Overview of Drugs
and Dry Mouth
The Complexities of the Drug-Dry Mouth Relationship
Search for drugs that may cause Dry Mouth
Diagnosis of Dry Mouth: Symptoms, signs, causes
Dry Mouth and
Salivary Flow
Treatment of Drug-induced Xerostomia
Sources of Information/Abbreviations
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Treatment of Drug-induced Xerostomia

The first step in the treatment of drug-induced xerostomia is to obtain an accurate and complete accounting of the patient's current prescription and non-prescription drug intake: the "drug-log". It should include the name of each drug, the dose, the intake schedule, the prescribing doctor's name and the date the prescription was issued. In some cases, these facts may readily be obtained by asking the patient to provide such a list. Where this is difficult or not possible, it may be necessary to ask them to bring all of their drugs to the office or clinic. Once this list is prepared, this portal can readily be used to identify and categorize those drugs which may be xerogenic.

The desiccation which occurs as a result of the intake of xerogenic drugs is generally the result of neural effects, not to irreversible destruction of the parenchyma of the salivary glands. Removal of the offending drugs almost invariably eliminates or diminishes the oral dryness. Moreover, since salivary glands are usually able, when stimulated, to produce some saliva, it may be possible to improve the patient's sensation of dryness even in the presence of xerogenic drugs.

A number of techniques may be tried to modify the patient's intake of xerogenic drugs. Included among these are: (1) the elimination or reduction of select drugs, (2) a change in the manner in which they are taken and (3) the substitution of one drug for another with less noxious effects. Such changes should generally be conducted in consort with the health providers who prescribed the original medications.


The Elimination or Reduction of Select Drugs

It is common, in our society, for a patient to have many doctors. Many doctors usually means many “doctor-prescribed” drugs. Since the feeling of oral dryness is not only related to the intake of xerogenic medications but also to the number of drugs taken per day, it is important to thoroughly investigate the patient’s drug-log. Sometimes, doctors are unaware of the precise mix of drugs that the patient consumes. In such cases, they should be provided with a copy of the log and a listing of those medications that are xerogenic. Moreover, they should be told that the patient is truly troubled by oral dryness and that there is a need to reduce or modify her or his drug intake. It is not uncommon that, when confronted with such facts, the physician, dentist or other health worker may recognize that the intake of one or another drug may no longer be necessary or that it may be reduced in amount.

Drugs are taken for many reasons. For some, they are prescribed for life-threatening or life-prolonging situations. In such cases, it may be difficult, if not impossible, to delete the offending medications. For others, however, they are taken for conditions in which they are of equivocal value. In these cases, one can readily advise that they be eliminated or altered. Frequently, patients take over-the-counter (OTC) medications, many of which are xerogenic. Doctors should be aware of this fact and patients should be counselled to modify their intake of these drugs.


Modification of the Drug-Intake Schedule

In general, the intensity of oral dryness is a direct function of the level of the offending drugs in the blood; the higher the concentration, the more severe the desiccation. A change in the way that drugs are taken may reduce the patient’s feeling of oral dryness. For some, the mere splitting of the prescribed dose into smaller, more frequently taken doses, is helpful. For others, this may not be enough.

Patients generally know when they feel most dry. Relief may occasionally be obtained by modifying the drug intake schedule so that the dryness-inducing drug’s peak blood level does not coincide with the times at which the patient feels most dry.


Drug Substitution

Drugs vary in their capacity to induce oral dryness. Given the huge numbers of drugs on the market, it seems reasonable to suggest that if a patient complains that the taking of a particular drug makes their mouth feel dry, one should substitute it with another, less-drying one. However, this is easier said than done, since only few studies exist which directly compare the relative desiccatory potential of one drug to another. Still, some general deductions can be made and a few examples of beneficial “drug substitution” can be offered. Given the state of our knowledge, drug substitutions must often be done empirically.


The Antidepressants

The tricyclic drugs were prominent among the first generation of medications used to treat depression. These drugs were effective because they enhanced serotoninergic and/or noradrenergic mechanisms. Unfortunately, they also blocked histaminic, cholinergic and alpha-1-adrenergic receptor sites. This action brought about a number of unwanted side effects; especially, dry mouth. Indeed, it is not uncommon for the most xerogenic of these agents to cause desiccation in greater than 40% of the patients. The table below lists the tricyclics in order of their antimuscarinic potential 2,3,4. Since xerosotomia is the consequence of antimuscarinic activity, it is tempting to believe that the incidence of oral dryness also follows this order. Unfortunately, there is no direct evidence to support this belief. Still, if the necessity arises to substitute one tricyclic drug for another, less xerogenic one, it seems reasonable to give credence to the cited antimuscarinic ordering of these drugs (Figure 3).

[ FIGURE 3 ]  The Tricyclic Antidepressants: listed in order of their antimuscarinic potential
amitriptyline > clomipramine = amoxapine = protriptyline > doxepin = imipramine = trimipramine = nortriptyline > desipramine

The next generation of antidepressants are selective serotonin reuptake inhibitors (SSRI's). Included among these are citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. As a class, these drugs are less anticholinergic than the tricyclics5. It has been reported that the incidence of oral dryness with the SSRI's is 21%; with the tricyclics, 55%6. Few tests have directly compared the incidence of dryness among drugs between these groups. But those that have been done, support these statements. It has been shown, for example, that the frequency of xerostomia with paroxetine was 25%; with imipramine, 63%7 and sertraline is associated with a lower frequency of dry mouth than amitritpyline8.

Newer, multiple-receptor antidepressants are also less anticholinergic than the tricyclic drugs; nefazadone and mirtazapine are examples of these drugs9. In one "direct comparison" study, 39% of a group of patients given amitriptyline developed xerostomia; for those given nefazadone, it was 11%10. Another study demonstrated that mirtazapine was less xerogenic than amitriptyline11. Recent tests demonstrated that the incidence of dry mouth in patients given reboxitine, a selective nor-adrenaline reuptake inhibitor, was 22%12.

The data thus suggest that the "newer" antidepressants are less xerogenic than the older, tricyclic, drugs. If, therefore, in the treatment of a patient with depression, dry mouth is a severe side effect, these newer medications may be tried.


The Antipsychotics

Anticholinergic effects, including dry mouth, are also among the side-effects induced by the antipsychotic drugs. The reported relative anticholinergic potentials of some of these agents are shown below13 (Figure 4).

[ FIGURE 4 ]  Relative Anticholinergic Potencies of Select Antipsychotic Drugs
+++ Promazine, triflupromazine, mesoridazine, thioridazine, clozapine, olanzapine
++ Chlorpromazine, pimozide
+ Fluphenazine, perphenazine, prochlorperazine, trifluoperazine, thiothixene, haloperidol, multimode, loxapine.
0 Quetiapine, risperidone
(+++ = strong; ++ = moderate; + = weak; 0 = none)

As with the tricyclics, there is no evidence to support the belief that the incidence of oral dryness is in accord with this categorization. For example, clozapine and olanzapine, drugs which are listed in the “+++” category, respectively induced 6 and 7% xerostomia in test patients. On the other hand, 7% of a group of patients who took quetiapine complained of oral dryness; yet this drug is listed in the “0" group.


The Antihistaminics

Dry mouth is also a common complaint among patients who take antihistamines. The anticholinergic properties of those that are categorized as “First Generation” drugs are, in general, greater than those that are classified as “Second Generation” medications. But again, there is little information that directly compares the relative capacity of these agents to induce dry mouth.

[ FIGURE 5 ]  The Anticholinergic Effects of the Antihistaminic Drugs
+++ = HIGH;    ++ = MODERATE;    + = LOW;    ± = LOW or NONE
First Generation Antihistaminic Drugs
+++ Clemastine, Diphenhydramine, Promethazine
++ Azatadine, Brompheniramine, Chlorpheniramine, Cyproheptadine, Dexchlopheniramine, Hydroxyzine, Phenindamine
_ Tripelennamine
Second Generation Antihistaminic Drugs
± Astemizole, Azelastine, Cetirizine, Fexofenadine, Loratadine
The incidences of dry mouth for astemizole = 5.2%; cetirizine = 5%; loaratidine = 3%.


Specific Examples of Drug Substitution with Other Medications:
  1. Anticholinergics / Antispasmodics - Tolterodine tartrate, a relatively new urinary anticholinergic and antispasmodic drug has been found to be less-drying than oxybutynin chloride16,17 The extended release form of oxybutynin has been shown to exert a less xerogenic effect than the immediate release form of the drug18.

  2. Antiemetics - (a) Nabilone causes more dry mouth than prochlorperazine19 .(b) More dry mouth was associated with an antiemetic regimen composed of hyoscine, clemastine, lorazepam, dexamethasone and a high dose of metoclopromide than with a regimen comprised of haloperidol, lorazepam, dexamethazone and low doses of metoclopromide20.

  3. Analgesic - Dry mouth is less severe in patients receiving controlled release oxycodone than immediate release oxycodone21.

  4. Antiparkinson drugs - The antiparkinson anticholinergic drugs like benztropine, biperiden, procyclidine and trihexphenidyl are alleged to be more xerogenic than the dopaminergic agents. In single tests conduced on individual agents, 30-50% of the patients who used trihexphenidyl drugs complained of dry mouth. The rate of appearance of dry mouth among those using dopaminergic drugs was less: pramipexole, 7%; rapinirole and tolcapone, 5% to 6%; pergolide, 3.7% selegiline, 3%22.

The findings clearly show that the knowledge about the relative effects of drugs to induce dry mouth is limited. A few generalizations, as shown, can be made. But, in general, substitution from a drug to one of lesser xerogenic capacity has to be done by trial and error. For those who regard xerostomia as a trivial complaint, such an effort would seem massive. But it should be recognized that for many patients, dry mouth is, indeed, a chronic, most troubling, matter.

When drug-therapies are not enough

There are times when it is impossible to determine or eliminate the cause of the patient’s oral dryness, and when the drug modifications suggested in this report do not, or only minimally, help. Mindful that drugs generally do not destroy the functional capacity of the salivary system, attempts should next be made to stimulate the patient’s saliva. Finally, if this does not help or, in addition to the use of sialogogues, one should seek to “moisturize” the patient’s oral mucosa. Saliva can be stimulated by mechanical (masticatory), chemical, electronic and pharmacologic methods. These, along with oral moisturizers and salivary substitutes are shown in Table 6.

[ TABLE 6 ]  Sialogogues / Oral Moisturizers / Salivary Substitutes
Type of Product Brand Names Select Characteristics Distributor
1.Mechanical (Masticatory) Stimulants
FOODS which require mastication (apples, carrots, celery, hard breads and rolls, meats, etc)
Sugarless Gums   Sweeteners  
Biotene Xylitol Laclede Professional Products
Eclipse maltitol, sorbitol,mannitol, aspartame, acesulfame K
Certified by the American Dental Association to “prevent cavities, reduce plaque and strengthen teeth.”
Wm. Wrigley, Jr. Co.
Extra sorbitol, mannitol, maltitol, acesulfame K and aspartamel
Certified by the American Dental Association to “prevent cavities, reduce plaque and strengthen teeth.”
Wm. Wrigley, Jr. Co.
Orbit Sorbitol, mannnitol, xylitol, aspartame, acesulfame K
Certified by the American Dental Association to “prevent cavities, reduce plaque and strengthen teeth.”
Wm. Wrigley, Jr. Co.
Orbit White Maltitol, sorbitol, mannitol,aspartame, acesulfame K Wm. Wrigley, Jr. Co.
Orbit Ice White sorbitol, mannitol, maltitol syrup, aspartame, acesulfame K Wm. Wrigley, Jr. Co.
Airwaves Isomalt,sorbitol, mannitol, maltitol syrup (in Honey Lemon only), aspartame, acesulfame K Wm. Wrigley, Jr. Co.
Trident sorbitol, mannitol, acesulfame, aspartame Warner-Lambert
Xylifresh xylitol Leaf Specialty Products
Sugarless Tablet Salix *   Scandinavian Natural Products
* contains citric acid
2. Chemical Stimulants
Solutions Mouth-Kote Mucopolysaccaharide Sol., contains citric acid Parnell Pharmaceuticals
Optimoist Contains citric acid Colgate-Palmolive, Co.
3. Electrical Stimulant
Electrical Stimulation Salitron
  Prescription required
Intra-oral electronic stimulator of saliva Biosonics, Inc.
4. Pharmacologic Stimulant
Drugs “Salagen” (Pilocarpine HCl); Prescription required Cholinergic agonist MGI Pharma, Inc.
“Evoxac” (Cevimeline HCl); Prescription required Cholinergic agonist Daiichi Parmaceutical Co. Ltd.
5. Oral Moisturizers / Salivary Substitutes
Solutions WATER ***** *****
Salivart Contain carboxymethyl cellulose and hydroxyethyl cellulose Xenex Laboratories, Inc.
Oralube
Xero-Lube Colgate Hoyt/Gel-Kam
Plax Water-glycerin agent Pfizer Inc.
Gel Oral Balance Glycerate polymer Laclede Professional Products

TEXT REFERENCES:

1. Drug Facts and Comparisons, On Line, 2001
2. Goodman and Gilman, 6th Edition, 1980
3. Richelson and Diventz-Romero, 1977
4. Snyder and Yamamura, 1977
5. Drug Facts and Comparisons, 2001, pg. 902/3
6. Centre for Evidence Based Mental Health, U.K., 2001
7. Cohn JB et al, Psychopharmacology Bulletin, 26(2):185-189, 1990
8. Drug Facts and Comparisons, 2001, pg. 902
9. Ansseau M et al, Psychopharmacology 115 (1-2): 254-60, 1994
10. Smith WT et al, Psychopharmacology Bulletin, 26 (2): 191-196, 1990).
11. Versiani M Int’l. J. of Psychiatry in Clinical Practice 4(3):210-208, 2000
12. Adapted from Drug Facts & Comparisons, 55th Edition, 2001, pg 945/6
13. Drug Facts & Comparisons, 55th Edition, 2001, pg 950
14. Drug Facts and Comparisons, 55th Edition, 2001, pg 711
15. Abrams P et al, Brit J Urology, 81(6):801-810, 1998
16. Drutz HP et al, Intl Urogynecology J & Pelvic Floor Dysfunction 10(5):238-239, 1999
17. Goldenberg MM, Clinical Therapeutics 21(4):634-642, 1999
18. Herman TS et al, New England J Med, 300(23):1295-1297, 1979
19. Findlay M et al, European J of Cancer, 29A(3):309-315, 1993
20. Robbins L, Headache Quarterly, 10(4):305-309, 1999
21. Drug Facts and Comparisons, 55th Edition, 2001, pp 1113-1136

 

 

 


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