Drug-induced complications and side effects

Age-related risks and ulcerogenic action

Elderly and geriatric patients are particularly vulnerable to drug-induced complications. Prescribing ulcerogenic drugs—primarily nonsteroidal anti-inflammatory drugs (NSAIDs)—frequently leads to severe gastroduodenal ulcers.

In addition to classical factors (acid-peptic aggression and Helicobacter pylori infection), concomitant gastric vascular atherosclerosis and underlying chronic diseases (such as pulmonary diseases) that deplete the mucosal barrier play a major role in the pathogenesis.

Features of such drug-induced ulcers:

• Predominant localization in the stomach (subcardiac region or lesser curvature).
• Ability to reach giant sizes against the background of masked, vague symptoms.
• Extremely slow healing.
• Propensity for life-threatening gastrointestinal bleeding.
• High risk of perforation even after hemostatic interventions.

Teratogenic effects and FDA classification

Pharmacotherapy during pregnancy requires strict justification: the expected benefit for the mother must unequivocally outweigh the risk to the fetus. The main rule is prescribing the minimum effective dose for the shortest possible duration.

According to FDA guidelines, drugs are divided into 5 categories based on teratogenic risk:

1. Category A: Safety fully established by controlled trials (iron supplements, potassium chloride).
2. Category B: Relatively safe agents. No teratogenic risk demonstrated in animals or confirmed in humans (insulin, acetylsalicylic acid, metronidazole).
3. Category C: Potential risk. Danger demonstrated in animals, but no adequate human studies available. Prescribed only if benefits outweigh risks.
4. Category D: Proven risk to the fetus. Use is acceptable strictly for life-saving indications (e.g., diazepam).
5. Category X: Strictly contraindicated during pregnancy and when planning conception. Risks vastly outweigh any potential benefits (carbamazepine, isotretinoin, streptomycin).

Complications of psychopharmacotherapy

Treatment of depression is accompanied by several paradoxical and dangerous side effects. For instance, tricyclic antidepressants (TCAs), such as amitriptyline, exhibit pronounced anticholinergic and sedative effects, as well as high toxicity in overdose.

Critical treatment risks:

• Increased suicide risk: The likelihood of suicide increases during the first days of treatment. This is because medications rapidly relieve motor retardation, while depressive despair persists for a long time.
• Phase inversion: In some patients, depression may abruptly shift into mania. In such scenarios, antidepressants are discontinued immediately and neuroleptics are initiated.
• Drug resistance: True resistance is diagnosed only after many months of maximum dosing (since treatment efficacy cannot be evaluated earlier than 2–3 weeks). To overcome it, intravenous infusion, sleep deprivation, electroconvulsive therapy (ECT), or abrupt drug withdrawal are employed.
• Withdrawal syndrome: Once the acute episode is resolved, drugs are tapered strictly and gradually, often maintaining maintenance doses for prevention.

Therapy limitations and systemic effects in allergy

Physicians have numerous agents at their disposal to control allergic processes (ranging from antihistamines to leukotriene antagonists). However, the main drawback of modern therapy is that it acts exclusively on the effector stage—for example, by blocking mast cell degranulation or histamine action. Medications are unable to affect the initial sensitization phase and eliminate the immunological basis of the disease.

Glucocorticoids pose a particular risk during treatment. Although they powerfully suppress inflammation and the synthesis of allergic mediators, their systemic use causes severe side effects. Therefore, local routes of administration—ointments and sprays—are always preferred today.

The situation can be further complicated by secondary infection (e.g., resulting from scratching due to severe pruritus in atopic dermatitis). Infection acts as a factor switching the immune response to a Th1-dependent pathway, making the pathogenesis mixed and complicating subsequent patient management.

Class and exam questions

What else to study on this topic

• Differential diagnosis of gastric ulcers and infiltrative-ulcerative gastric cancer.
• Electroconvulsive therapy (ECT) as a method to overcome psychopharmacotherapy resistance.
• Specifics of using tranquilizers and hypnotics for short-term anxiety relief.
• The role of Th1 and Th2 lymphocytes in the pathogenesis of atopic dermatitis and the evolution of inflammation.
• Features of fetal circulation and maternal adaptation to pregnancy.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.