drug interactions i lecture #36. drug interactions terms therapeutic drug interaction adr additive...

DRUG INTERACTIONS ILecture #36

Drug Interactions Terms

• Therapeutic Drug Interaction• ADR• Additive• Synergism

DDIs

• PD– complementary responses– opposing responses

• PK– induce metabolism– inhibit metabolism– reduce absorption– decrease volume distribution– alter renal clearance

PD

nAChR = nicotinic acetylcholine receptor

GABAA=g-aminobutyric acid receptor

MutualSedativeEffects

No Counter Ion

competitiveantagonist

GABAA agonist

PD

μ-opioid receptor competitive antagonist

μ-opioid receptor agonist

NMDA = N-methyl-D-aspartate receptor

for opioid overdose opioid analgesic

PK: Induce Metabolism

CYP2C9

anticoagulant

antibiotic

warfarin

PK: Inhibit MetabolismSedative

HIV protease inhibitor

PK: Inhibit Metabolism

antibiotic

Metabolites

CYP3A4inhibits

PK: Reduced Absorption

antacid

log P = 4.63

+

reduce gastric pH

hydrophobic drug

= DecreasedAbsorption

PK: Decrease Volume Distribution

log P = 3.44

log P = 1.26

• Quinidine displaces digoxin from tissues• Reduces volume distribution (V)

PK: Renal Clearance

Na+ Lithium

Drug Combinations: Inhibit Metabolism

HIV protease inhibitor HIV protease inhibitor

CYP3A4 inhibitor

Decrease ClearanceIncrease Oral Bioavailabilityt = 12 hr t = 8 hr

Drug Combinations: Inhibit Metabolism

Parkinson’s Disease

Drug Combinations: Inhibit Metabolism

Metabolites

renaldehydropeptidase

penicillin antibioticdehydropeptidase

inhibitor

PK: Inhibit Bacterial Enzymes

b-lactam antibiotic

bacterialb-lactamase

Inactive antibiotic

mechanism-basedβ-lactamase inhibitor

Interaction Types

• Mutual Effects – Competing for the same target

• Bidirectional Effects–

• Unidirectional Effects– AB

• Beneficial Interactions

Mutual Effects

Mutual Effects

Mutual EffectsD = DisplacedC = Control

Total

Unbound

Mutual Effects

anti-seizure

anti-seizure

Extraction Ratio?

Bidirectional

anti-seizure

diuretic

Absorption

diureticanti-seizure

Renal Clearance

Unidirectional

Antibiotic

Metabolites

Chronic ObstructivePulmonary Disease

CYP1A2

Antibiotic

Metabolites

No Effect

Unidirectional

Unidirectional

enoxacin