Drug Interactions Keeping it all Straight. Peter Lin MD CCFP Director Primary Care Initiatives Canadian Heart Research Centre

Transcription

1 Drug Interactions Keeping it all Straight Peter Lin MD CCFP Director Primary Care Initiatives Canadian Heart Research Centre

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Prescription Drug Use # Drugs Under 65 Over % 27% 2 25 % 21 % 3 13 % 16 % 4 7 % 11 % % 23 %

4 Potential Rate of Drug Interaction 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2 Rx 5 Rx 8 Rx Rate Johnson AG, et al. J Clin Pharmacol Ther 1994;32:

5 Toxic Dosing Useful Dosing

6 Toxic Dosing Toxic Dosing Useful Dosing Useful Dosing

7 Drug Interactions PharmacoDYNAMICS PharmacoKINETICS What the drug does to you. What your body does to the drug.

8 Drug Interactions PharmacoDYNAMICS What the drug does to you. PharmacoKINETICS A bsorption D istribution M etabolism E limination

9 Cytochrome P450 Substrate

10 Substrate Cytochrome P450 Competition Inhibitors Inducers Cupp MJ, Tracy TS. Am Fam Phys 1998;57:107-16

11 Substrate Cytochrome P450 Competition Inhibitors Inducers

12 Substrate Cytochrome P450 Competition Inhibitors Inducers

13 CYP 2 D 6 Inhibitor Fluoxetine Paroxetine Sertraline Quinidine Substrate B-Blockers Desipramine Fluoxetine Paroxetine Codeine Oxycodone Inducer Rifampin Phenobarbital Preskorn SH Clinical Pharmacology of Selective Serotonin Reuptake Inhibitors. 1998; Chapter 7

14 CYP 2 D 6 Inhibitor Fluoxetine Paroxetine Sertraline Quinidine Substrate B-Blockers Desipramine Fluoxetine Paroxetine Codeine Oxycodone Inducer Rifampin Phenobarbital

15 CYP 2 D 6 Inhibitor Fluoxetine Paroxetine Sertraline Quinidine Substrate B-Blockers Desipramine Fluoxetine Paroxetine Codeine Oxycodone Inducer Rifampin Phenobarbital

16 CYP 2 D 6 CYP 2 D 6 10% Caucasians don t have it. 3% Asians/African Americans Converts Codeine to Morphine Spatzeneger M, Jaeger W. Drug Metab Rev 1995;27:

17 CYP 2 D 6 Inhibitor Fluoxetine Paroxetine Sertraline Quinidine Substrate B-Blockers Desipramine Fluoxetine Paroxetine Codeine Oxycodone Inducer Rifampin Phenobarbital Desmeules J, Eur J Clin Pharmacol 1991;41(1):23-26

18 Codeine Chinese, Japanese, Hispanic 1% African 3% Caucasians 1-10% North Africa, Ethiopia, Arab 16-28% CYP 2 D 6 Morphine

19 Terfenadine is a Potassium channel blocker Yap YG et Al Clin Allergy Immunol. 2002;17: Review.

20 Cytochromes are found in: Small Intestine Liver Kidney Lung Brain

21 CYP 3 A 4 Inhibitor Macrolides Antifungals Grapefruit Juice Substrate Cisapride Terfenadine Ca Blockers Sex Hormones Cyclosporine Lovastatin Inducer Rifampin Phenobarbital Dresser GK, et al Clin Pharmacokinet Jan;38(1): Review.

22 CYP 3 A 4 Inhibitor Macrolides Antifungals Grapefruit Juice Substrate Cisapride Terfenadine Ca Blockers Sex Hormones Cyclosporin Lovastatin Inducer Rifampin Phenobarbital Dresser GK, et al Clin Pharmacokinet Jan;38(1): Review.

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24 Ca ++ Michael AC et al Pharmacotherapy 23(7): , 2003

25 + K

26 Torsade de Pointes

27 Fexofenadine Terfenadine 3 A 4

28 Terfenadine Terfenadine Erythro 3 A 4

29 New warning for heartburn drug Propulsid June 30, 1998 Web posted at: 11:15 a.m. EDT (1515 GMT) WASHINGTON (CNN) -- The Food and Drug Administration is urging doctors to try everything else before prescribing Propulsid, a heartburn drug taken by President Clinton, out of concern the drug may cause serious heart problems.

30 Toxic Dosing (160mg) Useful Dosing (40mg)

31 CYP 3 A 4 Inhibitor Macrolides Antifungals Grapefruit Juice Substrate Cisapride Terfenadine Ca Blockers Sex Hormones Cyclosporin Lovastatin Inducer Rifampin Phenobarbital

32 20% 100% Simvastatin 3 A 4 3 A 4 Beaird SL J Am Pharm Assoc 40(5): , 2000

33 100% (20) 100% Simvastatin 3 A 4 3 A 4

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35 3 A 4 3 A 4

36 Felodipine Interactions Bailey DG et al. Clin Pharmacol Ther. 1996;60:25-33

37 3 A 4 3 A 4

38 Sildenafil Interactions PharmacoDYNAMICS PharmacoKINETICS What Sildenafil will do to Bill. What Bill will do to Sildenafil.

39 Sexual Stimulation NO Vasodilation cgmp cgmp Breakdown PDE-5

40 Vasodilation Nitrates NO cgmp PDE-5 cgmp Breakdown Kloner RA, Am J Cardiol Dec 26;96(12B):42M-46M. Epub 2005 Dec 5.

41 Sildenafil CYP 3 A 4 Erythromycin 3-8 x Blood levels after 24 hours Muirhead GJ. Br J Clin Pharmacol. 2002;53(suppl 1):37S

42 Co-morbidity Schizophrenia Gen. Population Smoking Up to 85% 23% Goff et al. J Clin Psych, 2005 Sokal et al. J Nerv Ment Disord, 2004 Carney et al. J Gen Intern Med,

43 30% decrease in Olanzapine in blood plasma eliminated Conley & Kelly, Psychopharmacol Bull, 2007

44 30% increase in Olanzapine in blood plasma eliminated 44 Conley & Kelly, Psychopharmacol Bull, 2007

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49 Thanks for staying awake.