Adverse drug reactions in humans

1. ADVERSE DRUG
REACTIONS
P R E S E N T E D B Y- M S . TA H S I N AT TA R .
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2. ADVERSE DRUG REACTION(ADR)
DEFINITION:
Adverse effect is ‘any undesirable or unintended consequence of drug
administration’.
‘any noxious change which is suspected to be due to a drug, occurs at
doses normally used in man, requires treatment or decrease in dose or
indicates caution in the future use of the same drug’.
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3. CLASSIFICATIONS OF ADR
1. A (Augmented)
2. B (Bizarre)
3. C (Continuous)
4. D (Delayed)
5. E (Ending Use)
6. F (Failure of Efficacy)
Broadly
Type- A (Predictable)- Based on pharmacological properties
Type- B (Non-predictable) – Based on Immunological response
and genetic makeup of person
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4. TYPE A- AUGMENTED OR PREDICTABLE
These are based on the pharmacological properties of the drug so can be
predicted.
They are common and account for 75% of ADRs
Dose related and preventable mostly reversible.
Examples:-
I. Anticoagulants (e.g., warfarin, heparin) – bleeding
II. Anti-hypertensives (e.g.. α1-antagonists) – hypotension
III. Anti-diabetics (e.g. insulin) - hypoglycemia
Predictable
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5. TYPE B- BIZZARE OR UNPREDICTABLE
Have no direct relationship to the dose of the drug or the
pharmacological mechanism of drug action.
Develop on the basis of:
• Immunological reaction on a drug (Allergy)
• Genetic predisposition (Idiosyncratic reactions)
More serious clinical outcomes with higher mortality and morbidity.
Mostly require immediate withdrawal of the drug.
Un-predictable
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6. TYPE C – CHRONIC (CONTINOUS) USE
They are mostly associated with cumulative-long term exposure.
Example:-
Analgesic (NSAID)– interstitial nephritis, necrosis
Predictable
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7. TYPE D – DELAYED
 They manifest themselves with significant delay
• Teratogenesis -Thalidomide – Phocomelia (flipper-like fore limbs)
• Mutagenesis/Cancerogenesis
Predictable
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8. TYPE E – END OF USE
Drug withdrawal syndromes
• Example – sudden withdrawal of long term therapy with β-blockers
can induce rebound tachycardia and hypertension
Predictable
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10. EXCESSIVE PHARMACOLOGICAL
EFFECTS:
• It is common effect of patient those are receiving cardio active agent
CNS depressant etc.
• If the patient are gives excess form of such agent will cause such type
of reaction in patient.
• Some patient are very sensitive to this reaction even in small doses
which show pharmacological effect which include : Hepatocellular
dysfunction, hepatitis or cirrhosis, can reduce the Clarence of drugs
like phenytoin, theophylline and warfarin
• A reduction in hepatic blood flow, as in heart failure can reduce the
hepatic Clarence of drug like phenytoin.
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11. SECONDARY EFFECTS
These are indirect consequences of a primary action of the drug,
For example, morphine is an analgesic that can cause two adverse secondary
effects, i.e., constipation and respiratory depression.
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12. TOXIC EFFECTS
⚫ Result of excessive pharmacological action due to over dosage or
prolonged use.
⚫ Over dosage may be absolute(accidental, homicidal, suicidal)or
relative(i.e. usual dose of gentamicin in presence of renal failure).
⚫ The effects are predictable and dose related.
⚫ They result from functional alteration(high dose of atropine causing
delirium) or drug induced tissue damage (hepatic necrosis from
paracetamol over dosage).
⚫ The CNS, CVS, kidney, liver, lung, skin and blood forming organs are
most commonly involved in drug toxicity.
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13. Another action may be responsible for toxicity, e.g.—
Morphine (analgesic) causes respiratory failure in overdosage.
Imipramine (antidepressant) overdose causes cardiac
arrhythmia.
Streptomycin (antitubercular) causes vestibular damage on
prolonged use.
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14. IDIOSYNCRASY
It is genetically determined abnormal reactivity to a chemical.
The drug interacts with some unique feature of the individual, not found
in majority of subjects, and produces the uncharacteristic reaction.
Example :-
Chloramphenicol produces non dose-related serious aplastic anemia in
rare individuals.
Barbiturates cause excitement and mental confusion in some individuals.
Quinine/quinidine cause cramps, diarrhea, purpura, asthma and vascular
collapse in some patients.
Un-Predictable
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15. DRUG ALLERGY
It is also called drug hypersensitivity.
It is an immunologically mediated reaction producing symptoms
which are unrelated to the pharmacodynamic profile of the drug.
It generally occur even with much smaller doses and have a different
time course of onset and duration.
The drug or its metabolite acts as antigen (AG) or more commonly
hapten (incomplete antigen) and induce production of antibody
(AB)/sensitized lymphocytes.
Un-Predictable
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17. DRUG DEPENDENCE
Use of drugs for personal satisfaction
Higher priority than other basic needs, often in the face of known risks to
health.
Physical dependence It is an altered physiological state produced by
repeated administration of a drug which necessitates the continued presence
of the drug to maintain physiological equilibrium.
Discontinuation of the drug results in a characteristic withdrawal
(abstinence) syndrome.
Drugs producing physical dependence are opioids, barbiturates and other
depressants including alcohol and benzodiazepines
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18. GENETICALLY DETERMINED TOXICITY
• Patients with special genotype or genetic make-up have an increased
risk of drug toxicity. Some examples of such reactions are:
• Isoniazid, hydralazine, and procainamide are metabolised in the liver
by N-acetyl transferase enzyme. Some individuals are slow and some
are fast acetylators. The slow acetylators of isoniazid suffer from
peripheral neuropathy; while the slow acetylators of hydralazine and
procainamide suffer from drug-induced lupus syndrome
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19. 1)Define adverse drug reaction.
2) Classify the types of allergic drug reactions.
3) Give two examples of excessive pharmacological effects.
4) Give examples of genetically determined toxicity.
5)Write a short note on genetically determined toxicity.
6) Discuss idiosyncrasy.
7) Write about excessive and secondary pharmacological effects.
8) Write an illustrative note on the classification of adverse drug reactions.
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20. DRUG INTERACTIONS

21. INTRODUCTION
• A situation in which a substance affects the drug activity (i.e., either
increases or decreases the effects) or produce a new effect that does
not produces on its own is termed as drug interaction.
• Interaction between drugs (i.e., drug-drug interaction) occurs most
commonly. However, interactions also occur between drugs and foods
(i.e., drug - food interactions), and drugs and herbs (i.e., drug-herb
interactions).
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22. BENEFICIAL INTERACTIONS
• Some drug interactions are beneficial and intended when a
combination of therapeutic agents shows improved therapy, produces
greater therapeutic window or safety margin, gives a good onset or
duration of action, and reduces toxicity or increases potency by
minimizing the side effects. These beneficial interactions are also
termed as intentional drug interactions.
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24. ADVERSE INTERACTIONS
• The drug-drug interactions which counteract or alter the therapeutic
effects of prescribed medications negatively are termed adverse
interactions.
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28. PHARMACOKINETIC DRUG
INTERACTIONS
• Pharmacokinetic drug interactions are those in which the absorption,
distribution, metabolism and/or excretion of object drug are altered by
the precipitant.
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34. METHODS FOR DETECTING DRUG
INTERACTIONS
• ADR is detected by the following two methods:
1) Pharmacovigilance, and
2) Epidemiological methods.
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35. PHARMACOVIGILANCE (SPONTANEOUS
CASE REPORTS AND
RECORD LINKAGE STUDIES)
• Pharmacovigilance is a branch of clinical pharmacy in which drug -
induced unknown adverse effects and their risk factors are
detected and promote safe and rational use of drugs.
• The WHO defined pharmacovigilance as “ the science and activities
relating to the detection, assessment, understanding and
prevention of adverse effects or any other medicine-related
problem”.
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36. • Spontaneous Case Reports
• The spontaneous case reports include the results obtained after
post –marketing surveillance of drugs
• Spontaneous reporting systems provide information about serious and
unpredicted drug reactions.
• They are relatively inexpensive „early warning systems‟ that inform
about any potential problems observed during the post-marketing
phase of a drug.
• Once the clinical trial is completed, the drug is marketed and
prescribed to a population that usually differ to a great extent from the
population on which it was tested during the clinical trials ( e.g.,
elderly people, people with co -morbidity patterns that differ from the
trial populations, pregnant women or children).
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37. Advantages of Spontaneous Reporting
1) This reporting process is relatively cheap.
2) A medicine can be monitored throughout its life.
3) Monitoring of over-the-counter medications and herbal therapies is
also possible.
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38. • Record Linkage Studies
• Details regarding the cause of death (as recorded on death certificate)
or of hospitalization (as recorded on the discharge letter) are collected
and analyzed routinely. This provides an early warning of an epidemic
of drug -related disease.
• Medical record linkage uses computer and related software to study
life and health events (birth, marriage, death, hospital admission) of
the population along with prescription event monitoring and history of
drug used. They are developed till resources are available.
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39. EPIDEMIOLOGICAL
METHODS
• 1) Case-Control Studies:
• In these studies, a group of patients having a disease assumed to be
caused by a drug (the „cases‟) is compared with another group of
patients not having the disease (the „controls‟). Drug histories of the
cases and controls are compared. If the disease is caused by the
suspected drug, the drugs have been extensively used in the cases that
in the controls. Such case -control studies are performed at relatively
low cost; however, they should be conducted properly and the
obtained data should be appropriate.
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40. 2) Cohort Studies:
Cohort is a group of recipients of drug of interest and studies involve
observing them for different time periods to check what happens to them.
These studies are used for short -term clinical trials of new drug.
Cohort studies are beneficial in detecting predictable adverse effects
arising due to excessive pharmacological effects during or after short-
term treatment.
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41. ADVERSE DRUG REACTION
REPORTING AND MANAGEMENT
• During reporting an ADR, the healthcare professional should keep in
mind that these reports are only showing suspected associations of a
drug with a particular adverse event. Reporting an ADR does not
confirm a causal relationship between the drug and the adverse
reaction. But, it is always better to report a case in a doubtful situation.
• Any undesirable ADR suspected to be resulted due to the use of any
drug, biological (including blood product s), herbal agents, cosmetics
or medical devices should be reported. Some of the examples are:
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42. • All suspected ADRs to be associated with a prescribed or non-
prescribed medication.
• All the information related to the unexpected reaction should be
reported regardless of their nature, severity, and frequency.
• The frequency of a given reaction is observed to be increased.
• Any serious reaction, whether expected or not should be reported.
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43. • All the adverse reactions that may occur due to drug -drug, drug -food
or drug –food supplements interactions should be monitored.
• Monitoring of ADRs in special cases, like drug abuse and drug use in
pregnancy and during lactation, should be done properly.
• ADRs due to overdose or medication error should also be reported.
• Reporting of ADRs that result due to unusual lack of efficacy or when
suspected pharmaceutical defects are observed.
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