TOBACCO’S INTERACTION WITH DRUGS Julie C. Kissack, Pharm.D., BCPP, FCCP Harding University College of Pharmacy May 14, 2015

LEARNING OBJECTIVES 1. Recognize nicotine product attributes that are implicated in drug-drug interactions. 2. Describe how ingestion of tobacco products impact medication levels. 3. Analyze and apply techniques to manage medication therapy when a person stops smoking cigarettes.

AS A CLINICIAN, HAVE YOU…..  Worked with patients who are tobacco users?  Provided support to help smoker quit?  Recognized that efficacy and/or side effects associated with medication treatment for chronic illness changes when a person quits smoking?

ARKANSAS CIGARETTE USE 2013  Overall cigarette use in adults % (males = 26.7%, females = 25.2%)  Overall use in high school age students – 19.1% (males = 22.2%, females = 16.1%) vs national – 15.1%  e-cigarette use by middle school students in % - increase to 3.9% in 2014; in high school students 2013 use 4.5% - increase to 13.4% in 2014 CDC: Behavioral Risk Factor Surveillance System (BRFSS). CDC Annual Youth Tobacco Survey

NICOTINE ATTRIBUTES  Toxic substance  Psychoactive component of tobacco products  Genetic makeup individualizes a person’s response to nicotine

GENETIC INFLUENCE  Nicotinic receptor α 5 subunit (CHRNA5 ) = NICOTINE DEPENDENCE and Cytochrome P450 2A6 (CYP2A6 ) genotypes influence smoking cessation success and response to pharmacotherapy.  Slow vs fast metabolism  Gender

DRUG-DRUG INTERACTIONS  Combustible products from tobacco smoke cause the clinically significant drug interactions, not nicotine.  Constituents in tobacco smoke (e.g., polycyclic aromatic hydrocarbons) may enhance the metabolism of other drugs, resulting in an altered pharmacologic response.  Pharmacokinetic interactions  Pharmacodynamic action Any change in tobacco use status may affect clinical response to medications

CYTOCHROME P-450 ENZYMES  1A2  2D6  3A4 Cigarette smoke may stimulate these enzyme systems thus causing a decreased medication effect

CAFFEINE  Metabolized through cyp1A2 enzyme system  Smoking cessation allows the cyp1A2 system to normalize  Essential to discuss caffeine intake and adjustment when a smoker is attempting a quit attempt.

SPECIFIC DISEASE STATES FOCUS  Cancer  Cardiovascular Disease  Psychiatric Illness

CIGARETTE SMOKE IMPACT ON CANCER TREATMENTS Oncology AgentsEffect irinotecan (Camptosar)Decreased efficacy erlotinib (Tarceva)Decreased efficacy anastrozole (Arimidex) Decreased efficacy bicalutamide (Casodex) Decreased efficacy everolimus (Afinitor) Decreased efficacy exemestane (Aromasin) Decreased efficacy docetaxel (Docefrez) Decreased efficacy

SMOKING EFFECTS ON SELECT CARDIOVASCULAR MEDICATIONS Cardiovascular Medications Effect propranolol (inderal)Increased clearance of propranolol thus it is less efficacious verapamil (Calan) flecanide (Tambocor)Increased clearance; may need to increase flecanide dose mexiletine (Mexitil)Increased clearance lowering mexiletine level approximately 25% warfarin (Coumadin)Decreased efficacy

RX FOR CHANGE  rxforchange.ucsf.edu/  Drug Interaction Sheet

SMOKING EFFECTS ON MEDICATIONS USED TO TREAT MENTAL ILLNESS  See Table 1

PATIENT CASE  32 year old treated for diabetes mellitus with insulin. Other medications include lisinopril 20 mg, and propranolol. On May 5, 2015 lab report reveals HbA1c – 6%. She informs you today that she plans to try again to quit smoking. She asks for your advice about medications to help her quit.  How will you manage her medication treatment if she is successful in her quit attempt?

ARKANSAS TOBACCO QUITLINE  QUIT-NOW ( )  obaccoprevent/pages/tobaccoquitline.aspx obaccoprevent/pages/tobaccoquitline.aspx

REFERENCE LIST 1. Arrojo-Romero, M., et al., Caffeine consumption in a long-term psychiatric hospital: Tobacco smoking may explain in large part the apparent association between schizophrenia and caffeine use. Schizophr Res Feb 20. pii: S (15) doi: /j.schres [Epub ahead of print] 2. Chaudhary KR, Batchu SN, Seubert JM. Cytochrome P450 enzymes and the heart. IUBMB Life 2009 Oct;61(10): doi: /iub Chena L, Bierut LJ. Genomics and personalized medicine: CHRNA5-CHRNA3-CHRNB4 and smoking cessation treatment. J Food Drug Anal December ; 21(4): S87–S90. doi: /j.jfda Chen L, Bloom AJ, Baker TB, Smith SS, Piper ME, Martinez M, et al. Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Addiction. 2014;109(1):128–137. doi: /add Clerici M, Colombo G, Secundo F, Gagliano N, Colombo R, Portinaro N, Giustarini D, Milzani A, Rossi R, Dalle-Donne I. Cigarette smoke induces alterations in the drug- binding properties of human serum albumin. Blood Cells Mol Dis Apr;52(4): doi: /j.bcmd de Jong FA, Sparreboom A, Verweij J, Mathijssen RHJ. Lifestyle habits as a contributor to anti-cancer treatment failure. Eur J Cancer 2008;44: Elsherbiny ME, Brocks DR. The ability of polycyclic aromatic hydrocarbons to alter physiological factors underlying drug disposition. Drug Metab Rev 2011 Nov;43(4): doi: / Epub 2011 Aug Gagne JJ, Bykov K, Choudhry NK, Toomey TJ, Connolly JG, Jerry Avorn J. Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison. BMJ 2013;347:f5307. doi: /bmj.f5307 (Published 17 September 2013) 9. Hukkanen J1, Jacob Iii P, Peng M, Dempsey D, Benowitz NL. Effects of nicotine on cytochrome P450 2A6 and 2E1 activities. Br J Clin Pharmacol Feb;69(2): doi: /j x. 10. Kennedy WK, Jann MW, Kutscher EC. Clinically significant drug interactions with atypical antipsychotics. CNS Drugs (2013) 27:1021–1048. DOI /s Kumar S, Rao PS, Earla R, Kumar A. Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems. Expert Opin Drug Metab Toxicol Mar;11(3): doi: / Epub 2014 Dec Nadkarni A, Oldham MA, Howeard M, Berenbaum I. Drug-drug interactions between warfarin and psychotropics: updated review of the literature. Pharmacotherapy Oct;32(10): doi: /j Petros WP, Younis IR, Ford JN, Weed SA. Effects of tobacco smoking & nicotine on cancer treatment pharmacotherapy. Pharmacotherapy 2012 Oct;32(10):. doi: /j /j Schaffer SD1, Yoon S, Zadezensky I. A review of smoking cessation: potentially risky effects on prescribed medications. J Clin Nurs Jun;18(11): doi: /j x. 15. Zale EL, Dorfman ML, Hooten WM, Warner DO, Zvolensky MJ, Ditre JW. Tobacco smoking, nicotine dependence, and patterns of prescription opioid misuse: results from a nationally representative sample. Nicotine Tob Res Oct 25. pii: ntu227. [Epub ahead of print]