TOBACCO’S INTERACTION WITH DRUGSJulie 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 - 25.9% (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 2013 1.1% - 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 Agents Effect

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

1-800-QUIT-NOW (1-800-784-8669)

http://www.healthy.arkansas.gov/programsservices/tobaccoprevent/pages/tobaccoquitline.aspx

REFERENCE LIST1. 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. 2015 Feb 20. pii: S0920-9964(15)00072-9. doi: 10.1016/j.schres.2015.01.042. [Epub ahead of print]

2. Chaudhary KR, Batchu SN, Seubert JM. Cytochrome P450 enzymes and the heart. IUBMB Life 2009 Oct;61(10):954-60. doi: 10.1002/iub.241.

3. Chena L, Bierut LJ. Genomics and personalized medicine: CHRNA5-CHRNA3-CHRNB4 and smoking cessation treatment. J Food Drug Anal. 2013 December ; 21(4): S87–S90. doi:10.1016/j.jfda.2013.09.041.

4. 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:10.1111/add.12353.

5. 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. 2014 Apr;52(4):166-74. doi: 10.1016/j.bcmd.2013.12.001.

6. de Jong FA, Sparreboom A, Verweij J, Mathijssen RHJ. Lifestyle habits as a contributor to anti-cancer treatment failure. Eur J Cancer 2008;44:374-82.

7. Elsherbiny ME, Brocks DR. The ability of polycyclic aromatic hydrocarbons to alter physiological factors underlying drug disposition. Drug Metab Rev 2011 Nov;43(4):457-75. doi: 10.3109/03602532.2011.596204. Epub 2011 Aug 8.

8. 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: 10.1136/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. 2010 Feb;69(2):152-9. doi: 10.1111/j.1365-2125.2009.03568.x.

10. Kennedy WK, Jann MW, Kutscher EC. Clinically significant drug interactions with atypical antipsychotics. CNS Drugs (2013) 27:1021–1048. DOI 10.1007/s40263-013-0114-6.

11. 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. 2015 Mar;11(3):343-55. doi: 10.1517/17425255.2015.996546. Epub 2014 Dec 24.

12. Nadkarni A, Oldham MA, Howeard M, Berenbaum I. Drug-drug interactions between warfarin and psychotropics: updated review of the literature. Pharmacotherapy. 2012 Oct;32(10):932-42. doi: 10.1002/j.1875-9114.2012.01119.

13. Petros WP, Younis IR, Ford JN, Weed SA. Effects of tobacco smoking & nicotine on cancer treatment pharmacotherapy. Pharmacotherapy 2012 Oct;32(10):. doi:10.1002/j.1875-9114.2012.01117.10.1002/j.1875-9114.2012.01117.

14. Schaffer SD1, Yoon S, Zadezensky I. A review of smoking cessation: potentially risky effects on prescribed medications. J Clin Nurs. 2009 Jun;18(11):1533-40. doi: 10.1111/j.1365-2702.2008.02724.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. 2014 Oct 25. pii: ntu227. [Epub ahead of print]