AIM CONCEPT INTEGRATION
3rd Year MBBS
Foundation Module
Pharmacology
Foundation Module
Pharmacology
Drug Excretion, Dosage Regimens and Pharmacokinetic Principles
Connect drug removal, clearance, maintenance dosing, half-life, steady state and elimination kinetics for rapid KMU revision.
1. THE TOPIC IN ONE CONNECTED FLOW
Drug concentration in the body depends on the balance between drug input and drug removal. Clearance describes how efficiently elimination occurs, while clearance together with volume of distribution determines half-life. These relationships then determine maintenance dosing, accumulation and the time required to approach steady state.
Drug in Body
Distributed drug available for removal
Distributed drug available for removal
→
Elimination
Metabolism + excretion
Metabolism + excretion
→
Clearance
Efficiency of drug removal
Efficiency of drug removal
→
Plasma Half-Life
Depends on Vd and clearance
Depends on Vd and clearance
→
Repeated Dosing
Drug progressively accumulates
Drug progressively accumulates
→
Steady State
Drug input = drug elimination
Drug input = drug elimination
Maintenance dose
→
replaces the amount removed by clearance
→
helps maintain the desired steady-state concentration.
→
replaces the amount removed by clearance
→
helps maintain the desired steady-state concentration.
2. KEY CLINICAL CONNECTIONS
Reduced Clearance
Renal function falls
→
drug removal decreases
→
half-life may increase
→
repeated doses accumulate
→
steady-state concentration rises if dosing is unchanged.
→
drug removal decreases
→
half-life may increase
→
repeated doses accumulate
→
steady-state concentration rises if dosing is unchanged.
Half-Life and Steady State
Longer half-life
→
slower accumulation
→
longer time to approach steady state
→
slower response after changing the maintenance regimen.
→
slower accumulation
→
longer time to approach steady state
→
slower response after changing the maintenance regimen.
Capacity-Limited Elimination
Elimination pathway becomes saturated
→
constant amount is removed per unit time
→
small dose increase may produce a disproportionate rise in concentration, as with phenytoin at higher concentrations.
→
constant amount is removed per unit time
→
small dose increase may produce a disproportionate rise in concentration, as with phenytoin at higher concentrations.
3. AIM HIGH-YIELD INTEGRATION REVIEW
⭐ Excretion physically removes drug or metabolites
→
elimination includes metabolism plus excretion
→
clearance expresses the efficiency of this removal.
→
elimination includes metabolism plus excretion
→
clearance expresses the efficiency of this removal.
Kidney
→
glomerular filtration + tubular secretion − tubular reabsorption
→
final urinary drug excretion.
→
glomerular filtration + tubular secretion − tubular reabsorption
→
final urinary drug excretion.
⭐ Clearance decreases
→
drug remains longer
→
half-life and accumulation tend to increase when other factors are unchanged.
→
drug remains longer
→
half-life and accumulation tend to increase when other factors are unchanged.
Maintenance dosing rate
→
target concentration × clearance ÷ bioavailability
→
greater clearance requires greater replacement dosing.
→
target concentration × clearance ÷ bioavailability
→
greater clearance requires greater replacement dosing.
Young’s and Dilling’s formulae
→
use age
→
Clark’s formula
→
uses body weight in pounds.
→
use age
→
Clark’s formula
→
uses body weight in pounds.
⭐ t½ = 0.693 × Vd ÷ clearance
→
larger Vd prolongs half-life
→
greater clearance shortens it.
→
larger Vd prolongs half-life
→
greater clearance shortens it.
First-order kinetics
→
constant fraction removed
→
relatively constant half-life
→
predictable approach to steady state over about 4–5 half-lives.
→
constant fraction removed
→
relatively constant half-life
→
predictable approach to steady state over about 4–5 half-lives.
AIM Exam Trap:
First-order
→
constant fraction eliminated;
zero-order
→
constant amount eliminated. Do not interchange these two descriptions.
First-order
→
constant fraction eliminated;
zero-order
→
constant amount eliminated. Do not interchange these two descriptions.