Drug interactions

1. Drug interactions Dr. S. Parthasarathy MD., DA., DNB, MD (Acu), Dip. Diab.DCA, Dip. Software statistics PhD (physio) Mahatma Gandhi medical college and research institute , puducherry – India

2. Object + precipitant = ???

3. An interaction is said to occur when the effects of one drug are changed by the presence of another drug

4. Fentanyl and propofol Object precipitant Fentanyl morphine Object , precipitant Object ?? Precipitant ??

5. As anaesthesiologists Why should we know about this

6. Anesthesiologists usually combine drugs to get better action and benefits Yes -- we combine drugs -- but what’s the problem ?? Combining dangerous drugs

8. pharmaceutical interaction • pharmacokinetic interaction • pharmacodynamic interaction (direction and intensity) • 1. antagonistic 1 + 1 = 0 • 2. additive 1+1 = 2 • 3. synergic 1+1 = 3 Types

9. A pharmaceutical interaction is a chemical or physical interaction that occurs before a drug is administered or absorbed systemically. A pharmacokinetic interaction occurs when one drug alters the absorption, distribution, metabolism, or elimination of another. A pharmacodynamic interaction occurs when one drug alters the sensitivity of a target receptor or tissue to the effects of a second drug. Definitions

10. WTG morton Ether day ether by itself could produce hypnosis, reasonable levels of analgesia, and muscle relaxation Guedel’ s stages History

11. No mask induction Pain free Quick recovery No delirium No vomiting Now patients want

12. IV Agents Narcotics Muscle relaxants So what happened to Guedel stages ?? What now ??

13. Agents with low safety margins warfarin, digoxin, and theophylline Conscious sedation Pethidineand MAOI Can we think like this ?? If a drugs fails to act - is it due to a drug interaction ?? Problems Created by Drug–Drug Interactions

14. Combination therapy can reduce toxicity atenololand hydralazine Drugs for Malignancy Drugs for Seizures Why to combine ??

15. Thio and scoline in the IV line Fortwin and taxim Bupivacaine and sodabicarb Adrenaline and soda bicarb pharmaceutical interaction

16. Heparin and hydrocortisone Inactivation of heparin Gentamicin and hydrocortisone Inactivation of gentamicin pharmaceutical interaction

17. Older anaesthetists Trilene and sodalime Younger ones Sevoflurane and sodalime Inhalational agents

18. Absorption distribution, metabolism, elimination of another drug Pharmacokinetic Interactions

19. Oral tetracycline can be inactivated by chelation if it is given together with antacids containing polyvalent cations such as Mg2+, Ca2+, or Al3+. Morphine delays gastric emptying Small gut drugs like para ?? Absorption

20. Adrenaline and local anaesthetics Second gas effect Absorption

21. Possible depression of cardiac function Propofol Agent VRG Distribution

22. Thyrotoxicosis Fever aspirin Plasma proteins

23. Enzyme induction

24. Neostigmine and scoline Ecothiophate and scoline Metabolism

25. sympathetic neurotransmission: CNS transmission Separate topic MAO inhibitors

26. Hepatic blood flow Agents decrease hepatic blood flow Extraction High Lidocaine and propranolol Low-extraction drugs such as diazepam, alfentanil, or mepivacaine have ERs of 0.3 or less. Hepatic Biotransformation

27. etomidate, blocks the synthesis of cortisol and aldosterone by inhibiting the P450-dependent mitochondrial enzymes, 17α-hydroxylase and 11β-hydroxylase. Protease inhibitors such as saquinavir and ritonavir can inhibit the metabolism of midazolam and fentanyl,

28. propofol competitively inhibits CYP3A4, and it can reduce the clearance of midazolam by 37% Co administration of cimetidine and diazepam causes clinically significant elevations in diazepam Alfentanil and erythromycin are both metabolized by CYP3A4, and the antibiotic greatly prolongs the effect of the opioid. Enzyme induction

29. Probenecid and penicillin Quinidine and digoxin The cation system handles the elimination of atropine, isoproterenol, neostigmine, and meperidine Drug Elimination

30. Acidic and alkaline urine

31. Pharmacodynamic Interactions-

32. Direction and intensity • 1. antagonistic 1 + 1 = 0 • 2. additive 1+1 = 2 • 3. synergic 1+1 = 3 Pharmacodynamic Interactions-

33. Rocuronium and vecuronium Nitrous oxide with volatile anesthetics is additive Two benzodiazepines likely to occur when drugs with identical mechanisms are combined Additive (1 +1 = 2)

34. potentiation of opioids by NSAIDs potentiation of nondepolarizing relaxants by the various volatile anesthetics supra-additive interaction occurs between aminosteroid and benzylisoquinolines Synergy

35. neostigmine, naloxone, or flumazenil. An antagonistic interaction occurs between succinylcholine and the nondepolarizing relaxants. drug combination may simultaneously be synergistic and antagonistic for different effects. When butorphanol is combined with midazolam, the mixture increases sedation but has less anterograde amnestic effect than midazolam alone antagonistic drug interactions

36. CLINICAL SCENARIO Pharmacodynamic Interactions Affecting Hemodynamics

37. Rapid-acting β2agonists (albuterol, terbutaline), anticholinergics (ipratropium) phosphodiesterase inhibitors (theophylline). increased risk for tachydysrhythmias and ectopic rhythms. Similar considerations apply to the patient receiving the IV β2agonist, ritodrine, for premature labor. Patients with bronchospasm

38. minimize the use of pancuronium, halothane, ketamine Prone for arrhythmias TCADs induced hypotension ??? TCADs

39. Patients with chronic cocaine intoxication are less of a problem, (THAN ACUTE) but they are still at risk for dysrhythmias (avoiding halothane, pancuronium, atropine, and sympathomimetics) Increase MAC – halothane Cocaine

40. Pharmacodynamic Interactions Affecting Analgesia or Hypnosis

41. THIOPENTONE – FENTANYL – THEN THIPENTONE fentanyl and midazolam are combined for conscious sedation, the opioid is producing sleep as well as analgesia.

42. Thiopental–midazolam interaction has been studied in humans, and the combination was found to have 1.8 times the expected potency of the individual agents PROPOFOL AND MIDAZ

44. IV lignocaine Clonidine. Midaz Decrease MAC of agents

45. Opioid Benzodiazepines Agents α2-Agonist Interactions

46. Agonist and antagonist Buprenorphine and morphine

47. Three-Way Interactions

48. Pharmacodynamic Interactions-

50. Separate topic