Dr. Neelam Mittal, Dr. Isha Narang, Dr. H.C Baranwal
Faculty of Dental Sciences I.M.S., B.H.U., Varanasi.

ABSTRACT
The safe and effective drug therapy should be learnt for effective management of medically compromised dental patients. Clinicians should have thorough knowledge of drug’s adverse reactions and their interactions with other drugs taken by medically compromised patients.

INTRODUCTION
The special focusing needs on drug interactions in medically compromised dental patients nevertheless arise to accentuate the complexity or deteriorate the integrity of the management plan but to treat the patient as a whole as it is said “first know the patient and then treat them”. The overall longevity of the life span and tremendous advancements in the medical field has probably rejuvenated the history of drug interactions in the patients requiring dental and medical care simultaneously. Therefore thorough evaluation of patient’s drug history becomes of utmost importance which includes prescription drugs, over the counter drugs, drugs of abuse and herbal medicines. It was reported by Miller et al in 2009 that 57% of the drugs used in dental care has potential to cause life threatening conditions. ^[1] Newer era drugs has resulted in overall longevity in the life span and there is rise in the geriatric population ^[2] taking plethora of medications. ^{[3, 4]} Thus special attention is needed for geriatric age group as it is reported that 40% of patients belonging to this age group take medications from two or more physicians and 12% prescribed by some one else. ^[5] Commonly used drugs are cardiovascular drugs, NSAIDs, gastrointestinal agents and psychotropic and endocrine agents. ^[6] Use of polypharmacy places these patients in higher risk category of adverse drug reactions and drug interactions.
Adverse drug reactions may be unwanted, unintended, preventable or toxic injuries. They include side effects, allergies and toxic reactions. ^[7] Drug interactions occur because of physiological changes in terms of absorption, metabolism and distribution and excretion of drugs. ^[5] Commonly used drugs in dentistry are analgesics [NSAIDs and narcotic drugs] , antibiotics, anti-inflammatory drugs and regional anesthetics. NSAIDs are highly protein bound drugs predisposing them to interact with wide variety of drugs such as ACEI, diuretics, beta blockers, lithium, anticoagulants, sulphonylureas, cyclosporine, phenytoin, valproic acid, digoxin, corticosteroids, aminoglycosides, carbonic anhydrase inhibitors, alcohol, probenacid, ziduvidine, acetaminophen and other NSAIDs.
This article lists the adverse reaction of nonnarcotic analgesics and their drug interactions with few commonly prescribed drugs in medically complex patients.

ADVERSE REACTIONS
NSAIDs show the ceiling effect that limits the maximal level of analgesia and induces side effects like gastrointestinal complications (3-11%), CNS (1-9% incidence of nausea and headache) and prothrombic effects (selective COX-2 inhibitors).^[8]

NSAIDS AND ANTIHYPERTENSIVES
Cyclooxygenase 1 and 2 play vital role in production of vasodilating prostaglandins that increase the renal flow and excretion of sodium and water from the body ^{[9, 10]}. NSAIDS inhibit production of prostaglandins which control renal vasodilatation, glomerular filteration, renal tubular secretion of Na and water ^{[11, 12]}. In particular, the antihypertensive effects of b-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, and diuretics seem to be especially dependent on these prostaglandin mechanisms. ^[13] This is reported that chronic use of NSAIDS increase the blood pressure by 3-6mm of Hg which increases the chances of stroke by 67% and coronary artery disease by 15% in patients with cardiovascular disease.
NSAIDs decrease the therapeutic effects of ACE inhibitors, natriuretic effect of spironolactone, hydralazine’s haemodynamic effects. Using NSAIDs for three weeks or longer reduces the antihypertensive effect of beta blockers. NSAIDs in combination with angiotensin II receptor blockers significantly reduce the glomerular filtration and renal function. Medline search shows that patients taking ACE inhibitors, diuretics or beta blockers may be prescribed NSAIDs provided the duration is four days or less.

NSAIDS AND ALCOHOL
Combination results in increased fecal blood loss due to gastrointestinal ulcers and haemorrhage. ^[14] Thus at least 12 hr gap is recommended between nonselective cyclooxygenase inhibitor particularly aspirin. ^[15] Moreover it is also written on the labels of drugs that there are increased chances of gastrointestinal toxicity with NSAIDS if 3 or more alcoholic drinks are consumed daily. ^[16] Hepatotoxicity is a complication of both chronic alcohol abuse and acute overdoses of acetaminophen. Four grams of acetaminophen is the daily recommended dose for healthy patients and two grams for persons taking 3 or more alcoholic drinks.

NSAIDS AND METHOTRAXATE
Methotraxte is an immunosuppression low therapeutic index drug prescribed for cancers and rheumatoid arthritis patients. ^[17] Concomitant non-steroidal anti-inflammatory drugs appear to increase the risk of serious methotrexate side effects, possibly because of a decrease in prostaglandin- dependent renal perfusion and subsequent elimination of methotraxate. ^{[18, 19]}

NSAIDS AND SELECTIVE SEROTONIN REUPTAKE INHIBITORS
Selective serotonin reuptake inhibitors, namely citalopram (Celexa), S-citalopram (Lexapro), fluoxetine (Prozac), paroxitene (Paxil), and sertraline (Zoloft) have replaced older tricyclic antidepressants like imipramines. Bruising, minor bleeding episodes and epistaxis have been reported after discontinuation of selective serotonin reuptake inhibitors.
While the significance of this interaction with the short-term use of non-steroidal anti-inflammatory drugs for control of postoperative dental pain is unknown, the combination could result in increased postoperative bleeding.

NSAIDS AND ORAL HYPOGYCEMIC AGENTS
It is reported that drugs that inhibit synthesis of PGE improve abnormal insulin secretion in human subjects with Type II diabetes mellitus ^[20]

NSAIDS AND HERBAL MEDICATIONS
Patients rarely gives the history of herbal medication use but natural does not mean safe always. NSAIDS particularly aspirin is known to show additive effects to antiplatelet effects of herbal medications like gingko, garlic, ginger, bilberry, feverfew, ginseng, meadowsweet, willow etc. Thus the concurrent use increases the chances of bleeding. Paracetamol also increases the risk of nephrotoxicity in patients taking herbs like Echinacea and Kawa.

CONCLUSION
Therefore it is concluded that the adverse reactions and serious drug interactions can be prevented by thorough evaluation of patients, Careful monitoring and assessment and systematic review of appointments for the unexpected drug interactions which may occur. Because our knowledge of subject is based on case reports, short clinical trials done on few patients belonging to specific category like elderly or ill patients.

REFERENCES
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More References are available on request.