Download adverse drug events - Case Western Reserve University School of

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
• Clinicians and
patients both
acknowledge the
major role played
by drugs in modern
health care
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Adverse Drug Events
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Adverse Drug Events
• There are no
“absolutely” safe
biologically active
therapeutic agents
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Adverse Drug Events
• Therapeutic agents
seldom exert their
beneficial effects
without also
causing adverse
drug events
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Adverse Drug Events
• OHCP should be
aware of the
spectrum of druginduced events and
should be actively
involved both in
monitoring for and
reporting such
events
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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
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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
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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
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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
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Adverse Drug Events
Type 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 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 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 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 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 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 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 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 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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 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 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type A Reactions
• Etiology and epidemiology
• Drug-disease interactions
• Pharmacodynamic mechanisms
 Beta1-adrenergic receptor antagonists can adversely
affect carbohydrate metabolism and inhibit epinephrinemediated hyperglycemic response to insulin
 Increase the risk of hypoglycemia and mask some of
its clinical manifestations in diabetic patients
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type B Reactions
• Etiology and epidemiology
• Allergic/immune reactions
• Type I (immediate) hypersensitivity
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Adverse Drug Events
Type B Reactions
• Etiology and epidemiology
• Allergic/immune reactions
• Type II (cytotoxic) hypersensitivity
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Adverse Drug Events
Type B Reactions
• Etiology and epidemiology
• Allergic/immune reactions
• Type III (immune-complex) hypersensitivity
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Adverse Drug Events
Type B Reactions
• Etiology and epidemiology
• Allergic/immune reactions
• Type IV (delayed) hypersensitivity
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Adverse Drug Events
Type 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 lipoxygenasedependent leukotrienes
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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 Events
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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
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Adverse Drug Events
Type A Reactions
• Clinical manifestations
• Cytotoxic reactions
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Adverse Drug Events
Type A: Cytotoxic Reactions
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Adverse Drug Events
Type A: Cytotoxic Reactions
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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 Reactions
• Clinical
manifestations
• Xerostomia
• Diuretics
• Drugs with
anticholinergic activity
 antihistamines,
psychotropic
drugs, CNS
stimulants,
antineoplastic
agents
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Adverse Drug Events
Type A Reactions: Xerostomia
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Adverse Drug Events
Type A Reactions
• Clinical
manifestations
• Mucositis
• Drugs that arrest the
growth and
maturation of
normal cells
 antineoplastic
agents
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Adverse Drug Events
Type A Reactions
• Clinical manifestations
• Bleeding diatheses
• Drugs that interfere
with platelet function
and the coagulation
phase of hemostasis
 COX-1
inhibitors
clopedigrol,
warfarin,
heparin
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Adverse Drug Events
Type A Reactions: Bleeding Diatheses
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Adverse Drug Events
Type A Reactions
• Clinical
manifestations
• Bacterial infections
• Drugs that alter the
normal flora
 antibacterial
agents
• Drugs that cause
immunosuppression
 immunosuppressants
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Adverse Drug Events
Type A Reactions
• Clinical
manifestations
• Fungal infections
• Drugs that alter the
normal flora
 antibacterial
agents
• Drugs that cause
immunosuppression
 immunosuppressants
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Adverse Drug Events
Type A Reactions
• Clinical
manifestations
• Viral infections
• Drugs that cause
immunosuppression
 immunosuppressants
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Adverse Drug Events
Type A Reactions: Viral Infections
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Adverse Drug Events
Type A Reactions
• Clinical
manifestations
• Gingival
hyperplasia
 phenytoin,
calciumchannel
blocking
agents,
cyclosporine
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Adverse Drug Events
Type A Reactions
• Clinical manifestations
• Neurological complications
• Oral pain
 drugs that cause mucositis and/or immunosuppression
 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 Reactions
• Clinical manifestations
• Inadequate nutrition
 drugs that produce nausea, vomiting, diarrhea
 drugs that produce mucositis, xerostomia,
 drugs that are hepatotoxic
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Allergic/
immunologic
reactions
• Type I (immediate)
hypersensitivity
reaction
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Allergic/
immunologic
reactions
• Type II (cytotoxic)
hypersensitivity
reaction
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Allergic/
immunologic
reactions
• Type III (immunecomplex)
hypersensitivity
reaction
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Allergic/
immunologic
reactions
• Type IV (delayed)
hypersensitivity
reaction
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Lichenoid
mucositis
 diuretics
 beta1adrenergic
antagonists
 ACE-inhibitors
 COX-1
inhibitors
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Erythema
multiforme
• Stevens-Johnson
syndrome
 sulfonamides
 anticonvulsive
agents
 COX-1
inhibitors
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Adverse Drug Events
Type B Reactions: SJS
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type 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
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Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Teratogenic effect
• 3rd to 8th week
 No measurable
effect
 Spontaneous
abortion
 Sublethal
 True
teratogenic
effect
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Adverse Drug Events
Type B Reactions: Teratogenic Effects
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Adverse Drug Events
Type 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 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 %
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84
Adverse Drug Events
Type B Reactions
• Clinical
manifestations
• Oncogenic effects
• Lymphoproliferative disease
• Lymphomas
• Leiomyoma
• Leiomyosarcoma
• Spindle-cell
sarcoma
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85
Adverse Drug Events
• Preventing adverse drug events
• Rational approach to the pharmacological
management of oral/odontogenic disease
•
•
•
•
•
•
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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
86
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
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87
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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88
Adverse Drug Events
• Reporting adverse drug events
• An event is serious and should be reported
when the patient outcome is
•
•
•
•
•
•
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Death
Life-threatening
Hospitalization
Disability
Congenital anomaly
Requires intervention to prevent permanent
impairment or damage
Terezhalmy
89
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
5/5/2017
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90
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
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91
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
not impossible
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92
Adverse Drug Events
• Conclusion
• Timely reporting
of ADEs
• Saves lives
• Reduces morbidity
• Decrease the cost
of health care
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Terezhalmy
93
Adverse Drug Events
5/5/2017
Terezhalmy
94
Adverse Drug Events
5/5/2017
Terezhalmy
95
Adverse Drug Events
5/5/2017
Terezhalmy
96