Drugs can have both beneficial and harmful effects. While drugs save lives and improve health, they can also threaten life. Whether the potential benefits of a medication outweigh the risks depends on the individual taking it. Adverse drug reactions (ADRs) are a common clinical problem that can have serious consequences for patients, from mere inconvenience to death. Anyone taking medication can experience an ADR, but some groups are at higher risk, such as the elderly, those taking multiple drugs, and those with multiple medical conditions. ADRs should be considered if new symptoms appear after starting or increasing a drug dose and disappear after stopping the drug. The most common causes of ADRs are antibiotics, anticancer drugs, cardiovascular drugs,

2. Drugs have:
Beneficial effects
Harmful effects
Facts
Drugs save life & improve health
Drugs also threaten life

3. “Cur’d yesterday of mydisease
I died last night of my physician”
- Mathew Prior:17th Century
From,the remedy worse than the disease
So, the important question is ALWAYS:
“Do the potential benefits ofthe medication
outweigh the potential risks forthe individual?”

4. Definition
 ‘An adverse drug reaction is any undesirable effect of a
drug beyond its anticipated therapeutic effects occurring
during clinical use.’
The term (ADR) usually excludes-
nontherapeutic overdosage (e.g. toxicities due to
accidental exposure or attempted suicide) and
lack of efficacy of drug

5. WHO definition:
• “Any response to a drug that is noxious and
unintended and that occurs at doses used in
humans for prophylaxis, diagnosis, or therapy of
disease, or for the modification of physiologic
function.”
• It excludes therapeutic failures, overdose, drug
abuse, noncompliance, and medication errors

6.  Injury resulting from the medical use of a drug.
 Includes Medication Error & ADR
 Medication error:An injury resulting from an
error in preparing, procuring, prescribing,
dispensing, administering, or monitoring.
 Adverse drug reaction (ADR):An injury
resulting from the medical use of a drug where
no error isinvolved.

7. ADRs are a common clinical problem.
Causes adverse consequences to
patients…
From mere inconvenience to death and
Have very high incidence in clinical
practice

8. For marketed drugs in USA
Occur in 5 % of all hospital admissions
10-20% of hospital inpatients
About 25% in general practice
Significantcause of death (0.5-0.9%)

9.  In the UK Non Steroidal Anti-Inflammatory Drug
(NSAID) use alone accounts for1
• 65,000 emergency admissions/year
• 12,000 ulcer bleeding episodes/year
• 2,000 deaths/year
1Blower et al. Emergency admissions for upper gastrointestinal
disease and their relation to NSAID use. Aliment Pharmacol Ther
1997; 11: 283-291

10. Consequences ofADRs:
Adversely affects patients’quality of life
Complicate drug therapy
Decrease compliance and delay cure
Increase cost of patient care
Cause patients to lose confidence in their
doctors
May mimic disease, resulting in unnecessary
investigations and delay in treatment

11. ADRs are usually classified dependingon
 Onset
 Severity
 Type

12. Acute
 Within 60 minutes
Sub-acute
 1 to 24 hours
Latent
 > 2 days
ADR: Onset of event:

13. prolongation
Mild
 D o not require an antidote, therapy, or
of hospitalization
Commonly known as side-effects
Moderate
Require a change in, but not necessarily cessation of the
drug and may prolong hospitalization or require special
treatment
ADR: Severity of event:

14. Severe
Are potentially life threatening, requiring
discontinuation of the drug and specific treatment of
the adverse reaction
Lethal
Directly or indirectly contributes to the patient's
death

15. • Result in death
• Life-threatening
• Require hospitalization
• Prolong hospitalization
• Cause disability
• Cause congenital anomalies
• Require intervention to prevent permanent
injury
FDA: Serious ADR

16. 2maintypes:


Type A (Augmented)
Type B(Bizarre)
3othersub-types:
Type C, D &E

17. Type A(knownpharmacological adverse drug
reactions)
 Type A reactions represent an Augmentation of
the pharmacological actions of a drug
 Predictable & dose-dependent

18. Readily reversible on reducing the dose or
withdrawing the drug.
Commonest type of ADRs (accounting for over
80% of all ADRs)
Not usually life threatening.

19. Type Aadverse reactions:
Are of 2 types:
A) Extension of primary effect
B)Secondary effect

20.  Effects due to extension of the primary
pharmacological actions of the drug
 Augmentation of the drug's therapeutic
actions
Example: Bradycardia withPropranolol
(due to effect on desirable beta1 blocking effect)

21. Effects due to the secondary pharmacology of the
drug
The action different from the drug's therapeutic
actions
The action still rationalisable from the known
pharmacology of the drug
 Example: Bronchospasm with propranolol (due to
effect on undesirable beta2 blocking effect)

22. Thus, for propranolol:
Bradycardia is primary pharmacological adverse
effects
Bronchospasm is a secondary pharmacological
adverse effect.
More emphasis is nowplaced on the secondary
pharmacology of new drugs during preclinical
evaluation to anticipate problems thatmight arise once
the drug is given to humans.

23. Type Badverse reactions: (unknown
pharmacological adverse drug reactions)
These are Bizarre
Not predictable i.e., cannot be predicted
from the known pharmacology of the drug.
Not dose dependent
Can’t be readilyreversed
Less common but often serious
Life threatening

24. Type BADRs may be:
1) Idiosyncrasy
2) Drug Allergy or Hypersensitivity

25. Idiosyncrasy: (Pharmacogenetics)
Inherent qualitative abnormal response to a drug
Due to genetic abnormality, mainly due to
deficiency of enzymes in the body
Also may be due to abnormal receptor activity
Incidence:
Happens to very small population
Rare but serious

26. Idiosyncrasy due toenzyme abnormality
Hemolysis with primaquine
if glucose 6-phosphate dehydrogenase (G6PD)
enzyme deficiency in any person

Ifprimaquine given

Hemolysis leading to hemolytic anemia

27. Idiosyncrasy due to receptor abnormality
Malignant hyperthermia with general anesthetics
(Halothane)
Sudden huge rise in IC calcium concentration
Increase in muscle contraction
Increase in metabolic activities
Rise of body temperature

28. Drug allergy
Also known as hypersensitive reaction
Due to antigen-antibody interactions
1st dose acts asan antigen
Antibody is produced against the antigen in the body
Subsequent dose causes antigen-antibody reaction
e.g. Penicillin inducedanaphylaxis
(Type 1 hypersensitivityreaction)

29. Types of allergicreactions
Type I - immediate, anaphylactic (IgE)
e.g., anaphylaxis with penicillins
Type II - cytotoxic antibody (IgG, IgM)
e.g., methyldopa and hemolytic anemia
Type III - serum sickness (IgG, IgM) antigen-
antibody complex
e.g., procainamide-induced lupus
Type IV - delayed hypersensitivity (T cell)
e.g., contact dermatitis

30. Type C or Continuous type:
Happens due to long term chronic use of a drug
Involves dose accumulation
e.g. Analgesic nephropathy with Paracetamol /
NSAIDs

31. Type D
Delayed effect
ADRs are found long term after use of drug
Teratogenesis
Carcinogenesis
Teratogenesis: birth defect that is evident after birth
but the drug taken during 1st trimester of pregnancy
Carcinigenesis: carcinoma detected long after use of a
drug

32. Teratogenesis
Teratogenesis is the abnormal congenital
malformation of fetus due to use of some drugs in 1st
trimester of pregnancy
(4-10 weeks: period of organogenesis)
Teratogenic drugs:
1st detected teratogenic drug is ‘thalidomide’
It causes ‘phocomelia’--flipper-like limb defect (like
penguin)
Thalidomide disaster in early ‘60s

33. Other teratogenic drugs:
Cytotoxic (anticancer) drugs
Vitamin A (retinoid)
Antithyroid drugs
Steroid preparations
OAHs
oral anticoagulantsetc.
In general, all drugs should be avoided in 1st
trimester of pregnancy to avoid teratogenic risk

34. Type E
 Ending of drug use
 ADRs are manifested after withdrawal of a drug which
was used for a long period
 When glucocorticoid is abruptly
withdrawn/discontinued after prolonged use
Adrenocortical insufficiency
Suddenly body suffers from glucocorticoid crisis

35. Who might get an ADR?
 Anyone who takes a medicine
 Differential diagnosis should include the
possibility of an ADR if the patient is taking any
form of medication

36. Who is most at risk from ADRs?
Patients who;
 are young, or old or female
 are taking multiple therapies
 50% of patients on 5 drugs or more
 have more than one medical problem
 have a history of allergy or a previous reaction to
drugs

37. What should raise suspicion of an ADR?
A symptomthat….
appears soon after a new drug is started
appears after a dosage increase
disappears when the drug is stopped
reappears when a drug is restarted

38. ADEs: Most Commonly Involved Drugs:
Antibiotics
Antineoplastics
Cardiovascular drugs
Hypoglycemics
NSAID/Analgesics
 C N S drugs

39. Most Common ADEs:
Gastrointestinal tractevents 22.1%
Electrolyte/renal 16.7%
Hemorrhagic 12.7%
Metabolic/endocrine 9.5%
Dermatologic (skin) /allergic 7.9%

40. Common Symptoms From ADEs:
Confusion
Nausea
Decreased balance
Change in bowel pattern
Sedation
Orthostatic hypotension

41. What conditions are often drug related?
 Anaphylaxis
antibiotics, iron dextraninjection
 Stevens Johnson Syndrome
associated with carbamazepine, antibiotics
 Blood dyscrasias
neutropenia with methotrexate and gold salts
thrombocytopenia with heparin

42. What questions should be asked if suspect an ADR?
 Does the patient have a history of other drug-
induced problems?
ask thepatient
 Does the patient take more than one drug ?
could an interaction be causing the ADR?
long term medication is unlikely to cause new
problems

43. What else ...?
 When did the reaction or symptoms begin?
timings are useful
 Have any of the clinical measurements or lab
results recently become abnormal?
 Does the patient have any medical problems?
that could be causing the symptoms?
some diseases predispose patients to ADRs

44. Causes of ADRs
ADRs may be due to:
Drug cause
Patient cause
Prescriber’s error---
Type C D & E
Polypharmacy

45. Factors predisposing to ADRs
A) Dose factor:
D ue to administration more than therapeutic dose
excessive insulin

hypoglycaemia

46. B) Pharmaceutical factor:
D ue to wrong pharmaceutical preparation
Slow release NSAID

Release in high concentration due to faulty
preparation

GIT bleeding

47. C) Pharmacokineticfactor:
D ue to decrease kinetic activities
Sulfonylurea

Decreased elimination in renal insufficiency

Hypoglycaemia

48. D)Pharmacodynamic factor:
D ue to drug’s mechanism of action
NSAID

LVF due to salt & water retention
E)Polypharmacy: Drug-drug interaction factor:
Erythromycin + terfenadine= Arrhythmia

49. Other factors:
age
gender
multiple disease
allergy

50. Prevention ofADRs
Whenever a drug is given a risk is taken
Risks may be avoidable or unavoidable
30-50% ADRs are preventable
Drug interaction
Inappropriate medication
Unnecessary medication

51. Reduction of ADRs can be achieved by:
Better knowledge of diseases
Better knowledge of drugs
Site-specific delivery
Informed, careful and responsible prescribing

52. Management ofADRs:
Mild ADRs can often be recognized before they
become serious.
If an ADR occurs, the type and precipitating factors
must be determined immediately if possible.

53. Discontinue the offending agent if:
it can be safely stopped
the event is life-threatening or intolerable
there is a reasonable alternative
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

54. Discontinue non-essentialmedications
Administer appropriate treatment
e.g., atropine,antihistamines, epinephrine,
corticosteroids, glucagon etc
Provide supportive or palliative care
e.g., hydration, glucocorticoids, warm / cold
compresses, analgesics etc
Consider desensitization

55. Generally,
For dose-relatedADRs:
Modify the dose or reduce precipitating factors
For ADRs unrelated to dose:
The drug usually should be withdrawn and re-
exposure should beavoided.

56. Thank you verymuch