CLINICALLY IMPORTANT DRUG INTERACTIONS

1 CLINICALLY IMPORTANT drug RANIPROFESSOR & HODDEPARTMENT OF PHARMACOLOGYDRUG INTERACTION A REVIEWDrug interaction refers to modification of response to one drug by another when they are administered simultaneously or in quick succession. The modification is mostly quantitative, the response is either increased or decreased in intensity, but sometimes it is qualitative, an abnormal or a different type of response is produced. Many medical conditions are treated with a combination of drugs and drug inhibitors + diuretics to treat hypertension + trimethoprim to treat bacterial infection + amiloride to prevent Probenecid + penicillin used in gonococcal Allopurinol + 6-Mercaptopurine & Azathioprine inhibition of metabolism; Reduce dose of 6-MP/azathioprine to 1/3 and used in cancer IMPORTANT drug INTERACTIONSPRECIPITANT DRUGOBJECT DRUGLIKELY INTERACTION AND COMMENTS1.

2 AmpicillinAmoxicillinTe t ra c y c l i n e sOral contraceptivesInterruption of enterohepatic circulation of the estrogen failure of contraception;Advised alternative contraception2. AmpicillinAmoxicillinTe t ra c y c l i n e sOral anticoagulantsInhibition of gut flora decreased vit K production in gut risk of bleeding; Monitor INR and reduce anticoagulant dose if CarbenicillinTicarcillinAspirin and other antiplatelet drugsCause additive platelet inhibition risk of bleeding; Avoid concurrent use. 4. Ceftriaxone CefoperazoneOral anticoagulantsAdditive hypoprothrombinaemia bleeding;Monitor INR and reduce dose of anticoagulant 5. SulfonamidesCotrimoxazolePhenytoinDispla cement + inhibition of metabolism phenytoin toxicity; Avoid concurrent SulfonamidesCotrimoxazoleWarfarin Displacement + inhibition of metabolism + decreased production of vit K in gut risk of bleeding; Monitor INR and reduce dose of SulfonamidesCotrimoxazoleSulfonylureasDi splacement + inhibition of metabolism hypoglycaemia; Avoid concurrent SulfonamidesCotrimoxazoleThiazide diureticsIncreased incidence of thrombocytopenia; Avoid concurrent MetronidazoleProcarbazineTinidazoleGrise ofulvinCefoperazoneCefotetanCeftriaxoneA lcoholAccumulation of acetaldehyde disulfiram like or bizarre reactions.

3 Warn the patient not to drink Metronidazole Tinidazole Lithium salts Decreased excretion Li toxicity; Monitor Li level and reduce lithium dose11. Metronidazole Tinidazole WarfarinInhibition of metabolism risk of bleeding; Avoid concurrent use12. CiprofloxacinNorfloxacinPefloxacinTheoph yllineWarfarinInhibition of metabolism toxicity of object drug ; Monitor and reduce dose of object ErythromycinClarithromycinKetoconazoleIt raconazoleFluconazoleProtease inhibitorsTerfenadineAstemizoleCisapride Inhibition of metabolism by CYP3A4 rise in blood level of object drug dangerous ventricular arrhythmia; Concurrent use ErythromycinClarithromycinKetoconazoleIt raconazoleFluconazoleProtease inhibitorsPhenytoinCarbamazepineWarfarin SulfonylureasDiazepamTheophyllineCyclosp orineHIV protease inhibitorsInhibition of metabolism by CYP3A4 toxicity of object drug .

4 Avoid concurrent use or readjust dose of object ErythromycinClarithromycinKetoconazoleIt raconazoleFluconazoleProtease inhibitorsStatinsInhibition of metabolism, higher risk of myopathy; Avoid concurrent GemfibrozilNicotinic acidStatinsIncreased risk of myopathy;Caution in concurrent TetracyclinesLithium saltsRise in plasma Li level due to decreased excretion; Avoid use of tetracycline or monitor and reduce dose of lithium. 18. Iron saltsCalcium saltsAntacidsSucralfateTe t ra c y c l i n e sFluoroquinolonesDecreased absorption due to formation of complexes in failure of antibiotic therapy; Stager drug administration by 2-3hours19. FurosemideMinocyclineAminoglycosideantib ioticsEnhanced vestibular toxicity; Avoid concurrent use.

5 Additive ototoxicity and nephrotoxicity; Avoid concurrent DiureticsTe t ra c y c l i n eAntianabolic effect of tetracycline increases urea production which is retained by the diuretic; Avoid concurrent DiureticsLithiumDecreased excretion rise in Li level toxicity; Reduce dose of lithium and monitor DiureticsDigoxinHypokalaemia caused by diuretic increases digoxintoxicity; Give K+ sparing diuretic /K+ TetracyclinesChloramphenicolMacrolide antibioticsClindamycinPenicillinsCephalo sporinsBactericidal action of penicillins and cephalosporins may be antagonized by the bacteriostatic antibiotics; Avoid concurrent Clindamycin ErythromycinClarithromycinAzithromycinCh loramphenicolMutual antagonism of antibacterial action due to proximal binding sites on bacterial ribosomes; Avoid concurrent PhenobarbitonePhenytoinCarbamazepineRifa mpinMetronidazoleDoxycyclineChlorampheni colProtease inhibitorsWarfarinCorticosteroidsOral contraceptivesSulfonyl ureasAntidepressantsInduction of metabolism loss of efficacy of object drug ; Avoid concurrent use or increase dose of object drug with NSAIDsCiprofloxacin and Other fluoroquinolonesEnhanced CNS toxicity, seizures.

6 Avoid concurrent Aspirin and other NSAIDsSulfonyl ureasPhenytoinValproateMethotrexateDispl acement and /or reduced elimination toxicity of object drug ;Avoid concurrent use/ substitute NSAID with paracetamol28. Aspirin and other NSAIDsWarfarinHeparinEnhanced risk opf bleeding due to antiplatelet action and gastric mucosal damage;Avoid concurrent use29. Aspirin and other NSAIDsACE inhibitors blockersThiazide diureticsReduced antihypertensive effect due to inhibition of renal PG synthesis;Avoid concurrent use30. Aspirin and other NSAIDsFurosemideReduced diuretic action due to PG synthesis inhibition in kidney; Avoid concurrent use31. AllopurinolAmpicillinIncreased incidence of rashes; Avoid concurrent use32.

7 Chronic alcoholismParacetamolHepatotoxic dose of paracetamol is reduced; Doses < 3 g/day are dopa - carbidopaAntagonism of antiparkinsonian effect;Concurrent use contraindicated34. SildenafilTadalafilNitratesMarked potentiation precipitous fall in BP; Concurrent use contraindicatedDRUG INTERACTIONS BEFORE ADMINISTRATIONC ertain drugs react with each other and get inactivateif their solutions are mixed before Penicillin G or ampicillin mixed with gentamicin or another aminoglycoside Thiopentone sodium when mixed with succinylcholine or Heparin when mixed with penicillin/ gentamicin/ Noradrenaline when added to sodium bicarbonate all patients taking inter acting drugs experience adverse consequences, However, it is prudent to consider the possibility of drug interaction whenever two or more drugs are prescribed to a patient, or any drug is added to what the patient is already taking.