Drug Interactions in Dentistry Iyad Abou Rabii DDS, OMFS, MRes, PhD
Pharmacodynamics Etymology: Gk, pharmakon, drug, dynamis, power the study of how a drug acts on a living organism, including the pharmacologic response and the duration and magnitude of response observed relative to the concentration of the drug at an active site in the organism.
Pharmacokinetics Etymology: Gk, pharmakon + kinesis, motion the study of the action of drugs within the body, which can, in many respects, be envisioned more accurately as the actions of the body on an administered drug. It includes studies of the mechanisms of drug absorption, distribution, metabolism, and excretion; onset of action; duration of effect; biotransformation; and effects and routes of excretion of the metabolites of the drug.
PK: absorption, distribution, metabolism, elimination CYP450, PgP Absorption from GI tract (laxatives) PD: pharmacological function Anticoagulant drugs plus anticoagulant herbs Sedative herbs plus anesthesia Negative Most Positive or synergistic Possible PD or PK Decrease side effects PK vs PD
Prilocaine Beta-Blockers Cardiac arrhythmia Cimetidine Decreased hepaticArticaine metabolism of Beta-Blockers Decreased hepatic Articaine of metabolism Cimetidine Decreased hepatic Articaine of metabolism Beta-Blockers Decreased hepatic Etidocaine of metabolismEtidocaine Centrally Active CNS depression Antihypertensives EtidocaineProcaine CNS Depressants CNS depression Local Anesthetics
Amoxicilline & Oral Contraceptive Inefficacy of OC 7 Ampicillin Allopurinol days afteretching of Rash and the end treatment Warfarin Enhance anti- Penicillin coagulation effects Decreases or stop of Warfarin Penicillin effects Ergotamine Increase level of Digoxin Ergotamine Increase digoxin Macrolides Lithium level and effect by Dangerous increase altering intestinal in lithium level Phenytoin Increase flora (lifeMetronidazole Penicillin Tetracycline phenytoinlevel and Decrease effect of threatening) effect by hepatic penicillin enzymes Antibiotics
NSAIDs Adregenic neurons Opposition of their blockers Beta Blockers anti-hypertensive Opposition of their effects anti-hypertensive Heparin Enhanced effects anticoagulation Lithium Decreased effects elimination of their Alpha blockers Opposition of Lithium anti-hypertensive Centrally Active Opposition of their Antihypertensives effects anti-hypertensive Corticosteroids Stomach ulcers and effects bleeding effect Loop Diuretics Diuretics decreased and renal toxic effects of NSAIDs increased NSAIDs
NSAIDs Methotrexate Decreased Vasodilators elimination of their Opposition of Methotrexate (toxic anti-hypertensive Phenytoin Increased plasma effects) effects phenytoin level of Lithium Decreased Other NSAIDs elimination of More side effects Lithium NSAIDs
Paracetamol Phenytoin Increased hepatic Beta Blockers toxicity due to Increased hepatic Paracetamol toxicity Warfarin Enhanced metabolism Barbiturates anticoagulation Increased hepatic alteration effects due to toxicity hepatic Isoniazid Increased Paracetamol to toxicity due metabolism Paracetamol alteration metabolism alteration Paracetamol
Opioid Analgesics Antihistamines CNS and Respiratory depression Barbiturates CNS and Respiratory depression, when injected together hypo-tension is resulted Anti-hypertensive Increased effects of anti- hypertensives (hypotension) Cimetidine Decreased metabolism of opioids (high serum levels) Local Anesthetics CNS and Respiratory depression MAOIs Hypertension or hypotension (combination not recommended) Opioid Analgesics
Drugs and food• Most oral drugs are best given with or after food.• However, the following oral drugs should be given at least 30 min before food, as their absorption is otherwise delayed: – Aspirin – Erythromycin – Paracetamol/acetoaminophen – Penicillins (some) – Rifampicin – Tetracyclines (except doxycycline
Drugs and Foods• Grapefruit juice disturbs absorption of ciclosporin, calcium channel blockers (e.g. nifedipine), or terfenadine.• Grapefruit juice and drinks that contain grapefruit juice or fresh, canned, or frozen grapefruit, may also alter the metabolism of several drugs, increasing the toxicity of benzodiazepines, carbamazepine and corticosteroids.
Drugs and Foods• Sour orange juice (e.g. Seville oranges), real lime juice, cranberry, and tangelos (a hybrid of grapefruit), may possibly also have this effect.• The effect appears to last for at least 3 days following ingestion, and could perhaps be longer in some patients.
Drugs and Foods• Citrus juice improves iron absorption, but may cause some medications to dissolve prematurely in the stomach rather than in the intestine as intended. Therefore, taking drugs with carbonated sodas and acid fruit juices is usually recommended.
Drugs and Foods• Calcium, in dairy foods and in calcium supplements, chelates tetracylines, which therefore pass through the body without being absorbed.• Avoid high-calcium foods (milk products or supplements) within 2 h of taking the medication, to minimize this problem.
Drugs and Foods• Iron, magnesium and aluminium in drugs can impair absorption of tetracyclines.• Iron reduces absorption of quinolones (e.g. ciprofloxacin).
Drugs and Foods• Aluminium can impair absorption of azole antifungals.• Phytates in chapattis bind calcium and impair its absorption.
Drugs and Foods• Warfarin can be antagonized by vitamin K in foods such as liver, cabbage, spinach, cauliflower, green tea and broccoli.• Warfarin activity can be enhanced by: – garlic supplements; – cranberry juice (Vaccinium macrocarpon);
Alters pharmacokinetic variables of acetaminophen Decreases blood concentrations of warfarin Produces hypoglycemia when taken with chlorpropamide (oral antidiabetic) Izzo AA, Ernst E. Drugs, 2001, 61:2163-2175 Garlic (Allium sativum)
One case report of coma induced by a combination of kava and alprazolam-a benzodiazepine Extrapyramidal side effects-4 cases of dopamine antagonism-oral, lingual and trunk dyskinesia Do not combine with alcohol, sedatives, tranquilizers Kava (Piper methysticum)
• Decrease blood levels of drugs by shortening gastrointestinal transit time Increase potassium loss Common herbal laxatives: aloe, cascara sagrada, rhubarb, senna Herbal laxatives
Feverfew,(Tanacetum parthenium): mouth sores and irritation if leaves are chewed Feverfew, ginkgo: gingival bleeding due to anticoagulant effect Echinacea (Echinacea purpurea) and kava (Piper methysticum): tongue numbness St John’s wort: xerostomia Yohimbine (Pausinystalia yohimbe): salivation Oral herb use side effects
Anticoagulant herbs: post-op bleeding and interaction with aspirin or other NSAIDs that may cause bleeding. Angelica, asafoetida, anise, astragalus, arnica, bogbean, bromelain, borage seed, capsicum, clove, curcumin, dong quai, fenugreek, fish oil, green tea, horsechestnut, juniper, licorice, meadowsweet, onion, pau d’arco, parsley, passionflower, quassia, red clover, reishi, salvia, turmeric, willow.. Surgery and Dental Procedures
CNS herbs: potential PD interactions with anesthesia: Valerian, kava, St. John’s wort (PK interaction ashwaganda, ginseng, ephedra (now illegal but may be available elsewhere), ginseng, bitter melon, chromium,fenugreek, cinnamon.. Surgery and Dental Procedures
Delayed bone healing (Biphosphanate) Pigmentation of oral mucosa (hydroxychloroquine) Gengival overgrowth and Ulceration Nifedipine Phenytoin Lichenoid Reactions Diuretics (Thiazide) Oral hypoglycimics medications for heart disease and arthritis Gold Salt Drug-Physiology Interaction
Stop herb and supplement use 7-14 days prior to surgery. All pre-surgical patients should be questionedabout herb/supplement use to determinerecent consumption of anticoagulant ordrug-interacting herbs. Drug Interaction Resolution
Require dosage adjustments Temporary or complete elimination of one or the other agent to avoid serious Close monitoring of the subject Total change of drug therapy Drug Interaction Resolution
1. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998;280:1569-1575. 2. Johnston BA. Prevention Magazine assesses use of dietary supplements. HerbalGram 2000;48:65. . 3. Ciocon JO, Ciocon DG, Galindo DJ. Dietary supplements in primary care. Botanicals can affect surgical outcomes and follow-up. Geriatrics. 2004;58:20-24. 4. Tsen LC, Segal S, Pothier M, et al. Alternative medicine use in presurgical patients [published correction appears in Anesthesiology. Nov 2000;93:1371]. Anesthesiology. Jul 2000;93:148-151. 5. Bent S, Ko R. Commonly used herbal medicines in the United States: a review. AmJ Med. 2004;116:478-485. 6. US Food and Drug Administration, Center for Food Safety and Applied Nutrition. Dietary supplement health and education act of 1994. http://vm.cfsan.fda.gov/~dms/dietsuppl.html. Published December 1, 1995. Accessed November 15, 2008. References
7. Yagiela JA, Dowd FJ, Neidle EA. Pharm acology and Therapeutics for Dentistry. 5th ed. St Louis, MO: Mosby; 2004:185-186. 8. Abebe W. An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations. J Dent Hyg. 2003;77:37-46. 9. Abebe W. Herbal supplements having the potential to interfere with blood clotting. GDA Action. 2003;22:23-26. 10. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin PharmTher. 2002;27:391-401. 11. Abebe W. Herbal supplements. Any relevancy to dental practice? N Y State Dent J. 2002;68:26- 30. 12. Ang-Lee KM, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA. 2001;286:208-216. 13. Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto, and Kava [published correction appears in Ann Intern Med. Jan 2003;136:42-53]. Ann Intern Med. Jan 2002;136:42-53. 14. American Academy of Orthopedic Surgeons. Herbal supplements and their interactions with medication. http://orthoinfo.aaos.org /topic.cfm?topic=A00206. Updated July 2007. Accessed November 21, 2008 References