drug interactions i lecture #36. drug interactions terms therapeutic drug interaction adr additive...
DESCRIPTION
DDIs PD – complementary responses – opposing responses PK – induce metabolism – inhibit metabolism – reduce absorption – decrease volume distribution – alter renal clearanceTRANSCRIPT
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