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BIOMEDIK

ADVERSE DRUG REACTION


(ADR)
Prof Dr dr Jazanul Anwar SpFK
Fakultas Kedokteran USU
Dept Farmakologi dan Terapi

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Kebanyakan obat membangkiitkanbanyak efek, biasanya hanya


satu efek dimanfaatkan untuk efek terapi, efek yag dimanfaatkan
untuk mengobati suatu gangguan kesehatan. Efek-efek lainnya
bisa dianggap tak diinginkan baik yang meusak atau tidak.
Umpamanya antihistaminika tertentu menyebabkan ngantuk atau
hoyong

Obat (O) + reseptor obat (R)

OR stimulus Efek

Ox + R1 OR1 Efek1
Ox + R2 OR2 Efek2
Ox

+ R3 OR3 Efek 3

Efek utama: efek yang paling menonjol


Efek samping

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EFEK OBAT YANG TAK DIINGINKAN


DAPAT DIPRAKIRAKAN
Keracunan
Teratogenik
Karsinogenik

TAK DAPAT DIPRAKIRAKAN


Adverse drug reaction, Alergi

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PENYEBAB KERACUNAN
Overdosis

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Bentuk ADR
Efek farmakologi yang meningkat
Alergi
Efek khronik
Efek tertunda
Kegagalan pengobatan
Kehebatan dan keparahan ADR
Kematian
Ancaman kehidupan
Dirawat rumah sakit ( pemulaan atnau
perpanjagan)
Gangguan fungsi (permanan, sementara,
Kelainana bawa lahir
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TAK DAPAT DIPRAKIRAKAN


Rekasi alergi:

hipersentivitas
Hapten: Obat + protein alergen
Antibodi
Antigen

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Hapten

Protein

An

-tigen

Antibodi

Antibodi
Kompleks antigen-antibodi
An

-tigen

Merangsang sel dan jaringan

Membebaskan mediator: histamin


Manifestasi alergik
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Mediator:
Autakoid:
Histamin
Bradikinin
Serotonin
Prostaglandine

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Bentuk alergi
Idiosyncrasy
Akut
Subakut
Khronis
Serum sickness

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GEJALA GEJALA
Kulit

REAKSI ALERGI

Selaput mukosa

Darah & RES

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Keradangan
hiperekskresi

Terut. Mata & hidung


Saluran nafas
Sistem vaskuler

Pruritus, urtikaria
Dermatitis exfoliativa

:
:

Susah bernafas
Tekanan darah

Pengurangan jumlah sel


darah

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TERATOGENIK
Pertumbuhan alat tubuh janin abnormal
Mekanisme kerja ???

KARSINOGENIK
Periode

laten

Karsinogen: radiasi, viruses, senyawa kimia

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What is an
Adverse Drug Reaction
(ADR)?
an unwanted or harmful reaction
experienced following the
administration of a drug or combination
of drugs under normal conditions of use
and suspected to be related to the drug
Ref. MCA/CSM Suspected adverse drug reaction (ADR)
reporting and the Yellow Card Scheme, Guidance
notes

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Definition
WHO
response to a drug that is noxious and
unintended and that occurs at doses
used in humans for prophylaxis,
diagnosis, or therapy of disease, or for
the modification of physiologic function

excludes therapeutic failures, overdose,


drug abuse, noncompliance, and medication
errors
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Examples of ADRs
Common ADRs
Constipation with opioids
Sedation with antihistamines
Nausea when starting fluoxetine
Gastrointestinal upset with non
steroidal anti-inflammatory drugs

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Who is most at risk from


ADRs?
Patients who;
are young, or old or female
are taking multiple therapies
50% of patients on 5 drugs or more

have more than one medical problem


have a history of allergy or a
previous reaction to drugs
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Why are ADRs a


problem?

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Because.
they account for around 5% of
hospital admissions
they cause death in 1 in 1000
medical inpatients
they complicate drug therapy
they decrease compliance and
delay cure
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Are ADRs avoidable?


30-50% are preventable
Obvious interactions

many drugs interact with warfarin

Use of contra-indicated drugs

use of a non-selective beta-blocker in an


asthmatic bronchospasm

Drug use in an inappropriate clinical


indication or medically unnecessary
antibiotics for a viral infection
antibiotics for viral infections

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How do I recognise
ADRs?

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What should raise


my suspicion of an ADR?
A symptom that
appears soon after a new drug is
started
appears after a dosage increase
disappears when the drug is stopped
reappears when a drug is restarted
(do not deliberately rechallenge!)
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Who might get an ADR?


Anyone who takes a medicine
Differential diagnosis should include
the possibility of an ADR if the patient
is taking any form of medication

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What you might see if an


ADR has occurred
Lab results
liver function tests, by statins and
methotrexte
full blood count, deranged by
carbimazole
biopsies, important for assessing liver
dysfunction
chest X-rays, pulmonary fibrosis with
pergolide
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What you might see if an


ADR has occurred
Clinical measurements
BP, by opiates
weight, by carbamzepine, increased
appetite
blood glucose, by corticosteroids

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How common are ADRs?


Up to 40% patients in the community experience
ADRs
In the UK Non Steroidal Anti-Inflammatory Drug
(NSAID) use alone accounts for1
65,000 emergency admissions/year
12,000 ulcer bleeding episodes/year
2,000 deaths/year
Blower et al. Emergency admissions for upper gastrointestinal disease and
their relation to NSAID use. Aliment Pharmacol Ther 1997; 11: 283-291

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Classification - Severity
Severity of reaction:
Mild
bothersome but requires no change in
therapy

Moderate
requires change in therapy, additional
treatment, hospitalization

Severe
disabling or life-threatening
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Classification
Types of allergic reactions
Type I - immediate, anaphylactic (IgE)
e.g., anaphylaxis with penicillins

Type II - cytotoxic antibody (IgG, IgM)


e.g., methyldopa and hemolytic anemia

Type III - serum sickness (IgG, IgM)


antigen-antibody complex
e.g., procainamide-induced lupus

Type IV - delayed hypersensitivity (T cell)


e.g., contact dermatitis
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Classification - Type
Reportable

Hypersensitivity
Life-threatening
Cause disability
Idiosyncratic
Secondary to
Drug interactions

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Unexpected
detrimental effect
Drug intolerance
Any ADR with
investigational
drug

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Common Causes of ADRs


Antibiotics
Antineoplastics*
Anticoagulants
Cardiovascular drugs*
Hypoglycemics
Antihypertensives
NSAID/Analgesics
Diagnostic agents
CNS drugs*
*account for 69% of fatal ADRs
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Body Systems Commonly


Involved
Hematologic
CNS
Dermatologic/Allergic
Metabolic
Cardiovascular
Gastrointestinal
Renal/Genitourinary
Respiratory
Sensory
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Interactions Before
Administration
Phenytoin precipitates in dextrose
solutions
(e.g. D5W)
Amphotericin precipitates in saline
Gentamicin is physically/chemically
incompatible with most betalactams, resulting in loss of antibiotic
effect
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Interactions Before
Administration
Phenytoin precipitates in dextrose
solutions
(e.g. D5W)
Amphotericin precipitates in saline
Gentamicin is physically/chemically
incompatible with most betalactams, resulting in loss of antibiotic
effect
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In the GI Tract
Sucralfate, some milk
products, antacids, and
oral iron preparations
Omeprazole,
lansoprazole,
H2-antagonists

Pharmacodynamic
interactions
Target organ
Didanosine (given
as a buffered tablet)
Cholestyramine
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Block absorption
of quinolones,
tetracycline, and
azithromycin
Reduce absorption
of ketoconazole,
delavirdine
Reduces
ketoconazole
absorption
Binds raloxifene,
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thyroid hormone, and

Interactions in the Serum


Protein bumping interactions in the
serum are a test-tube phenomenon
without clinical relevance

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Spectrum of Consequences
of Drug Metabolism

Inactive products
Active metabolites
Similar to parent drug
More active than parent
New action
Toxic metabolites

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Microsomal Enzymes
Cytochrome P450
Flavin mono-oxygenase (FMO3)

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Drug-Disease Interactions
Liver disease
Renal disease
Cardiac disease ( hepatic blood
flow)
Acute myocardial infarction?
Acute viral infection?
Hypothyroidism or hyperthyroidism?
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Drug-Food Interactions
Tetracycline and milk products
Warfarin and vitamin K-containing
foods
Grapefruit juice

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Some Serious Adverse Drug Reactions


Adverse Drug Reaction
Peptic ulcers or bleeding
Hydrocortisone stomach

Types of Drugs

Examples

Corticosteroids taken by
mouth from the or by injection
(not those applied to the skin
or lotions in creams)

Prednisone
Nonsteroidal antiinflammatory
drugs

Aspirin
Ibuprofen

Ketoprofen
Naproxen
Anticoagulants

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Heparin
Warfarin
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Adverse Drug Reaction

Types of Drugs

Anemia (resulting from


Certain antibiotics
a decreased production
or increased destruction
of red blood cells)

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Examples

Chlorampheni

Some nonsteroidal antiinflammatory drugs

Phenylbutazone

Antimalarial and
antituberculous drugs
in people with
enzyme deficiency

Chloroquine
Isoniazid
Primaquine

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Adverse Drug Reaction


Liver damage

Kidney damage

Types of Drugs
Some analgesics

Nonsteroidal antiinflammatory drug


(repeated use of
excessive doses)

Examples
Acetaminophen
(use of excessive
doses)
Ibuprofen
Ketoprofen
Naproxen

Aminoglycoside Kanamycin
antibiotics
Gentamicin
Cisplatin

Confusion and
drowsiness

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Sedatives,
Diphenhydramine
many antihistamines
Antidepressants
Amitriptyline
(especially in older people) Imipramine

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