ADVERSE DRUG REACTIONS AND DRUG INTERACTIONS USEFUL FOR PharmD, Bpharm and other medical professionals

1. MADE BY:
DR. S P SRINVAS NAYAK
ASSISTANT PROFESSOR,
DEPT OF PHARMACY PRACTICE
SULTAN-UL-ULOOM COLLEGE OF
PHARMACY, HYD.
ADVERSE DRUG REACTIONS
& DRUG INTERACTIONS

2. overview
 INTRODUCTION OF ADR
 Statistics and factors of ADR
 Classifications OF ADR
 ADR MONITORING
 MANAGEMENT OF ADR.
 DRUG INTERACTIONS
 METHODS OF DETECTING DRUG
INTERACTIONS

3. WONDER DRUG DISASTER

4. THALIDOMIDE

5. ADR DEFINITION
 WHO, (1972) 'A response to a drug which is
noxious and unintended, and which occurs at doses
normally used in man for the prophylaxis, diagnosis,
or therapy of disease, or for the modifications of
physiological function‘
 ADRs may lead to organ damage, prolong
hospitalization, may lead to ADE and sometimes
death.

6. WHAT ARE ADVERSE DRUG REACTIONS
(ADRS)?
Any noxious change which is
suspected to be due to a drug,
occurs at doses normally used in
man , requires treatment or
decrease in dose or indicates
caution for in future use of the
same drug.

7. Adverse drug event –
Any untoward medical occurrence
that may present during treatment
with medicine , but which may not
have causal relationship with the
treatment.

8. Difference b/t ADR and ADE
 ADR
 It’s a drug reaction
 Eg: sedation by
antihistamine.
 ADE
 its an event
 Eg: accident by seadation
caused due to
antihistamine

9. STATISTICS
 ADR to drugs are most common cause of
iatrogenic disease.
 3-5% hospitalisations due to adverse
reactions results in 3,00,000
hospitalisations annually in US.
 Once hospitalised → 30% chance of ADR
→ Risk of each course is 5%
 3% chance of life threatning reactions →
Risk of each course is 0.4 %

10. COMMON CAUSES OF ADRS
 Failing to take the correct dosages at the
correct times.
 Overdosing.
 Allergies to chemical components of the
medicine.
 Combining the medicine with alcohol.
 Taking other drugs or preparations that
interact with the medicine.
 Taking a medicine that was prescribed
for someone else.

11. FACTORS AFFECTING ADVERSE DRUG
REACTIONS :
Patient-related factors
• Age
• Sex
• Genetic influences
• Concurrent diseases (renal ,liver , cardiac)
• Previous adverse drug reactions
• Compliance with dosing regimen
• Total number of medications
• Misc. (diet, smoking, environmental
exposure)

12. AGE
 Children are often at risk
because their capacity to
metabolize drugs is usually not
fully developed
Children younger than 18 may be at risk
of developing Reye’s syndrome if given
acetylsalicylic acid (aspirin) while infected
with chickenpox or influenza.

13. ELDERLY
1. ADRs, including drug interactions,
are a common cause of admission to
hospitals in the elderly
2. Reasons for ADRs in the elderly:
Concomitant use of several
medications
Decreased drug ADME activity
due to age
3.These conditions are exacerbated
by malnutrition and dehydration,
common in the elderly

14. PREGNANCY
1.Sulfonamides → Jaundice and brain
damage in the fetus
2.Warfarin → Birth defects, and
increased risk of bleeding problems
in newborns and mothers
3.Lithium → Defects of the heart
(Ebstein’s Anomaly), lethargy,
reduced muscle tone, and
underactivity of the thyroid gland

15. BREAST FEEDING
→ Many drugs can be passed from
mother to infant via breast milk
– Amantadine (antiviral)
– Cyclophosphamide (antineoplastic)
– Cocaine (Schedule 2 FDA drug)
– Carisoprodol (skeletal muscle relaxant)

16. Drug-related factors
 Dose
 Duration
 Inherent toxicity of the
agent
 Pharmacodynamic
properties
 Pharmacokinetic
properties
FACTORS AFFECTING ADVERSE DRUG
REACTIONS :

17. GENETIC BASIS
1. Atypical pseodocholinesterase
→ Faulty hydrolysis: AR,
normal action of
succinylcholine hydrolysis
takes 5 min ,here it takes 1-2
hours, results in prolonged
respiratory failure.
2. Hydroxylase polymorphism →
Faulty oxidation, AR ,
Phenytoin toxicity ↑ in slow
hydroxylators.

18. GENETIC BASIS
3. Acetylator status → AR
In fast acetylators → INH → Acetyl
hydrazine → Hepatotoxicity
In slow acetylators → INH →
peripheral neuritis
In slow acetylators → Dapsone →
hemolysis.
4.G6PD deficiency → X linked recessive →
Primaquine , sulfonamides, nitrofurantoin
causes hemolytic anemia.

19. 5. Uroporphyrinogen Synthetase
Enzyme deficiency
→ AD ,required for haem
synthesis → Barbiturates ,
phenytoin , carbamazepine give
rise to acute intermittent
porphyria.
GENETIC BASIS

20.  Type A - (Augmented)
 Type B - (Bizarre)
 Type C - (Continuous)
 Type D - (Delayed)
 Type E - (Ending of Use)
 Type F - (Failure of Efficacy)
TYPES OF ADR

21. Type A (Augmented)
Predictable
Type B (Bizzare)
Unpredictable
Expected- Undesirable Unexpected- Undesirable
Based- Pharmacological
properties of drug
Based- Peculiarities of patient
More common Less common
Dose related Non dose related
Mostly preventable and reversible More serious, requires drug
withdrawl
Includes- Side effects ,
Secondary effects , Toxic
effects, Consequences of drug
withdrawal
Includes-Hypersensitivity/allergy
, Idiosyncrasy
ADR CLASSIFICATION

22. TYPES BASED ON ONSET
Onset of event:
 Acute -
within 60 minutes
 Sub-acute -
1 to 24 hours
 Latent -
> 2 days

23. SEVERITY OF ADR
Minor Moderate Severe Lethal
No Requires Requires Directly/
treatment/ treatment/ intensive Indirectly
Antidote/ Change in treatment , contributes
Prolongation treatment/ Life to the death
of Prolongation threatening, of the
hospitalisati
on
by at least 1
day
Permanent
damage
patient

24. FDA defines Serious ADR as which
 Results in death
 Life-threatening
 Require hospitalization
 Prolong hospitalization
 Cause disability
 Cause congenital anomalies
 Require intervention to prevent permanent
injury

25. Pharmacological properties of a drug
Extension effects
 Predictable
 Dose - Related responses
 Prevention - Adjustment of dosage regimen
Examples
 Benzodiazepines - Sedation
 Furosemide - Water and electrolyte imbalance
 Heparin, warfarin - Spontaneous bleeding
 Insulin - Hypoglycemia
TYPE A REACTIONS OR AUGMENTED

26. ADVERSE EFFECTS
 Predictable, dose-dependent reactions unrelated to
the goal of therapy
 Often produced by the same drug-receptor
interaction responsible for the therapeutic effect,
differing only in the tissue/s or organ/s affected

27. EXAMPLES OF ADVERSE EFFECTS
 INH, Rifampicin, PZA – Hepatotoxicity
 Streptomycin -Ototoxicity, nephrotoxicity
 Captopril - Cough
 Simvastatin – Rhabdomyolysis
 Nitrates – Headache
 Propranolol – Bronchial asthma
 Tetracycline – Hypoplasia of the teeth

28. TYPE B REACTIONS OR BIZARRE
 Abnormal effects
 Unrelated from the
drug’s known
pharmacological
actions

29. EXAMPLES OF BIZARRE REACTIONS
 Hypersensitivity reactions
 Stevens-Johnson’s Syndrome
 Hemolytic anemia

30. Long term effects are usually related to the dose
and duration of treatment
 Examples
 Ethambutol - Retinopathy
 NSAIDs - Nephrotoxicity
TYPE C REACTIONS OR CONTINUOUS

31.  Carcinogenesis
 Teratogenesis
 Examples: Thalidomide
TYPE D REACTIONS OR DELAYED

32. Withdrawal Syndromes
Examples:
• Benzodiazepines – Rebound insomnia,
agitation
• Clonidine – Rebound hypertension
• Corticosteroids – Acute adrenal
insufficiency
TYPE E REACTIONS OR ENDING OF USE

33. TYPE F REACTIONS OR FAILURE OF
EFFICACY
 Counterfeit medicines
 Underdosing of medications
 Drug interactions

34. DRUG
INTERACTION
 Warfarin which is highly protein
bound is displaced by valproic acid
leading to bleeding
 Aspirin inhibit platelet aggregation
together with heparin an
anticoagulant leads increased risk of
bleeding.

35. 1. Side Effects - Undesirable effects at
therapeutic doses
e.g a)Atropine → Preanaesthetic
medication → (undesirable ) dry mouth
b) Codiene → Suppresses Cough (desirable)
→ Constipation (undesirable)
Making Use of side effects -
Minoxidil → Antihypertension → Hypertrichosis
→ Male pattern baldness
Codeine → used in travellers diarrhoea
ADVERSE DRUG EFFECTS MAY BE
CATEGORISED INTO

36. 2.Secondary Effects- Indirect consequence of
primary action of drug
Examples -
a)Corticosteroids → ↓Immunity → Latent T.B.
activated
b)Tetracyclines → ↓Bacterial flora → Super-infection.
3. Toxic Effects-Exaggerated form of side effects due
to overdosage/prolonged use
Examples -
a)High dose heparin → Bleeding
b)Prolonged use of streptomycin →Ototoxicity,
nephrotoxicity

37. 4. Allergy/Hypersensitivity-Immunologically
mediated allergic responses occurs when sensitised
individuals are re-exposed to same drug again
 Humoral-Type I,II,III
 Cell mediated-Type IV

38. Type I - Anaphylactic reactions due toIgE
antibodies, min→2-3 hours
Examples - urticaria ,angioedema , anaphylactic
shock
Type II - Cytolytic reactions due to antigen
antibody complex , within 72 hours
Examples - hemolytic anemia , SLE.

39. Type III – Retarded or Arthus reaction -
Immune complex mediated reactions,
72 hours→1-2 weeks
Examples - serum sickness (fever, arthralgia,
lymphadenopathy),PAN , Steven Johnson
syndrome , procainamide induced systemic lupus
erythematous.
Type IV - Delayed hypersensitivity reaction
Examples - Contact dermatitis

40. 5. Idiosyncrasy - Genetically determined
abnormal reactivity to a chemical.
Here drug interacts with some unique features
of individuals , not found in majority of subjects
, produces uncharacteristic reaction.
Examples -
a)Barbiturates → excitement and mental
confusion in some patients.
b)Chloramphenicol → Aplastic anemia in
some patients.
c)Quinine/ quinidine → cramps, diarrhoea ,
purpura , asthma & vascular collapse.

41. 6. Drug Intolerance -
- Characteristic toxic effects at therapeutic
dose
- Converse of tolerance
- ↑ sensitivity to low doses
Examples -
Single dose triflupromazine → muscular
dystonia

42. 7. Photosensitivity -
Cutaneous reactions → sensitized skin
→ UV radiation.
Two types:
a) Phototoxicity
b) Photoallergicity

43. Phototoxicity Photoallergy
Drug/ metabolite accumulates
in skin → absorbs light →
photochemical and
photobiological reaction →
local tissue damage
i.e.erythema,edema,blistering,
hyperpigmentation
Drug/metabolite → cell
mediated immune response →
UV light → papular or
eczematous contact
dermatitis like picture
Short wavelengths
(290-320nm) UV-B
Longer wavelengths
(320-400nm) UV-A
More common
e.g. Tetracyclines
Less common
e.g. Sulfonamides,Griseofulvin

44. 8. Drug withdrawal reactions -
Sudden interruption of drug → worsens
clinical condition for which previously
drug was used.
Examples -
a) Corticosteroids in asthma →
precipitates acute attacks , myalgia,
depression
b) Beta Blockers → worsening of
angina , precipitates myocardial
infarction

45. 9. Teratogenicity –
Drug → pregnant mother → foetal
abnormalities
Examples-
1. Thalidomide → Phocomelia.
2. Diethylstilbesterol → Vaginal adenocarcinoma.
3. Valproic acid → Neural tube defects.
4. Antithyroid drugs → Foetal goiter,
hypothyroidism.
5. Phenytoin → Cleft lip , microcephaly.

46. DRUGS CAN AFFECT THE FOETUS
AT 3 STAGES
1)Fertilization &
implantation
(blastocyst
formation)
Conception to 17
days - failure of
pregnancy -
Cytotoxic drugs ,
alcohol .
2) Organogenesis
- 18-55 days of
gestation - most
vulnerable period
- deformities are
produced –
teratogens.
3) Growth and
development -
Developmental &
functional abnormality
ACE inhibitors -
Hypoplasia of organs
NSAIDS-
Premature closure of
ductus
arteriosus

47. RISK CATEGORY OF DRUGS DURING
PREGNANCY
Pregnancy
Category
Description
A
No risk :
Adequate and well-controlled human studies - Failed
to demonstrate a risk to the foetus
e.g. inj magnesium sulphate , thyroxine

48. Category Description
B
No evidence of risk in humans :
Animal reproduction studies - Failed to demonstrate a
risk to the foetus & no adequate and well-controlled studies in
pregnant women
OR
Animal studies have shown an adverse effect, but
adequate and well-controlled studies in pregnant women have
failed to demonstrate a risk to the foetus in any trimester.
E.g. Penicillin V, amoxicillin , cefaclor, erythromycin
paracetamol , lidocaine

49. Category Description
C
Risk cannot be ruled out:
Animal reproduction studies have shown an adverse effect
on the foetus and there are no adequate and well-controlled
studies in pregnant women,
But potential benefits may warrant use of the drug in
pregnant women despite potential risks.
E.g morphine , codeine , atropine , corticosteroids
,adrenaline , thiopentone, bupivacaine

50. category Description
D
Benefit may outweigh potential risk:
Positive evidence of human foetal risk - on
adverse reaction data from investigational or
marketing experience or studies in humans,
But potential benefits may warrant use of
the drug in pregnant women despite potential risks .
E.g. aspirin , phenytoin , carbamazepine,
valproate, lorazepam , methotrexate

51. Category Description
X
Contraindicated in Pregnancy:
Studies in animals or humans have
demonstrated foetal abnormalities
and/or
There is positive evidence of human foetal
risk based on adverse reaction data from
investigational or marketing experience, and the
risks involved in use of the drug in pregnant women
clearly outweigh potential benefits.
E.g oestrogens , isotretinoin ,
ergometrine, thalidomide.

52. 10. Carcinogenecity and mutagenecity
Carcinogenecity -
Oxidation → reactive metabolites →
structural gene damage
e.g. Anticancer drugs , estrogens .

53. MUTAGENICIT
Y
 Structural changes in DNA
 Oxidation of the drugs produces reactive
metabolites
 Covalent interaction with DNA
 Inheritable
 Takes 10-40 years to develop
 Anti cancer drugs, radioisotopes
 Usually marketed for life threatening conditions

54. 11. Iatrogenic (Drug induced diseases)-
Examples -
a) NSAID'S → Peptic ulcers
b) Hydralazine → DLE
c) Phenothiazines → Parkinsonism
d) INH → Hepatitis

55. 12. Drug Dependence - Use of drug produces a
state in which person believes that continuous use
is necessary for state of well being ( psychic
dependence) or to avoid withdrawal symptoms (
physical dependence.)
Psychological Physical
Here person believes Here repeated administration
that state of wellbeing of drug required to maintain
achieved only with action physiological equilibrium
of drugs. Discontinuation → withdrawl
e.g. Opiods ,
Benzodiazepins
e.g. Alcohol , Barbiturates ,
Benzodiazepins

56. PREVENTION OF ADR
1. Avoid all inappropriate use of drugs.
2. Use of appropriate dose , route & frequency of
drug administration.
3. Elicit & take into consideration previous history
of drug reactions.
4. Elicit h/o allergic diseases & exercise caution.
5. Rule out possibility of drug interaction.
6. Adopt correct drug administration technique.
7. Carry out appropriate laboratory investigation.
8. Be aware of interactions with certain
foods, alcohol and even with household
chemicals.

57. MANAGEMENT OF
ADR
Discontinue the offending agent if -
 It can be safely stopped
 The event is life-threatening or intolerable
 There is a reasonable alternative
 Continuing the medication will further
exacerbate the patient’s condition
Continue the medication (modified as needed) if
-
 It is medically necessary
 There is no reasonable alternative
 The problem is mild and will resolve with
time

58.  Discontinue non-essential medications
 Administer appropriate treatment -
e.g., atropine,protamine sulfate ,digibind
antibodies, flumazenil.
 Provide supportive or palliative care -
e.g., hydration, glucocorticoids, warm / cold
compresses, analgesics or antipruritics
 Consider rechallenge or desensitization

59. PRINCIPLES OF DESCRIPTIVE TOXICITY
TESTING IN ANIMALS
1. Effects of chemicals produced in laboratory
animals when properly quantified apply to
human beings.
2. Exposure of experimental animals to toxic
agents in high doses – necessary & valid method
to discover possible hazards to human beings.

60. MANAGEMENT OF
POISONING
A. Maintain vital & physiological functions from
impairment
B. Termination of exposure (decontamination)
C. Prevention of absorption of ingested
poison.(activated charcoal)
D. Hastening elimination
1. Urinary alkanlization
2. Multidose activated charcoal
3. Extracorporeal drug removal
E. Antidote therapy

61. PHARMACOVIGILANC
E
Definition – Science and activities relating to
the detection ,assessment , understanding and
prevention of adverse effects or any other drug
related problems .
Activities involved in it
1. Postmarketing surveillance
2. Dissemination of ADR data
3. Changes in labelling of medicines

62. ADR REPORTING FORM

63. CAUSALITY ASSESSMENT
 Routine procedure in Pharmacovigilance
 Relationship of cause & effect
 Most outcomes : multiple interacting causes
 Aim : to define contribution due to drugs
 Problems:
 ADRs rarely specific
 Diagnostic tests usually absent
 Re challenge rarely ethically justified
Various methods: None is precise, reliable

64. Causality Assessment Methods
 Algorithmic: (algorithm - specify how to solve problem)
 Series of questions
 Answers are weighted
 Overall score determines causality category
 e.g. Naranjo’s scale
 Probalistic: (based on probability)
 Set of explicitly defined causality categories
 e.g. WHO UMC method
Uses of causality assessment
• Initial review of report
• Signal detection
• Scientific publications

65. THE NARANJO ADR PROBABILITY SCALE
Questions Yes No Don’t
Know
1) Are there previous conclusive reports on this
reaction?
+1 0 0
2) Did the ADR appear after the suspected drug
was administered?
+2 -1 0
3) Did the ADR improve when the drug was
discontinued?
+1 0 0
4) Did the ADR appear with re-challenge? +2 -1 0
5) Are there alternative causes for the ADR? -1 +2 0
6) Did the reaction appear when placebo was given? -1 +1 0
7) Was the drug detected in blood at toxic levels? +1 0 0
8) Was the reaction more severe when the dose
was increased, or less severe when the dose was
decreased?
+1 0 0
9) Did the patient have a similar reaction to the
same or similar drug in any previous exposure?
+1 0 0
10) Was the ADR confirmed by any objective
evidence?
+1 0 0

66. THE NARANJO PROBABILITY SCALE
The score :-
≥ 9 = Definite
5-8 = Probable
1-4 = Possible
0 = Doubtful
Naranjo CA et al. Clin Pharmacol Ther
1981;30:239-45.

68. DRUG INTERACTIONS
 PHARMACOKINETIC DRUG INTERACTIONS
1) DRUG –DRUG interaction
Drug interaction (more precisely 'drug-drug
interaction') refers to modification of response to one
drug by another when they arc adminis-tered
simultaneously or in quick succession.
2) Drug – food
3) Drug – chemical
4) Drug – disease.. etc

69. Regular medication drugs (Likely to be
involved drug teract1ons)
 1. Antidiabetics
 2. Antihypertensives 3. Antianginal drugs
 4. Antiarthritic drugs 5. Antiepileptic drugs 6.
Antiparkinsonian drugs 7. Oral contraceptives
 8. Anticoagulants 9. Antiasthmatic drugs
 10. Psychopharmacological agents
 11. Antipeptic ulcer/reflux drugs
 12. Corticosteroids 13. Antitubercular drugs
 14. Anti-HIV drugs

70. Drug interactions at ABSORBTION
 Absorption of an orally administered drug can be
affectcd by other concurrently ingested drugs.
 This is mostly due to formation of insoluble and
poorly aborbed complexes in the gut lumen, as
occurs between tetracyclines and calcium/iron
salts, antacids or sucralfate.
 Phcnytoin absorption is decreased by sucralfate due
to binding in the g.i. lumen.

71.  Ketoconazole absorption is reduced by H2 blockers and
PPIs because they decrease gastric acidity which
promotes dissolution and absorption of ketoconazole.
 Antibiotics like ampicillin, tetracyclines, cotrimoxazole
markedly reduce gut flora that normally deconjugates
oral contraceptive steroids secreted in the bile as
glucuronides and permits their enterohepatic circulation.
 contraceptive failure have been reported with concurent
use of these antibiotics due to lowering of the
contraceptive blood levels.
 AIteration of gut motility by atropinic drugs, tricyclic
antidepressants, opioids and prokinetic drugs like
metoclopramide can also affect drug absorption.

72. Distribution Interactions
drug distribution are primarily due to displacement of
one drug from its binding sites on plasma proteins
by another drug.
Drugs highly bound to plasma proteins that have a
relatively small volume of distribution like
coumarine anticoagulants, sulfonylureas, certain
NSAIDs and antiepileptics are particularly liable to
displacement interactions.
Displacement of bound drug will initially raise the
concentration of the free and active form of the drug
in plasma that may result in toxicity.

73.  Quinidine has been shown to reduce the binding of
digoxin to tissue proteins as well as its renal and
biliary clearance by inhibing the efflux transporter P-
glycoprotein, resulting in nearly doubling of digoxin
blood levels and toxicity.

74. Metabolism interaction
 Certain drugs reduce or enhance the rate of
metabolism of other drugs. Macrolide antibiotics,
azole anti fungals, chloramphenicol, omcprazole,
SSRls, HIV-protease inhibitors, cimctidine,
ciprofloxacin and metronidazolc are some important
inhibitors of metabolism of multiple drugs.
 Risk of statin induced myopathy is increased by
fibrates, niacin, erythromycin, azole antifungals and
HIV-protease inhibitors, probably due to inhibition
of statin metabolism.

75.  Barbiturates, phenytoin, carbamazepine,
rifampin, cigarelle smoking, chronic alcoholism
and certain pollutants are important microsomal
enzyme inducers.
 Contraceptive failure and loss of therapeutic effect of
many other drugs have occurred due to enzyme
induction.
 On the other hand, paracetamol toxicity occurs in
chronic alcoholics and in those on enzyme inducing
medication, because one of the metabolites of
paracetamol is responsible for its overdose
hepatotoxicity.

76. Excretion interactions
lnteraction involving excretion are important mostly in
case of drugs actively secreted by tubular transport
mechanisms, e.g. probenecid inhibits tubular
secretion of penicillins and cephalosporins and
prolongs their plasma t½.
This is particularly utilized in the single dose
treatment of gonorrhoea.
Aspirin blocks the uricosuric action of probenecid and
decreases tubular secretion of methotrexate.

77.  Change in the pH of urine can also affect excretion of
weakly acidic or weakly basic drugs. This has been
utilized in the treatment of poisonings.
 Diuretics and to some extent tetracyclines, ACE
inhibitors and certain I SAIDs have been found to
raise steady-state blood levels of lithium by
promoting its tubular reabsorption.

78. CONCLUSION
 Every drug which has an effect has an adverse
effect every time a drug is given risk is involved.
 What is there that is not a poison ? all things are
poison & nothing is with out poison, solely dose
determines that a thing is not a poison.
 For rational use of drug not only its clinical
indications are important to be remembered
equally important is remembering adverse
effects.
 Early detection of adverse effects and its
proper management can be life saving in many
situations.

79. REFERENCES
 Goodman and Gilman's -12th The Pharmacological
basis of therapeutics
 Parthasaradhi clinical pharmacy, 2nd edition
 Essentials of pharmacotherapeutics 5th edition –
F.S.K. Barar
 Essentials of Medical Pharmacology 7th
- K. D. Tripathi

81. Reports
from
Participating
Hospitals
Reports
from
Private
Practitioners
Report
from
Drug Mfr.
Traders/
Outlets
Reports
on
Clinical
Investiga-
tions
Reports
from
Regulatory
Authorities
Reports
from
Int’l
ADR
Centers
BFAD ADR UNIT
NADRAC WHO Collaborating Center
Director - BFAD
Secretary of
Health - DOH
ADR Monitoring System

82. ADRS: 4TH LEADING CAUSE OF DEATH
Study: Drug reactions kill an estimated 100,000 a
year
 April 14, 1998

83. KEY POINTS TO REMEMBER
ADRs