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Adverse Drug Reaction-27Sept

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10 views5 pages

Adverse Drug Reaction-27Sept

Uploaded by

Muskan Sharma
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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Sept 2024

Adverse Drug Reactions


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 for
modification of physiological function.
(Adverse drug event- is a broader term- Any untoward medical occurrence
presented during the administration of the drug)
Serious ADRs can result in Death, Morbidity, Life threatening, Requires patients to
be hospitalized leading to disability, congenital birth anomaly in future generation
ADR vs Side Effect
Any effect caused by drug other than ‘intended therapeutic effect’ – whether
beneficial, neutral or harmful. Side effects and Unwanted but are often
UNAVOIDABLE. These are known to occur in a large population of patients under
a specific therapy (viz., based on therapy like dryness of mouth in patients
administered with Atropine; Acidosis after administration of Acetazolamide
(Diuretic); Sedation after administration of anti-allergic Promethazine; Codeine
induces Constipation as side effect)

 ADR Classification and examples


 Traditional
Type A – Augmented
Type B – Bizzare
(Rawlins and Thompson Classification in 1977, classified as either Type A or B
only. In 1997 Rene Royer extended the classification beyond Type A and B, upto
D. However the longer classification upto Type H from A including U was
proposed by Wills and Brown)
Type C – Continuous (Chronic)
Type D – Delayed
Type E – End of Treatment
Type F – Failure of Treatment
Type G – Genotoxic
Type H – Hypersensitivity
Type U – Unclassified

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Sept 2024

Type A – AUGMENTED –
Exacerbation/ Exaggeration of Pharmacological effect of Drug
Dose dependent
Predictable (since known pharmacological effect is demonstrated), so Preventable
High incidence, however low Mortality
Eg.: Insulin induced Hypoglycemia
Hypotension induced by Anti-hypertensive
Dehydration caused by Diuretics
Gastric ulcer caused by Aspirin
Bradycardia by beta-blockers
Bleeding caused by anti-coagulants
Head ache caused by nitrates
Postural hypotension caused by Prazocin

Type – B – Bizzare
NOT AN INTENDED PHARMACOLOGICAL ACTION OF THE DRUG
Hypersensitivity, Dose “Independent”
Not-predictable, so Not-preventable (unless patient demonstrates past history.
Low Incidence than Type A in occurrence, however HIGH level of Morbidity
Eg.: Pencillin induced hypersensitivity/Anaphylaxis
Stevens Johnson Syndrome with Sulphonamides
Agranulocytosis by Clozapine

Type- C – Chronic
Observed in cases in high frequency of patients with LONG exposure to drug
Exact mechanism of the adverse effect not understood
Eg. : High frequency of CVS events exposed to COX-2 inhibitor (Rofecoxib)
Osteoporosis caused by Corticosteroids
Tardive Dyskinesia anti-psychotics

Type- D – Delayed response


Observed after prolonged period from exposure to drug.
Eg.: Malignacies – After use of Immunosuppressive esp. post transplantation
Aplastic anemia – Long exposure to Chloramphenicol
Vaginal cancer – Exposure to Contraceptive – Diethyl stilbestrol (DES)
Nephropathy – Long exposure to NSAIDs
Phocomelia (limb deformity in new born), Teratogenesis – Thalidomide

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Sept 2024

Type- E – End of Treatment


Withdrawal symptoms are presented in patients
Eg. : Withdrawal of Phenytoin – Seizures
Withdrawal of Steroids – Adreno cortical Insufficiency
Withdrawal of Opioids – Hallucinations
Withdrawal of Alcohol – Anxiety, panic, Delusion
Withdrawal of Clonidine – Rebound hypertension

Type- F – Failure of Treatment


Resulting from Drug Interactions
Eg. : Failure of Oral Contraceptives on concurrent administration of Antibiotics
Hemolytic anemia with Primaquin in G6PD deficient individuals

Type- G – Genotoxicity
Irreversible genetic damage caused by drugs
Teratogenic agent like Thalidomide causes Genetic damage

 DoTS classification of ADRs

In Do-T-S : Do refers to Dose; T refers to Timing and S refers to Susceptibility

Dose:
1) Adverse reactions may be observed below the therapeutics dose (TD) levels
Eg: Analphylaxis with Penicillin
2) Adverse reactions after administration of Therapeutic dose
Eg: Nausea with Morphine
3) At higher doses – Hepatotoxicity with Paracetamol

Timing:
1) With 1st dose - Analphylaxis with Penicillin
2) Early stage of treatment – Hypo-natremia with diuretics
3) On stopping treatment – Benzodiazepine withdrawal syndrome
4) Delayed response – Carcinoma with Diethyl stilboestrol (DES)

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Sept 2024

Susceptibility:
1) Age related – In elderly - Postural hypotension with Nitrates and ACE inhibitors
In New born – Gray baby syndrome with Chloramphenicol
2) Gender – Prevalent to women – Aplastic anemia induced by Chloramphenicol
Agranulocytosis induced by Phenyl butazone
3) Polypharmacy – Prescription with long list of medicines – causing Drug
interactions
4) Genetic predisposition – Patient with G6PD (Glucose 6-phosphate
dehydrogenase) deficiency – Risk of developing hemolysis
5) Underlying disease with potential to alter pharmacokinetics

6) Adherence issues

7) NTI drugs (Drugs with Narrow Therapeutic Index)


NTI presents the Ratio of Therapeutic Dose to Toxic Dose.
The Ratio between Therapeutics Dose to Toxic Dose (TTR) should be Larger/
Bigger to consider the drug to be SAFER.
Drugs with LOW TTR – are NOT safe and warrants close monitoring of the patient
Eg: - Anticoagulants like Warfarin, Heparin
Hypoglycemics like Insulin, Sulfonyl Ureas
Anti-arrythmic drugs like Amiodarone, Lidocaine

 Mechanism of ADRs-
Pharmaceutical causes
Pharmacokinetic causes
Pharmacodynamic causes

Pharmaceutical causes –
Includes effect of drug excipients like propylene glycol, CMC that causes
hypersensitivity
Changes in effective drug concentration due to decomposition/ poor stability of
drug
Drug releasing properties from formulation due to alteration in physicochemical
environment like pH, pKa etc
Eg.: Griseofulvin with different particle size – as the particle size reduces, the
surface area increases – leading to toxicity

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Sept 2024

Pharmacokinetic causes – Change in ADME properties – leading to change in the


concentration of the drug at the site of action; Change in distribution due to
variation in plasma or tissue binding; Reduced metabolism – causing increase in
active drug concentration leading to hypersensitivity issues.

Pharmacodynamic effects - Increase in sensitivity of tissues, variation in drug


receptor, hemostatic mechanism (Eg. – Asthmatic patient developing
bronchoconstriction after taking non-selective beta-blocker/ Propranolol)

 Managing ADRs –
1) Monitoring the patient 24X7
2) Genetic testing – to assess variations
3) Patient education – to report his experiences during treatment
4) Alternative therapies to assess extent of adverse reactions, if any.
5) Dose adjustments is required based on Renal function and Genetic make
up
6) Genetic factor (Eg. – CYP2D6 gene – causes serious ADRs in patients
administered with Codeine and Tramadol)
7) Emerging concerns – Like in COVID patients – treated with Remdesivir
and Dexamethasone)

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