1. Drug Interactions in Dentistry
Iyad Abou Rabii
DDS, OMFS, MRes, PhD

2. 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.

3. 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.

4.  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

5. Drug - Drug interaction

6. Local Anesthesia Antiarrythmics Cardiac suppression
Anticholinesterases Opposite effects
Antidepressants CNS depression
Antihistamines CNS depression
Antipsychotics CNS depression
Centrally Active CNS depression
Antihypertensives
CNS Depressants CNS depression
Magnesium Sulphate CNS depression
Opoid Analgesics CNS depression
Local Anesthetics

7. Prilocaine Beta-Blockers Cardiac arrhythmia
Cimetidine Decreased hepatic
Articaine metabolism of
Beta-Blockers Decreased hepatic
Articaine of
metabolism
Cimetidine Decreased hepatic
Articaine of
metabolism
Beta-Blockers Decreased hepatic
Etidocaine of
metabolism
Etidocaine Centrally Active CNS depression
Antihypertensives Etidocaine
Procaine CNS Depressants CNS depression
Local Anesthetics

8. 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 (life
Metronidazole
Penicillin Tetracycline phenytoinlevel and
Decrease effect of
threatening)
effect by hepatic
penicillin
enzymes
Antibiotics

9. 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

10. 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

11. 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

12. 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

13. Food - Drug Interaction

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

19. Drugs and Foods
• Iron, magnesium and aluminium in
drugs can impair absorption of tetracyclines.
• Iron reduces absorption of quinolones (e.g.
ciprofloxacin).

20. Drugs and Foods
• Aluminium can impair absorption of
azole antifungals.
• Phytates in chapattis bind calcium and
impair its absorption.

21. 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);

22. Herbal - Drug Interaction

23.  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)

24. • Aspirin – hyphema (blood in eye)
• Acetaminophen - bilateral subdural hematomas
• Warfarin - intracerebral hemorrhage
• Valproate: 2 cases of siezures
Ginkgo

25.  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)

26. •
 Decrease blood levels of drugs by shortening
gastrointestinal transit time
 Increase potassium loss
 Common herbal laxatives: aloe, cascara sagrada,
rhubarb, senna
Herbal laxatives

27. Herbal and Drug - Physiology
Interaction

28.  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

29.  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

30.  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

31.  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

32. Drug Interaction Resolution

33.  Stop herb and supplement use 7-14 days prior
to surgery.
 All pre-surgical patients should be questioned
about herb/supplement use to determine
recent consumption of anticoagulant or
drug-interacting herbs.
Drug Interaction Resolution

34.  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

35. Use Technology - Websites

36. Use Technology - Websites

37. Use Technology – Websites

38. Use Technology – Hand Held

39. Use Technology – Hand Held

40. Use Technology – Hand Held

41. Use Technology – Hand Held

42. Use Technology – PC programs

43.  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

44.  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