A drug interaction occurs when one drug alters the activity of another. Pharmacokinetic interactions arise when absorption, distribution, metabolism, or excretion is altered, for example when one drug inhibits or induces a CYP450 enzyme and changes the blood levels of another. Pharmacodynamic interactions arise at the site of action and may be additive, synergistic, or antagonistic. Synergism occurs when two drugs together produce an effect greater than the sum of their individual effects, as seen with trimethoprim and sulfamethoxazole, which block successive steps in bacterial folate synthesis. Antagonism occurs when one drug reduces or blocks the effect of another; naloxone, for example, antagonizes morphine by competitively binding to opioid receptors and is used clinically as an antidote in opioid overdose.
Adverse drug reactions are unwanted, harmful effects that occur at normally therapeutic doses and are classified into types. Type A (augmented) reactions are dose-dependent, predictable from the drug's pharmacology, and are illustrated by bleeding with anticoagulants. Type B (bizarre) reactions are dose-independent, unpredictable, and often immune-mediated, as in drug allergy. A side effect is any effect other than the intended therapeutic effect and may be neutral, beneficial, or harmful, whereas an adverse effect specifically denotes a harmful and undesired outcome. Repeated drug exposure can also lead to drug tolerance, a decreased response that requires higher doses for the same effect, which may be pharmacokinetic in origin (such as increased metabolism), pharmacodynamic in origin (such as receptor desensitization), or behavioral. Tachyphylaxis is a particularly rapid form of tolerance that develops after repeated doses over a short period, as in the rebound congestion seen with prolonged use of nasal decongestant sprays. Drug dependence refers to a state in which discontinuation produces withdrawal symptoms and may be physical, with physiological adaptation, or psychological, with emotional craving, and is characteristic of opioids, benzodiazepines, and alcohol.
Several additional safety concepts complete this picture. Drug allergies are immune-mediated reactions, with Type I immediate IgE-mediated reactions producing anaphylaxis within minutes, as can occur with penicillins, and Type IV delayed T-cell-mediated reactions producing rashes days after exposure. Anaphylaxis itself is a severe, life-threatening, multi-system allergic reaction involving airway swelling, hypotension, urticaria, and bronchospasm, and it is treated with immediate intramuscular epinephrine, followed by antihistamines and corticosteroids. Polypharmacy, generally defined as the simultaneous use of five or more medications, is common in older adults and increases the risk of drug interactions, adverse effects, non-adherence, falls, and cognitive impairment, so regular medication review is essential. A black box warning is the strongest caution the FDA places on a drug label and indicates serious or life-threatening risks, such as suicidality in young adults taking SSRIs, tendon rupture with fluoroquinolones, or heart failure with rosiglitazone, although it does not mean that the drug is banned. Pharmacogenomics studies how genetic variation affects drug response by altering CYP enzymes, transporters, and receptors, and it underlies the move toward personalized medicine, in which drug choice and dose are tailored to a patient's genetic profile. A related concept is the prodrug, an inactive compound that is converted to its active form by metabolism in the body, with examples including enalapril to enalaprilat, codeine to morphine, and levodopa to dopamine, often designed to improve absorption or target delivery.