Anticholinergics and Tricyclic Antidepressants (TCAs)

Examples of Common Medications

Anticholinergics

1. Oxybutynin

   • Indication: Urinary incontinence (urge incontinence/overactive bladder)

   • Mechanism: Blocks muscarinic receptors in the bladder → reduces detrusor muscle overactivity

2. Benztropine (Benzatropine)

   • Indication: Extrapyramidal side effects (EPSE) management, e.g. in Parkinson’s disease or antipsychotic-induced EPSE

3. Sedating Antihistamines

   • Promethazine, doxylamine

   • Often used for insomnia, motion sickness, or allergy relief, but sedation and anticholinergic effects can be problematic

Tricyclic Antidepressants (TCAs)

• Amitriptyline, Nortriptyline

• Imipramine, Clomipramine, Trimipramine

• Dothiepin (dosulepin), Doxepin

These medications inhibit the reuptake of noradrenaline (norepinephrine) and serotonin, improving mood in depressive disorders. However, their receptor-blocking profiles (anticholinergic, alpha-1 blockade, antihistamine) cause multiple side effects.

Key Side Effects

Anticholinergic Side Effects (Mnemonic: A B C C D’ S S)

• Arrhythmias (tachycardia)

• Blurred vision

• Constipation

• Confusion (especially in elderly)

• Dry eyes/mouth (xerostomia)

• Sedation

• Stasis of urine (urinary retention, especially in benign prostatic hyperplasia)

These side effects can be remembered via the phrase: “Dry as a bone, Red as a beet, Hot as a hare, Blind as a bat, Mad as a hatter” for severe anticholinergic toxicity.

Additional TCA-Specific Side Effects

• Orthostatic intolerance (postural hypotension) due to alpha-1 blockade

• Sexual dysfunction (e.g. decreased libido, erectile dysfunction)

• Cardiotoxicity:

  • QRS widening

  • QTc prolongation

  • High risk of arrhythmias in overdose

Note: The risk of life-threatening arrhythmias is substantial in TCA overdose, making them particularly hazardous if patients are at risk of intentional overdose.

Special Considerations

Anticholinergics

• Elderly:

  • Increased risk of confusion, falls, delirium.

  • Polypharmacy issues: Combining multiple anticholinergic drugs (including over-the-counter sedating antihistamines) can lead to anticholinergic burden.

  • RACGP and Therapeutic Guidelines (eTG) advise caution, especially if there are safer alternatives.

• Urinary retention: High caution in men with benign prostatic hyperplasia (BPH).

• Ocular: Potential worsening of narrow-angle glaucoma due to mydriasis.

Tricyclic Antidepressants (TCAs)

1. Cardiovascular Disease

   • Avoid or use with extreme caution in patients with known heart disease (e.g. ischaemic heart disease, conduction abnormalities, arrhythmias) due to arrhythmic risk.

   • An ECG is advisable before starting in higher-risk individuals or in older adults.

2. Overdose Risk

   • TCAs are a frequent cause of fatal overdose due to cardiotoxicity and CNS toxicity (seizures, coma).

3. Dose-Related Side Effects

   • Lower doses (e.g. of amitriptyline or nortriptyline) can be used for neuropathic pain with fewer side effects.

   • Monitor sedation levels, anticholinergic burden, and vital signs in at-risk patients.

4. Therapeutic Monitoring

   • Some TCAs (e.g. nortriptyline) can have serum levels measured. However, this is not commonly done in routine practice unless side-effect concerns or poor response.

Clinical Pearls

• When prescribing anticholinergics or TCAs, thoroughly assess the patient’s comorbid conditions, including:

  • Glaucoma (risk of acute angle-closure)

  • Prostate issues (urinary retention)

  • Elderly with cognitive impairment (risk of delirium)

  • Cardiac history (for TCAs)

• In neuropathic pain management (e.g. diabetic neuropathy, post-herpetic neuralgia), low-dose TCAs may be considered (e.g. amitriptyline 10–25 mg nocte), though safer alternatives like SNRIs or gabapentinoids may be preferable in some cases.

• Medication Review is crucial if multiple anticholinergic or sedative agents are being used—deprescribing may reduce fall risk and cognitive impairment in older adults.

• Patient Education: Advise on hydration, monitoring for constipation or urinary symptoms, and avoiding other sedating/anticholinergic over-the-counter medications.