Pharmacodynamics & Kinetics – FCPS Part 1

PHARMACOKINETICS

Pharmacokinetics describes what the body does to a drug: absorption, distribution, metabolism and excretion (ADME).

Bioavailability (F)

Bioavailability is the fraction of an administered dose that reaches systemic circulation in unchanged form.

Route	Bioavailability
IV	100%
Oral	Variable; affected by absorption and first-pass metabolism
Sublingual	Often avoids much of the first-pass effect
IM/SC	Depends on drug and local absorption

First-pass metabolism: A drug absorbed from the gastrointestinal tract may undergo metabolism in the intestinal wall and liver before reaching systemic circulation.

Volume of Distribution (Vd)

Vd estimates how extensively a drug distributes outside the plasma.

Vd= Amount of drug in body \ Plasma drug concentration

Vd	Interpretation
Low	Drug mainly remains in plasma
Moderate	Drug distributes into extracellular fluid
High	Extensive tissue distribution or tissue binding

Drugs bound strongly to plasma proteins often have a relatively low Vd.
Lipid-soluble drugs may distribute widely into tissues.
Vd is an apparent volume, not necessarily an actual anatomical volume.

3. Clearance (CL)

Clearance is the volume of plasma from which a drug is completely removed per unit time.

CL= Rate of drug elimination \ Plasma concentration

Total clearance combines renal, hepatic and other routes of elimination.

4. Half-life

Half-life is the time required for plasma drug concentration to fall by 50% during elimination.

Percentage remaining after each half-life

Half-lives elapsed	Drug remaining	Drug eliminated
1	50%	50%
2	25%	75%
3	12.5%	87.5%
4	6.25%	93.75%
5	3.125%	96.875%

MCQ tip: Steady state is generally approached after about 4–5 half-lives with repeated dosing or continuous infusion, assuming first-order kinetics.

Loading and Maintenance Doses

Dose	Purpose	Main determinant
Loading dose	Reaches target concentration quickly	Vd and target concentration
Maintenance dose	Replaces drug eliminated over time	Clearance and target concentration

Drug Metabolism

Phase I versus Phase II

Feature	Phase I	Phase II
Main reactions	Oxidation, reduction, hydrolysis	Conjugation
Typical system	Cytochrome P450 enzymes for many reactions	Transferase enzymes
Main effect	Introduces or exposes functional groups	Attaches a conjugated group
Outcome	May inactivate, activate or toxify a drug	Often increases water solubility

Not every drug follows both phases, and Phase II reactions do not always follow Phase I.

Enzyme induction versus inhibition

Enzyme induction	Enzyme inhibition
Often increases metabolism of substrate drugs	Often decreases metabolism of substrate drugs
May reduce drug concentrations and efficacy	May increase drug concentrations and toxicity
Examples: rifampin, carbamazepine, phenytoin	Examples: clarithromycin, azole antifungals, ritonavir

The net effect depends on whether the drug is active, inactive or a prodrug.

Elimination Kinetics

Feature	First-order kinetics	Zero-order kinetics
Amount eliminated per unit time	Depends on concentration	Approximately constant
Fraction eliminated per unit time	Approximately constant	Changes with concentration
Typical behavior	Most drugs at therapeutic concentrations	Occurs when elimination pathways become saturated
Examples	Many drugs	Ethanol; phenytoin can show capacity-limited kinetics

Exam tip: Zero-order elimination means a constant amount, not a constant percentage, is eliminated per unit time.

PHARMACODYNAMICS

Pharmacodynamics describes what a drug does to the body, including its effects on receptors, organs and physiological processes.

Efficacy versus potency

Feature	Efficacy	Potency
Meaning	Maximum effect a drug can produce	Dose or concentration needed for an effect
Related to	Maximum response (Emax)	Dose-response curve position
High value means	Greater maximum effect	Less drug needed for a given effect
Clinical importance	Often central to therapeutic choice	Important for dose comparison

Remember: A more potent drug is not necessarily more effective.

Agonists and antagonists

Drug type	Action
Full agonist	Produces maximal receptor-mediated response
Partial agonist	Produces a submaximal response even at full receptor occupancy
Competitive antagonist	Competes at the same receptor site; its effect can often be overcome by increasing agonist concentration
Noncompetitive antagonist	Reduces the maximum response; increasing agonist concentration does not fully overcome the blockade
Inverse agonist	Reduces constitutive receptor activity

Classic examples

Partial agonist: Buprenorphine at μ-opioid receptors.
Competitive antagonist: Naloxone at opioid receptors.
Noncompetitive/irreversible antagonist: Phenoxybenzamine at α-adrenoceptors.
Inverse agonist: Some H₁ antihistamines.

Therapeutic index

The therapeutic index compares a toxic dose with an effective dose.

TI= TD50 / ED50

A larger therapeutic index generally indicates a wider separation between effective and toxic doses.

Drug	Clinical significance
Warfarin	Requires careful monitoring
Lithium	Narrow therapeutic range
Digoxin	Narrow therapeutic range
Aminoglycosides	Concentration and toxicity monitoring may be required

Drug interactions

Interaction	Meaning	Example
Additive	Combined effect approximates the sum of individual effects	Two sedatives causing increased sedation
Synergistic	Combined effect exceeds the expected additive effect	Some combinations of antimicrobial agents
Potentiation	One drug enhances another's effect despite having little effect of its own on that endpoint	Clavulanate protecting amoxicillin from certain β-lactamases
Antagonism	One drug reduces another's effect	Naloxone reversing opioid effects
Tachyphylaxis	Rapid reduction in response after repeated exposure	Ephedrine with repeated doses
Tolerance	Reduced response developing over time	Opioids with repeated use