drug interaction polluiton

8/2/2019 Drug Interaction Polluiton

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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

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