important drug interactions

8/10/2019 Important Drug Interactions

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Mechanisms of drug

interactions Pharmacokinetic interactions

Pharmacodynamic interactions

Combined interactions


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Antacids

Antacids may adsorp drugs in G.I.Tract, thus reducingabsorption. Antacids may alkalinize the urine, thus altering theexcretion of drugs sensitive to urinary pH.

Decreased G.I. absorption of digoxin (NP, not predictable=

occurs only in some patients) Decreased absorption of Fe w/ Ca-containing antacids (P,

predictable = occurs in most patients) Reduced absorption of itraconazole/ ketoconazole due to

increased pH (they require acid for absorption) (P) Decreased absorption of quinolones (HP, highly predictable=

occurs in almost all patients) Decreased absorption of tetracycline (HP) Decreased absorption of thyroxine (NP) Increased renal clearance of salicylates (P).


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Alcohol

Chronic alcoholism results in increasedformation of hepatotoxic acetaminophen

metabolites in overdoses (P) Disulfiram-like reactions :cefamandole,

cefoperazone, cefotetan,metronidazole,chlorpropamide (NP), disulfiram(HP)

Additive or synergistic CNS depression w/CNS depressants (HP)


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Allopurinol

Xanthine oxidase inhibitor

Azathioprine : decreased metabolism

resulting in increased toxicity (P). Mercaptopurine: decreased

metabolism resulting in increased

toxicity.(P). Increased hypoprothrombinemic effect

of warfarin (NP).


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Drugs that may increase

oral anticoagulant effect Amiodarone(P), cimetidine(HP) ,ciprofloxacin(NP),

erythromycin(NP), fluconazole(P), metronidazole(P): inhibits anticoagulant metabolism

Anabolic steroids:alter clotting factor disposition (P) Dextrothyroxine: probably enhanced clotting

catabolism (P).

NSAIDs : inhibition of platelet function (P).

Salicylates : platelet inhibition w/ aspirin but not w/others (HP)

Co-trimoxazole : protein binding displacing (P)


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Drugs that may decrease

anticoagulant effect Barbiturates : enzyme induction (P)

Carbamazepine : enzyme induction (P)

Cholestyramine:reduced absorption(P)

Primidone : enzyme induction (P)

Rifampicin : enzyme induction (P)


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Antidepressants, tricyclic

& heterocyclic Barbiturates:increased metabolism(P)

Cimetidine: decreased metabolism(P)

Clonidine: decreased clonidineantihypertensive effect (P).

Sympathomimetics : increased pressorresponse to epinephrine, norepinephrine,

and phenylephrine (P) SSRIs :inhibit the metabolism of TCAs (P)

Rifampin : increased AD metabolism (P)


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Beta-blockers

Cimetidine : decreased metabolism of propranolol,but less effect (if any) on those cleared by thekidneys, eg. atenolol, nadolol (P)

Enzyme inducers : enhanced BBs metabolism (P) NSAIDs :reduce antihypertensive effect of BBs (P)

Inhibition of glucose recovery from insulinhypoglycemia; inhibition of symptoms of

hypoglycemia (except sweating) (P) Prazosin: increased first-dose syncope (P)


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Ca channel blockers

Verapamil, diltiazem & perhaps nicardipine (but notnifedipine) inhibit hepatic metabolising enzymes.Metabolism of CCBs subject to induction &

inhibition. Carbamazepine: decreased carbamazepine

metabolism w/ diltiazem & verapamil; possibleincrease in CCB metabolism (P)

Cimetidine : dereased metabolism of CCBs (NP)

Cyclosporine : decreased cyclosporine metabolismw/ diltiazem, verapamil, nicardipine (P)

Rifampin : increased metabolism of CCBs (P)


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Iron (Fe)

Binds w/ drugs in G.I.T. , reducingabsorption

Quinolones : decreased absorption ofciprofloxacin (P)

Tetracycline: decreased absorption oftetracycline;decreased efficacy of Fe (P)

Thyroid hormones : decreased thyroxineabsorption (P)


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NSAIDs

ACEIs : decreased antihypertensiveresponse (P)

Furosemide :decreased diuretic,natriuretic, & antihypertensiveresponse to furosemide (P)

Phenytoin : decreased hepaticphenytoin metabolism (P)


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Quinolone antibiotics

Caffeine : ciprofloxacin, enoxacin, pipemidicacid, & to a lesser extent, norfloxacin,inhibit caffeine metabolism (P).

Sucralfate: reduced G.I.absorption ofciprofloxacin, norfloxacin, & probably otherquinolones (HP)

Theophylline: ciprofloxacin,enoxacin, & to a

lesser extent, norfloxacin inhibit theophyllinemetabolism; gatifloxacin, levofloxacin,lomefloxacin, ofloxacin, & sparfloxacinappear to have little effect.(P)


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Theophylline

Diltiazem : decreased theophylline metabolism (P). Clarithromycin : decreased theophylline metabolism

(NE)

Erythromycin decreased theophylline metabolism(P) Fluvoxamine : decreased theophylline metabolism

(P) Smoking : increased theophylline metabolism (HP) Troleandomycin decrease theophylline metabolism

(P) Verapamil: decreased theophylline metabolism (P) Zileuton : decreased theophylline metabolism(P)


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Azole antifungals

Barbiturates : increased metabolism of itraconazole,ketoconazole,& voriconazole (P)

CCBs : decreased CCB metabolism (P) Carbamazepine :decreased carbamazepine metabolism(P) Cisapride: decreased metabolism of cisapride; possible

ventricular arrhythmias (NP) Rifampin : increased metabolism of itraconazole, ketoconazole

& voriconazole (P). PPIs :decreased absorption of itraconazole & ketoconazole (P) Phenytoin : decreased metabolism of phenytoin w/

fluconazole (P)


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Barbiturates

Induction of hepatic microsomal drug-metabolizing enzymes

Additive CNS depression w/ other CNS

depressants.(HP) Increase the metabolism of BB, CCB,

corticosteroids, doxycycline, estrogen,phenothiazine, quinidine (P)

Increase the metabolism of cyclosporin,methadone, sirolimus, tacrolimus,theophylline (NE)


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Digoxin

Amiodarone : reduced renal digoxin excretion (P)

Diltiazem : increased plasma digoxin (20-30%) dueto reduced renal and nonrenal clearance (P)

Potassium-depleting drugs : increased likelihood ofdigitalis toxicity (P)

Propafenone: increased plasma digoxin levels (P)

Quinidine : reduced digoxin excretion; displacement

of digoxin from tissue binding sites; digitoxin mayalso be affected.(HP)

Verapamil: increased plasma digoxin levels (P)

important drug interactions

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