Transcript Adverse Drug Reactions (ADR)

Adverse Drug Reactions (ADR)
TOPICS
 Introduce Adverse Drug Reactions (ADR)
 Scope/impact of ADR
 Different types/mechanism of ADR
Let’s define ‘adr’
 Every DRUG use has risk of UNWANTED or UNINTENDED effects
 Health care providers need to know the RISKS, duration/magnitude
 WHO Definition of ADR:
 “ Any response to drug which is noxious (harmful/unpleasant) and
unintended, which occurs at Dose that used for prophylaxis, diagnosis
or treatment of disease”
Let’s define ‘adr’
 “ Any response to drug which is noxious (harmful/unpleasant) and
unintended, which occurs at Dose that used for prophylaxis, diagnosis
or treatment of disease”
 Response at Dose which is Normal, So this excludes all
1. Drug Overdose
2. Drug Abuse
3. Treatment failure/errors
Compare Adr vs ade
Adverse Drug Reaction
Adverse Drug Event
Reaction is directly related to drug
Caused by Drug
Adverse event happed during drug
administration
NOT necessary caused by Drug
Once established that event due to
drug, it converts to ADR
Classification of adr
ADR Types
Type A
Type B
What are Type ‘a’ reactions
Also called “Augmented” reactions
Exacerbation (worsening) of pharmacological effect of drug
DOSE dependent
Can be predicted based on known pharmacology
High MOBIDITY but Low MORTALITY, since effect remove by lowering of dose
What are Type ‘B’ reactions
Also called “HYPERSENSITIVITY” reactions
DOSE IN-dependent (Not dependent on Dose)
Cannot be predicted/prevented
Low MOBIDITY (Rare) but HIGH MORTALITY (serious)
Some newer types of classification
Type A
Type B
ADR
Type C
Continuou
s
Delayed
Type D
ADR
Type A Type B Type C Type D
Type E
Type F
Type G
Type H
Type U
Epidemiology of adr
 What’s the frequency of ADR in a society, Typical data is admissions
to hospitals
 In One study; 6 % of Hospital Admissions due to ADR
 Another study (Bigger size); 6 % of Hospital Admissions due to ADR ,
0.3 % Fatal
Outcome
 5th Leading cause of Death in US
Epidemiology of adr
 How BIG is the problem in INDIA
 Not much data available
 Study at PGI (Chandigarh)
 3 % of visits to hospital were due to ADR
 Study at AIIMS
 Data from both In-patient & Out-Patient
 22 % of patients experience drug related ADR
 Vast majority were drug related, avoidable
Predisposing factors for adr
 What factors make a patient MORE likely to have an ADR
1. Polypharmacy (Patients taking > 1medications)
• ADR very likely due to DDI
• Effect due to synergistic effect
• Risk increases as number of medicines increases
Predisposing factors for adr
 What factors make a patient MORE likely to have an ADR
1. Multiple Diseases
• Multiple disease would lead to multiple drugs
• Concurrent liver or Renal impairment
• Ex. Patients with Renal impairment treated with Aminoglycosides risk Nephrotoxicity due to accumulation
Predisposing factors for adr
 What factors make a patient MORE likely to have an ADR
1. Age
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Elderly & Pediatric most RISKY category
For OLD, changes in physiology (Poor body functions)
Response to drug increased sometimes
For pediatrics: Organs not matured esp liver
Higher than expected conc
Predisposing factors for adr
 What factors make a patient MORE likely to have an ADR
1. Drug Characteristic
• Some drugs are toxic in nature esp Chemotherapy for cancer
• Leading to ADR such as Nausea, vomiting
• Narrow Therapeutic Index drugs
2. Gender
• Women more susceptible to ADR, reasons not known
Mechanism of type ‘a’ drug reactions
Pharmaceutica
l
Pharmacokinetic
Pharmacodynamic
Pharmaceutical reason for type a adr
 Changes in DRUG quantity present
 Changes in DRUG release properties
 Examples:
1. GI bleeding incidence with rate-controlled preparation of
Indomethacin
2. Corrosive effects of Doxycycline salts on esophagus
Pharmacokinetic reason for adr
 Change in ADME of drug affects concentration at site
 Increase in conc might lead to Adverse event
 Change in ADME can be cause by another Drug, Food, Alcohol,
Tobaco
Pharmacodynamic reason for adr
 Increased sensitivity might lead to ADR
 Increased sensitivity could be influenced by
1. Drug Receptors:
1. Expression, sensitivity may differ between individuals
2. Some might have higher level of expression leading to greater effect
2. Homeostatic Mechanism:
1. Drugs ultimately affect the homeostatic balance
2. This balance could be very different in some individuals
3. Intravenous Atropine causes Tachycardia in some while NO effect in others
Pharmacodynamic reason for adr
 Increased sensitivity might lead to ADR
 Increased sensitivity could be influenced by
1. Disease State:
1. Effect of Drugs NOT seen in healthy might get masked in Patients
2. Ex. Asthamatic patient develops broncho-constriction while taking non-selective
beta-blockers
Classification of adr
ADR Types
Type A
Type B
Type ‘B’ reactions
 Unrelated to pharmacology of DRUG
 Heterogeneous group of unpredictable reactions
 What causes these types of reactions ?
 Decomposition of drug products, additives, coloring, preservatives
etc
 Decomposed products in some cases is lethal, highly toxic
 Ex. Paraldehyde = Acetaldehyde = Acetic Acid
 Additives: Propylene glycol, CMC may cause hypersensitive reactions
Type ‘B’ reactions
 Unrelated to pharmacology of DRUG
 Heterogeneous group of unpredictable reactions
 What causes these types of reactions ?
 Metabolism to unusual reactive metabolite
 Ex. Carbamazepine induced hypersensitive reaction
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