Compilation on adverse drug reactions based on textbooks of modern pharmacology ,ayurvedic references etc

1. Adverse Drug Reactions-An
Overview
DR APARNA NANDAKUMAR

2. History
• Thalidomide tragedy (1961)- greatest of all
drug disasters.
• 1960 marketed in 46 countries .
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• Drug proved to be a potent human teratogen
• Major birth defects in an estimated 20,000
Children.
• Phocomelia (absence of proximal part of
limbs) was a characteristic feature

4. What is ADR???
The World Health Organization defines
an ADR as “any response to a drug which is
noxious and unintended, and which occurs at
doses normally used in man for prophylaxis,
diagnosis, or therapy of disease, or for the
modification of physiological function.”
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5. AIMS of Knowing ADR
To improve patient care and safety.
To improve public health and safety.
To contribute to the assessment of benefit,
harm, effectiveness and risk of medicines.
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6. Classification
• Depending on
Onset of event:
Acute(<60 min)
Sub acute(1-24 hrs)
Late(>2days)
Types of Reactions:
Type A(Augmented)
Type B (Bizarre)
Type C (Chronic)
Type D (Delayed)
Type E (End of Rx)
Type F (Failure of
therapy)
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7. Type A(Augmented)
Reactions that can be predicted from the known
pharmacology of the drug.
Dose dependent.
Can be alleviated by dose reduction.
 Skilled management reduces incidence.
• Eg Anticoagulants- Bleeding
Beta Blockers- Bradycardia
Nitrates- Headache
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8. Type B(Bizarre)
• Predictable where the mechanism is known,
otherwise unpredictable for the individual,
although the incidence may be known.
• Dose Independent and rare.
• Eg- Penincillin- Anaphylaxis
Anti convulsant – hypersensitivity
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9. Type C(Chronic)
• Reactions due to long time exposure.
e.g Analgesic- neuropathy
Dyskinesia with levodopa
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10. Type D(Delayed)
• Occur due to prolonged exposure
• Can be due to accumulation
• Chemotherapy – Secondary tumors
• Phenytoin during pregnancy – Teratogenic
effects
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11. Type E(End of use )
• Occur on withdrawal especially when drug is
stopped abruptly.
• Phenytoin withdrawal- Seizures
• Steroid withdrawal – Adrenocortical
insufficiency.
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12. Type F ( Failure of therapy)
• Common
• Dose related
• Often caused by drug interactions
-inadequate dosage of an oral contraceptive
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13. Classification of ADR (Severity)
• Minor ADRs: No therapy is required, antidote
therapy is ideal.
• Moderate ADRs: Requires change in drug
therapy, specific treatment or prolongs hospital
stay by at least one day.
• Severe ADRs: Potentially life threatening,
causes permanent damage or requires intensive
medical treatment
• Lethal: Direct or indirectly contributes to death
of the patient.
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14. Other Categories
Side effects
• Unwanted but often unavoidable, occur at
therapeutic doses.
• Predicted from the pharmacological profile of a drug.
• Known to occur in a given percentage of drug
recipients.
Atropine – dryness of mouth
Promethazine (anti- allergic) – sedation
Codeine (anti- tussive )- constipation – used in
traveller’s diarrhoea
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15. Secondary effects
• Indirect consequences of a primary action of the
drug.
• Tetracyclines- Suppression of Bacterial flora-
Superinfections.
• Corticosteroids- Weaken host defence- Activation of
latent Tuberculosis
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16. Toxic Effects
Result of excessive pharmacological action of the drug due to
over dosage or prolonged use.
Over dosage may be
1. Absolute (accidental, homicidal, suicidal)
2. Relative (Gentamycin in renal failure) .
 Result from
1. Extension of Therapeutic effect(barbiturates-coma,
heparin- bleeding)
2. Function alteration(atropine- delirium)
3. Drug induced tissue damage(Paracetamol-hepatic necrosis)
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17. Intolerance
• Appearance of characteristic toxic effects of a drug in
an individual at therapeutic doses
• Indicates a low threshold of the individual.
• Triflupromazine(single dose)- muscular dystonia in
some individuals
• Carbamazepine (few doses)- Ataxia in some
individuals.
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18. Idiosyncrasy
• Genetically determined abnormal reactivity to a
chemical.
• Drug interacts with some unique feature of the
individual not found in majority subjects, and
produces the uncharacteristic reaction.
• Barbiturates- excitement and mental confusion in
some individuals .
• Quinine – Cramps, diarrhoea, asthma, vascular
collapse in some individuals.
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19. Drug Allergy
• Immunologically mediated reaction producing
symptoms, unrelated to the pharmacodynamic
profile of the drug
• Generally occur even with much smaller doses
• Also called as ‘Drug Hypersensitivity’.
• Penicillin - Anaphylaxis
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20. Photosensitivity
• Cutaneous reaction resulting from drug induced
sensitization of the skin to UV radiation.
• Two types:
1. Photo toxic 2. Photo allergic
Drug metabolites accumulates in
the skin, absorbs light and
undergoes a photochemical
reactions resulting in local tissue
damage(sunburn..i.e erythemia,
edema, blistering etc.
Drug metabolites induces a cell
mediated immune response
which on exposure to light
produces a papular or
excematous contact dermatitis.
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21. Drug dependence
• Drugs capable of altering mood and feelings are
liable to repetitive use to derive euphoria,
withdrawal from reality , social adjustment.
• Psychological dependence: eg Opiods, Cocaine
• Physical dependence: Eg Barbiturates, Alcohol etc
• Drug Abuse
• Drug Addiction
• Drug Habituation
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22. Drug withdrawal reactions
• Sudden interruption of therapy with certain drugs
result in adverse consequences, mostly in the form
of worsening of the clinical condition for which the
drug was used.
• β-blockers – worsening of angina, precipitation of MI
• Clonidine – Severe HTN, restlessness etc
• Antiepileptic – frequency of seizure
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23. Teratogenicity
• Capacity of a drug to cause foetal abnormalities
when administered to the pregnant mother.
• Drug can affect the foetus at 3 stages:
1. Fertilization and implantation(conception to 17
days)
2. Organogenesis(18- 55 days)
3. Growth and development(>56 days)
• Thalidomide- Phocomelia, multiple defects.
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24. Mutagenicity and Carcinogenicity
• Capacity of a drug to cause genetic defects and
cancer respectively.
• Chemical carcinogenesis generally takes several (10-
40) years to develop.
• Anticancer drugs
• Radio isotopes
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25. Drug Induced Disease(Iatrogenic)
• Functional disturbances caused by drugs which
persist even after the offending drug has been
withdrawn and largely eliminated.
• Salicylates, Corticosteroids- Peptic ulcer
• Isoniazid - hepatitis
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योगादपि पिषं तीक्ष्णं उत्तमम् भेषजं भिेत् ।
भेषजं चापि दुयुुक्तम् तीक्ष्णं संिद्यते पिषं॥
(च सू १/१२६ )
यथापिषं यथाशस्त्रं यथाऽपिशपियुथा ।
तथौषधमपिज्ञातं पिज्ञातममृतं यथा॥ (च.सू १/१२४)
अभेषजपमपत ज्ञेयं पििरीतं यदौषधात् ।
तद् सेव्यं पिषेव्यं तु……॥ (च.पच १/१५ )

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• Drug – Drug interaction
सप्ताहेि गुणालाभे पियामन्ां प्रयोजयेत् ।
िूिुस्ां शान्तिेगायां ि पियासंकरो पहत:॥ (अ.स. सू २३/२४)
• Diet-Drug Interactions
पारदसेवने वर्ज्ाानन- र.र.स १२/१२४-१२७
गन्धकसेवने वर्ज्ाानन – र.र.स ३/३७
• Concept of Viruddha Ahara- Food-Food Interaction

29. To prevent ADR….
तस्मादौषौषधादीनन परीक्ष्य दश तत्वत:।
क
ु र्ााच्चिनकच्चितं प्राज्ञो न र्ोगेरेव क
े वलम् ॥
(च.नच ३०/२३३)
रोगं सात्म्यं च देशं च कालं देहं च बुच्चिमान् ।
अवेक्ष्याग्न्यानदकान् भावान् रोगवृत्ते: प्रर्ोेर्ेत् ॥ (सु.सू २०/९)
सदा दोषौषधादीनन वीक्ष्य द्वादश तत्वत:।
क
ु र्ााच्चिनकच्चितं प्राज्ञो न र्ोगेरेव क
े वलम् ॥
(अ.स.उ ५०/८४)
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Apakwa Bhasma sevana janya vikaras.
Dose of Visha and Upavisha dravyas .
Sahapana, anupana, pathya ahara and viharas
Eg- Parada- Avoid kakarashtaka dravyas.
Acharya Charaka has mentioned that drugs like
Pippali, Kshara and lavana if taken for a long time is
not good for the body.

31. Prevention of ADR
Drug related prevention
Disease related prevention
Patient related
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33. PHARMACOVIGILANCE
Pharmacovigilance has been defined by the WHO
as the ‘science and activities relating to
the detection, assessment, understanding and
prevention of adverse effects or any other drug
related problems.’
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34. Why Pharmacovigilance for ASU drugs?
• Phenomenal growth in the use of ASU Drugs.
• Irrational combinations of ASU
• Aggressive marketing of ASU
• Poor Quality control
• Improper use
• Inadequate regulatory control
• Uncontrolled distribution
• Internet sale,
• Powerful DTC advertising
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35. Why Pharmacovigilance for ASU Drugs?
• OTC availability and self use
• Uninformed consumer
• Lack of unbiased drug information
• Comparison of ASU Formulations safety with
Allopathic system
• Unqualified practise:
Antistress,Aphrodisiacs,memory tonic
• Less reporting ,lack of effective
communication,ADR Monitoring
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37. How to report ADR???
• WHAT TO REPORT
 ADR caused by ASU alone or caused with
any other drug.
 All suspected drug interactions
• WHO TO REPORT
 Any health care professional
• WHERE TO REPORT
 The reporting on prescribed format will be
done at any pharmacovigilance centers
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38. PHARMACOVIGILANCE - ACTIVITIES
• Post marketing surveillance and other methods
of ADR monitoring.
• Dissemination of ADR data.
• Changes in the labelling of medicines
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39. Prevention of adverse effects due to
drugs
1. Avoid all inappropriate use of drugs in the
context of patient’s clinical condition.
2. Use appropriate dose, route and frequency of
drug administration based on patient’s specific
variables.
3. Elicit and take into consideration previous
history of drug reactions.
4. Elicit history of allergic diseases and exercise
caution
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5. Rule out possibility of drug interactions when
more than one drug is prescribed.
6. Adopt correct drug administration technique.
7. Carry out appropriate laboratory monitoring.

41. PHARMACOVIGILANCE – ASU&H
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3 tier network
• National Pharmacovigilance
Coordination Centre (1)
• Intermediary
Pharmacovigilance Centres(5)
• Peripheral
Pharmacovigilance Centres (63)
NPvCC
IPvCs
PPvCs

42. Objectives
• To improve patient healthcare and safety in
relation to the use of medicines.
• To develop the culture of documenting adverse
effects.
• To promote understanding ,education and
training in Pharmacovigilance and its
communication to healthcare professionals and
the public.
• Surveillance of misleading advertisements
appearing in the print and electronic media.
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46. Conclusion
• Proper reporting of ADRs are very essential for
proper diagnosis and treatment.
• Creating awareness about ADRs among the
physicians and patient has to be made compulsory.
• Proper diagnosis and treatment is the best measure
to avoid ADRs in daily practise.
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48. References
• Essentials of Pharmacology by K.D.Tripathi
• Charaka Samhita
• Ashtanga Hridaya
• Ashtanga Sangraha
• Sushruta Samhita
• www.ayursuraksha.com
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