drug interaction polluiton
TRANSCRIPT
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Drug Interactions with SmokingChristian Mark Gerard T. Tuvera RPh
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American Journal of Health-
System Pharmacy.2007;64(18):1917-1921
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Mechanisms for Drug Interactions
with Smoking
Pharmacokinetic Pharmacodynamic
Smoking
When the patient issmoking
Smoking Cessation
When the patient stops
smoking
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ec an sms or rugInteractions with Smoking
Polycyclic aromatic hydrocarbons (PAHs)
products of incomplete
major lung carcinogens Potent inducer
hepatic cytochrome P-450 (CYP)
isoenzymes 1A1, 1A2, and, possibly,2E1
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Other Compounds
acetone
pyridine
heavy metals benzene
carbon monoxide
Nicotine may also interact with hepatic enzymes but
their effects appear to be less significant
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Glucuronide conjugation
Also induced by PAHs
Targets both Phase I and Phase II pharmacokinetic drug interactions are
caused by the PAHs in tobacco smoke,
not the nicotine
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Potential for Drug Interactions
After Smoking Cessation
After a person quits smoking, an importantconsideration is how quickly the inductionof CYP1A2 dissipates
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Clozapine
atypical antipsychotic drug
narrow therapeutic range
metabolized primarily by CYP1A2 also by CYP2C19
possibly CYP3A4
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Study
average plasma clozapine levels ofsmokers were 81.8% of those ofnonsmokers
In male smokers, the plasma clozapinelevels were only 67.9% of theconcentrations of nonsmokers
nonsmokers had 3.2-fold higher plasmaclozapine levels compared with smokers
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Olanzapine
atypical antipsychotic
extensively metabolized by direct N-glucuronidation,
with CYP1A2 and CYP2D6 being minormetabolic pathways
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Smokers have been found to have anapproximate fivefold-lower dose-correctedsteady-state plasma olanzapine
concentration compared with nonsmokers
Olanzapine's clearance is increased by98% in smokers
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Tacrine
drug for the treatment of Alzheimer'sdisease
The half-life of tacrine is decreased by50%
serum tacrine concentrations arethreefold lower in patients who smoke.
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Theophylline's
clearance is increased by 58-100%
half-life is decreased by 63% in smokerscompared with nonsmokers
Plasma theophylline levels should be
routinely monitored in smokers dosages should be adjusted accordingly
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armaco ynam c rugInteractions
significant interaction occurs withcombined hormonal contraceptives
use of oral contraceptives increases therisk of cardiovascular adverse effects,
Specifically thromboembolism (e.g., venousthrombosis, pulmonary embolism), ischemic
stroke, and myocardial infarction (MI) Smoking increases the risk of arterial adverse
events
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the absolute risk of death fromcardiovascular disease in nonsmokingwomen ages 15-34 years is 0.65 per
100,000 and 6.21 per 100,000 for womenages 35-44 years.
This risk greatly increases in women who
smoke: 3.3 per 100,000 women ages 15-34 years versus 29.4 per 100,000 womenages 35-44 years
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Practitioners should target smoking-cessation interventions toward women inthis high-risk population.
If unsuccessful, an alternative form ofcontraception should be recommended,such as a progestin-only contraceptive
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efficacy of inhaled corticosteroids may bereduced in patients with asthma who
smoke
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Study
In patients with mild asthma receiving1000 g daily of inhaled fluticasone
peak expiratory flow at three months wassignificantly greater in nonsmokers (27 L/min)
compared with a decrease of 5 L/min insmokers
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Conclusion
Smokers Increase Dose
Cessation decrease Dose