Adverse Drug Reaction

1. DRUG TOXICITY &
ADVERSE DRUG
REACTIONS
UNDER THE PRESENTED BY:
GUIDANCE OF: ANSH DEV RAVI
Dr. Amrish Chandra A4513309001

2.  ADVERSE DRUG REACTION/ADE/DRUG TOXICITY can be "an
appreciably harmful or unpleasant reaction, resulting from an
intervention related to the use of a medicinal product, which
predicts hazard from future administration and warrants prevention
or specific treatment, or alteration of the dosage regimen, or
withdrawal of the product.“
 Adverse drug reactions are classified into six types:
Dose-related (Augmented)
Non-dose-related (Bizarre)
 Dose-related and time-related (chronic)
Time-related (delayed)
 Withdrawal (end of use)
Failure of therapy (failure) 2

3. DRUG TOXICITY/ADR/ADE is defined as "manifestations of
the adverse effects of drugs administered therapeutically or
in the course of diagnostic techniques. It does not include
accidental or intentional poisoning...“
It may result when :
the dose is too high
the liver or kidneys are unable
to remove the drug from the
bloodstream
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4. GIVEN BY WHO
• Noxious and unintended response to medicinal product if a
medicine is properly prescribed and administered.
• Casual reaction between medicinal product and adverse event
cannot be ruled out.
• Medical errors are not included in this definition.
GIVEN BY MHRA
• an unwanted or harmful reaction experienced following
the administration of a drug or drugs.
• suspected to be related to the drug or drugs.
• The reaction may be a known side-effect of the drug or it may be
new and previously unrecognised.
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6. TYPE A REACTIONS TYPE B REACTIONS
CHARACTERISTICS
1. Predictable 1. Unpredictable
2. Usually dose dependent 2. Rarely dose dependent
3. High morbidity 3. Low morbidity
4. Low mortality 4. High mortality
5. Responds to drug reactions 5. Responds to drug withdrawal
6. Identified pre -marketing 6. Identified post- marketing
EXAMPLES
Sulphonylureas- hypoglycaemia Penicillins- anaphylaxis
Phenothiazines- orthostatic
Chloramphenicol- aplastic anaemia
hypotension
Carbamazepine- Stevens- Johnson
Stilboestrol- vaginal carcinoma
syndrome 6

7.  TYPE C :
 Dose-related and time-related
 Related to duration and dosage of exposure.
Example: hypothalamic-pituitary-adrenal suppression from
glucocorticoid therapy.
 TYPE D :
 Time-related
 Delayed reaction
Example: tardive dyskinesia.
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8.  Type E:
 Withdrawal
 Lend of dose reaction
Example: narcotic or beta-blocker withdrawal
 Type F:
 Unexpected failure of therapy
 May be caused by drug interactions
Example: failure of oral contraceptives due to induction
of enzymes by a second drug.
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9.  Drug reaction with eosinophilia and systemic symptoms may
be caused by medications including:
 Allopurinol
 Phenytoin
 Dapsone
 Carbamazepine
 Trimethoprim-sulfamethoxazole
 Penicillin
 Non-steroidal anti-inflammatory agents
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10.  Defined as the phenomenon that occurs
when the effect of pharmacokinetics of
the drugs are altered by prior
administration or co administration of
second drug.
 A particularly important type of adverse
drug event
 Complex, involving either increasing or
decreasing the activity of a given
cytochrome pathway, or preferentially
using the pathway rather than other drugs.
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11. • Monoamine oxidase inhibitors can cause fatal hypertension in
patients who have also consumed food containing high
concentrations of tyramine.
• The suspect foods form an odd assortment
EXAMPLE: Chianti wine, some smoked fish and aged cheese
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12.  BY FREQUENCY
The recommendations of WHO have been summarized by:
 very common (1/10 patients)
 common (1/100)
 uncommon (1/1000)
 rare (1/10,000)
 very rare (1/100,000)
 BY SEVERITY
The American Food and Drug Administration defines severe
effects as:
 Death
 Life-Threatening
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13.  Hospitalization (initial or prolonged)
 Disability - significant, persistent, or permanent change,
impairment, damage or disruption in the patient's body
function/structure, physical activities or quality of life.
 Requires Intervention to Prevent Permanent Impairment
or Damage
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14.  As research better explains the biochemistry of drug use, less
ADRs are Type B and more are Type A
 Risk factors are:
 The number of drugs
 History of prior drug toxicity
 Presence of heart failure
 Presence of liver disease
 Presence of renal failure
 Presence of 4 or more medical conditions
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15. Common Mechanisms……
1. ABNORMAL PHARMACOKINETICS due to
– Comorbid disease states:
Various diseases, especially those that cause renal or
hepatic insufficiency, may alter drug metabolism.
– Genetic factors:
Abnormal drug metabolism may be due to inherited factors
of either Phase I oxidation or Phase II conjugation.
2. SYNERGISTIC EFFECTS between either
– a drug and a disease
– two drugs
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16. FACTORS INCREASING
ADR’s
1. POLYPHARMACY
― The risk of drug interactions may be increased.
― Using 11 or more chronic medications is a risk factor for
drug toxicity
2. FRAGMENTED HEALTH CARE
When controlled for other factors such as the number of
prescribing physicians, the number of medications may
not be a risk factor for adverse drug reactions.
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17. ASSESSING CAUSALITY
A scale proposed by the World Health Organization (WHO) is
below:
a. Certain d. Unlikely
b. Probable/likely e. Conditional/ unclassified
c. Possible f. Unassessable/ unclassifiable
4. INTOLERANCE TO MULTIPLE DRUGS
― Amplification may contribute to multiple-drug intolerance.
― This is distinct from multiple drug hypersensitivity.
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18. SYPMTOMS OF DRUG
TOXICITY
1.SYMPTOMS OF GHB:
i. PALPITATION
ii. COMA
iii. HYPOTENSION
iv. HYPOTHERMIA
v. MUSCLE CRAMPS
vi. NAUSEA AND VOMITING
vii. SLOW BREATHING
viii. VOILENT BEHAVIOR
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19. 2. SYMPTOMS OF HALLUCINOGEN
i. ANXIETY
ii. DELUSION
iii. DEPRESSION
iv. HALUCINATIONS
v. PANIC ATTACK
vi. PARANOIA
vii. RESTLESSNESS
viii. VIOLENT BEHAVIOR
ix. SEIZURES
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20. List of drugs that have been identified as
those with the highest potential for harm:
• Warfarin
• Aspirin
• Metformin
• Insulin
• Glyburide
• Digoxinvalproic Acid
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21. To Avoid Drug Toxicity
• Keep a careful record of what drugs you are taking including over
the counter drugs.
• Inform all doctors you see of every medication you are taking and be
aware of what the dosage is. Also list supplements, herbs or other
OTC medicine you are taking.
• If blood tests do not bring your doctor to a diagnosis, ask him to do a
specific test for drug toxicity.
• Eliminate or reduce the dose of a suspected medication under
doctors care.
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22. REFERENCES
• Essentials of Medical Pharmacology (6th edition) by KD Tripathi
• Drug Toxicity Encyclopedia Article- Citizendium
• thepharmacist.co.uk
• pubmedresult.com
• wikipedia
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