ADR, types, reprting and monitoring

1. THUSHARA C
1ST YEAR MPHARM
GRACE COLLEGE OF PHARMACY

2. 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

3.  Type A (Augmented)
 Type B (Bizarre)
 Type C (Chemical)
 Type D (Delayed)
 Type E (Exit/End of treatment)
 Type F (Familial)
 Type G (Genotoxicity)
 Type H (Hypersensitivity)
 Type U (Un classified)

4. • Reactions which can be predicted from the known
pharmacology of the drug
• Dose dependent,
• Can be alleviated by a dose reduction
E.g.
• Anticoagulants  Bleeding,
• Beta blockers  Bradycardia,
• Nitrates  Headache,
• Prazosin  Postural hypotension.
Type A (Augmented) reactions
TYPE A (AUGMENTED)

5. • Cannot be predicted from the pharmacology of the drug
• Not dose dependent,
• Host dependent factors important in predisposition
E.g.
• Penicillin  Anaphylaxis,
• Anticonvulsant  Hypersensitivity
TYPE B (BIZZARE) REACTIONS

6. • Biological characteristics can be predicted from the
chemical structure of the drug/metabolite
E.g.
• Paracetamol  Hepatotoxicity
TYPE C (CHEMICAL) REACTIONS
TYPE C (CHEMICAL REACTIONS

7. TYPE D (DELAYED) REACTIONS
• Occur after many years of treatment.
• Can be due to accumulation.
E.g.
• Chemotherapy  Secondary tumours
• Phenytoin during pregnancy  Teratogenic effects
• Antipsychotics  Tardive dyskinesia
• Analgesics  Nephropathy
TYPE D (DELAYED) REACTIONS

8. TYPE E (END OF TREATMENT) REACTIONS
• Occur on withdrawal especially when drug is stopped
abruptly
E.g.
• Phenytoin withdrawal  Seizures,
• Steroid withdrawal  Adrenocortical insufficiency.
TYPE D (END OF TREATMENT ) REACTIONS

9. POLY PHARMACY :
 Patients on multiple drug therapy are more prone to
develop an ADR
 Alteration of drug effect through interaction
mechanism or by synergism
 Risk increases with increase in the no: of drugs
administered

10.  Increased risk due to multiple drugs use for their diseses
 Impaired hepatic and renal status are also at high risk of
developing an ADR
 Patient with decreased renal function treated with
aminoglycosides increased risk of nephrotoxicity

11. AGE
 Elderly and pediatric patients are more vulnerable to
ADRs
 In elderly patients physiological changes
 Eg: nitrate or ACE inhibitor induce postural
hypotension
 In neonates drug handling capacity differ compared
to adults
 Eg: grey baby syndrome with chloramphenicol

12. DRUG CHARACTERISTICS:
 Some drugs are highly toxic in nature
 Eg: cytotoxic drugs result in nausea and
vomiting
 Narrow therapeutic range drugs like digoxin
and gentamicin slight increase in concentration
may result in toxicity

13. GENDER
 Womens are more susceptible to ADRs than
males,
reasons are physiological, pharmacokinetic,
pharmacodynamic and hormonal.
 Eg: chloramphenicol induced aplastic
anaemia and phenylbutazone induced
agranulocytosis are twice and thrice as
common in women as in man,respectivley

14. RACE AND GENETIC FACTORS
 ADRs are more common in genetically predispose
individuals
 Eg : G6PD deficient patient high risk of devoleping
heamolysis due to primaquine

15. DETECTION OF ADRS
1. pre- marketing studies
2. Post –marketing surveillance
3. Under reporting
4. Communicating ADRs

16.  Identifying adverse drug reaction
(ADR).
 Assessing causality between drug and
suspected reaction by using various
algorithms.
 Documentation of ADR in patient’s medical
records.
 Reporting serious ADRs to
pharmacovigilance centers /ADR regulating
authorities

17.  During the development of new medicines,
their safety is tested in animal models.
 Specific animal studies for carcinogenicity,
teratogenicity and mutagenicity are also
available
 Clinical trials are carried out in 3 different
phases prior to the submission of a
marketing authorization application
 Clinical trials normally identifies ADRs of
frequency greater that .5-1.0%

18.  Pharmavigilance methodologies are used for detection
of risk and for the collection of risk information
 Powerful and cost effective system for the
identification of unknown drug-related risk is
spontaneous adverse drug reactions reporting
 Health care practitioner should see it as a part of
professional duty report ADR result in a patient under
his care
 Concerned identifying product defect, intoxicants and
abuse and unexpected lack of therapeutic effect

19.  Two epidemiological methods are most commonly
used are
1. Cohort studies
2. Control studies
 Cohort studies: Patient exposed to a particular drug
are followed up actively and systematically and ADR
frequencies are compared to an unexposed control
population

20. control studies :
 Individuals affected by the adverse event being
studied are identified . Each case is matched
with several disease – free control patients
randomly recruited from the study base.
 Both cases and controls are investigated their
exposure to possible causative agents prior to
occurrence of the event.
 The odd ratio calculated on the basis of
exposure data

21. The health care professionals should be
very vigilant in detecting ADRs.
ADR may be detected during ward
rounds with medical team
ADRs detected during review of patient
chart , patient counseling, medication
history review, communicating with
other health professionals

22.  To assist ADR health care professionals
should closely monitor patients who are at
high risk include
1. Patients with renal or hepatic impairment
2. Patients taking drugs which have potential to
cause ADR . Eg: DIGITOXIN
3. Patient who have had previous allergic
reactions
4. Patient taking multiple drugs
5. Pregnant and breast feeding women

23.  First step in the detection of ADRs is collection of
data.
 Data collected includes ,
1. patients demographic information
2. Presenting complaints
3. Past medication history
4. Drug therapy details including over the
counter, current medications , medication on
admission
5. Lab data such as hematological, liver and
renal function test.

24.  The information can be obtained from the following
sources
1. Patient’s case note and treatment chart
2. Patient interview
3. Laboratory data sources
4. Communication with healthcare professionals

28.  Under reporting varies with no: of factors
1. Reporting higher for new drugs than for old
2. Serious reactions are reported to a higher degree
3. Type B reactions are reported more commonly
than their share of events in practice
4. Reporting is affected by promotional claims of the
drug sponsor.
5. Reporting is affected by general publicity around
the ADR reporting scheme.

29.  The reasons more often by health
professionals for not reporting are:
1. Lack of time
2. Lack of knowledge on what, how or where to report
3. The drug-reaction association is uncertain
4. The reaction is already well known
5. Guilt or fear of litigation
6. Belief that all registered medicines are safe
7. Non-availability of reporting forms

30.  Activities that may increase the reporting rate
include
1. Ease of reporting, improve the design of reporting
form, using online reporting
2. Providing feedback to clinicians in the form of
articles in journals, ADR bulletins, news letters
3. Participate in pre and post graduate education
programmes
4. Collaboration with local Drug and Therapeutics
committees
5. Integrating pharmacovigilance in public healthcare
programmes

31.  Knowledge about rational and safe use of
medicines needs to be provided,
1. During basic training of health professionals
2. Through continuous education programmes to
health professionals.
3. By specially designated drug information centers.
4. Through packaged inserts and patient counseling

32. REFERENCE
Text book of clinical pharmacy practice – G
Parthasarathy . Page no: 105-118