Definition and Overview
Drug-induced autonomic side effects are a condition in which a drug administered for treatment unintentionally causes abnormalities in the function of the autonomic nervous system. It acts directly on the receptors of autonomic neurotransmitters (norepinephrine, acetylcholine, dopamine, etc.) or occurs through a mechanism that changes the synthesis, decomposition, and reabsorption of neurotransmitters.
Drug-induced autonomic side effects affect various autonomic regulatory functions, including the cardiovascular system (blood pressure, heart rate), digestive system (gastrointestinal motility), urinary system (bladder function), skin (sweating, vascular response), and temperature regulation. The risk and severity of side effects are high in the elderly, patients with underlying autonomic disease, and patients taking multiple medications.
Major autonomic side effects by drug group
Anticholinergic drugs inhibit parasympathetic nerve function by blocking muscarinic acetylcholine receptors. These include antihistamines, tricyclic antidepressants (amitriptyline, imipramine), bladder relaxants (oxybutynin, tolterodine), anti-Parkinson drugs (trihexyphenidyl), and some antipsychotics. Major side effects include dry mouth, constipation, urinary retention, tachycardia, blurred vision, reduced sweating, and cognitive decline (especially in the elderly).
Alpha-1 blockers (doxazosin, terazosin, prazosin) cause vasodilation by blocking alpha-1 receptors on vascular smooth muscles. Orthostatic hypotension is a major side effect, and the risk of falls increases, especially during first administration or when the dose is increased.
Beta-blockers (metoprolol, atenolol, carvedilol) block beta-adrenergic receptors, causing bradycardia, exercise intolerance, peripheral vasoconstriction (exacerbation of Raynaud's phenomenon), and bronchoconstriction (non-selective beta-blockers).
Antiparkinson drugs (levodopa, dopamine agonists) act on dopamine receptors in the autonomic nervous system, causing orthostatic hypotension, abnormal sweating (hyperhidrosis), and gastrointestinal motility abnormalities.
Antipsychotics (haloperidol, clozapine, olanzapine) cause orthostatic hypotension, tachycardia, and sweating abnormalities through alpha-1 blocking and anticholinergic effects.
Chemotherapy agents (vincristine, cisplatin, paclitaxel) cause autonomic neuropathy as part of peripheral neurotoxicity, and orthostatic hypotension, gastrointestinal motility disorders, and bladder dysfunction occur.
pathophysiology
The main mechanisms of drug-induced autonomic side effects are as follows.
Mechanisms of receptor blocking or activation include blocking muscarinic receptors (anticholinergic effects), blocking alpha or beta adrenergic receptors, and modulating dopamine receptors.
Changes in neurotransmitter metabolism include monoamine oxidase inhibition (MAOI), inhibition of catecholamine reuptake, and inhibition of adrenaline synthesis.
In terms of neurotoxicity, anticancer drugs can directly damage autonomic nerve fibers (especially small-diameter unmyelinated C-fibers), causing permanent autonomic neuropathy.
In the elderly, the risk of side effects increases at the same dose due to decreased drug metabolism (reduced hepatic metabolism, decreased renal excretion), changes in receptor sensitivity, and decreased underlying autonomic function.
symptoms
In relation to blood pressure, orthostatic hypotension (a decrease in systolic blood pressure of more than 20 mmHg within 3 minutes of standing), supine hypertension, and increased blood pressure variability occur.
In relation to heart rate, tachycardia (anticholinergic effect), bradycardia (beta blocker), and heart rate variability are decreased.
Constipation (anticholinergic effect), gastroparesis, and decreased gastrointestinal motility occur in relation to the digestive system.
Urinary retention (anticholinergic effect) and bladder overactivity may occur due to urinary system involvement.
Other symptoms include dry mouth, decreased or increased sweating, blurred vision, and abnormalities in temperature regulation.
diagnosis
Evaluation of autonomic side effects is based on detailed drug intake history and correlation analysis with the time of symptom onset. Functional abnormalities can be objectively assessed through autonomic nerve function tests (orthostatic tilt test, HRV test, QSART).
Tools that quantify the anticholinergic risk in patients taking polypharmacy using the anticholinergic burden of drugs (e.g., ACB scale) are used in clinical practice.
Treatment and Management
After confirming the causative drug, priority is given to discontinuation or dose reduction if possible. Replace with an alternative drug (an equally effective drug with fewer autonomic side effects).
Side effects related to orthostatic hypotension are first managed through non-pharmacological methods (getting up slowly, drinking water and salt, and compression stockings).
Management of anticholinergic side effects includes drinking enough water (dry mouth), taking dietary fiber and stool softeners (constipation), and bladder retraining (urinary retention).
For anticancer drug-induced autonomic neuropathy, adjusting or discontinuing the causative drug dose is considered, along with supportive treatment (symptom management).
In patients taking multiple medications, regular medication review (medication reconciliation) eliminates unnecessary medications and minimizes the risk of autonomic side effects.
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This information is provided for medical educational purposes and is not a substitute for individual medical care or treatment. If you have any symptoms, be sure to seek professional advice. Inquiries: Osang Neurosurgery 1599-5453 | osns.co.kr