Pharmacodynamics (PD) describes what a drug does to the body: where it acts, how it produces its effect, and how the size of the effect relates to the dose. Most drugs act by binding to a target — usually a receptor, but also enzymes, ion channels, or transport proteins. Many adverse effects are simply the intended action taken too far (antihypertensive → hypotension, insulin → hypoglycemia, opioid → respiratory depression, anticoagulant → bleeding).

Drug targets

Agonists and antagonists

Selectivity. A drug that prefers one receptor subtype has fewer off-target effects, but selectivity is lost at higher doses. Example: metoprolol and atenolol are beta₁-selective, but at high doses they can block beta₂ receptors and cause bronchospasm in asthma.

Dose–response relationship. As the dose rises, the effect rises until it reaches a maximum (plateau). Beyond this, more drug adds toxicity, not benefit.

"More potent" does not mean "better" or "stronger maximum effect." Exam questions often test this distinction.

Onset, peak, and duration describe the time course of the effect (e.g., rapid-acting vs long-acting insulin). The duration of effect can differ from the plasma half-life when a drug binds irreversibly (aspirin) or has active metabolites.

Receptor adaptation with long-term use

Placebo and nocebo effects — expectation alone can produce improvement or adverse effects; relevant to pain and symptom reporting.

• Extension of the therapeutic effect (dose-related, predictable): hypotension, bradycardia, hypoglycemia, bleeding, sedation, respiratory depression
• Off-target receptor effects: anticholinergic effects of first-generation antihistamines and tricyclic antidepressants (dry mouth, urinary retention, constipation, confusion); beta₂ blockade by nonselective beta blockers (bronchospasm)
• Withdrawal and rebound after abrupt stopping: beta blockers (angina, dysrhythmias), clonidine (rebound hypertension), benzodiazepines and alcohol (anxiety, tremor, seizures), corticosteroids (adrenal insufficiency), opioids (uncomfortable but rarely life-threatening in adults)
• Precipitated withdrawal: giving an antagonist (naloxone) or partial agonist (buprenorphine) to a person physically dependent on full opioid agonists

Pharmacodynamic interactions (effects combine at the target level, not through drug levels)

Serious PD combinations to recognize

• Serotonergic drugs (SSRIs, SNRIs, MAOIs, tramadol, linezolid, triptans, St. John's wort) → serotonin syndrome
• QT-prolonging drugs together (some antipsychotics, macrolides, fluoroquinolones, ondansetron, methadone, amiodarone) → torsades de pointes, especially with low potassium or magnesium
• Multiple anticholinergic drugs in older adults → confusion, urinary retention, falls
• Anticoagulant + antiplatelet + NSAID → bleeding
• Potassium-sparing drugs together (ACE inhibitor or ARB + spironolactone + potassium supplements) → hyperkalemia
• Nonselective beta blockers in asthma — contraindicated; they also mask tachycardia and tremor of hypoglycemia in diabetes (sweating is not masked)

Listed in priority order.

1. Assess the target effect before each dose — the parameter the drug changes: respiratory rate and sedation level before opioids; blood pressure before antihypertensives; apical pulse before digoxin and beta blockers; blood glucose before insulin. Hold and notify when outside the ordered parameters
2. Monitor for extension of the effect, especially after a dose increase, a new interacting drug, or in older adults
3. Screen combinations: opioid + benzodiazepine or other sedatives; serotonergic, QT-prolonging, or anticholinergic combinations
4. Prevent withdrawal and rebound: do not stop beta blockers, clonidine, benzodiazepines, antiepileptics, or long-term corticosteroids abruptly — taper as ordered; ensure these drugs are continued or bridged when the client is NPO
5. Watch for tolerance: rising opioid requirements need reassessment, not assumptions of drug seeking; schedule nitrate-free periods
6. Evaluate effectiveness and document response (pain score, blood pressure, glucose, symptom change)
7. Have reversal agents available for high-alert drugs (naloxone, flumazenil only where appropriate, glucose or glucagon, protamine, vitamin K)

• Take the dose as prescribed; a higher dose is not always more effective and may be more toxic
• Do not stop certain drugs suddenly (beta blockers, clonidine, antiseizure drugs, benzodiazepines, steroids) — ask about tapering
• Avoid alcohol and other sedatives with opioids, benzodiazepines, sleep drugs, and sedating antihistamines
• Check with a pharmacist before adding over-the-counter drugs — many cold remedies, sleep aids, and herbal products add to sedative, anticholinergic, or serotonergic effects
• Physical dependence on a prescribed drug is expected and is not the same as addiction; report cravings or loss of control
• For clients with opioid prescriptions, family members should know how to recognize overdose and use naloxone

Toxicity is often an exaggerated pharmacologic effect, and many antidotes work by receptor antagonism or by removing the drug.

Buprenorphine overdose is less likely to cause fatal respiratory depression alone (ceiling effect), but combinations with benzodiazepines or alcohol can be fatal, and reversal may need higher or repeated naloxone doses.

• PD = what the drug does to the body; PK = what the body does to the drug
• Agonist activates; antagonist blocks; partial agonist (buprenorphine) has a ceiling and can precipitate withdrawal
• Potency = dose needed; efficacy = maximum effect — more potent is not more effective
• Therapeutic index = TD50/ED50; narrow TI (warfarin, digoxin, lithium, phenytoin) needs monitoring
• Beta₁-selectivity is lost at high doses
• Tolerance ≠ physical dependence ≠ addiction
• Abrupt stop of beta blockers or clonidine → rebound (angina, hypertension); taper
• Opioid + benzodiazepine = synergistic respiratory depression (boxed warning)
• Naloxone is shorter-acting than most opioids — reassess for re-sedation
• Flumazenil can cause seizures in chronic benzodiazepine users
• Assess the parameter the drug changes before giving it; hold and notify when outside parameters
• Aspirin's antiplatelet effect lasts the life of the platelet (about 7–10 days)