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ADVERSE DRUG EVENTS. Géza T. Terézhalmy, D.D.S., M.A. Professor and Dean Emeritus School of Dental Medicine Case Western Reserve University Cleveland, Ohio. Adverse Drug Events.

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adverse drug events

ADVERSE DRUG EVENTS

Géza T. Terézhalmy, D.D.S., M.A. Professor and Dean Emeritus School of Dental Medicine Case Western Reserve University Cleveland, Ohio

adverse drug events1
Adverse Drug Events
  • Clinicians and patients both acknowledge the major role played by drugs in modern health care

Terezhalmy

adverse drug events3
Adverse Drug Events
  • There are no “absolutely” safe biologically active therapeutic agents

Terezhalmy

adverse drug events4
Adverse Drug Events
  • Therapeutic agents seldom exert their beneficial effects without also causing adverse drug events

Terezhalmy

adverse drug events5
Adverse Drug Events
  • OHCP should be aware of the spectrum of drug-induced events and should be actively involved both in monitoring for and reporting such events

Terezhalmy

adverse drug events6
Adverse Drug Events
  • Etiology and epidemiology
    • 75 % of office visits to general medical practitioners and internists are associated with the initiation or continuation of pharmacotherapy
      • 3 to 11 % of hospital admissions are attributed to adverse drug events
      • 0.3 to 44 % of hospitalizations are complicated by adverse drug events

Terezhalmy

adverse drug events7
Adverse Drug Events
  • Etiology and epidemiology
    • The FDA has the most rigorous approval requirements in the world
      • Clinical trials cannot and are not expected to uncover every potential adverse drug event
        • Pre-marketing study populations generally include 3,000 to 4,000 subjects
          • Only adverse events, which occur more frequently than 1 in 1,000 will be observed
          • Detecting an adverse event with a incidence of 1 in 10,000 would require a study population of 30,000

Terezhalmy

adverse drug events8
Adverse Drug Events
  • Etiology and epidemiology
    • Classification of adverse drug events
      • Type A reactions
        • Associated with the administration of therapeutic dosages of a drug (exception: drug overdose)
        • Usually predictable and avoidable
        • Responsible for most adverse drug events
          • Overdose
          • Cytotoxic reactions
          • Drug-drug interactions
          • Drug-food interactions
          • Drug-disease interactions

Terezhalmy

adverse drug events9
Adverse Drug Events
  • Etiology and epidemiology
    • Classification of adverse drug events
      • Type B reactions
        • Generally independent of dose
        • Rarely predictable or avoidable
        • While they are uncommon, they are often among the most serious and potentially life threatening
          • Idiosyncratic reactions
          • Immunologic/allergic reactions
          • Pseudo-allergic reactions
          • Teratogenic effects
          • Oncogenic effects

Terezhalmy

adverse drug events type a reactions
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Cytotoxic effects
      • Formation of unstable or reactive metabolites related to some abnormality that interferes with normal metabolism and/or excretion of a drug
        • Two mechanisms
          • Oxidative pathway: the formation of electrophilic compounds, which bind covalently with cellular macromolecules
          • Reductive pathway: gives rise to intermediate compounds with an excess of electrons, which interact with O2 to produce free radicals

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adverse drug events type a reactions1
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Two or more drugs administered at the same time or in close sequence
        • May act independently
        • May interact to  or  the magnitude or duration of action of one or more of the drugs
        • May interact to cause an unintended reaction
      • Drug-drug interactions all seem to have either a pharmacodynamic or a pharmacokinetic basis

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adverse drug events type a reactions2
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacodynamic mechanisms
        • The intended or expected effect produced by a given plasma level of drug A is altered in the presence of drug B
          • Pharmacological drug-drug interactions
          • Physiological drug-drug interactions
          • Chemical drug-drug interactions
          • Drug-related receptor alterations

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adverse drug events type a reactions3
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacodynamic mechanisms
        • Pharmacological drug-drug interactions
          • Drug A and drug B compete for the same receptor site and as a function of their respective concentrations either produce (an agonist) or prevent (an antagonist) an effect respectively
          • opioids vs. naloxone
          • acetylcholine vs. atropine
          • epinephrine vs. adrenergic receptor blocking agents

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adverse drug events type a reactions4
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacodynamic mechanisms
        • Physiological interactions
          • Drug A and drug B interact with different receptor sites and either enhance each other’s action or produce an opposing effect via different cellular mechanisms
          • cholinergic agents vs diazepam
          • epinephrine vs. lidocaine
          • epinephrine vs. histamine

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adverse drug events type a reactions5
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacodynamic mechanisms
        • Chemical interactions
          • Drug A interacts with drug B and prevents drug B from interacting with its intended receptor
          • protamine sulfate vs. heparin

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adverse drug events type a reactions6
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacodynamic mechanisms
        • Drug-related receptor alterations
          • Drug A, when administered chronically, may either  or  the number of its own receptors or alter the adaptability of its receptors to physiological events
          • alpha1-adrenergic receptor agonists down-regulate their own receptors
          • beta1-adrenergic receptor antagonists up-regulate their own receptors

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adverse drug events type a reactions7
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Following concomitant administration, drug A may  or  the plasma level of drug B
          • Interactions affecting absorption
          • Interactions affecting distribution
          • Interactions affecting metabolism
          • Interactions affecting renal excretion
          • Interactions affecting biliary excretion

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adverse drug events type a reactions8
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting absorption
          • Drug A, by causing vasoconstriction, interferes with the systemic absorption of drug B
          • epinephrine  the systemic absorption of lidocaine
          • Drug A, by forming a complex with drug B, interferes with the systemic absorption of drug B
          • calcium  the systemic absorption of tetracycline

Terezhalmy

adverse drug events type a reactions9
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting absorption
          • Drug A, by delaying gastric emptying, delays the systemic absorption of drug B, which is absorbed primarily in the small intestine
          • opioids delay the absorption of acetaminophen
          • Drug A, by elevating gastric pH, prevents the absorption of drug B (weak acids)
          • antacids  absorption of acetylsalicylic acid

Terezhalmy

adverse drug events type a reactions10
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting distribution
          • Drug A ( a weak acid), by competing for plasma protein binding with drug B,  the plasma level of drug B
          • acetylsalicylic acid  the plasma level of many drugs

Terezhalmy

adverse drug events type a reactions11
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting metabolism
          • Drug A, by  or  hepatic microsomal enzyme activity responsible for the metabolism of drug B,  or  plasma level of drug B respectively
          • H2-receptor antagonists  the plasma level of many drugs
          • macrolides, azole antifungal agents, ethanol (chronic use)  plasma level of many drugs

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adverse drug events type a reactions12
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting metabolism
          • Drug A, by  hepatic non-microsomal enzyme activity responsible for the metabolism of drug B,  the plasma level of drug B
          • MAO-inhibitors  the plasma level of benzodiazepines

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adverse drug events type a reactions13
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting metabolism
          • Drug A, by inhibiting the enzyme acetaldehyde dehydrogenize, interferes with the further metabolism of intermediate metabolites (oxidation products) of drug B
          • disulfuram and metronidazole interfere with the metabolism of ethanol

Terezhalmy

adverse drug events type a reactions14
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting renal excretion
          • Drug A, which competes with drug B for the same excretory transport mechanisms in the proximal tubules,  the plasma level of drug B
          • acetylsalicylic acid and probenecid  the plasma level of penicillin and other weak acids

Terezhalmy

adverse drug events type a reactions15
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting renal excretion
          • Drug A, by alkalizing the urine,  the plasma level of drug B
          • sodium bicarbonate  the plasma level of weak acids
          • Drug A, by acidifying the urine,  the plasma level of drug B
          • ammonium chloride  the plasma level of weak bases

Terezhalmy

adverse drug events type a reactions16
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-drug interactions
      • Pharmacokinetic mechanisms
        • Interactions affecting biliary excretion
          • Drug A, by increasing bile flow and the synthesis of proteins, which function in biliary conjugation mechanisms,  the plasma level of drug B
          • Phenobarbital  the plasma level of many drugs
          • Drug A binds drug B, which undergoes extensive hepatic recirculation,  the plasma level of drug B
          • activated charcoal and cholestyramine  the plasma level of many drugs

Terezhalmy

adverse drug events type a reactions17
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-food interactions
      • Most known drug-food interactions appear to be associated with pharmacokinetic mechanisms
        • Interactions affecting absorption
          • Nutrients may act as a mechanical barrier that prevents drug access to mucosal surfaces and  the rate of absorption of some drugs
          • Nutrients with high fatty acid content may actually  the rate of absorption of drugs with high lipid solubility

Terezhalmy

adverse drug events type a reactions18
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-food interactions
      • Interactions affecting absorption
        • Chemical interactions between a drug and food component can result in the formation of inactive complexes and  the absorption of the drug
          • calcium  the absorption of tetracyclines
          • ferrous or ferric salts  the absorption of tetracyclines and fluoroquinolones
          • zinc  the absorption of fluoroquinolones

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adverse drug events type a reactions19
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-food interactions
      • Interactions affecting metabolism
        • Components of some nutrients can inhibit CYP450 isoenzymes and  the metabolism of some drugs
          • grapefruit juice  the metabolism of warfarin, benzodiazepines, and calcium-channel blocking agents

Terezhalmy

adverse drug events type a reactions20
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • A drug prescribed for the treatment of one disease can adversely affect a different condition that has been generally well controlled
        • Pharmacodynamic mechanisms
        • Pharmacokinetic mechanisms

Terezhalmy

adverse drug events type a reactions21
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • Pharmacodynamic mechanisms
        • Non-selective beta1-adrenergic receptor antagonists, prescribed for the treatment of chronic stable angina, hypertension, or cardiac arrhythmia can increase airway resistance by interacting with beta2-adrenergic receptors
          • induce asthma in susceptible patients

Terezhalmy

adverse drug events type a reactions22
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • Pharmacodynamic mechanisms
        • Beta1-adrenergic receptor antagonists and calcium-channel blocking agents prescribed for the treatment of chronic stable angina, hypertension, or cardiac arrhythmia interacting with their own receptors
          • precipitate cardiac complications secondary to negative inotropism (decreased contractility), decreased nodal conductance, and peripheral vasodilatation (cardiac steal syndrome) in susceptible patients

Terezhalmy

adverse drug events type a reactions23
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • Pharmacodynamic mechanisms
        • Beta1-adrenergic receptor antagonists can adversely affect carbohydrate metabolism and inhibit epinephrine-mediated hyperglycemic response to insulin
          • Increase the risk of hypoglycemia and mask some of its clinical manifestations in diabetic patients

Terezhalmy

adverse drug events type a reactions24
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • Pharmacodynamic mechanisms
        • COX-1 inhibitors block cyclooxygenase-dependent prostaglandin and thrombaxane A2 synthesis
          • Exacerbate peptic ulcer disease and gastroesophageal reflux disease in susceptible patients

Terezhalmy

adverse drug events type a reactions25
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • Pharmacodynamic mechanisms
        • Hypothyroidism
          •  sensitivity to CNS depressants in susceptible patients
        • Hyperthyroidism
          •  susceptibility to epinephrine-induced hypertension and cardiac arrhythmia

Terezhalmy

adverse drug events type a reactions26
Adverse Drug EventsType A Reactions
  • Etiology and epidemiology
    • Drug-disease interactions
      • Pharmacokinetic mechanisms
        • Cardiac dysfunction
          •  metabolism and excretion of drugs
        • Hepatic dysfunction
          •  metabolism and biliary and renal excretion of drugs
        • Renal dysfunction
          •  hepatic metabolism and renal excretion of drugs

Terezhalmy

adverse drug events type b reactions
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Idiosyncratic reactions
      • Drug metabolism is largely dominated by oxidation reactions catalyzed by the cytochrome P450 enzyme system
        • Genetic polymorphism is the primary factor responsible for inter-individual variability in response to drugs
          • Therapeutic consequences
          • intrinsic characteristics of the drug
          • importance of the deficient metabolic pathway
          • existence of alternative pathways

Terezhalmy

adverse drug events type b reactions1
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Allergic/immune reactions
      • In susceptible patients alkylation and/or oxidation of cellular macromolecules by drug metabolites can lead to the production of immunogens
        • Not related to the dose administered
          • Specificity to a given agent
          • Transferability by antibodies or lymphocytes
          • Recurrence when re-exposure to the offending drug occurs
        • Most reactions occur in young or middle aged adults
        • Drug allergy is twice a frequent in women than in man

Terezhalmy

adverse drug events type b reactions2
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Allergic/immune reactions
      • Type I (immediate) hypersensitivity

Terezhalmy

adverse drug events type b reactions3
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Allergic/immune reactions
      • Type II (cytotoxic) hypersensitivity

Terezhalmy

adverse drug events type b reactions4
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Allergic/immune reactions
      • Type III (immune-complex) hypersensitivity

Terezhalmy

adverse drug events type b reactions5
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Allergic/immune reactions
      • Type IV (delayed) hypersensitivity

Terezhalmy

adverse drug events type b reactions6
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Pseudoallergic reactions
      • Cannot be explained on an immunologic basis
      • Occur in patients who had no prior exposure to the drug
        • Certain medications directly activate mast cells through non-IgE-receptor pathways and initiate the release of bioactive substances
        • Other medications block the degradation of bioactive substances
        • Still other medications, by inhibiting the action of cyclooxygenase activity,  synthesis of lipoxygenase-dependent leukotrienes

Terezhalmy

adverse drug events type b reactions7
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Teratogenic/developmental effects
      • Teratogens are substances capable of causing physical or functional defects in the fetus in the absence of toxic effects in the mother
        • Teratogenic effects depend on the accumulation of a drug or its metabolite in the fetus at critical time periods
          • 3rd to 12th week of gestation

Terezhalmy

adverse drug events type b reactions8
Adverse Drug EventsType B Reactions
  • Etiology and epidemiology
    • Oncogenic effects
      • Primary oncogenic effects
        • Produced by certain procarcinogenic drugs, which have been converted into carcinogens by polymorphic oxidative reactions
          • Reactive metabolites bind covalently to DNA
      • Secondary oncogenic effects
        • Therapeutic immunosuppression in the presence of infection with oncogenic viruses
          • HBV, HCV, CMV, HSV, HPV, and EMV
          • Pattern of cancer is different than in the general population

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adverse drug events11
Adverse Drug Events
  • Clinical manifestations
    • Type A reactions
      • Primary (direct effects) or secondary (indirect effects)
        • Dose dependent
          • Exaggerations of direct effects
          • Multiple concurrent “side “ effects
    • Type B reactions
      • Primary (direct effects) or secondary (indirect effects)
        • Generally independent of the dose

Terezhalmy

adverse drug events type a reactions27
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Cytotoxic reactions

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adverse drug events type a reactions28
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Gastrointestinal disturbances
      • Nausea and vomiting
        • Vomiting center
          • Chemoreceptor trigger zone
          • Pharynx
          • Gastrointestinal tract
          • Cerebral cortex (emotion, olfaction, visual stimuli)
          • Stimulation of the vestibular apparatus
          • opioid-, dopaminergic (D2)-, histaminic (H1)-, muscarinic-, and serotonengic (5-HT3)-receptor agonists

Terezhalmy

adverse drug events type a reactions29
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Gastrointestinal disturbances
      • Constipation
        • Diet, functional abnormalities, colonic disease, rectal problems, neurological disease, metabolic disorders, drugs
          • anticholinergic agents, antihistamines, antidepressants, anticonvulsants, antiparkinsonian drugs, opioid analgesics, antacids

Terezhalmy

adverse drug events type a reactions30
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Gastrointestinal disturbances
      • Diarrhea
        • Chronic
          • Functional abnormalities, colonic disease, neurological disease, and metabolic disorders
        • Acute
          • Osmotic changes when poorly absorbable solutes are present in the intestine
          • Inhibition of ion transport or stimulation of ion secretion
          • Toxins, infection (viral, bacterial), drugs
          • cholinergic agents, antibacterial agents

Terezhalmy

adverse drug events type a reactions31
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Urinary incontinence
      • Increased urinary flow
          • diuretics, cholinergic agents
      • Overflow secondary to urinary retention
          • anticholinergic agents, adrenergic agonists
      • Increased ADH release
        • Painful stimuli, fear, anger, drugs
          • opioid analgesics
      • Decrease ADH release
          • alcohol

Terezhalmy

adverse drug events type a reactions32
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Mood alterations
      • Depression
          • beta1-adrenergic blocking agents, cardiac glycosides, benzodiazepines, phenothiazines, corticosteroids,
      • Delirium (acute confusional states)
          • drugs with anticholinergic properties, cardiac glycosides, opioid analgesics, benzodiazepines, other CNS depressants

Terezhalmy

adverse drug events type a reactions33
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Cardiac dysfunction
      • Orthostatic hypotension
          • antihypertensive agents (reduce BP), psychotropic drugs (impair autonomic reflexes)
      • Arrhythmia
          • cardiac glycosides, macrolides, calcium-channel blocking agents, azoles (antifungal agents), protease inhibitors

Terezhalmy

adverse drug events type a reactions34
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Equilibrium problems
      • Increased risk of falls (patients with decreased vision, impaired mobility and cognition, postural hypotension, peripheral neuropathy)
          • drugs that impair autonomic reflexes (benzodiazepines, alcohol)

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adverse drug events type a reactions35
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Xerostomia
      • Diuretics
      • Drugs with anticholinergic activity
          • antihistamines, psychotropic drugs, CNS stimulants, antineoplastic agents

Terezhalmy

adverse drug events type a reactions36
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Mucositis
      • Drugs that arrest the growth and maturation of normal cells
          • antineoplastic agents

Terezhalmy

adverse drug events type a reactions37
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Bleeding diatheses
      • Drugs that interfere with platelet function and the coagulation phase of hemostasis
          • COX-1 inhibitors clopedigrol, warfarin, heparin

Terezhalmy

adverse drug events type a reactions38
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Bacterial infections
      • Drugs that alter the normal flora
          • antibacterial agents
      • Drugs that cause immuno-suppression
          • immuno-suppressants

Terezhalmy

adverse drug events type a reactions39
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Fungal infections
      • Drugs that alter the normal flora
          • antibacterial agents
      • Drugs that cause immuno-suppression
          • immuno-suppressants

Terezhalmy

adverse drug events type a reactions40
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Viral infections
      • Drugs that cause immuno-suppression
          • immuno-suppressants

Terezhalmy

adverse drug events type a reactions41
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Gingival hyperplasia
          • phenytoin, calcium-channel blocking agents, cyclosporine

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adverse drug events type a reactions42
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Neurological complications
      • Oral pain
          • drugs that cause mucositis and/or immuno-suppression
          • certain antineoplastic agents (vincristine)
      • Tardive dyskinesia
          • neuroleptic agents, which alter striatal dopaminergic receptor activity
      • Taste alterations
          • drugs that affect trace metal homeostasis

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adverse drug events type a reactions43
Adverse Drug EventsType A Reactions
  • Clinical manifestations
    • Inadequate nutrition
          • drugs that produce nausea, vomiting, diarrhea
          • drugs that produce mucositis, xerostomia,
          • drugs that are hepatotoxic

Terezhalmy

adverse drug events type b reactions9
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Idiosyncratic reactions
      • An unusual reaction of any intensity observed in a small number of patients
        • Hypo-reactive patient
          • The drug produces its usual effect at an unexpectedly high dose
        • Hyper-reactive patient
          • The drug produces its usual effect at an unexpectedly low dose

Terezhalmy

adverse drug events type b reactions10
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Allergic/ immunologic reactions
      • Type I (immediate) hypersensitivity reaction

Terezhalmy

adverse drug events type b reactions11
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Allergic/ immunologic reactions
      • Type II (cytotoxic) hypersensitivity reaction

Terezhalmy

adverse drug events type b reactions12
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Allergic/ immunologic reactions
      • Type III (immune-complex) hypersensitivity reaction

Terezhalmy

adverse drug events type b reactions13
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Allergic/ immunologic reactions
      • Type IV (delayed) hypersensitivity reaction

Terezhalmy

adverse drug events type b reactions14
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Lichenoid mucositis
          • diuretics
          • beta1-adrenergic antagonists
          • ACE-inhibitors
          • COX-1 inhibitors

Terezhalmy

adverse drug events type b reactions15
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Erythema multiforme
      • Stevens-Johnson syndrome
          • sulfonamides
          • anticonvulsive agents
          • COX-1 inhibitors

Terezhalmy

adverse drug events type b reactions16
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Teratogenic effect
      • Drugs given during pregnancy can affect the fetus by producing lethal, toxic, or teratogenic effect
        • Constricting placental vessels
        • Impairing gas and nutrient exchange between fetus and mother
        • Producing hypertonia resulting in anoxic injury
        • Indirectly, changing the biochemical dynamics of the mother

Terezhalmy

adverse drug events type b reactions17
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Teratogenic effect
      • Fetal age, drug potency, and dosage
        • < 20 days after fertilization
          • An all-or-nothing effect
        • 2nd to 3rd trimesters
          • Unlikely to be teratogenic
          • Alter growth and function of normally formed fetal organs and tissues

Terezhalmy

adverse drug events type b reactions18
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Teratogenic effect
      • 3rd to 8th week
        • No measurable effect
        • Spontaneous abortion
        • Sublethal
          • True teratogenic effect

Terezhalmy

adverse drug events type b reactions19
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Oncogenic effects
      • SCC of the skin
      • SCC of the lips
        • 7 to 8.1 %
          • vs. 0.3 %
        • Average age 42 years
          • vs. 60 years
        • Latency 5.3 years

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adverse drug events type b reactions20
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Oncogenic effects
      • Kaposi sarcoma
        • 5.6 %
          • vs. 0.03-0.07 %
        • 60 % non-visceral
          • Skin
          • Oral ( 2 %)
        • Visceral
          • Skin (24 %)
          • Oral 3 %

Terezhalmy

adverse drug events type b reactions21
Adverse Drug EventsType B Reactions
  • Clinical manifestations
    • Oncogenic effects
      • Lympho-proliferative disease
      • Lymphomas
      • Leiomyoma
      • Leiomyosarcoma
      • Spindle-cell sarcoma

Terezhalmy

adverse drug events12
Adverse Drug Events
  • Preventing adverse drug events
    • Rational approach to the pharmacological management of oral/odontogenic disease
      • Accurate diagnosis
      • Critical assessment of the need for pharmacotherapy
      • Benefits versus risks of drug therapy
      • Individualization of drug therapy
      • Patient education
      • Continuous reassessment of drug therapy

Terezhalmy

adverse drug events13
Adverse Drug Events
  • Diagnosing adverse drug events
    • Step 1
      • Identify the drug(s) taken by the patient
    • Step 2
      • Verify that the onset of signs and symptoms was after the initiation of pharmacological intervention
    • Step 3
      • Determine the time interval between the initiation of drug therapy and the onset of the adverse drug event

Terezhalmy

adverse drug events14
Adverse Drug Events
  • Diagnosing adverse drug events
    • Step 4
      • Stop drug therapy and monitor the patient’s status
    • Step 5
      • If appropriate, restart drug therapy and monitor for recurrence of adverse drug event

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adverse drug events15
Adverse Drug Events
  • Reporting adverse drug events
    • An event is serious and should be reported when the patient outcome is
      • Death
      • Life-threatening
      • Hospitalization
      • Disability
      • Congenital anomaly
      • Requires intervention to prevent permanent impairment or damage

Terezhalmy

adverse drug events16
Adverse Drug Events
  • Reporting adverse drug events
    • FDA Form 3500
      • http://www.fda.gov/medwatch/report/hcp.htm
        • Complete the voluntary form 3500 online
        • Download a copy of the form
          • Fax it to 1-800-FDA-0178 OR
          • Mail it back using the postage-paid addressed form
      • Call 1-800-FDA-1088 to report by telephone

Terezhalmy

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Adverse Drug Events
  • Conclusion
    • ADEs evolve through the same physiological and pathological pathways as normal disease
      • Prerequisites to consider ADEs in the differential diagnosis
        • An awareness that an ever increasing number of patients are taking more and more medications (polypharmacy)
        • Recognition that many drugs will remain in the body for weeks after therapy is discontinued
        • Clinical experience
        • Familiarity with relevant literature about ADEs

Terezhalmy

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Adverse Drug Events
  • Conclusion
    • Recognize that some ADEs occur rarely and detection based on clinical experience or reports in the medical literature at time is difficult if notimpossible

Terezhalmy

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Adverse Drug Events
  • Conclusion
    • Timely reporting of ADEs
      • Saves lives
      • Reduces morbidity
      • Decrease the cost of health care

Terezhalmy