An adverse drug reaction (ADR) is an unwanted or harmful reaction that occurs when taking a medication. ADRs can range from mild to severe or life-threatening. They are classified based on their cause and severity. Serious ADRs are those that result in death, are life-threatening, cause hospitalization or disability, or require intervention to prevent impairment or damage. Managing ADRs involves withdrawing the drug if possible and treating the effects. All suspected ADRs should be reported to help monitor drug safety.

1. ADVERSE DRUG REACTION
&
SERIOUS ADVERSE EVENT
PRESENTED BY:MUKESH JAISWAL
SOMYA VERMA
APGDCR
DEHRADUN

2. 

Most drugs produce several effects, but usually
only one effect—the therapeutic effect—is wanted
for the treatment of a disorder. The other effects
may be regarded as unwanted
certain antihistamines cause drowsiness as well as
control the symptoms of allergies. When an overthe-counter sleep aid containing an antihistamine
is taken, drowsiness is considered a therapeutic
effect. But when an antihistamine is taken to
control allergy symptoms during the
daytime, drowsiness is considered an
annoying, unwanted effect.

3. 


adverse drug reaction is technically more
appropriate for drug effects that are
unwanted, unpleasant, noxious, or potentially
harmful.
An adverse drug reaction (abbreviated ADR)
is an expression that describes harm associated
with the use of given medications at a normal
dose.
The study of ADRs is the concern of the field
known as pharmacovigilance.

4. •

Classification
ADRs may be classified by e.g. cause and severity.
Cause
Type A: Augmented pharmacologic effects - dose dependent and
predictable
Type B: Bizarre effects (or idiosyncratic) - dose independent and
unpredictable
Type C: Chronic effects(dose related & time related)
Type D: Delayed effects(time related)
Type E: End-of-treatment effects(withdrawal)
Type F: Failure of therapy(failure)

5. Seriousness and Severity
1.
2.
3.
4.
5.
The American Food and Drug Administration defines a
serious adverse event as one when the patient outcome
is one of the following:
Death
Life-Threatening
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.
Congenital Anomaly

6. • The terms "severe" and "serious" when applied to adverse events
are technically very different.
• A headache is severe, if it causes intense pain. There are scales
that help us assess the severity. On the other hand, a headache can
hardly ever be serious, unless it also satisfies the criteria for
seriousness.
• Overall Drug Risk
While no official scale exists yet to communicate overall drug risk,
the iGuard Drug Risk Rating System is a five colour rating scale
1. Red (High Risk)
2. Orange (Elevated Risk)
3. Yellow (Guarded Risk)
4. Blue (General Risk)
5. Green (Low Risk)

7. • Location
Adverse effects may be local, i.e. limited to a certain location, or
systemic, where a medication has caused adverse effects
throughout the systemic circulation.
For instance, some ocular antihypertensive cause systemic
effects, although they are administered locally as eye drops, since a
fraction escapes to the systemic circulation
• Mechanisms
As research better explains the biochemistry of drug use, fewer
ADRs are Type B and more are Type A. Common mechanisms are:
1) Abnormal pharmacokinetics due to
genetic factors
co morbid disease states
2) Synergistic effects between either
a drug and a disease & two drugs

8. • Abnormal pharmacokinetics
Comorbid disease states
Various diseases, especially those that cause renal or
hepatic insufficiency, may alter drug metabolism.
Resources are available that report changes in a drug's
metabolism due to disease states
• Genetic factors
Abnormal drug metabolism may be due to inherited factors of
either Phase I oxidation or Phase II conjugation.Pharmacogenomics is
the study of the inherited basis for abnormal drug reactions.
1.
Phase I reactions
. Inheriting abnormal alleles of cytochrome P450 can alter drug
metabolism.
. Inheriting abnormal butyrylcholinesterase
(pseudocholinesterase) may affect metabolism of drugs such as
succinylcholine

9. 2. Phase II reactions
. Inheriting abnormal N-acetyltransferase which
conjugated some drugs to facilitate excretion may
affect the metabolism of drugs such as
isoniazid, hydralazine, and procainamide.
. Inheriting abnormal thiopurine Smethyltransferase may affect the metabolism of the
thiopurine drugs mercaptopurine and azathioprine
• Interactions with other drugs
The risk of drug interactions is increased with polypharmacy.
1. Protein binding
These interactions are usually transient and mild until a new steady
state is achieved. These are mainly for drugs without much first-pass
liver metabolism. The principal plasma proteins for drug binding are
• albumin
• α1-acid glycoprotein
• lipoproteins

10. • Cytochrome P450
Patients have abnormal metabolism by cytochrome P450 due to
either inheriting abnormal alleles or due to drug interactions.
• Synergistic effect
• Monitoring bodies
Many countries have official bodies that monitor drug safety and
reactions. On an international level, the WHO runs the Uppsala
Monitoring Centre, and the European Union runs the European
Medicines Agency (EMEA). In the United States, the Food and Drug
Administration (FDA) is responsible for monitoring post-marketing
studies.

11. ADR
EXAMPLE
Abortion, miscarriage or uterine
hemorrhage
misoprostol (Cytotec), a laborinducing drug (this is a case where the
adverse effect has been used legally
and illegally for performing abortions)
Addiction
many sedatives and analgesics such as
diazepam, morphine, etc.
Birth defects
Thalidomide and Accutane
Bleeding of the intestine
aspirin therapy
Cardiovascular disease
COX-2 inhibitors (i.e. Vioxx)

12. Deafness and kidney failure
gentamicin (an antibiotic)
Death, following sedation
Propofol (Diprivan)
Dementia
heart bypass surgery
Depression or hepatic injury
interferon
Diabetes
antipsychotic medications
Diarrhea
orlistat (Xenical)
Erectile dysfunction
many drugs, such as antidepressants

13. Fever
vaccination (in the past,
imperfectly manufactured
vaccines, such as BCG and
poliomyelitis, have caused the
very disease they intended to
fight).
Glaucoma
corticosteroid-based eye drops
Hair loss and anemia
chemotherapy against cancer,
leukemia, etc.
Headache
spinal anesthesia
Hypertension
ephedrine users, which
prompted FDA to remove the
status of dietary supplement of
ephedra extracts
Insomnia
stimulants, etc.

14. • MANAGEMENT
Management includes withdrawal of the drug if
possible and specific treatment of its effects. Suspected
adverse drug reactions should be reported.
• Severity
- Mild - symptomatic treatment,
alter dose, no change of drug
- Moderate - change in drug therapy
- Severe - unexpected untoward
leading to possible debility, or death

15. An adverse event is any undesirable experience
associated with the use of a medical product in a
patient. The event is serious and should be reported to
FDA when the patient outcome is:
Death
Report if you suspect that the death was an outcome of
the adverse event, and include the date if known.
Life-threatening
Report if suspected that the patient was at substantial
risk of dying at the time of the adverse event, or use or
continued use of the device or other medical product
might have resulted in the death of the patient.


16. Congenital Anomaly/Birth Defect
Report if you suspect that exposure to a medical
product prior to conception or during pregnancy
may have resulted in an adverse outcome in the
child.
Required Intervention to Prevent Permanent
Impairment or Damage (Devices)
Report if you believe that medical or surgical
intervention was necessary to preclude permanent
impairment of a body function, or prevent
permanent damage to a body structure, either
situation suspected to be due to the use of a
medical product.

17. Hospitalization (initial or prolonged)
Report if admission to the hospital or prolongation of
hospitalization was a result of the adverse event.Emergency
room visits that do not result in admission to the hospital
should be evaluated for one of the other serious outcomes
(e.g., life-threatening; required intervention to prevent
permanent impairment or damage; other serious medically
important event).
Disability or Permanent Damage
Report if the adverse event resulted in a substantial
disruption of a person's ability to conduct normal life
functions, i.e., the adverse event resulted in a significant,
persistent or permanent change, impairment, damage or
disruption in the patient's body function/structure, physical
activities and/or quality of life.

18. Other Serious (Important Medical Events)
Report when the event does not fit the other
outcomes, but the event may jeopardize the patient
and may require medical or surgical intervention
(treatment) to prevent one of the other outcomes.
Examples include allergic brochospasm (a serious
problem with breathing) requiring treatment in an
emergency room, serious blood dyscrasias (blood
disorders) or seizures/convulsions that do not
result in hospitalization. The development of drug
dependence or drug abuse would also be examples
of important medical events.

19. THANKS !