Adverse Drug Reaction

THERAPEUTIC INCOMPATIBILITIES(DRUG INTERACTIONS)Learning Objectives:Define and know the causes and effect of drug interactions.To know the factors that contributes to drug interaction.Differentiate pharmacokinetics and pharmacodynamics drug incompatibilities.To be knowledgeable on different drug-drug, drug-food, and drug-herbal interactions, including their mechanisms.

Drug Interactions

Pharmacokinetic interactions are those that can affect the processes by which the drugs are absorbed, distributed, metabolized, or excreted. AN AGENT ALTERS THE ADME OF THE SECOND AGENTSUCH interactions may result in a change in the drug concentration at the site of action with subsequent toxicity or decreased efficacy.

Pharmacodynamic interaction are those in which drugs having similar or opposing pharmacoligical effects are administered concurrently and situations in which the sensitivity or responsiveness of the tissues to one drug is altered by the another.THERE IS A CHANGE IN DRUG EFFECT BUT NOT IN THE PLASMA CONCENTRATIONThe administration of one drug (A) can alter the action of another (B) by:

3Pharmacokinetic interactions are those that can affect the processes by which the drugs are absorbed, distributed, metabolized, or excreted. AN AGENT ALTERS THE ADME OF THE SECOND AGENTSUCH interactions may result in a change in the drug concentration at the site of action with subsequent toxicity or decreased efficacy.

Pharmacodynamic interaction are those in which drugs having similar or opposing pharmacoligical effects are administered concurrently and situations in which the sensitivity or responsiveness of the tissues to one drug is altered by the another.THERE IS A CHANGE IN DRUG EFFECT BUT NOT IN THE PLASMA CONCENTRATIONThe administration of one drug (A) can alter the action of another (B) by:

Drug InteractionsDrug interactions are said to occur when the effects of one drug are changed by the presence of another drug, herbal medicine, food, drink or some environmental chemical agent. Drug interactions are an increasingly important cause of adverse drug reactions.When dispensing medication against a prescription, pharmacists should always consider the following points:

Determine who is the patient? Is it for a child, an adult or an elderly person? This is very important or it needs to be established because many of the other decisions you may make about the patients therapy will utilize this information. Is the dose of the prescribed item suitable for the patient? Doses of medication will differ for different patients. For example, for many drugs, a childs dose will be less than that for an adult. In addition, there are a number of patient-specific factors that will alter the dose.The condition of the patient should be determined. Special considerations for the presence of renal (kidney) or hepatic (liver) problems. 6Determine who is the patient? Is it for a child, an adult or an elderly person? This is very important or it needs to be established because many of the other decisions you may make about the patients therapy will utilize this information. Is the dose of the prescribed item suitable for the patient? Doses of medication will differ for different patients. For example, for many drugs, a childs dose will be less than that for an adult. In addition, there are a number of patient-specific factors that will alter the dose.The condition of the patient should be determined. Special considerations for the presence of renal (kidney) or hepatic (liver) problems.

The concept of drug interaction often is extended to:Food or certain dietary items influence the activity of a drug.Herbs or other natural products influence the activity of a drug.Environmental chemicals or smoking influences the activity of a drug.A drug causes alterations of laboratory test resultsA drug causes undesired effects in patients with certain disease states.

One of the most important consequences of a drug interaction is an excessive response to one or more agents being used.Drug activity is decreased resulting to loss of efficacy.. THEY MAY BE MISTAKEN FOR THER. Failure or progression of the disease8The concept of drug interaction often is extended to:Food or certain dietary items influence the activity of a drug.Herbs or other natural products influence the activity of a drug.Environmental chemicals or smoking influences the activity of a drug.A drug causes alterations of laboratory test resultsA drug causes undesired effects in patients with certain disease states.

One of the most important consequences of a drug interaction is an excessive response to one or more agents being used.Drug activity is decreased resulting to loss of efficacy.. THEY MAY BE MISTAKEN FOR THER. Failure or progression of the disease

Factors Contributing to Drug InteractionReasons for the occurrence of di10Causes of Drug InteractionsDecreased drug activity with diminished efficacyIncreased drug activity with exaggerated or unusual effectsDrugs with a narrow therapeutic rangeSteep dose response curve e.g. anticoagulant, oral contraceptives, antiepileptics

Digoxin lithium theophylline11Drugs with Narrow Therapeutic IndexAnticoagulants (warfarin, heparin)Levothyroxine sodiumAspirinLithiumCarbamazepinePhenytoinAmino glycoside antibiotics (gentamicin, tobramycin)ProcainamideHypoglycemic agents

Quinidine sulfateDigoxinTheophyllineAminophyllineValproic AcidA toxic dose of these drugs may be only slightly above the therapeutic dose.

12Using Drug-Interaction Information1. Interacting Drugs usually can be used together2. Beneficial Interactions3. Nature of Reports4. Depth of Information5. Current Literature6. Recommendations and Therapeutic AlternativePatients Variable Age Genetic factors Disease states Renal function Hepatic function Alcohol consumption Smoking Diet Individual variation

14Drug InteractionsTHERAPEUTIC INCOMPATIBILITIESClassifications:A therapeutic incompatibility is a problem that occurs when two or more drugs are administered to a patient.

Aka as drug interaction OBJECT DRUG THE ONE THAT IS AFFECTED THEN PRECIPITANT OR INTERACTANT IA THE ONE THAT INDUCES THE INTERACTION

Pharmacodynamic drug interactions are interactions between drugs that have either similar or antagonistic actions. Although drug interactions will affect different patients differently, pharmacodynamic drug interactions are easy to predict and occur in a majority of patients who take the drugs affected. These interactions will, for example, include drugs that compete at the same receptor site or affect the same body systems. A pharmacist can use their knowledge of body systems and about drugs to make a decision as to the importance of the interaction.

15A therapeutic incompatibility is a problem that occurs when two or more drugs are administered to a patient.

Aka as drug interaction OBJECT DRUG THE ONE THAT IS AFFECTED THEN PRECIPITANT OR INTERACTANT IA THE ONE THAT INDUCES THE INTERACTION

Pharmacodynamic drug interactions are interactions between drugs that have either similar or antagonistic actions. Although drug interactions will affect different patients differently, pharmacodynamic drug interactions are easy to predict and occur in a majority of patients who take the drugs affected. These interactions will, for example, include drugs that compete at the same receptor site or affect the same body systems. A pharmacist can use their knowledge of body systems and about drugs to make a decision as to the importance of the interaction.

AbsorptionPharmacokinetic interactionChanges in GI pHThe non-ionized form of the drug (more lipid soluble) will be absorbed more readily than ionized form (more water soluble).

Acidic drugs exist primarily in the non-ionized form in the upper region of the GI tract (having a lower pH).

17The non-ionized form of the drug (more lipid soluble) will be absorbed more readily than ionized form (more water soluble).

Acidic drugs exist primarily in the non-ionized form in the upper region of the GI tract (having a lower pH).

Common drug InteactionsCommon Drug InteractionKetoconazoleAntacid/milk/H2 antagonistLessen therapeutic effectCommon Drug Interaction20

Alteration of Motility/Rate of Gastric EmptyingCatharticsOther drugsDecreased effect of drugCommon Drug Interaction22Common drug InteactionsCommon Drug Interaction23Common drug InteactionsCommon Drug InteractionResult: Reduced serum adsorption of flouroquinolones such as moxifloxacin.Avoid: antacids, milk, iron supplements, yogurt and sucralfate.

24Result: Reduced serum adsorption of flouroquinolones such as moxifloxacin.Avoid: antacids, milk, iron supplements, yogurt and sucralfate.

Common drug InteractionsCommon Drug Interaction-can decrease GI motility and can influence drug absorption. The effect may be a decreased in absorption, since the reduced peristalsis may retard dissolution and the slowing of gastric emptying may delay absorption from the small intestine, or increased absorption if the drug is retained for a longer period of time in the area from which it is optimally absorbed.

26-can decrease GI motility and can influence drug absorption. The effect may be a decreased in absorption, since the reduced peristalsis may retard dissolution and the slowing of gastric emptying may delay absorption from the small intestine, or increased absorption if the drug is retained for a longer period of time in the area from which it is optimally absorbed.

Common drug InteractionsCommon Drug Interaction increases motility of the upper GI track, it should be anticipatedthat it may influence the absorption of other drugs administered concurrently.

28 increases motility of the upper GI track, it should be anticipatedthat it may influence the absorption of other drugs administered concurrently.

Common drug InteractionsCommon Drug InteractionThe presence of food in the GI tract will reduce the absorption of many anti-infective agents (except penicillin V, amoxicillin, Doxycycline and minocycline).It is generally recommended that the penicillin and tetracycline derivatives as well as certain other anti-infective agents be given at least 1hr before meals or 2 hr after meals, to achieve optimum absorption. For erythromycin stearate formulations should be administered at least 1 hr before meals or 2 hr after a meal, whereas formulations of erythromycin ethylsuccinate may be given without regards to meals30The presence of food in the GI tract will reduce the absorption of many anti-infective agents (except penicillin V, amoxicillin, Doxycycline and minocycline).It is generally recommended that the penicillin and tetracycline derivatives as well as certain other anti-infective agents be given at least 1hr before meals or 2 hr after meals, to achieve optimum absorption. For erythromycin stearate formulations should be administered at least 1 hr before meals or 2 hr after a meal, whereas formulations of erythromycin ethylsuccinate may be given without regards to meals

AbsorptionPharmacokinetic interactionAlteration of GI FloraThe non-ionized form of the drug (more lipid soluble) will be absorbed more readily than ionized form (more water soluble).

Acidic drugs exist primarily in the non-ionized form in the upper region of the GI tract (having a lower pH).

32The non-ionized form of the drug (more lipid soluble) will be absorbed more readily than ionized form (more water soluble).

Acidic drugs exist primarily in the non-ionized form in the upper region of the GI tract (having a lower pH).

Common drug InteractionsCommon Drug InteractionThe presence of food in the GI tract will reduce the absorption of many anti-infective agents (except penicillin V, amoxicillin, Doxycycline and minocycline).It is generally recommended that the penicillin and tetracycline derivatives as well as certain other anti-infective agents be given at least 1hr before meals or 2 hr after meals, to achieve optimum absorption. For erythromycin stearate formulations should be administered at least 1 hr before meals or 2 hr after a meal, whereas formulations of erythromycin ethylsuccinate may be given without regards to meals34Common drug InteractionsCommon Drug InteractionThe presence of food in the GI tract will reduce the absorption of many anti-infective agents (except penicillin V, amoxicillin, Doxycycline and minocycline).It is generally recommended that the penicillin and tetracycline derivatives as well as certain other anti-infective agents be given at least 1hr before meals or 2 hr after meals, to achieve optimum absorption. For erythromycin stearate formulations should be administered at least 1 hr before meals or 2 hr after a meal, whereas formulations of erythromycin ethylsuccinate may be given without regards to meals35Effects of Food on Drugs

Acetaminophen, Aspirin, DigoxinDecreased/delayed drug absorptionACE inhibitors (captopril, lisinopril)Significant decrease in serum drug levelsFluoroquinolones (ciprofloxacin, levofloxacin,ofloxacin), TetracyclineAvoid taking with antacids (esp. Mg and Al types) and Iron products; significantly decrease drug absorptionDidanosineFood in general and acidic foods/juices significantly decrease drug absorptionSaquinavir, Griseofulvin, Itraconazole, Lovastatin, SpironolactoneFood, especially high fat meals, improves drug absorption; take with foodEffects of Food on Drugs

FamotidineDecreased/delayed drug absorptionKetoconazoleAcidic foods/juices and sodas (eg, cola), significantly increase drug absorptionIron, Levodopa, most Penicillins, Tetracycline, ErythromycinHigh carbohydrate meals decrease drug absorption When the increased or decreased absorption effects of food are undesirable, take drug on an empty stomach, either one hour before or two hours after meals.

Common drug InteractionsCommon Drug Interaction-food may have an effect on the absorption of theophylline (except for controlled release)

38-food may have an effect on the absorption of theophylline (except for controlled release)

Common drug InteractionsCommon Drug InteractionFood and even orange juice, coffee, and mineral water may markedly reduce the bioavailability of alendronate and risedronate.

40Food and even orange juice, coffee, and mineral water may markedly reduce the bioavailability of alendronate and risedronate.

Common drug InteractionsCommon Drug Interaction-in this case food is important to obtain maximum benefit of these drugs. Both are effective in the treatment of diabetes mellitus because they delay the digestion of ingested carbohydrates and reduce the elevation of blood glucose concentrations following meals.Recommendation: Maximum effectiveness is attained when doses are administered at the start with the first bite of each main meal42-in this case food is important to obtain maximum benefit of these drugs. Both are effective in the treatment of diabetes mellitus because they delay the digestion of ingested carbohydrates and reduce the elevation of blood glucose concentrations following meals.Recommendation: Maximum effectiveness is attained when doses are administered at the start with the first bite of each main meal

Common drug InteractionsCommon Drug InteractionThe bioavailability of these agents is generally low, primarily as a result of extensive first-pass metabolism. lt has been suggested that components of grapefruit juice reduce the activity of the cytochrome P-450 enzymes primarily CYP3A4) in the gut wall. As e result, larger amounts of un-metabolized drug is absorbed, and serum concentrations are increased.

44The bioavailability of these agents is generally low, primarily as a result of extensive first-pass metabolism. lt has been suggested that components of grapefruit juice reduce the activity of the cytochrome P-450 enzymes primarily CYP3A4) in the gut wall. As e result, larger amounts of un-metabolized drug is absorbed, and serum concentrations are increased.

The mechanisms by which drug interactions alter drug distribution include: * competition for plasma protein binding * displacement from tissue binding sites

Displacement from tissue binding sites would tend to increase the blood concentration of the displaced drug.

Ex: Elevation of serum digoxin concentration by concurrent quinidine therapy = may lead to digoxin toxicity

DISTRIBUTIONProtein-bound drugs that are given in large dosage act as displacing agents Ex: aspirin, sulphonamides, trichloroacetic acid binds strongly to plasma albumin.

DISTRIBUTIONDrugs that alter protein-binding additionally reduce elimination of the displaced drug: Salicylates (NSAIDs) + Methotrexate

MTX NSAIDS free drug

Quinidine/Verapamil/Amiodarone + Digoxin = displace and inhibit renal excretion of digoxin = severe dysrhytmias

DISTRIBUTION

due to digoxin toxicity48

ENZYME INDUCTION and ENZYME INHIBITIONMETABOLISM Enzyme inducers Ex. barbiturates, carbamazepine, phenytoin, rifampicin

Enzyme inhibitors Ex. allopurinol, amiodarone, androgens, chloramphenicol, cimetidine, ciprofloxacin, diltiazem, disulfiram, erythromycin, isoniazidEnzyme induction does not take place quickly; maximal effects usually occur after 7-10 days and require an equal or longer time to dissipate after the enzyme inducer is stopped.

METABOLISMEnzyme induction does not take place quickly; maximal effects usually occur after 7-10 days and require an equal or longer time to dissipate after the enzyme inducer is stopped. 50Enzyme Induction drugs/substrates on repeated administration, have the ability to induce cytochrome P450

Phenobarbital + Warfarin = decrease in anticoagulant effectLevodopa + Pyridoxine = decrease effect of Levodopa

METABOLISM

= thrombus formation

Pyridoxine + Levodopa = levodopa activity (antidote)increasing or enhancing the rate of the synthesis of microsomal metabolizing enzymes

reducing the rate of degradation resulting in decrease in the pharmacological activity of the inducing drug or other drugs co administered with itIf the drugs are transformed into reactive metabolites, enzyme induction may exacerbate metabolite-mediated tissue toxicity.

51= thrombus formation

Pyridoxine + Levodopa = levodopa activity (antidote)increasing or enhancing the rate of the synthesis of microsomal metabolizing enzymes

reducing the rate of degradation resulting in decrease in the pharmacological activity of the inducing drug or other drugs co administered with itIf the drugs are transformed into reactive metabolites, enzyme induction may exacerbate metabolite-mediated tissue toxicity.

Enzyme Inhibition certain drugs may inhibit cytochrome P450 enzyme activity:

Alcohol + Disulfiram = inhibits activity of aldehyde dehydrogenase, inhibiting oxidation of acetaldehyde

Cimetidine + Diazepam/Carbamazepine/Phenytoin = increase the effect of Drug B

Allopurinol + Mercaptopurine/Azathioprine = increase effect of Drug B

binding to the cytochrome molecule (heme-iron), and thereby competitively inhibiting the metabolism of other drugs irreversibly inhibits the enzyme by covalent interactions alkylates the enzyme protein and therefore inactivates the enzyme

53 binding to the cytochrome molecule (heme-iron), and thereby competitively inhibiting the metabolism of other drugs irreversibly inhibits the enzyme by covalent interactions alkylates the enzyme protein and therefore inactivates the enzyme

Common drug InteractionsCommon Drug InteractionThe bioavailability of these agents is generally low, primarily as a result of extensive first-pass metabolism. lt has been suggested that components of grapefruit juice reduce the activity of the cytochrome P-450 enzymes primarily CYP3A4) in the gut wall. As e result, larger amounts of un-metabolized drug is absorbed, and serum concentrations are increased.

55The bioavailability of these agents is generally low, primarily as a result of extensive first-pass metabolism. lt has been suggested that components of grapefruit juice reduce the activity of the cytochrome P-450 enzymes primarily CYP3A4) in the gut wall. As e result, larger amounts of un-metabolized drug is absorbed, and serum concentrations are increased.

Common drug InteractionsCommon Drug InteractionThe bioavailability of these agents is generally low, primarily as a result of extensive first-pass metabolism. lt has been suggested that components of grapefruit juice reduce the activity of the cytochrome P-450 enzymes primarily CYP3A4) in the gut wall. As e result, larger amounts of un-metabolized drug is absorbed, and serum concentrations are increased.

57Enzyme inductionExamples of powerful enzyme inducers:RifampicinBarbituratesCarbamazepinePhenytoinCigarette smokingChronic alcohol useSt. Johns wortPhenobarbitalINDUCERS---- DECREASED PHARMACOLOGICAL EFFECT58

Enzyme inhibitionInhibitors:CimetidineCiprofloxacinFluoxetineOmeprazoleClarithromycinErythromycinGrapefruit JuiceTOXICITY59The most important clinical implications of altering renal excretion involve the use of drugs that are excreted in their unchanged form or in the form of an active metabolite.

Most drug interactions of elimination system happen at site of active anion and cation transport with the object drug displaced by the precipitant drug.

EXCRETIONMost drugs and their metabolites are excreted via the kidneys. Renal elimination of drugs happens by glomerular filtration, active tubular secretion and by passive tubular re-absorption.

60Most drugs and their metabolites are excreted via the kidneys. Renal elimination of drugs happens by glomerular filtration, active tubular secretion and by passive tubular re-absorption.

The main mechanisms by which one drug can affect the rate of renalexcretion of another are:by altering protein-binding and hence rate of filtration

Methotrexate NSAIDs = eg. ketoprofen inhibit the active renal tubular secretion of methotrexate

EXCRETION

by inhibiting tubular secretion Probenecid + Penicillin= secretion to prolong its action.

by altering urine flow and/or urine pH Diuretics - increase the urinary secretion of other drugs and lowers the plasma concentrations of the co-administered drugs. Salicylates = Acidifying Agents Amphetamines = Alkalinizing Agents The effect of urinary pH on the excretion of weak acids and bases is put to use in the treatment of poisoning.

62by inhibiting tubular secretion Probenecid + Penicillin= secretion to prolong its action.

by altering urine flow and/or urine pH Diuretics - increase the urinary secretion of other drugs and lowers the plasma concentrations of the co-administered drugs. Salicylates = Acidifying Agents Amphetamines = Alkalinizing Agents The effect of urinary pH on the excretion of weak acids and bases is put to use in the treatment of poisoning.

Group ReportDivide the class into 7 groups

COMMON DRUG-DRUG INTERACTION (20 D-D interaction)Group No. 1 OTC DrugsGroup No. 2 and 3 Cardiovascular Drugs (Anti-thrombotic, anticoagulant, antihypertensive drugs)Group No. 4 Oral Hypoglycemic agentsGroup No. 5 Oral hypolipidemic agentsGroup No. 6 Vitamins and antineoplastic agentsGroup No. 7 Antipsychotic, antidepressant, anxiolytic agentsAre those where the effects of one drug are changed by the presence of another drug at its site of action.

Pharmacodynamic InteractionSometimes these interactions involve competition for specific receptor sites but often they are indirect and involve interference with physiological systems,65Antagonistic interactionsAdditive or synergistic interactionsDrug or neurotransmitter uptake interactionsDrug-food interactionsPharmacodynamic InteractionSerotonin syndrome

66Common drug InteractionsCommon Drug-Food InteractionAlteration of Metabolism in the Gl Tract. The absorption of certain agents is influenced by the extent to which they are metabolized in the GI tract. Tyramine is metabolized by MAO, and normally these enzymes are found in the intestinal wall and in the liver. However if these enzymes are inhibited, large quantities of unmetabolized tyramine can accumulate and act to release norepinephrine from adrenergic neurons where greater-than-usual stores of this catecholamine are concentrated as a result of MAO inhibition.

67Alteration of Metabolism in the Gl Tract. The absorption of certain agents is influenced by the extent to which they are metabolized in the GI tract. Tyramine is metabolized by MAO, and normally these enzymes are found in the intestinal wall and in the liver. However if these enzymes are inhibited, large quantities of unmetabolized tyramine can accumulate and act to release norepinephrine from adrenergic neurons where greater-than-usual stores of this catecholamine are concentrated as a result of MAO inhibition.

Drugs Having Similar Pharmacological EffectsCNS DepressantsE.g.sedative hypnoticsAntipsychoticsTCAOpiod analgesicsAntihistamines

Alcohol-CNS depressantsDrugs Having Anticholinergic ActivityDrugs Exhibiting Hypotensive Effect

Pharmacodynamic InteractionAlteration of Electrolyte ConcentrationsCertain drugs can alter the concentrations of electrolytes such as Na and K. Digoxin + Diuretics (thiazide) = arrythmia

ACE inhibitors + Potassium Sparing Diuretics = hyperkalemia

Lithium + Diuretics = Lithium ToxicityIn cases like these, concentrations of said electrolytes must be monitored periodically.

70Reducing The Risk of Drug InteractionsIdentify the patient risk factors

Take a thorough drug history

Know the actions of the drugs being taken

Consider therapeutic alternatives

Avoid complex therapeutic regimens when possible

Educate the patient

Monitor therapy

Individualize therapy

DRUGS MEDICINAL HERBS INTERACTIONMedicinal HerbDrugInteractionChamomileWarfarinOther AnticoagulantsIncrease risk of bleedingPhenobarbitalOther barbituratesOther sedativesIntensifies or prolongs the sedative effectIronReduces iron absorptionGarlicWarfarinOther anticoagulantsIncrease risk of bleedingGinkgoWarfarinOther anticoagulantsAspirinNSAIDSIncrease risk of bleeding

PhenytoinOther anticonvulsantsReduces effectiveness of anticonvulsantMAO inhibitors

Intensifies antidepressant effect and increase risk of headache, tremors, manic episodesMedicinal HerbDrugInteractionGinsengWarfarinOther anticoagulantsAspirinNSAIDSIncrease risk of bleedingHypoglycemic drugsIntensifies hypoglycemic effectCorticosteroidsIntensifies SEEstrogen replacement therapyIntensifies SE

DigoxinIncrease serum level of DigoxinMAOiincrease risk of headache, tremors, manic episodesOpium and derivativesReduces effectivenessMedicinal HerbDrugInteractionLicoriceAntiarrythmicsNegates antiarrythmic effect by increasing the heart rhythmDigoxinIncreases risk of digoxin toxicity by lowering potassium levels through increased urine formationDiureticsIntensifies diuretic effect causing rapid loss of potassiumPrimrose oil

Phenytoinwhich may lower seizure thresholdSt. Johns wortCyclosporinmay decrease level of the drugTamarindAspirinIncrease bioavailability of ASAAdverse Drug ReactionAdverse Drug Reactionis an unwanted or harmful reaction experienced after the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug.is any undesirable effect of a drug beyond its anticipated therapeutic effects occuring during clinical use.

A response to a drug that is noxious and unintended, and that occurs at doses normally used in humans for the prophylaxis, diagnosis or therapy of disease or for the modification of physiological function.- WHO

is any undesirable effect of a drug beyond its anticipated therapeutic effects occurring during clinical use.77ADR and ADEADR- Adverse Drug Reactionis the result of the intrinsic properties of the drug and cannot be prevented.

ADE- Adverse Drug Eventis an injury resulting from medical intervention related to a drug and includes ADRs, but also includes preventable reactions including those caused by human error.ADR doesnt include drugs administered or taken in error or given by erroneous method.78Types of ADRType A Reactionare extension of the drugs known pharmacological action and are responsible for the majority of ADRs.

Type B Reactionincludes idiosyncratic reactions, immunological or allergic reactions and carcinogenic/teratogenic reactions.Type AType BPharmacologically predictableYesNoDose dependentYesNoIncidenceHighLowMorbidityHighLowMortalityLowHighManagementDosage adjustment often appropriateStop Types of ADR Type A refers to a reaction that occurs from the known pharmacological action of a drug given to a patient in therapeutic dosesType Brefers to totally abnormal effects that are unrelated to the known therapeutic or pharmacologic action of the drug.Type Cis a dose-related reaction that is observed after long term use of a drug.

81Types of ADRType Dis a reaction to a drug that is manifested long after drug exposureType Eis manifested by symptoms that result from termination or sudden discontinuation of the drug.Type Fresults from lack or insufficiency of drug products, antimicrobial resistance, drug instability, patient non-compliance, expired or fake drugs and drug interactions.D= such as carcinogenesis and teratogenesis.E= metoprololF failure of drug

D= such as carcinogenesis and teratogenesis.E= metoprololF failure of drug

82Risk factors for ADRsAgeConcurrent medicinesDuration of TherapyGenderComorbid conditionsNarrow Therapeutic Index drugsEthnicity and GeneticsCommon Adverse Drug ReactionName of DrugAdverse ReactionAcetaminophenNausea, rash, headacheNaproxenDyspepsia, nausea, abdominal pain, constipation, dizziness, drowsiness, rashCelecoxibMay increase risk of serious and potentially fatal CV thrombotic events-headache, dyspepsia, diarrhea, abdominal pain, nausea and vomiting, rash, flatulenceGuaifenesinRash, vomiting, nauseaCommon Adverse Drug ReactionName of DrugAdverse ReactionDigoxinDizziness, headache, diarrhea, nausea and vomiting, anorexia, weakness, bradycardia or tachycardia, confusion, rash, mental disturbance, apathyCaptoprilRash, pruritus, taste changes, hypotension, dizziness, fatigue, cough, hyperkalemia, nausea and vomitingAmlodipinePeripheral edema, headache, fatigue, palpitations, dizziness, nausea, flushingMetoprololFatigue, dizziness, diarrhea, pruritus, rash, depression, dyspnea, bradycardiaNifedipinePeripheral edema, headache, dizziness, flushing, fatigue/ weakness, palpitationsLosartanFetal/neonatal morbity/ mortality may occurMETOPROLOL AVOID abrupt cessation severe angina exacerbation, MI, and ventricular arrythmias.85Examples of Serious Adverse Drug ReactionAdverse Drug ReactionTypes of DrugsExamplesPeptic ulcers or bleeding from the stomachOral corticosteroidsHydrocortisonePrednisoneNSAIDSAspirinIbuprofenKetoprofenNaproxenAnticoagulantsHeparinWarfarin

Examples of Serious Adverse Drug ReactionAdverse Drug ReactionTypes of DrugsExamplesAnemia(resulting from a decreased production or increased destruction of red blood cells)Certain antibioticsChloramphenicolSome NSAIDSPhenylbutazoneAntimalarial and anti tuberculosis drugs in people with G6PD enzyme deficiency)ChloroquineIsoniazidPrimaquineExamples of Serious Adverse Drug ReactionAdverse Drug ReactionTypes of DrugsExamplesDecreased production of white blood cells Certain antipsychotic drugsClozapineChemotherapy drugsCyclophosphamideMercaptopurineMethotrexateVinblastineSome drugs used to treat thyroid disordersPTUwith increased risk of infection88Examples of Serious Adverse Drug ReactionAdverse Drug ReactionTypes of DrugsExamplesKidney DamageSome anti TB drugsINHIron supplement in high dosageNSAIDS in repeated use of excessive dosage

IbuprofenKetoprofenNaproxenAminoglycoside antibioticsGentamicinKanamycinSome chemotherapy drugsSplatinExamples of Serious Adverse Drug ReactionAdverse Drug ReactionTypes of DrugsExamplesLiver damageSome analgesicsAcetaminophen in excessive dosesConfusion and drowsinessSedatives, including many antihistaminesDiphenhydramineConfusion and drowsinessAnti-depressantsAmitriptylineImipramine