DRUG INTERACTIONS IN DENTISTRY- ODONTOS DENTAl HOSPITAL

DRUG INTERACTIONS IN

DENTISTRY

INDEX

 Pages-

1-2                             Introduction & definition

3                                Antibiotics, Antifungals, antiinfectives

4-7                            Antibiotics/oral contraceptives;antibiotics-   

                                                                             enzyme induction                      

                                                                                                          

7-8                           Antibiotics/Cationic agents

9 -13                       LA & vasoconstrictor interactions

14                           Drugs causing P450 enzyme induction

15-16                     Opioid analgesic interactions

17-18                     Serotonin Syndrome

19-21                    NSAID interactions

22                          References & Conclusion

DEFINITION-

Drug interaction may be defined as a measurable modification (in magnitude and/or duration) of the action of one drug by prior or concomitant administration of another substance, including prescription, non-prescription drugs, food, alcohol, cigarette smoking or diagnostic tests.

The mechanism of drug-drug interactions can be categorized

    into 5 major areas:

Ø Additive or synergistic pharmacological responses

Ø Antagonistic pharmacological responses

Ø Incompatibility

Ø Common pharmacokinetic pathways

Ø Altered defense mechanism of the host

Ø ADDITIVE OR SYNERGISTIC PHARMACOLOGICAL RESPONSE

EXAMPLE:

    When opioid analgesics such as hydrocodine or oxycodine are prescribed for pain and phenothiazine anti-emetics such as promethazine are prescribed for nausea, each causes sedation and will have an additive effect of potentially excessive sedation.

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Ø ANTAGONISTIC PHARMACOLOGICAL RESPONSE

 EXAMPLE:

    Patients treated for attention deficit disorder may be more difficult to sedate with benzodiazepines such as midazolam because of the stimulant effects of psychostimulants

Ø INCOMPATIBILITY

 EXAMPLE:

•         When the antibiotic vancomycin is administered parenterally through the same intravenous line either before or after the antibiotic ceftazidime, a cephalosporin, a precipitate will be formed which may occlude the line. Thus to avoid this ceftazidime should be administered first and the intravenous line should be flushed before administering vancomycin.

•         Tetracycline antibiotics such as doxycycline form insoluble complexes called chelates with divalent cations, such as calcium or magnesium. Therefore, if doxycycline is taken with milk, other dairy products or antacids, a chelate will form and doxycycline will not be absorbed in the GIT but will be excreted. To avoid this tetracyclines should not be administered within 2 hrs of calcium sources.

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Ø COMMON PHARMACOKINETIC PATHWAY

  EXAMPLE:

  The drug probenecid was designed to occupy the tubular secretion site for organic acids in the kidney. By administering probenecid to a patient, their kidneys did not tubularly secrete other organic acids such as penicillins, prolonging the length of time that the penicillin stayed in the body.

    ( this drug interaction was utilized to preserve the small supplies   of penicillin antibiotics when treating the wounded during          World War II) 

ANTIBIOTICS, ANTIFUNGALS AND OTHER ANTI-INFECTIVE AGENTS

Antibiotic prophylaxis before treatment for periodontal patients is required in following cases:

Ø Patients at risk of developing endocarditis

Ø Patients with prosthetic cardiac valve

Ø Congenital heart disease

Ø Orthopedic joint replacement

Ø Patients who have received an organ transplant

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ANTIBIOTICS 

                    &

           

                 ORAL CONTRACEPTIVES

Mechanism of interaction:

  

  The mechanism in this interaction involves the enterohepatic recycling of the conjugated estrogen excreted in the bile, reactivated by the gastrointestinal flora and reabsorbed as active drug. Because today’s oral contraceptives are low-dose or very low-dose estrogen products, it is theorised that even small decreases in estrogen absorption could render the pill ineffective.

Table: Inhibition of cytochrome P450 enzymes by antibiotics, antifungals

and anti-infectives which increase interacting drug effects

                                              

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kz

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Ø The macrolide antibiotic azithromycin does not inhibit hepatic enzymes and is a safe alternative in patients taking these interacting medications.

Ø  Nystatin may be used as an alternative antifungal for mild oral fungal infections in patients who are not immunocompromised, but true therapeutic alternatives do not exist for treatment with azole anti-fungals.

Ø Metronidazole is used to treat the anaerobic component of oral infection with penicillin treating the aerobic component, clindamycin may be used alone as an alternative to treat those mixed infections.

Ø ANTIBIOTICS Vs CATIONIC AGENTS

Ø Several agents can substantially reduce the absorption of fluoroquinolones and tetracyclines thereby causing treatment failure.

Ø Divalent cations (calcium and magnesium) and trivalent cations (aluminum and ferrous sulfate) can form insoluble complexes in the gut if they are taken concurrently with fluoroquinolones thus reducing absorption of fluoroquinolones and tetracyclines by 60-75%.

Ø To avoid this, the fluoroquinolone/tetracycline and cation product should be administered at least two hours apart (preferably four hours apart).

Ø Common products containing divalent or trivalent cations are listed in Table .

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TABLE
Common Products Containing Divalent or Trivalent Cations

Aluminum	Alu-Cap, AlternaGel, Amphojel, Basaljel
Aluminum and magnesium combinations	Gelusil, Maalox, Mylanta, Riopan
Calcium	Caltrate, Citracal, Os-Cal, PhosLo, Titralac, Tums
Iron	Feosol, Fergon, Niferex, Nu-Iron, Slow Fe
Magnesium	Almora, Citrate of Magnesia, Mag-Ox 400, Milk of Magnesia, Slow-Mag, Uro-Mag

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LOCAL ANESTHETICS

   The most common time for an emergent or adverse event to occur in a dental office is around the time of the administration of the local anesthetic. Local anesthetics carpules used in dentistry frequently contain a vasoconstrictor in addition to the local anesthetic. The presence of vasoconstrictor provide the greater source for potential drug-drug interactions than does the local anesthetic.

VASOCONSTRICTOR

The vasoconstrictor is present to localise the injection to the site of administration and to decrease bleeding in the area. The two vasoconstrictors commonly used in dentistry are epinephrine and levonordefrin.

Ø Epinephrine stimulates both alpha and beta (both beta-1 and beta-2) adrenergic receptors equally(50/50)

Ø Levonordefrin stimulates alpha receptors 3 times more than beta-1 receptors(75/25).