The best type of mouthguard for a 15 year-old adolescent inv…
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The best type оf mоuthguаrd fоr а 15 yeаr-old adolescent involved in contact sports is
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T½ (HALF-LIFE) & ELIMINATION KINETICS Definitiоn Time required fоr plаsmа drug cоncentrаtion to decrease by 50% after stopping administration t½ is independent of dose (in first-order kinetics) Clinical relevance Determines drug duration of action Influences dosing interval Controls time to reach steady state (Css) Determinants of Half-life t½ ∝ Vd / Clearance Clearance (CL): Inverse relationship; ↓ CL → ↑ t½ Volume of distribution (Vd): Direct relationship; ↑ Vd → ↑ t½ Plasma protein binding (PPB); ↑ PPB → ↓ free drug → ↓ clearance → ↑ t½ (indirect effect) First-Order Elimination Kinetics Definition; Constant FRACTION of drug eliminated per unit time Key featuresRate proportional to concentrationNon-saturable pathwayst½ constant Clinical implicationPredictable eliminationMost drugs follow this pattern Zero-Order Elimination Kinetics Definition: Constant AMOUNT of drug eliminated per unit time Key featuresSaturable metabolism (enzyme capacity limited)Rate independent of concentrationt½ NOT constant (variable) Clinical implicationSmall dose increases → large toxicity riskNonlinear pharmacokinetics High-yield drugsPhenytoinAlcohol (ethanol)WarfarinAspirin (high dose)TheophyllineTolbutamide Steady-State Concentration (Css) Definition: Rate of drug administration = rate of elimination Key principlesReached after ~4–5 t½≈ 97% of Css achieved at this pointSame rule applies for drug elimination after stopping therapy Dose-response relationshipFirst-order: doubling dose → doubles Css (predictable)Zero-order: doubling dose → disproportionate increase (unpredictable toxicity) DeterminantsDepends on dose and clearanceIndependent of half-life (affects only time to reach Css) Clinical Significance Therapeutic effect: Marks onset of full drug response (especially first-order drugs) Dose optimization: Guides maintenance and adjustment strategies Loading dose Rapidly achieves target plasma concentration Avoids waiting multiple t½ Not dependent on clearance for timing Maintenance dose Maintains Css over time Given intermittently or by infusion Adjusted based on clearance Therapeutic drug monitoring (TDM) Maintains drug levels between toxic and subtherapeutic range Important for narrow therapeutic index drugs Key drugs: gentamicin, digoxin, phenytoin, theophylline Question: A patient is taking a drug that demonstrates zero-order elimination kinetics; which of the following best describes its pharmacokinetic behavior?
DRUG ABSORPTION = mоvement оf drug frоm аdministrаtion site into systemic circulаtion (not applicable for intravascular administration since no absorption phase) Drug-related factors affecting absorption Dosage form: controls dissolution rate and bioavailability Administration route: determines exposure to absorption barriers Molecular weight: ↑ MW → ↓ membrane permeability → ↓ absorption Lipid solubility: ↑ lipophilicity → ↑ membrane crossing → ↑ absorption Ionization: ↑ ionization → ↓ lipid membrane permeability → ↓ absorption Ionization & ion trapping Most drugs are weak acids or weak bases existing in equilibrium (ionized ↔ unionized) Governed by Henderson–Hasselbalch relationship (pH vs pKa determines ratio) Unionized form: lipid soluble → ↑ GIT absorption, ↑ renal reabsorption, ↓ excretion Ionized form: water soluble → ↓ membrane passage → ↓ absorption, ↑ excretion Ion trapping: accumulation in compartments where drug becomes ionized due to pH differences 2. Absorption site & membrane-related factors GI transit time: ↑ transit speed → ↓ absorption (reduced contact time) Blood flow: ↑ perfusion at absorption site → ↑ absorption (maintains gradient) Fick’s law of diffusion (core principle): ↑ concentration gradient → ↑ diffusion rate → ↑ absorption ↑ surface area → ↑ diffusion rate → ↑ absorption (e.g., intestinal villi) ↑ membrane thickness → ↓ diffusion rate → ↓ absorption Question: A weakly acidic drug is administered orally and is predominantly in its unionized form in the stomach, facilitating membrane crossing; which factor most increases its gastrointestinal absorption? A weakly acidic drug is administered orally and is predominantly in its unionized form in the stomach, facilitating membrane crossing; which factor most increases its gastrointestinal absorption?