THIS CLASS IS IN BRIEF FOR UNDERGRADUATE UNDERSTANDING AND EXAMINATION PURPOSE

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.

2.  An adverse drug reaction (ADR) is any untoward
medical occurrence in a patient administered a
pharmaceutical product, which is suspected to have
a causal relationship with this treatment.
 A response to a drug which is noxious and
unintended, and which occurs at doses normally
used in man.
 Spontaneous reports from consumers and
healthcare professionals should be regarded as
suspected ADRs.

3.  Adverse Event (AE) – any untoward medical
occurrence that may present during treatment with
a pharmaceutical product but which does not
necessarily have a casual relationship with this
treatment
 Serious Adverse Event (SAE) – AE that is either life-
threatening, fatal, cause of prolong hospital
admission, cause persistent disability or concern
misuse or dependence

4. Adverse Drug Reaction
(event attributed to drug)
Adverse Event
All Spontaneous
reports
Events not attributed to drug
Diseases
Other Drugs
Environment
Diet
Genetics
Compliance
Other
factors

6. Normal larynx Laryngeal oedema

7. ADR database
No of reports: more than 3.5 million
Each year increase ~160,000 / year

8. Withdrawn Drugs From the Market
Drug Year Reason
Lumiracoxib 2008 Hepatotoxicity
Aprotinin 2008 Kidney and cardiovascular toxicity
Tegaserod 2007 Cardiovascular ischemic events
Ximelagatran 2006 Hepatotoxicity
Valdecoxib 2005 Dermatology adverse events
Pemoline 2005 Hepatotoxicity
Rofecoxib 2004 Thrombotic cardiovascular events
Levomethadyl 2003 Fatal Arrhytmia
Rapacuronium 2001 Risk of fatal bronchospasm
Cerivastatin 2001 Rhabdomyolosis
Trovafloxacin 2001 Hepatotoxicity
Amineptine 2000 Hepatotoxicity, dermatological side effects, abuse potential
Cisapride 2000 Cardiac arrhythmias
Troglitazone 2000 Hepatotoxicity

9. Drug Year Adverse Reaction Outcome
Sulfanilamide 1937 Liver damage due to
diethylene glycol
Solvent changed; FDA
established
Thalidomide 1961 Congenital Malformations Withdrawn
Chloramphenicol 1966 Blood Dyscrasias Uses restricted
Benoxaprofan 1982 Liver damage Withdrawn
Aspirin 1986 Reye’s syndrome Uses restricted
Flecainide 1989 Cardiac Arrhythmias Uses restricted
Noscapine 1991 Gene toxicity Withdrawn
Triazolam 1991 Psychiatric disorders Withdrawn
Withdrawn Drugs From the Market

10. drug year Adverse reaction Outcome
Temafloxacin 1992 Various serious
adverse effects
Withdrawn
Co-trimoxazole 1995 Serious allergic
reactions
Uses restricted
Terfenadine 1997 Interactions
(e.g. with grapefruit
juice)
Withdrawn from OTC
sale
Sotalol 1997 Cardiac arrhythmias Uses restricted
Astemizole 1998 Interactions Withdrawn
Cisapride 2000 Cardiac arrhythmias Withdrawn
Cerivastatin 2001 Rhabdomylosis Withdrawn
Withdrawn Drugs From the Market

11. Type A (Augumented):
Common->1%
Pharmacological mechanism based reactions Suggestive
time relationship and Dose relationship
Reproducible Ex- side effects, toxic effects
Type B (Bizzare): (“Patient Reactions”)
Immuno allergic reactions peculiarities related to patients
Idiosyncrasy. Less common, non-dose related, Unexpected,
Causality uncertain, Not reproducible experimentally
Characteristic-serious, Rare <1%
Anaphylaxis with penicillin

12. Type C adverse effects (Statistical effects)
Often long latency
Mechanism unknown
Difficult to reproduce experimentally
Associated with long term drug therapy
E.g., Benzodiazepines dependence
Analgesic Nephropathy
Classification of adverse effects

13. Type D
These reactions refers to teratogenic & carcinogenic effects
These reactions are delayed in onset of action
They are well known and can be anticipated
Type E
End of dose effects
e.g. Abrupt cessation of corticosteroids produces acute
adrenal insufficiency
Propanolol – hypertension
Type F
Failure of therapy
E.g. Anti tubercular therapy

14. MINOR No need of therapy
MODERATE requires drug change, specific treatment,
hospitalization
SEVERE Potentially life threatening, permanent
damage, prolonged hospitalization
LETHAL Directly or indirectly lead to death

15. Type of rash Description Examples of drugs
causing it
Erythema multiform Target like lesions on the extensor surface
of the limbs.
Penicillamine
Penicillin
Sulphonamides
Erythema nodosum Tender red nodules, sometimes with
bruising on the extensor surface of the
limbs.
Phenobarbitals
Sulphonamides
Oral contraceptives
Exfoliative dermatitis Red, scaly, Exfoliative lesions sometimes
involving extensive areas of skin
Carbamazepine
Gold salts
Phenylbutazone
Pemphigus Widespread blistering Penicillamine
Rifampicin
Urticaria Red raised lesions surrounded by oedema
often confluent
Codiene
Dextrans
Penicillin

16. SIDE EFFECTS
Unavoidable, predictable
Occur at extension of same therapeutic effect
E.g. Atropine - Dry mouth
Promethazine – Sedation
Estrogen (Antiovulatory) - Nausea
Codeine (antitussive) –Constipation

17. Indirect consequences of primary effect of therapy
E.g. microflora killed by tetracycline super infection
Corticosteroids' (immunity) –Oral candidiasis

18. Over dose or prolonged use of drugs
The manifestations are predictable and dose related
They result from functional alteration or drug induced
tissue damage
Atropine – delirium
Paracetamol – hepatic necrosis
Barbiturates – coma
Morphine – Respiratory failure

19. Appearance of characteristic toxic effects of a drug in
an individual at therapeutic doses.
Opposite to tolerance –sensitive to low doses
Few doses of Carbamazipines causes ataxia, defective
movement, goiter
Single dose of Triflupromazine –Muscular dystonia

20. Genetically determined
abnormal reactivity to a chemical
atypical, bizarre effects
Barbiturates- excitement & mental confusion
Streptomycin –Deafness with single dose
Deficiency of glucose 6 phosphate enzyme in
individual, causes Haemorhoidal necrosis

21. Immunologically mediated reactions producing
stereotype symptoms which are unrelated to
pharmacodynamic profile of the drug
Independent of dose
Occur in small proportion
Prior sensitization required
1-2 weeks required after 1st dose
Drug acts as a Antigen
Same drug may cause different allergy in different
individuals

22. Classification (Gell & Coombs)
Type I reactions (IgE-mediated)
Type II reactions (cytotoxic)
Type III reactions (immune complex)
Type IV (delayed, cell mediated)

23. (anaphylaxis; immediate hypersensitivity):
The drug or metabolite interacts with IgE molecules fixed
to cells, particularly tissue mast cells and basophiles
leukocytes.
This triggers a process that lead to the release of
pharmacological mediators like histamine, 5-HT, kinins,
and arachidonic acid derivatives, which cause allergic
response.
Manifest as Urticaria, Rhinitis, Bronchial Asthma, Angio-
oedema and Anaphylactic Shock.
Drugs likely to cause type 1 are Penicillins, Streptomycin,
Local Anaesthetics

24. Serious allergic reactions i.e. rapid in
onset & may cause death
It typically results in a no. of symptoms including an
itchy, rashes , throat swelling & low B. P.
On a pathologic level, anaphylaxis is due to Release of
mediators or non immunologic mechanism
Primary treatment is injection of Epinephrine with
other complementary measures

25. Skin –
Generalized hives
Itchiness, Flushing
Angiodema
Swelling of tongue and throat
Respiratory –
Shortness of breath
Wheeze
Strider ( upper respiratory obstructions)

26. Can occur in response to almost any foreign
substances
Common trigger includes venom from insect bites &
stings , food and medication
Less common causes
Physical factor - Exercise
Biological agent , Latex
hormonal changes,
food additives (mono sodium glutamate)
topical medications

27. It is due to release of inflammatory mediators &
cytokines from mast cells & basophiles , typically due
to immunological response
Ig E + Antigens activates
FcRi receptor on mast cells & basophil
Lead to release of Histamines causes contraction of
bronchial smooth muscle

28. Epinephrine (Adrenaline) -
Is primary treatment for anaphylaxis with no absolute
contra indications
It is given I. m. into mid anterolateral thigh as soon as
diagnosed
The injection is repeated every 10- 20 min. if there is
insufficiency response
A second dose is administered 16- 30 % of episode

29. People on beta b can blockers may be resistant to the
effect
In that case I.v. glucagon can be administered
Antihistamines (both H1 & H2)
Corticosteroids
Nebulized Salbutamol
Use the Airway ,Breathing , Circulation, Disability,
Exposure (ABCDE) approach to treat at primary level

30. Cytotoxic Reactions
A circulating antibody of the IgG, IgM, or IgA class
interact with an antigen formed by hapten.
Complement is then activated and cell lysis occurs.
Example: Thrombocytopenia, Haemolytic Anaemia
Quinidine or Quinine.

31. Immune Complex Reactions
Antibody (IgG) combines with antigen i.e. the hapten-
protein complex in circulation
Complex thus formed is deposited in the tissues,
complement is activated, and damage to capillary
endothelium results.
Serum sickness is the typical drug reaction of this type.
Penicillin, Sulfonamides & Anti-thyroiddrugs may be
responsible.

32. Cell Mediated
T-lymphocytes are sensitized by a hapten-protein
antigenic complex.
Inflammatory response ensues when lymphocytes come
in contact with the antigen.
E.g. Dermatitis caused by local anesthetic creams, topical
antibiotics and antifungal creams.
Pseudo Allergic Reactions:
Term applied to reactions that resemble allergic
reactions clinically but for which no immunological basis
can be found.
Asthma and Skin Rashes caused by aspirin are the
examples

33. Phototoxic – drugs accumulates in skin absorbs light
to give photochemical reactions, photo biologic
reactions
Eg. Erythma edema blistering
Photo allergic- drugs with cell mediated immune
response, contact dermatitis on exposure to light
Eg. Sulfonamides, Griseofulvin

34. Drugs used in pregnancy affects offspring's
Eg. Thalidomide - phocomalia
Phenytoine – cleft palate
Oral hypoglycemic- neonatal hypoglycemia
Tetracycline– Anomaly of teeth & bones
Valproic acid – neural tube disorder
Warfarin - skeletal & CNS defects
Carcinogenicity/ Mutagenicity
Ant cancerous drugs
Estrogen

35. Avoid inappropriate drugs in the context of clinical
conditions
Use right dose, route ,frequency based on patient
variables
Elicit medication history
Elicit history of allergy
Rule out drug interactions
Adopt right technique of medication
Carry out adequate monitoring-pharmacovigilance,
Periodic Safety Update Reports (PSURs)

36. “All substances are poisons;
there is none which is not a poison.
The right dose differentiates a poison from a remedy.”
Paracelsus (1493-1541)
THANKYOU
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