Deecher DC, et al. Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther. 2006;318(2):657–65.

    Article  PubMed  Google Scholar 

  20. Malone-Lee JG, Walsh JB, Maugourd MF. Tolterodine: a safe and effective treatment for older patients with overactive bladder. J Am Geriatr Soc. 2001;49(6):700–5.

    Article  PubMed  Google Scholar 

  21. Takei M, Homma Y. Long-term safety, tolerability and efficacy of extended- release tolterodine in the treatment of overactive bladder in Japanese patients. Int J Urol. 2005;12(5):456–64.

    Article  PubMed  Google Scholar 

  22. Scully C. Drug effects on salivary glands: dry mouth. Oral Dis. 2003;9(4):165–76.

    Article  PubMed  Google Scholar 

  23. Appell RA, et al. Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study. Mayo Clin Proc. 2001;76(4):358–63.

    Article  PubMed  Google Scholar 

  24. Diokno AC, et al. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc. 2003;78(6):687–95.

    Article  PubMed  Google Scholar 

  25. Elinoff V, et al. Symptom-specific efficacy of tolterodine extended release in patients with overactive bladder: the IMPACT trial. Int J Clin Pract. 2006;60(6):745–51.

    Article  PubMed  Google Scholar 

  26. Gupta SK, Sathyan G. Pharmacokinetics of an oral once-a-day controlled- release oxybutynin formulation compared with immediate-release oxybutynin. J Clin Pharmacol. 1999;39(3):289–96.

    PubMed  Google Scholar 

  27. Chung SD, et al. The efficacy of additive tolterodine extended release for 1-year in older men with storage symptoms and clinical benign prostatic hyperplasia. Neurourol Urodyn. 2011;30(4):568–71.

    Article  PubMed  Google Scholar 

  28. Kaplan SA, Walmsley K, Te AE. Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol. 2005;174(6):2273–5; discussion 2275–6.

    Article  PubMed  Google Scholar 

  29. Breidthardt J, Schumacher H, Mehlburger L. Long-term (5 year) experience with transdermal clonidine in the treatment of mild to moderate hypertension. Clin Auton Res. 1993;3(6):385–90.

    Article  PubMed  Google Scholar 

  30. Burris JF, Mroczek WJ. Transdermal administration of clonidine: a new approach to antihypertensive therapy. Pharmacotherapy. 1986;6(1):30–4.

    PubMed  Google Scholar 

  31. Ravindran AV, et al. A double-blind, multicenter study in primary care comparing paroxetine and clomipramine in patients with depression and associated anxiety. Paroxetine Study Group. J Clin Psychiatry. 1997;58(3):112–8.

    Article  PubMed  Google Scholar 

  32. Wolff M, Kleinberg I. Oral mucosal wetness in hypo- and normosalivators. Arch Oral Biol. 1998;43(6):455–62.

    Article  PubMed  Google Scholar 

  33. Osailan S, et al. Investigating the relationship between hyposalivation and mucosal wetness. Oral Dis. 2011;17(1):109–14.

    Article  PubMed  Google Scholar 

  34. Smidt D, Torpet LA, Nauntofte B, et al. Associations between oral and ocular dryness, labial and whole salivary flow rates, systemic diseases and medications in a sample of older people. Community Dent Oral Epidemiol. 2011;39(3):276–88.

    Article  PubMed  Google Scholar 

  35. Dawes C. Physiological factors affecting salivary flow rate, oral sugar clearance, and the sensation of dry mouth in man. J Dent Res. 1987;66(Spec):648–53.

    PubMed  Google Scholar 

  36. Napenas JJ, Brennan MT, Fox PC. Diagnosis and treatment of xerostomia (dry mouth). Odontology. 2009;97(2):76–83.

    Article  PubMed  Google Scholar 

  37. Navazesh M, Kumar SK. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008;139(Suppl):35S–40.

    Article  PubMed  Google Scholar 

  38. Dawes C. Circadian rhythms in human salivary flow rate and composition. J Physiol. 1972;220(3):529–45.

    PubMed  PubMed Central  Google Scholar 

  39. Dodds MW, Johnson DA, Yeh CK. Health benefits of saliva: a review. J Dent. 2005;33(3):223–33.

    Article  PubMed  Google Scholar 

  40. Heintze U, Birkhed D, Bjorn H. Secretion rate and buffer effect of resting and stimulated whole saliva as a function of age and sex. Swed Dent J. 1983;7(6):227–38.

    PubMed  Google Scholar 

  41. Percival RS, Challacombe SJ, Marsh PD. Flow rates of resting whole and stimulated parotid saliva in relation to age and gender. J Dent Res. 1994;73(8):1416–20.

    PubMed  Google Scholar 

  42. Pramanik R, et al. Protein and mucin retention on oral mucosal surfaces in dry mouth patients. Eur J Oral Sci. 2010;118(3):245–53.

    Article  PubMed  Google Scholar 

  43. Hector MP, Linden RW. Reflexes of salivary secretion. In: Garrett JR, Ekstrom J, Anderson LC, editors. Neural mechanisms of salivary secretion. Basel: Karger; 1999. p. 196–217.

    Chapter  Google Scholar 

  44. Speirs RL. Secretion of saliva by human lip mucous glands and parotid glands in response to gustatory stimuli and chewing. Arch Oral Biol. 1984;29(11):945–8.

    Article  PubMed  Google Scholar 

  45. Boros I, Keszler P, Zelles T. Study of saliva secretion and the salivary fluoride concentration of the human minor labial glands by a new method. Arch Oral Biol. 1999;44 Suppl 1:S59–62.

    Article  PubMed  Google Scholar 

  46. Veerman ECI, et al. Human glandular salivas: their separate collection and analysis. Eur J Oral Sci. 1996;104(4):346–52.

    Article  PubMed  Google Scholar 

  47. Proctor GB, Carpenter GH. Regulation of salivary gland function by autonomic nerves. Auton Neurosci. 2007;133(1):3–18.

    Article  PubMed  Google Scholar 

  48. Emmelin N. Nervous control of mammalian salivary-glands. Phil Trans Roy Soc London Ser B Biol Sci. 1981;296(1080):27–35.

    Article  Google Scholar 

  49. Matsuo R, et al. Reflex secretion of proteins into submandibular saliva in conscious rats, before and after preganglionic sympathectomy. J Physiol. 2000;527(Pt 1):175–84.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Culp DJ, et al. Rat sublingual gland as a model to study glandular mucous cell secretion. Am J Physiol. 1991;260(6 Pt 1):C1233–44.

    PubMed  Google Scholar 

  51. Nakamura T, et al. M(3) muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice. J Physiol. 2004;558(Pt 2):561–75.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Gautam D, et al. Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice. Mol Pharmacol. 2004;66(2):260–7.

    Article  PubMed  Google Scholar 

  53. Glavind K, Chancellor M. Antimuscarinics for the treatment of overactive bladder: understanding the role of muscarinic subtype selectivity. Int Urogynecol J. 2011;22(8):907–17.

    Article  PubMed  Google Scholar 

  54. Dmochowski RR, Gomelsky A. Update on the treatment of overactive bladder. Curr Opin Urol. 2011;21(4):286–90.

    Article  PubMed  Google Scholar 

  55. Kaplan SA, Schneider T, Foote JE, et al. Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head-to-head, placebo-controlled trial. BJU Int. 2011;107(9):1432–40.

    Article  PubMed  Google Scholar 

  56. Chung SD, Chang HC, Chiu B, et al. The efficacy of additive tolterodine extended release for 1-year in older men with storage symptoms and clinical benign proastatic hyperplasia. NeurourolUrodyn. 2011;30(4):568–71.

    Google Scholar 

  57. Oki T, Takeuchi C, Yamada S. Comparative evaluation of exocrine muscarinic receptor binding characteristics and inhibition of salivation of solifenacin in mice. Biol Pharm Bull. 2006;29(7):1397–400.

    Article  PubMed  Google Scholar 

  58. Versi E, et al. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group. Obstet Gynecol. 2000;95(5):718–21.

    Article  PubMed  Google Scholar 

  59. Casaburi R, et al. The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial. The US Tiotropium Study Group. Chest. 2000;118(5):1294–302.

    Article  PubMed  Google Scholar 

  60. Tashkin D, Kesten S. Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses. Chest. 2003;123(5):1441–9.

    Article  PubMed  Google Scholar 

  61. Vogelmeier C, Banerji D. NVA237, a long-acting muscarinic antagonist, as an emerging therapy for chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2011;5(3):163–73. Epub 2011 Apr 20.

    Article  PubMed  Google Scholar 

  62. Leonard B, Richelson H. Synaptic effects of antidepressants: relationship to their therapeutic and adverse effects. In: Buckley P, Waddington JL, editors. Schizophrenia and mood disorders: the new drug therapies in clinical practice. Oxford: Butterworth- Heinemann; 2000.

    Google Scholar 

  63. Trindade E, et al. Use of granulocyte macrophage colony stimulating factor in children after orthotopic liver transplantation. J Hepatol. 1998;28(6):1054–7.

    Article  PubMed  Google Scholar 

  64. Bertram U, et al. Saliva secretion following long-term antidepressant treatment with nortriptyline controlled by plasma levels. Scand J Dent Res. 1979;87(1):58–64.

    PubMed  Google Scholar 

  65. von Knorring L, Mornstad H. Qualitative changes in saliva composition after short-term administration of imipramine and zimelidine in healthy volunteers. Scand J Dent Res. 1981;89(4):313–20.

    Google Scholar 

  66. Hunter KD, Wilson WS. The effects of antidepressant drugs on salivary flow and content of sodium and potassium ions in human parotid saliva. Arch Oral Biol. 1995;40(11):983–9.

    Article  PubMed  Google Scholar 

  67. Bradley RM, Fukami H, Suwabe T. Neurobiology of the gustatory-salivary reflex. Chem Senses. 2005;30:I70–1.

    Article  PubMed  Google Scholar 

  68. Ishizuka KI, et al. Multi-source inputs converge on the superior salivatory nucleus neurons in anaesthetized rats. Auton Neurosci. 2010;156(1–2):104–10.

    Article  PubMed  Google Scholar 

  69. Ueda H, et al. Muscarinic receptor immunoreactivity in the superior salivatory nucleus neurons innervating the salivary glands of the rat. Neurosci Lett. 2011;499(1):42–6.

    Article  PubMed  Google Scholar 

  70. Renzi A, De Luca Jr LA, Menani JV. Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats. Brain Res Bull. 2002;58(5):455–9.

    Article  PubMed  Google Scholar 

  71. Takakura AC, et al. Effects of AV3V lesion on pilocarpine-induced pressor response and salivary gland vasodilation. Brain Res. 2005;1055(1–2):111–21.

    Article  PubMed  Google Scholar 

  72. Takakura AC, et al. Activation of alpha(2)-adrenoceptors in the lateral hypothalamus reduces pilocarpine-induced salivation in rats. Neurosci Lett. 2009;450(3):225–8.

    Article  PubMed  Google Scholar 

  73. Moreira TS, et al. Central moxonidine on salivary gland blood flow and cardiovascular responses to pilocarpine. Brain Res. 2003;987(2):155–63.

    Article  PubMed  Google Scholar 

  74. Phillips MA, Szabadi E, Bradshaw CM. Comparison of the effects of clonidine and yohimbine on pupillary diameter at different illumination levels. Br J Clin Pharmacol. 2000;50(1):65–8.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Moreira Tdos S, et al. Inhibition of pilocarpine-induced salivation in rats by central noradrenaline. Arch Oral Biol. 2002;47(6):429–34.

    Article  PubMed  Google Scholar 

  76. Gotrick B, Giglio D, Tobin G. Effects of amphetamine on salivary secretion. Eur J Oral Sci. 2009;117(3):218–23.

    Article  PubMed  Google Scholar 

  77. Abdelmawla AH, et al. Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein. Br J Clin Pharmacol. 1999;48(3):345–54.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Hassan SM, Wainscott G, Turner P. A comparison of the effect of paroxetine and amitriptyline on the tyramine pressor response test. Br J Clin Pharmacol. 1985;19(5):705–6.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Michna E, et al. Systematic literature review and meta-analysis of the efficacy and safety of prescription opioids, including abuse-deterrent formulations, in non-cancer pain management. Pain Med. 2014;15(1):79–92.

    Article  PubMed  Google Scholar 

  80. Gotrick B, Tobin G. The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats. Arch Oral Biol. 2004;49(12):969–73.

    Article  PubMed  Google Scholar 

  81. Fox PC, et al. Pilocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia). Arch Intern Med. 1991;151(6):1149–52.

    Article  PubMed  Google Scholar 

  82. Greenspan D, Daniels TE. Effectiveness of pilocarpine in postradiation xerostomia. Cancer. 1987;59(6):1123–5.

    Article  PubMed  Google Scholar 

  83. Gotrick B, et al. Oral pilocarpine for treatment of opioid-induced oral dryness in healthy adults. J Dent Res. 2004;83(5):393–7.

    Article  PubMed  Google Scholar 

  84. Thomson WM, et al. Shortening the xerostomia inventory. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(3):322–7.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Wolff A, Zuk-Paz L, Kaplan I. Major salivary gland output differs between users and non-users of specific medication categories. Gerodontology. 2008;25(4):210–6.

    Article  PubMed  Google Scholar 

  86. Furness S, et al. Interventions for the management of dry mouth: topical therapies. Cochrane Database Syst Rev. 2011;12:CD008934.

    PubMed  Google Scholar 

  87. Bots CP, et al. The management of xerostomia in patients on haemodialysis: comparison of artificial saliva and chewing gum. Palliat Med. 2005;19(3):202–7.

    Article  PubMed  Google Scholar 

  88. Davies AN. A comparison of artificial saliva and chewing gum in the management of xerostomia in patients with advanced cancer. Palliat Med. 2000;14(3):197–203.

    Article  PubMed  Google Scholar 

  89. Gomez-Moreno G, Aguilar-Salvatierra A, Guardia J, et al. The efficacy of a topical sialogogue spray containing 1 % malic acid in patients with antidepressant-induced dry mouth: a double-blind, randomized clinical trial. Depress Anxiety. 2013;30(2):137–42.

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

The author thanks Dr. Abeer Shaalan, King’s College London - Dental Institute, for the preparation of Fig. 3.1 and for help in preparing the manuscript.

Author information

Authors and Affiliations

  1. Mucosal and Salivary Biology Division, King’s College London Dental Institute, Floor 17 Guy’s Tower Strand, London, SE1 9RT, UK

    Gordon B. Proctor BSc, PhD

Authors
  1. Gordon B. Proctor BSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gordon B. Proctor BSc, PhD .

Editor information

Editors and Affiliations

  1. Department of Salivary Research, Kings College London Dental Institute, London, United Kingdom

    Guy Carpenter

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Proctor, G.B. (2015). Medication-Induced Dry Mouth. In: Carpenter, G. (eds) Dry Mouth. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55154-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-55154-3_3

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-55153-6

  • Online ISBN: 978-3-642-55154-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation