Smoking -Drug interactions

1,199 views
984 views

Published on


Pharmacokinetic interactions of Smoking with drugs such as Duloxetine (SNRI Antidepressant), Fluvoxamine (SSRI Antidepressant), Tricyclic Antidepressants ( Amitriptyline, Clomipramine, Imipramine, Nortriptyline, etc.), Benzodiazepines (Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Loprazolam, Lorazepam, Lormetazepam, Nitrazepam, Oxazepam, Temazepam), Antipsychotics (Olanzapine, Clozapine, Haloperidol, Thioridazine, Chlorpromazine and Fluphenazine), Opioids (Methadone, Dextropropoxyphene, Fentanyl, Hydrocodone, Oxycodone, Morphine, Nalbuphine and Pethidine (Meperidine)), NSAIDs (Diflunisal, Phenazone and Phenylbutazone), Paracetamol (Acetaminophen), Theophylline, Caffeine, Tacrine, Insulin and Warfarin are discussed in this presentation.

Pharmacodynamic interactions of Smoking with drugs like Beta blockers, Benzodiazepines, Oral antidiabetics, Inhaled corticosteroids and Oral contraceptive pills are also dealt in this presentation.

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,199
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
32
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Smoking -Drug interactions

  1. 1. Smoking - Drug Interactions Dr. P.Naina Mohamed Pharmacologist
  2. 2. Introduction o Many drug interactions have been reported with cigarette smoking. o Tobacco smoke contains the chemicals like Polycyclic aromatic hydrocarbons (PAHs) and Nicotine which interact with drugs either by• Pharmacokinetic mechanisms (mostly PAHs mediated) or • Pharmacodynamic mechanisms (mostly Nicotine mediated)
  3. 3. Pharmacokinetic Interactions  Pharmacokinetic interactions of smoking may affect the absorption, distribution, metabolism, or elimination of other drugs, which leads to altered pharmacologic response.  Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1.  CYP1A1 is primarily an extrahepatic enzyme found in lung and placenta. The patients with lung cancer have high inducibility of CYP1A1.  CYP1A2 is a hepatic enzyme responsible for the metabolism of a number of drugs and activation of some procarcinogens.  CYP2E1 metabolises a number of drugs as well as activating some carcinogens.  The mechanism involved in most interactions between cigarette smoking and drugs involves the induction of metabolism. Enzyme induction results in faster clearance of medication from the body reducing serum drug levels and decreasing efficacy.  Such interactions may cause smokers to require larger doses of certain drugs through an increase in plasma clearance, a decrease in absorption, enzyme induction or a combination of these factors.
  4. 4. Insulin Smoking interacts with insulin by both pharmacokinetic and pharmacodynamic mechanisms to reduce its efficacy. Smoking Peripheral vasoconstriction which reduces absorption of Insulin from s.c tissue & Increase the levels of hormones opposing Insulin actions Decreased efficacy of Insulins • • • • Caution is advised with concurrent insulin treatment and cigarette smoking. Increased insulin dosages may be required in patients who smoke cigarettes. Conversely, a decrease in the insulin regimen may be necessary in patients who achieve smoking cessation. Close monitoring may be warranted.
  5. 5. Warfarin Tobacco smoke Induce or inhibit warfarin metabolism Increased or decreased international normalized ratio (INR) or prothrombin time • • The effect of smoking tobacco on warfarin metabolism may vary from one patient to the next. The INR or prothrombin time should be monitored carefully if the patient begins or stops tobacco use while taking warfarin.
  6. 6. Duloxetine (SNRI Antidepressant) Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzymes Increased metabolism of Duloxetine Reduced Plasma levels • • • Smokers may have plasma levels 50% lower than nonsmokers due to enzyme induction and increased metabolism. Advise patients to stop smoking during treatment with Duloxetine due to the potential reduction in efficacy. If Duloxetine therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the Duloxetine dosage if needed.
  7. 7. Fluvoxamine (SSRI Antidepressant) Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzymes Increased metabolism of Fluvoxamine Altered drug clearance of Fluvoxamine • • • Serum levels of Fluvoxamine is significantly lower in smokers than nonsmokers. Advise patients to stop smoking during treatment with Fluvoxamine due to the potential reduction in efficacy. If Fluvoxamine therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the Fluvoxamine dosage if needed.
  8. 8. Tricyclic Antidepressants (TCAs) Smoking reduces the plasma levels of Tricyclic Antidepressants like Amitriptyline, Clomipramine, Imipramine, Nortriptyline, etc. Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzymes Increased metabolism of TCAs Reduced Plasma levels • • • Although serum levels of tricyclic antidepressants fall in smokers, free drug levels rise, minimising the clinical significance. Advise patients to stop smoking during treatment with TCAs due to the potential reduction in efficacy. If TCA therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the TCA dosage if needed.
  9. 9. Benzodiazepines Smoking interacts with Benzodiazepines (Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Loprazolam, Lorazepam, Lormetazepam, Nitrazepam, Oxazepam, Temazepam) and Zolpidem and decreases their plasma levels. Tobacco smoke Stimulation of CYP enzymes Increased metabolism of Benzodiazepines Reduced Plasma levels • • • • Plasma concentrations of Benzodiazepines may be decreased up to 50% in smokers compared to non-smokers. Patients should be advised not to smoke cigarettes. An increase in the Benzodiazepines dose should be considered for those patients who smoke concurrently with Benzodiazepines treatment. A decrease in the Benzodiazepines dose should be considered when a patient treated with Benzodiazepines stops smoking.
  10. 10. Antipsychotics Tobacco smoke interacts with Antipsychotics like Olanzapine, Clozapine, Haloperidol, Thioridazine, Chlorpromazine and Fluphenazine and reduces their serum levels. Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzyme Increased metabolism of Antipsychotics Reduced Serum levels • • • Several studies have shown that smokers require and are prescribed higher doses of psychotropic medication than non-smokers. Advise patients to stop smoking during treatment with Antipsychotics due to the potential reduction in efficacy. If Antipsychotics therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the Antipsychotics dosage if needed.
  11. 11. Opioids Smoking decreases the plasma levels of Opioids such as Methadone, Dextropropoxyphene, Fentanyl, Hydrocodone, Oxycodone, Morphine, Nalbuphine and Pethidine (Meperidine). Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzyme Increased metabolism of Opioids Reduced Plasma levels • • Reduction or cessation of tobacco use may increase the risk for methadone toxicity (increasing sedation, confusion, and labored breathing). Patients who use tobacco products concomitantly while on stable opioids may require close monitoring and dose adjustments to avoid opioid toxicity upon reduction or cessation of tobacco products.
  12. 12. • NSAIDs Smoking decreases the plasma levels of NSAIDs such as Diflunisal, Phenazone and Phenylbutazone. Tobacco smoke Stimulation of CYP enzymes Increased metabolism of NSAIDs Reduced Plasma levels May require higher doses • The clearance of diflunisal and phenylbutazone from the body is greater in smokers than in non-smokers.
  13. 13. Paracetamol (Acetaminophen) Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzyme Increased metabolism of Paracetamol Increased Clearance of Paracetamol Reduced Plasma levels • • Advise patients to stop smoking during treatment with Paracetamol due to the potential reduction in efficacy. If Paracetamol therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the Paracetamol dosage if needed.
  14. 14. Theophylline Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzyme Increased metabolism of Theophylline Reduced Plasma levels Higher maintenance dose needed • • • • • In smokers, the halflife of theophylline is reduced, clearance is considerably more rapid, due to enzyme induction. Smokers need higher doses than nonsmokers. For heavy smokers the dose may need to be doubled. Advise patients to stop smoking during treatment with Theophylline due to the potential reduction in efficacy. If Theophylline therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the Theophylline dosage if needed.
  15. 15. Caffeine Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzyme Increased metabolism of Caffeine Reduced Plasma levels Require higher doses • Caffeine is highly dependent on CYP1A2 for its metabolism. • Smokers drink more often tea or coffee than nonsmokers.
  16. 16. • Tacrine Higher doses of Tacrine (Anticholiesterase) are needed to treat Alzheimer’s disease in Smokers. Tobacco smoke Release of polycyclic aromatic hydrocarbons Stimulation of CYP1A2 enzyme Increased metabolism of Tacrine Reduced Plasma levels • • More dose needed Advise patients to stop smoking during treatment with Tacrine due to the potential reduction in efficacy. If Tacrine therapy is required in patients who smoke, consider monitoring for reduced efficacy and adjusting the Tacrine dosage if needed.
  17. 17. • Flecainide The therapeutic efficacy of Flecainide (Antiarrhythmic) is reduced by tobacco smoke. Tobacco smoke Stimulation of CYP enzymes Increased metabolism (O- dealkylation) of Flecainide Increased Clearance from the body Rdeuced therapeutic efficacy • • • Caution is advised with concurrent flecainide treatment and cigarette smoking. Smokers require higher doses to control arrythmia. Monitor patients who smoke cigarettes for decreased efficacy of flecainide, and consider dose increases as warranted.
  18. 18. Pharmacodynamic Interactions • Pharmacodynamic interactions alter the expected response or actions of other drugs. • Such interactions may increase the risk of adverse events. • The nicotine in tobacco is highly addictive and can cause pharmacodynamic interactions.
  19. 19. Beta blockers • Smoking interacts with Beta blockers and reduces their efficacy. Smoking Nicotine mediated Sympathetic activation Increased HR and BP Less effective antihypertensive and heart rate control effects of Beta blockers Smokers may need more dosage • • Smoking can reduce the beneficial effect of beta-blockers on blood pressure and heart rate. Smokers may need larger doses due to increased clearance.
  20. 20. Benzodiazepines • Tobacco smoke interacts with Benzodiazepines like diazepam and chlordiazepoxide pharmacokinetically and pharmacodynamically and reduces their therapeutic efficacy. Tobacco smoke Nicotine mediated CNS Stimulation Counteracts the sedation and drowsiness induced by Benzodiazepines Smokers may need higher dose
  21. 21. Oral Antidiabetics Smoking Impaired Peripheral Insulin action Reduced peripheral glucose utilisation & Increased hepatic glucose production Decreased effectiveness of oral antidiabetics  The effectiveness of oral antidiabetics is reduced by smoking.
  22. 22. Inhaled corticosteroids Smoking Increased Oxidative stress Reduced Histone deacetylase activity Impaired glucocorticoid receptor function Reduced response to corticosteroids  Smokers with asthma may have less of a response to inhaled corticosteroids such as Beclomethasone, Budesonide and Fluticasone.
  23. 23. Combined oral contraceptive pill Smoking Reduced Oxygen carrying Capacity of blood Increased severity of ischemia Increased cardiovascular risk of Oral contraceptives  Smoking also increases the incidence of bleeding which decreases the acceptibility of oral contraceptives.  Oral contraceptive pills are contraindicated in 35 years or more older women who smoke 15 or more cigerettes per day.
  24. 24. CONCLUSION • Numerous drug interactions exist with smoking. • Cigarette smoking can affect drug metabolism via pharmacokinetic and pharmacodynamic mechanisms. • A change in smoking status may put the patients at risk of serious adverse reactions. • Smokers taking a medication that interacts with smoking may require higher dosages than nonsmokers. • Conversely, upon smoking cessation, smokers may require a reduction of dose of an interacting medication. • Patients should be regularly monitored with regard to their smoking status and extent of cigarette consumption and doses of relevant medications adjusted accordingly.
  25. 25. References o o o o o o o o o Stockley’s Drug Interactions, 9th edition. Karen Baxter http://www.micromedexsolutions.com http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087705 http://www.ncbi.nlm.nih.gov/pubmed/10427467 http://www0.health.nsw.gov.au/pubs/2012/pdf/tool_14_medication_in tera.pdf http://www.oregon.gov/oha/amh/tobacco-freedom/docs/druginteractions.pdf http://www.health.gov.bc.ca/pharmacare/pdf/sc-interact.pdf http://www.australianprescriber.com/magazine/36/3/102/4 http://www.merseycare.nhs.uk/Library/What_we_do/Clinical_Services/ Public_Health/Smoking_Interactions.pdf

×