Understanding Side Effects in Medicine
Side effects are unintended effects resulting from medications or interventions that occur in addition to their intended therapeutic action, even when administered at recommended doses. 1
Definition and Classification
- Side effects are conceptually distinct from adverse events, adverse drug reactions, and placebo effects, representing specifically unintended effects due to the causal properties of an intervention 1
- In clinical trials, a distinction is made between general adverse effects (AEs) and Serious Adverse Events (SAEs), with SAEs typically defined as events causing death, permanent damage, birth defects, or requiring hospitalization 2
- Side effects can be classified based on their mechanism, severity, predictability, and relationship to drug dosage 3
Mechanisms of Side Effects
Most common side effects are linked to the pharmacology of medications through two main mechanisms 3:
- Pharmacokinetic factors: how the body processes medicines (absorption, distribution, metabolism, excretion)
- Pharmacodynamic factors: how medicines affect the body through their mode of action
Side effects often occur because medications rarely have a single physiological effect and may act on multiple systems simultaneously 3
Common Types of Side Effects
Gastrointestinal Effects
- Nausea, vomiting, diarrhea, and abdominal pain are common with many medications including immunomodulators like cyclosporin 4
- GI upset is frequently reported with medications such as methotrexate, azathioprine, and apremilast 4
Dermatologic Reactions
- Skin reactions range from mild rashes to severe conditions 4
- Injection site reactions (pain, erythema, allergic effects) are common with injectable medications like PCSK9 inhibitors 4
- Application site stinging or burning is the most common adverse effect with topical medications like crisaborole 4
Neurological Effects
- Headache, dizziness, and drowsiness are frequently reported with many medications 4, 5
- Psychiatric effects may include agitation, anxiety, insomnia, and in some cases depression 4, 5
Cardiovascular Effects
- Blood pressure changes and heart rate alterations can occur with medications like stimulants used for ADHD 4
- Orthostatic hypotension is reported with some antipsychotics 4
Metabolic Effects
- Weight changes (both gain and loss) are associated with various medications 4
- Metabolic disturbances may include changes in glucose metabolism, lipid profiles, and electrolyte imbalances 5
Factors Affecting Side Effect Risk
- Polypharmacy significantly increases the risk of adverse drug reactions - the higher the number of medicines people take, the higher their risk 3
- Patient-specific factors such as age, renal/hepatic function, and genetic variations can affect drug metabolism and side effect susceptibility 5, 3
- Drug interactions can potentiate side effects or create new ones 6, 3
Monitoring and Management
- Regular monitoring through blood tests and clinical visits is recommended for many medications with potential serious side effects 4
- For medications with narrow therapeutic windows or serious potential side effects (like clozapine), specific monitoring protocols are essential 4
- Dose adjustments may be necessary for special populations such as elderly patients, those with renal/hepatic impairment, or patients with genetic variations affecting drug metabolism 5
Categorizing Reactions to Medications
- Drug allergy: Involves immunological mechanisms, may be severe, tends to be reproducible, and may cross-react with structurally related drugs 7
- Drug side effects: More common and predictable, vary in severity, and depend on the drug's pharmacological action 7
- Drug intolerance: Tends to be less severe and may depend on individual susceptibility factors 7
Clinical Decision-Making
- The decision to prescribe a medication with a history of previous adverse reaction requires careful assessment of risks and potential benefits 7
- Some reactions constitute absolute contraindications, while others may be mild and manageable 7
- Understanding the mechanism of side effects can help predict and prevent harmful interactions and unwanted responses 3