17 Drugs that reduce salivary flow

The case of reduced saliva flow

Saliva is a complex fluid that consists of two components: a fluid component and a protein component. These components are secreted by independent mechanisms and serve different functions.

The fluid component, which includes ions, is mainly produced through parasympathetic stimulation. On the other hand, the protein component is released mainly in response to sympathetic stimulation.

The secretion of saliva is primarily controlled by the autonomic nervous system, although hormonal influences can also modulate its composition. The process of salivary secretion involves cyclic AMP or calcium-dependent pathways, which are influenced by various modulatory factors.

Parasympathetic vs. sympathetic saliva stimulation

Parasympathetic stimulation is often referred to as the “rest and digest” response, which is responsible for promoting relaxation, digestion, and the conservation of energy. When the parasympathetic nervous system is activated, it stimulates the salivary glands to produce saliva. Saliva produced under parasympathetic stimulation is watery and rich in enzymes, helping with the initial stages of digestion and providing lubrication to the oral cavity.

On the other hand, sympathetic stimulation is associated with the “fight or flight” response, which prepares the body for intense physical activity or stressful situations. When the sympathetic nervous system is activated, it inhibits salivary gland secretion. The saliva produced under sympathetic stimulation is minimal and has a higher protein content, which can give a sensation of dryness in the mouth.

The balance between parasympathetic and sympathetic activity is crucial for maintaining normal salivary function. In a relaxed state, parasympathetic activity predominates, promoting saliva production and maintaining adequate oral moisture. However, during times of stress or intense physical activity, sympathetic activity increases, leading to a decrease in saliva production and potentially causing a dry mouth sensation.

Impact of medications on (para)-sympathetic saliva stimulation

Medications can have different effects on parasympathetic and sympathetic saliva stimulation, leading to changes in salivary secretion.

Parasympathetic Stimulation

Medications that enhance parasympathetic activity or mimic its effects can increase salivary secretion; they are known as parasympathomimetic or cholinergic drugs.

Examples of such medications include pilocarpine and cevimeline. These drugs are used to treat conditions like dry mouth (xerostomia) caused by various factors, such as Sjögren’s syndrome or radiation therapy.

Sympathetic Stimulation

Medications that enhance sympathetic activity or mimic its effects can decrease salivary secretion, and are known as sympathomimetic drugs.

Examples of such medications include certain decongestants, such as pseudoephedrine, and medications used for asthma or allergies, like some beta-agonists.

Additionally, some medications that block parasympathetic activity or antagonize its effects can indirectly lead to sympathetic dominance and decreased salivary secretion. Anticholinergic drugs, such as certain antihistamines, tricyclic antidepressants, and antipsychotics, may have this effect.

Drugs that affect the cholinergic system

1. Tricyclic antidepressants (TCAs)

These medications have been widely used to treat depression. They work by enhancing certain chemicals in the brain, but they can also block other receptors in the body, leading to side effects like dry mouth, weight gain, constipation, drowsiness, and dizziness.

TCAs tend to have the biggest impact on reducing saliva flow compared to other antidepressants. In fact, selective serotonin re-uptake inhibitors (SSRIs), another class of newer generation antidepressants, does not have this side effect.

That said, you should keep in mind that there may be differences in how men and women respond to TCAs, both in terms of their bodily

2. Muscarinic receptor antagonists

These drugs are commonly used to treat overactive bladder (OAB), a condition characterized by symptoms like frequent urination and sudden urges to urinate. They work by blocking certain receptors in the bladder muscles, reducing muscle contractions. However, they can also affect other receptors in the body, leading to side effects like dry mouth.

For instance, Oxybutynin is a commonly used muscarinic receptor antagonist, but it can cause dry mouth along with other side effects like constipation and increased heart rate. To reduce the side effects, patients may be given extended-release formulations of oxybutynin that release the medication slowly over a 24-hour period, allowing for better control of symptoms with fewer side effects.

• Propiverine hydrochloride and tolterodine are other muscarinic receptor antagonists used to treat OAB. They have shown similar effectiveness to oxybutynin but with lower severity and incidence of dry mouth.
• Tamsulosin is an alpha receptor antagonist used to treat urinary outflow obstruction associated with benign prostatic hyperplasia. Compared to other alpha antagonists like terazosin, tamsulosin has been found to cause less dry mouth and dizziness.

While muscarinic receptor antagonists and alpha receptor antagonists used to treat OAB and urinary outflow obstruction can have side effects such as dry mouth, newer formulations and selective medications have been developed to minimize these side effects while effectively treating the underlying conditions.

3. Antipsychotics

Different antipsychotics may result in either increased salivation or dry mouth.

• The long-term use of conventional phenothiazine antipsychotics for the treatment of schizophrenia has been associated with dry mouth.
• Clozapine, an atypical antipsychotic, is known for its superior efficacy and fewer motor adverse effects compared to typical antipsychotics. However, it carries a significant risk of serious blood disorders and is associated with more hypersalivation but less dry mouth compared to conventional neuroleptics.
• Olanzapine, another atypical antipsychotic, is commonly associated with dizziness and dry mouth. However, olanzapine-treated patients have a lower discontinuation rate due to adverse drug reactions compared to those treated with clozapine.
• Quetiapine and risperidone, both atypical antipsychotics, have been reported to cause dry mouth in a significant percentage of patients.
• Tiapride, an atypical neuroleptic, is associated with less drowsiness, extrapyramidal symptoms, and dry mouth compared to chlorpromazine.
• Pipamperone dihydrochloride, another atypical neuroleptic, can also produce dry mouth.
• Donepezil, an acetylcholinesterase inhibitor used for Alzheimer’s disease, has been found to reduce dry mouth.
• Lithium, commonly used in the treatment of bipolar disorder, may cause dry mouth as a side effect, particularly when used in combination with olanzapine.

In summary, dry mouth is a recognized side effect of antipsychotic medications, both conventional and atypical. The incidence and severity of dry mouth can vary among different antipsychotics, and the underlying mechanisms may involve their affinity for dopamine receptors and other neuronal receptor systems.

4. Diuretics

Among elderly patients, diuretic medications and psychotropic medications tend to be the most commonly used drugs that can cause dry mouth.

In a subjective assessment, patients reported experiencing dry mouth ten times more often after taking furosemide (a diuretic) compared to a placebo (inactive substance). However, when researchers analyzed the actual saliva samples, they found no significant differences in the amount of saliva produced, the composition of saliva, or the concentration of certain electrolytes between patients taking furosemide and those taking the placebo.

This suggests that the sensation of dryness in the mouth may not be solely due to a decrease in saliva production.

In simple terms, diuretic medications and certain psychotropic medications can cause dry mouth, but the exact mechanism behind this side effect is not fully understood. While patients may feel that their mouth is dry after taking these medications, the actual amount and composition of saliva may not be significantly affected.

5. Antihistamines

Many older antihistamine medications had therapeutic effects but also caused sedation and dry mouth. For example, clemastine, one of these older antihistamines, was found to have a higher incidence of dry mouth as a side effect (6%).

These antihistamines worked by blocking the effects of histamine in the body, but they also had sedating effects on the central nervous system and caused dryness in the mouth.

To address these side effects, newer antihistamines have been developed that are less likely to cause sedation. These newer antihistamines, such as acrivastine, astemizole, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine, still block histamine and have additional actions that help reduce allergic inflammation.

While they are generally associated with fewer incidences of dry mouth compared to the older antihistamines, they are not entirely free from side effects. However, they offer a potential improvement in terms of reducing the occurrence of dry mouth.

Drugs that affect the sympathetic system

6. Antihypertensives 

These medications are used to treat high blood pressure, and can sometimes cause dry mouth as a side effect. This includes centrally acting antihypertensives like clonidine, guanfacine, and alpha-methyl-DOPA.

Antihypertensives work by stimulating certain receptors in the brain to lower blood pressure, but they can also activate receptors in the salivary glands, leading to dryness in the mouth.

• Older centrally acting antihypertensive drugs, such as reserpine, methyldopa, and clonidine, are less commonly used nowadays due to their side effects, which can include dry mouth, sedation, dizziness, and swelling.
• Beta-blockers, another type of antihypertensive medication, can also cause dry mouth. These drugs block certain receptors in the body, including those in the central nervous system and salivary glands, leading to reduced saliva production and dryness in the mouth.
• Newer centrally acting antihypertensives, such as moxonidine and rilmenidine, have been developed to have a more selective effect on receptors in the brain that regulate blood pressure, without significantly affecting salivary flow or causing dry mouth. These medications are considered to have a better side effect profile compared to older antihypertensives.
• Angiotensin-converting enzyme (ACE) inhibitors, another class of antihypertensive drugs, can also sometimes cause dry mouth as a side effect. ACE inhibitors block an enzyme involved in regulating blood pressure, but this inhibition can lead to the accumulation of certain substances in the body that may contribute to dry mouth.

It’s important to note that not everyone will experience dry mouth when taking these medications, and the incidence and severity of side effects can vary between individuals.

7. Antidepressants

Newer antidepressant medications work by affecting chemicals in the brain that regulate mood, such as serotonin and noradrenaline. While selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed as a first-line treatment for depression, they can still cause dry mouth as a side effect in some patients. However, SSRIs like paroxetine may result in less dry mouth compared to older antidepressants called tricyclic antidepressants (TCAs).

• Venlafaxine, a mixed reuptake inhibitor, can also cause dry mouth along with other side effects like dizziness, insomnia, and abnormal ejaculation. Similarly, duloxetine, another medication that affects both serotonin and noradrenaline, can lead to dry mouth, nausea, and sleepiness.
• Other antidepressants such as mianserin, nefazodone, reboxetine, and mirtazapine may also have the potential to cause dry mouth, but their overall side effect profiles vary.
• Bupropion, originally developed as an antidepressant but also used to help quit smoking, can reduce nicotine withdrawal symptoms but is associated with a common side effect of dry mouth.

It’s important to note that individual responses to these medications can vary, and not everyone will experience dry mouth.

8. Appetite suppressants

Appetite suppressants are medications used to help reduce appetite and promote weight loss by affecting certain chemicals in the brain to reduce hunger and increase feelings of fullness. One common side effect of appetite suppressants is dry mouth. Appetite suppressants such as sibutramine, fenfluramine plus phentermine, and herbal supplements containing ephedrine alkaloids/caffeine, have been associated with dry mouth as a side effect.

9. Decongestants and cold cures

Decongestants and cold cures are medications commonly used to alleviate symptoms of nasal congestion and the common cold. However, one side effect that can occur with these medications is dry mouth.

Decongestants such as pseudoephedrine and cetirizine work by reducing nasal congestion and swelling of the nasal passages, allowing for easier breathing. While effective in relieving congestion, they can also have drying effects on the mucous membranes, including the mouth.

10. Bronchodilators

Bronchodilators are medications used to relax and widen the airways, making it easier to breathe for individuals with conditions such as asthma or chronic obstructive pulmonary disease (COPD). While these drugs are effective in improving respiratory symptoms, one common side effect associated with their use is dry mouth.

For example, the tiotropium bronchodilator is known to have dry mouth as a reported side effect. This occurs because bronchodilators can affect the function of the salivary glands, leading to a decrease in saliva production.

11. Skeletal muscle relaxants

Skeletal muscle relaxants are a class of medications commonly prescribed to relieve muscle spasms, stiffness, or pain associated with conditions such as muscle strains, sprains, or musculoskeletal disorders. While these medications are effective in promoting muscle relaxation, one potential side effect that some individuals may experience is dry mouth.

Skeletal muscle relaxants, such as tizanidine, can interfere with the normal function of the salivary glands, leading to reduced saliva production and the sensation of dryness in the mouth.

12. Antimigraine drugs

Antimigraine drugs are medications specifically designed to treat or prevent migraines, a neurological condition characterized by severe headaches, often accompanied by other symptoms such as nausea, sensitivity to light and sound, and visual disturbances. While these medications can provide relief from migraines, some individuals may experience dry mouth as a side effect.

For instance, rizatriptan, which is a serotonin agonist used to treat migraines in adolescents, can affect the normal functioning of the salivary glands, leading to a decrease in saliva production and the sensation of dryness in the mouth.

13. Opioids, benzodiazepines, and drugs of abuse

Opioids are a class of drugs commonly used for pain management. They include medications such as morphine, codeine, and oxycodone. Opioids are known to affect the central nervous system and can inhibit the normal functioning of the salivary glands, leading to decreased saliva production and the sensation of dry mouth.

Benzodiazepines, such as diazepam (Valium), are medications primarily used for their sedative, anti-anxiety, and muscle relaxant properties. While dry mouth is not a common side effect of benzodiazepines, some individuals may experience a slight dryness in the mouth when taking these medications.

Certain drugs of abuse can also cause dry mouth. For example, opioids, such as heroin, and stimulants, such as methamphetamine and ecstasy (MDMA), can lead to a decrease in saliva production. There are some substances like cocaine that seem to exert sympathomimetic effects, and have no effect on dry mouth. However, it’s important to note that drug abuse can have numerous negative effects on overall health, including dental and oral health.

14. Cytotoxic drugs

Cytotoxic drugs, also known as chemotherapy medications, are commonly used in the treatment of various types of cancer. These drugs work by targeting and killing rapidly dividing cancer cells. While the primary focus of cytotoxic drugs is their anticancer effects, they can also have side effects on healthy cells and tissues, including the salivary glands, which may result in dry mouth.

The severity and frequency of dry mouth caused by cytotoxic drugs can vary depending on the specific medication used, the dosage, the duration of treatment, and individual factors. Some cytotoxic drugs are more likely to cause dry mouth than others. For example, drugs such as retinoids (e.g., isotretinoin) and 5-fluorouracil have been associated with dry mouth as a potential side effect.

15. Retinoids

Retinoids are a class of medications that are derived from vitamin A and are used for various medical purposes. They are known to cause dryness of the mouth and changes in the oral and lip mucosa as potential side effects.

Retinoids, such as etretinate and isotretinoin, have been associated with dry mouth. Etretinate, which is no longer commonly used, was used in the treatment of psoriasis and other skin disorders. Isotretinoin, on the other hand, is primarily used for the treatment of severe acne.

The exact mechanism by which retinoids cause dry mouth is not fully understood. However, it is believed that retinoids can affect the function of the salivary glands, leading to a reduction in saliva production.

16. Anti-HIV drugs

Certain anti-HIV drugs, including didanosine and HIV protease inhibitors, have been associated with the side effect of dry mouth.

Didanosine (also known as ddl or DDI) is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV infection. Dry mouth is a known side effect of didanosine, probably due to the drug’s effects on the salivary glands, leading to reduced saliva production.

HIV protease inhibitors (PIs) are another class of anti-HIV medications. While they have greatly improved the management of HIV infection, they can also have oral side effects, including dry mouth.

17. Cytokines in regard to dry mouth

Cytokines, which are small proteins involved in cell signaling (such as interferon and interleukin-2 (IL-2)) can affect salivary gland cells and potentially contribute to the development of salivary gland dysfunction and dry mouth.

Interferon, a cytokine used in the treatment of various conditions including viral infections and certain cancers, has been found to have pronounced effects on salivary gland cells. It has been used to treat Sjogren’s syndrome, a chronic autoimmune disorder characterized by dry mouth and dry eyes. However, interferon therapy for the treatment of chronic hepatitis C infection has been associated with significant dry mouth as a side effect.

IL-2, another cytokine used in cancer treatment, has also been linked to impaired salivation. Studies have reported major salivary gland dysfunction in patients with hematological malignancies receiving IL-2-based immunotherapy after autologous blood stem cell transplantation. Reductions in both resting and stimulated salivary flow rates have been observed during IL-2 administration.

Polypharmacy and dry mouth

Polypharmacy, the use of multiple medications, is strongly correlated with dry mouth symptoms. The number of medications used is positively correlated with the prevalence and severity of dry mouth.

While no specific drug or drug group is particularly xerogenic, the cumulative effect of polypharmacy increases the risk of dry mouth symptoms, which can in turn lead to an increased risk of dental caries, especially among individuals taking multiple prescription medications.

Management of dry mouth

Managing dry mouth associated with certain drugs may involve various strategies:

• Maintain good oral hygiene by brushing teeth regularly with fluoride toothpaste, using a soft toothbrush, and flossing gently
• Drink plenty of water and staying hydrated can also help alleviate dryness
• Use saliva substitutes or artificial saliva products, available over-the-counter or by prescription, as temporary relief for lubricating the mouth
• Chewing sugar-free gum or using lozenges can stimulate saliva flow
• Prescription medications

If you’re taking any medications, it’s important that you communicate any dry mouth symptoms to your healthcare team. They can provide guidance on managing dry mouth, recommend appropriate interventions, and monitor overall oral health during treatment.

Dental professionals, such as dentists or oncology dental specialists, can also play a crucial role in preventive care and oral health management.

Final thoughts

Please note that the specific effects of medications on saliva stimulation can vary depending on the drug, dosage, and individual response. Some medications may have both parasympathetic and sympathetic effects on salivary glands, while others may primarily affect one branch of the autonomic nervous system.

If dry mouth is a significant concern when taking your medication following the prescribed dosage and other instructions, it is advisable to speak with your healthcare professional. They may be able to provide recommendations or adjust the dosage or medication to alleviate the discomfort of dry mouth. 

It is also important to maintain good oral hygiene practices, such as drinking plenty of water and using sugar-free lozenges or gum, can help alleviate the discomfort associated with dry mouth.