1. DRUG INTERACTIONS I Lecture #36

2. Drug Interactions Terms Therapeutic Drug Interaction ADR Additive Synergism

3. DDIs PD – complementary responses – opposing responses PK – induce metabolism – inhibit metabolism – reduce absorption – decrease volume distribution – alter renal clearance

4. PD nAChR = nicotinic acetylcholine receptor GABA A =  - aminobutyric acid receptor Mutual Sedative Effects No Counter Ion competitive antagonist GABA A agonist

5. PD μ-opioid receptor competitive antagonist μ-opioid receptor agonist NMDA = N-methyl-D-aspartate receptor for opioid overdose opioid analgesic

6. PK: Induce Metabolism CYP2C9 anticoagulant antibiotic warfarin

8. PK: Inhibit Metabolism Sedative HIV protease inhibitor

9. PK: Inhibit Metabolism antibiotic Metabolites CYP3A4 inhibits

10. PK: Reduced Absorption antacid log P = 4.63 + reduce gastric pH hydrophobic drug = Decreased Absorption

11. PK: Decrease Volume Distribution log P = 3.44 log P = 1.26 Quinidine displaces digoxin from tissues Reduces volume distribution (V)

12. PK: Renal Clearance Na + Lithium

13. Drug Combinations: Inhibit Metabolism HIV protease inhibitor CYP3A4 inhibitor Decrease Clearance Increase Oral Bioavailability  = 12 hr   = 8 hr

14. Drug Combinations: Inhibit Metabolism Parkinson’s Disease

15. Drug Combinations: Inhibit Metabolism Metabolites renal dehydropeptidase penicillin antibiotic dehydropeptidase inhibitor

16. PK: Inhibit Bacterial Enzymes  -lactam antibiotic bacterial  -lactamase Inactive antibiotic mechanism-based β-lactamase inhibitor

17. Interaction Types Mutual Effects – Competing for the same target Bidirectional Effects – Unidirectional Effects – A  B Beneficial Interactions

18. Mutual Effects

20. D = Displaced C = Control Total Unbound

22. Mutual Effects anti-seizure Extraction Ratio?

23. Bidirectional anti-seizure diuretic Absorption diuretic anti-seizure Renal Clearance

24. Unidirectional Antibiotic Metabolites Chronic Obstructive Pulmonary Disease CYP1A2 Antibiotic Metabolites No Effect

25. Unidirectional

26. enoxacin