09/08/2025
overview of Pharmacokinetics (PK) and Pharmacodynamics (PD)
1. Pharmacokinetics (PK)
"What the body does to the drug" – describes absorption, distribution, metabolism, and excretion (ADME).
Step Key Points in Adults Clinical Implications
Absorption • Usually via oral, IV, IM, SC, transdermal, inhalation, etc.
• Influenced by gastric pH (more acidic in adults than in elderly), motility, food-drug interactions. • Antacids can reduce absorption of some drugs (e.g., tetracyclines).
• Food can slow absorption but not always bioavailability.
Distribution • Dependent on plasma protein binding (albumin), body fat %, water content.
• Lipid-soluble drugs distribute more into fat; water-soluble drugs into plasma & tissues. • Hypoalbuminemia ↑ free drug levels (e.g., warfarin toxicity).
• Obesity affects volume of distribution for lipophilic drugs.
Metabolism • Mostly in liver via Phase I (oxidation, reduction, hydrolysis – CYP450 enzymes) and Phase II (conjugation – glucuronidation, sulfation, acetylation). • CYP inducers (e.g., rifampicin) ↑ drug clearance.
• CYP inhibitors (e.g., erythromycin) ↑ drug levels.
Excretion • Mainly renal (glomerular filtration, tubular secretion, reabsorption), some biliary/f***l.
• Renal function declines with age; less so in healthy adults under 60. • Renal dose adjustment required for aminoglycosides, digoxin, etc.
2. Pharmacodynamics (PD)
"What the drug does to the body" – describes drug–receptor interactions, dose–response, and therapeutic/toxic effects.
Concept Description Clinical Example
Receptor binding Drug binds to receptors (agonist, partial agonist, antagonist). β-agonist → ↑ heart rate; β-blocker → ↓ heart rate.
Dose–response relationship As dose ↑, effect ↑ until maximal efficacy (Emax). Morphine: higher doses ↑ analgesia until plateau.
Potency vs. Efficacy Potency: how much drug needed for effect (lower dose = higher potency).
Efficacy: maximum effect achievable. Fentanyl (high potency) vs. morphine (lower potency).
Therapeutic index (TI) Ratio between toxic dose and effective dose.
Narrow TI = requires close monitoring. Warfarin, lithium, digoxin.
Tolerance & resistance Tolerance: reduced response over time.
Resistance: loss of drug effect due to biological adaptation. Tolerance: opioids.
Resistance: antibiotics.
3. PK–PD Integration in Adults
Onset of action: Dependent on absorption rate & distribution.
Peak effect: Linked to drug reaching adequate receptor occupancy.
Duration of action: Controlled by metabolism & elimination rate.
Steady state: Usually reached after ~4–5 half-lives in continuous dosing.
4. Adult-Specific Considerations
Liver disease → ↓ metabolism → risk of toxicity.
Kidney disease → ↓ clearance → adjust dose.
Drug–drug interactions → especially with polypharmacy.
Genetic polymorphisms in CYP450 enzymes → variable responses.
Obesity or low body weight → altered volume of distribution.