From Volume 43, Issue 2, March 2016 | Pages 186-191
Many common prescription and over-the-counter medications have antimuscarinic effects. Antimuscarinics are a well recognized cause of dry mouth, with potential to cause other physical and cognitive adverse effects. A comprehensive medication review in a patient presenting with dry mouth can lead to overall health improvements. Scoring systems can be helpful in identifying antimuscarinic drugs and their adverse effects.
The number of older people worldwide is increasing. By 2050, 16% of the global population will be over 65.1 Approximately one-fifth of people in the United Kingdom are now aged 65 or older.2,3 Most people over 65 live with a long-term medical condition and most people over 75 live with two or more long-term medical conditions.4 Older people are more likely to take multiple medications. Around 20% of people over 70 take at least five medications, and 16% take 10 or more medications.4
Antimuscarinics are commonly prescribed drugs with significant oral effects. This is illustrated in the following case study and review. Following recognition of a drug-related oral problem, it is advisable to ask patients to attend their general medical practitioner for a medication review. A medication review is a ‘structured, critical examination of a patient’s medicines with the objective of reaching an agreement with the patient about treatment, optimizing the impact of medicines, minimizing the number of medication-related problems, and reducing waste'.5 Key points for general dental practitioners can be summarized as follows:
A 75-year-old gentleman presented to his general dental practitioner with symptoms of dry mouth. His mouth felt uncomfortable and his dentures felt loose (Figure 1). Past medical history included ischaemic heart disease, post-herpetic neuralgia and gastro-oesophageal reflux disease. Further questioning revealed that he recently started taking oxybutynin for bladder urgency. His wife reported that he had been muddled and constipated.
On examination, he was found to have a dry mouth with some areas of atrophic mucous membranes (Figure 2). His full upper denture fitted quite well but was poorly retained in position due to lack of saliva film. His lower denture fitted less well due to more advanced ridge resorption.
Anticholinergic (antimuscarinic) drugs are a well recognized and common cause of dry mouth. It has been estimated that around 50% of the general elderly population use at least one antimuscarinic medication.6 Around 30% of these people report experiencing dry mouth.7 If a patient with dry mouth presents to a dental practitioner there is an opportunity to communicate with his/her general medical practitioner and trigger a medication review. Greater awareness of antimuscarinic medications, uses and adverse effects can prompt intervention with positive health benefits.
Antimuscarinic drugs are antagonists of the muscarinic acetylcholine receptor (mAChR). mAChRs are G-protein coupled receptors located in the central nervous system (hippocampus, cortex, thalamus) and peripherally (mainly autonomic effector cells of the parasympathetic nervous system).8
Atropine is a naturally occurring antimuscarinic which blocks all mAChRs. Peripheral antimuscarinic effects are parasympatholytic because they block the actions of parasympathetic nerve activity. Different organs vary in their sensitivity to antimuscarinic actions (Figure 3). Dry mouth is one of the most common antimuscarinic effects.
Antimuscarinic drugs have a variety of important therapeutic indications (Table 1).
| Therapeutic Indications | Antimuscarinic Medication |
|---|---|
| Gastro-intestinal antispasmotics | Dicycloverine hydrochloride |
| Overactive bladder syndrome: urgency with or without urge incontinence | Oxybutynin hydrochloride |
| Bronchodilatation in airways disease | Ipratropium (Atrovent, Boehringer Ingelheim) |
| Emergency management of bradycardia | Atropine sulphate |
| Antiemetics | Hyoscine hydrobromide (Kwells, Bayer Consumer Care) (Joy rides, Forrest) |
| Management of tremor in Idiopathic Parkinson’s disease | Trihexyphenidyl hydrochloride |
| Management of drug/neuroleptic induced extrapyramidal symptoms | Procyclidine hydrochloride |
| Pupillary dilatation for opthalmological examination | Tropicamide |
Despite a number of important and useful clinical applications, antimuscarinic drugs have a number of unfortunate peripheral and central adverse effects (Table 2). Older people are more likely to be taking multiple medications, and polypharmacy carries an increased risk of adverse drug reactions. Older people are more susceptible to medication adverse effects due to changes in pharmacokinetics and reduced hepatic and renal function. Older individuals are at particular risk of central antimuscarinic effects, such as falls and confusion, which is in part due to disruption of the blood brain barrier with age.
| PERIPHERAL | CENTRAL |
|---|---|
| Dry mouth | Memory impairment |
| Dry eyes | Confusion |
| Constipation | Disorientation |
| Reduced peristalsis | Agitation |
| Blurred vision | Hallucinations |
| Acute angle closure glaucoma | Delirium |
| Urinary retention | Falls |
| Tachycardia | Dizziness |
| Increased body temperature |
The drug history was confirmed with the general medical practitioner as: aspirin, amitriptyline and oxybutynin. The patient had also been sourcing over-the-counter ranitidine (Zantac, GlaxoSmithKline) from his local pharmacy for heart burn.
In addition to the antimuscarinic medications listed in Table 1, there are many drugs with well recognized antimuscarinic effects, including: tricyclic antidepressants (eg amitriptyline), antipsychotics (eg chlorpromazine), antihistamines (eg chlorpheniramine [Piriton, GSK Consumer Healthcare]) and antiemetics (eg prochlorperazine [Stemetil, Sanofi-Aventis; Buccastem, Alliance]). There are also many drugs that are not classically considered to be antimuscarinics, but that have been shown to have antimuscarinic effects (eg ranitidine [Zantac, GlaxoSmithKline]).
Antimuscarinic scoring systems have been developed to aid in the identification of antimuscarinic drugs, and to assist in quantifying the likely antimuscarinic effect. A simple and well-validated tool in older people is the Anticholinergic Risk Scale (ARS) (Table 3). The ARS was designed to estimate the extent to which an older patient may be at risk of antimuscarinic adverse effects.9 Each medication listed on the ARS has a score depending on its antimuscarinic activity of either: 1 (moderate), 2 (strong) or 3 (very strong). The ARS for a patient is the sum of the scores of all medication taken by that patient. Unlisted medications score zero. An ARS of 3 gives a 70% chance of two or more adverse antimuscarinic effects being reported. It is important to check all medications, including over-the-counter medications and inhaled medications. Inhaled tiotropium and ipratropium, used in the treatment of lung disease, have been shown to have systemic antimuscarinic adverse effects10 and, in recent studies, have been assigned an ARS score of 2 for tiotropium and 3 for ipratropium,11 and have therefore been added to Table 3.9
| 3 Points (very strong) | 2 Points (strong) | 1 Point (moderate) |
|---|---|---|
| Amitriptyline hydrochloride | Amantadine hydrochloride | Carbidopa-levodopa |
| Atropine products | Baclofen | Entacapone |
| Benztropine mesylate | Cetirizine hydrochloride | Haloperidol |
| Carisoprodol | Cimetidine (Tagamet, Chemidex) | Methocarbamol |
| Chlorpheniramine maleate (Piriton, GSK Consumer Healthcare) | Clozapine | Metoclopramide hydrochloride (Maxolon, AMCo) |
| Cyproheptadine hydrochloride | Cyclobenzaprine hydrochloride | Mirtazapine |
| Dicycloverine hydrochloride | Desipramine hydrochloride | Paroxetine hydrochloride |
| Diphenhydramine hydrochloride | Loperamide hydrochloride (Imodium, Janssen) | Pramipexole dihydrochloride |
| Fluphenazine hydrochloride | Loratadine | Quetiapine fumarate |
| Hydroxyzine hydrochloride and hydroxyzine pamoate | Nortriptyline hydrochloride | Ranitidine hydrochloride (Zantac, GlaxoSmithKline) |
| Hyoscyamine products | Olanzapine | Risperidone |
| Imipramine hydrochloride | Prochlorperazine maleate (Stemetil, Sanofi-Aventis; Buccastem, Alliance) | Selegiline hydrochloride |
| Ipratropium (Atrovent) | Pseudoephedrine hydrochloride (Sudafed, McNeil) | |
| Meclizine hydrochloride | Tiotropium (Spiriva, Boehringer Ingelheim) | Trazodone hydrochloride |
| Oxybutynin chloride | Tolterodine tartrate (Detrusitol, Pfizer) | Ziprasidone hydrochloride |
| Perphenazine | ||
| Promethazine hydrochloride | ||
| Thioridazine hydrochloride | ||
| Thiothixene | ||
| Tizanidine hydrochloride | ||
| Trifluoperazine hydrochloride |
The patient's ARS was calculated to be: oxybutynin (3) + amitriptyline (3) + ranitidine (1) = 7. As an ARS of 3 gives a 70% chance of ≥2 adverse antimuscarinic effects, a strategy to reduce this score should help in alleviating his oral symptoms.
Identification of antimuscarinic drugs in the causality of dry mouth can be assisted through the use of scoring systems, such as the ARS. In a patient presenting with dry mouth, the authors recommend:
These steps can prompt medication review with positive health implications. Reduction of antimuscarinic medication may be a modifiable risk factor to reduce morbidity and cognitive impairment, with consequent improvements in quality of life.
The general medical practitioner was contacted and a medication review requested in view of antimuscarinic use and adverse effects, particularly with regards to the patient's dry mouth. Oxybutynin was discontinued, and nonpharmacological measures were employed for the management of an overactive bladder. The patient's amitriptyline dose was gradually reduced and then stopped. Consequently, dry mouth, constipation and confusion all resolved and the patient reported feeling much better. His mouth felt more comfortable and his full upper denture felt more retentive (Figure 4). His presenting complaint had been resolved, together with an overall improvement in quality of life.
