2. Case Scenario
A 40-year-old laborer presented with itching and scaly lesions on the
dorsum of hands, erythematous papules and macules on face, neck, both
arms and chest which worsened on exposure to sun. He had been
prescribed tablet moxifloxacin 400 mg once a day for five days for a
respiratory tract infection. He developed the above lesions on third day of
therapy. History revealed that patient had taken ciprofloxacin in the past
and had no allergic reaction to it which suggested that the patient was
not allergic to fluoroquinolones. Moxifloxacin was stopped and the
lesions subsided. It was diagnosed to be moxifloxacin induced
phototoxicity.
3. What is an ADR???
Any noxious change which is suspected to be due to
a drug, can occur at doses normally used in man,
requires treatment or decrease in dose or indicates
caution in the future use of the same drug.
4. SEVERITY OF ADRs
• Minor – no therapy, antidote or prolongation of hospitalization
is required
• Moderate – requires change in drug therapy, specific treatment
or prolongs hospital stay by atleast one day
• Severe – potentially life-threatening, causes permanent
damage or requires intensive medical treatment
• Lethal – directly or indirectly contributes to death of the patient
5. FACTORS CAUSING ADRS
• PATIENT FACTORS – age, sex, genetics,
• DRUG FACTORS – type A or Breaction
• CLINICIAN/PRESCRIBER FACTOR – duration of treatment,
when to discontinue, which drug to be prescribed in pregnancy,
7. TYPES OF ADVERSE DRUG
REACTIONS
• Type A(augmented/predictable)
• Type B (bizarre/non-predictable)
• Type C (chronic use)
• Type D (delayed effect)
• Type E (end of use/abrupt withdrawal)
• Others
8. Type A Type B Type C Type D Type E Others
Side effects Allergic
reactions
Drug
dependence
Teratogenicity Withdrawal
reactions
Iatrogenic
Secondary
effects
Idiosyncrasy Cumulative
toxicity
Mutagenicity Photosensitive
reactions
Toxic effects Organ damage Carcinogenicity Masking of
diseases
Poisoning Immuno
suppression
Exacerbation
of disease
Intolerance
9. Type A (augmented) Type B (bizarre)
• Due to extension of
pharmacological
action
• Immunological/ genetic basis
• Predictable • Mostly not predictable
• Quantitative (dose dependent) • Qualitative (dose dependent)
• High incidence but low
mortality
• Low incidence but high
mortality
• Dose reduction is needed • Drugs has to be discontinued
• Examples: dryness of mouth & • Anaphylactic reaction due to
blurring of vision due to penicillin G; hemolysis with
atropine; hypoglycemia with primaquine
glibenclamide
10. Type A reactions
• Side effect
• Toxic effect and drug toxicity or poisoning
• Secondary effect
• Intolerance
11. SIDE EFFECTS
• Unwanted & unavoidable effects at therapeutic doses
• It may be same as therapeutic effect (atropine, GTN)
• It may be a different facet of action (promethazine, estrogen)
• May be therapeutic in one context but side effect in another
context (codeine)
• Discovery based on side effects (sulfonamides)
12. SECONDARY EFFECTS
• Indirect consequences of a primary action of a drug
• Examples : suppression of bacterial flora by tetracyclines leads to
superinfections
• Corticosteroids weaken host defence mechanisms so that latent
TB gets activated.
13. TOXIC EFFECTS
• Result from excessive pharmacological action of the drug due to
over dosage (absolute/relative) or prolonged use.
• Manifestations are predictable & dose related
• Functional alteration (atropine), drug induced tissue damage
(paracetamol), extension of therapeutic effect (barbiturates,
heparin), additional action of a drug (morphine, streptomycin)
14. POISONING
• Poisoning - harmful effects of a chemical on biological system
• Result from large doses (it is the dose which distinguishes a drug
from a poison)
• Management protocol
15. INTOLERANCE
• It is the appearance of characteristic toxic effects of a drug in an
individual at therapeutic doses.
• Indicates low threshold of the individual to the action of the drug
• Eg. Chloroquine (vomiting & abdominal pain), triflupromazine
(muscular dystonias), carbamazepine (ataxia)
16. Type B reactions
• Drug allergy / allergic reactions
• Idiosyncratic reactions (pharmacogenomics)
17. IDIOSYNCRASY
• Genetically determined abnormal reaction to a chemical
• total absence or reduced activity of some enzyme ( eg. G6PD
deficiency – primaquine, salicylates, sulfonamides - hemolysis
• Examples: barbiturates (excitement & mental confusion),
chloramphenicol (aplastic anemia)
21. TYPE C REACTIONS
• Drug dependence
• Organ damage
• Cumulative toxicity
• Immunosuppression
22. DRUG DEPENDENCE
• Drugs for personal satisfaction is accorded a
higher priority than other basic needs, oftenin
the face of known risks tohealth.
• Psychological (reinforcement) &
physical dependence
• Drug abuse, addiction &habituation
23. • Psychological –individual believes that optimal
state of well being is achieved only through
action of drug (emotionally distressed if drugis
not taken – compulsive drug use)
• Physical –altered physiological state produced
by repeated administration of a drug,
necessitates continuous presence of drug to
maintain physiological equilibrium
(discontinuation –
withdrawal syndrome) –
neuroadaptation
24. • Drug abuse –use of a drug by self medication
(deviates from the approved medical and
social pattern) –
continuous, occasional
• Drug addiction – compulsive drug
use/ overwhelming involvement,
• Drug habituation – less intense involvement
with drug, withdrawal produces only mild
discomfort
26. MUTAGENICITY &
CARCINOGENICITY
• Drug cause genetic defects and cancer respectively.
• Oxidation of drug - produce reactive intermediates – affect genes
and cause structural changes in chromosomes – covalent
interaction with DNA – induce mutations.
27. TERATOGENICITY
• Fetal abnormalities when given to pregnant mothers
• Affect fetus at 3 stages:
1. Fertilization & implantation – conception to 17days – failure
2. Organogenesis – 18 to 55 days – most vulnerable (deformities)
3. Growth & development – 56 days onwards – developmental &
functional abnormalities.
28. DRUG EFFECT
Thalidomide Phocomelia, heart defects, gut
atresia
Warfarin Saddle nose, retarded growth, defects of limbs,
eyes and CNS
Corticosteroids Cleft palate and congenital cataract
Androgens Masculinisation in
female
Oestrogens Testicular atrophy in males
Ethanol Fetal alcohol
syndrome
Valproate Neural tube defects
Phenytoin Cleft lip/palate, microcephaly, mental retardation
Aminoglycosides Deafness
29. category Examples
A
No risk
Adequate studies in pregnant women have
failed to demonstrate a risk to the fetus
Inj. Magnesium
sulfate, thyroxine
B
No evidence of
risk in humans
Adequate human studies are lacking, but
animal studies have failed to demonstrate a
risk to the fetus
Penicillin,
amoxicillin,
erythromycin,
paracetamol
C
Risk cannot be
ruled out
No adequate studies in preg women, &
animal studies are lacking or have shown an
adverse effect on fetus, but potential benefit
may warrant use of drug in preg women
despite potential risk
Morphine, atropine,
corticosteroids,
thiopentone,
bupivacaine
D
Benefit may out
weigh potential
risk
There is evidence of human fetal risk, but
the potential benefits from use of drug
may be acceptable despite the potential
risk
Aspirin, phenytoin,
carbamazepine,
valproate,
lorazepam
X
Contraindicated
Studies in humans or animals have
demonstrated fetal abnormalities, and
potential risk outweighs possible benefit
Estrogens,
isotretinoin,
ergometrine
30. Type E (End of treatment)
reactions/ DRUG WITHDRAWL
Occur on withdrawal especially when drug is stopped
abruptly
E.g.
• Phenytoin withdrawal : Seizures,
• Steroid withdrawal : Adrenocortical insufficiency.
31. PHOTOSENSITIVITY
• Cutaneous reaction resulting from druginduced
sensitization of the skin to UVradiation
• phototoxic (tetracyclines, nalidixic acid,
fluoroquinolones) - short wavelengths (290-320nm)
–
shorter duration after exposure ends
• photoallergic (sulfonamides, sulfonylureas,
chloroquine) –longer wavelengths (320-400nm) –
persist long after exposure –lesion extend
beyond exposed areas.
33. PHARMACOVIGILANCE
• “Science and activities relating to the detection,
assessment, understanding and prevention of adverse
effects or any other drug related problems.”
• Usefulness – educate doctors, official regulation of drug
use, reduction in drug-related harm to patients, rationale
use of medicines.
34. Activities involved in pharmacovigilance
• Post marketing surveillance & other methods of ADR
monitoring
• Dissemination of ADR data – drug alerts, medical
letters, advisories sent by FDA
• Changes in labelling of medications
35. Governing bodies of
Pharmacovigilance
• Uppsala Monitoring Committee (Sweden) – international
collaborating centre
• Central Drugs Standard Control Organization (CDSCO) – India
• Assess causality (Naranjo algorithm) and severity (modified
Hartwig scale
36.
37. PREVENTION OF ADVERSE
EFFECTS
• Avoid inappropriate use of drugs
• Use appropriate dose, route & frequency of drug administration
• Previous history of drug interactions, allergic diseases
• Rule out drug interactions
• Adopt correct administration technique
• Carry out appropriate laboratory monitoring
