ADVERSE DRUG REACTION

ADVERSE DRUG REACTION

Definisi
ADR
Any respon to a drug which is noxious and unintended, and
which occurs at doses normally used in man for
prophylaxis,diagnosis or therapy of disease, or for the
modification of physiological function (WHO)

Side effect
Expected, well-known reaction resulting in little or no
change in patient management (e.g dry mouth due
to administration of certain anhistamine), predictable
frequency, intensity and occurrences are related to
the size of dose (ASHP)
Adverse event
Any untoward medical occurrence that may present during
treatment with a pharmaceutical product but which does
not necessarily have a causal relationship with this
treatment (WHO)
Medication error
Any preventable event that may cause or lead to
inappropriate medication use or patient harm while the
medication is in the control of the health care professional,
patient, or consumer
Adverse drug event
An injury resulting from medical intervention related to a
drug or an injury resulting from the use of a drug
 Epidemiologi
- penyakit iatrogenik yg sering tjd, 5-15%
- kunjungan RS 3-6% ok ESO
- Pasien rawat inap 6-15% ok ESO
- faktor risiko umum wanita, pasien HIV, herpes
Summary of definition Relevant to Drug-Related Harm
 Figure. Relationships of key terms

-The gray areas represent injuries caused by drug use (adverse drug events).
-The dark gray area represents harm caused by a drug (adverse drug reactions).
-The light gray area represents harm from appropriate drug use that is generally excluded from studies of adverse
drug events.
-Medication errors are much more common than adverse drug events.About one quarter of adverse drug events are
due to medication errors (4).
 Classification of Adverse Drug Reactions
Type A reactions
Predictable ,common and related to pharmacological
action of the drug
Type of reaction :
Toxicity of overdose : e.g. hepatic failure with high dose
Paracetamol
Side effects :e.g sedation with antihistamines
Secondary effects : e.g. development of diarrhea with
antibiotic therapy due to altered gastrointestinal
bacterial flora
Drug interaction :e.g. theophylline toxicity in the
presence of erythromycin therapy
 Type B (alergi, hypersensitivity)
Unpredictable, uncommon, usually not related to the
pharmacological actions of the drug.
Macam reaksi :
Intolerance : e.g. tinnitus with use of Aspirin
Hypersensitivity: Immunological reaction (e.g. Anaphy-
laxis with penicillin administration.
Pseudoallergic :Non-Immunological reaction e.g. radio
contrast dye reaction
Idiosyncratic reaction :e.g. development of anemia with
the use of anti-oxidant drugs in the presence of glucose-6
phosphate dehydrogenase deficiency
 Type C
Associated with long-term drug therapy
e.g. Benzodiazepine dependence and Analgesic
nephropathy.
Well known and can be anticipated.

Type D
Refer to carcinogenic and teratogenic effects
Delayed in onset and are very rare.
 Klasifikasi lain
1. Tipe I ( reaksi hipersensitivitas)
- immediate type ( tiba-tiba dan mengancam jiwa)
- terjadi dlm 1 jam stlh konsumsi obat
- anafilaksis
2. Tipe II ( reaksi sitotoksik)
- terjadi ok melekatnya antibodi IgG atau IgM pd sel drh
merah atau sel intersisial ginjal yg punya antigen sel
lisis
- onset gejala bisa delayed ( bbrp hari ad minggu)
- gejala : hematuria, proteinuria, trombositopenia
3. Tipe III ( delayed)
- Reaksi kompleks alergi
- terjadi ok antibodi IgG atau IgM + antigen induksi fiksasi
komplemen terjebak pd pemb drh kecil/kulit/ginjal/sendi
reaksi inflamasi
- contoh : serum sicknes
- tjd 7-10 hari sth paparan obat demam, athralgia, myalgia,
purpura

4. Tipe IV ( cell mediated reaction)

- ok terlepasnya sitokin akibat interaksi antara limfosit T dan
antigen inflamasi lokal
- akibat obat topikal
- cth : dermatitis kontak
 Faktor risiko
a. Riwayat alergi
- Diperantarai respon imunologik dgn gambaran :
* tidak terkait efek farmakologik
* delayed ( sampai 2 minggu)
* bila alergi telah terbentuk, dosis kecil dpt timbulkan
reaksi
* reaksi hilang setelah penghentian obat
* kesakitan
* bentuk reaksi alergi : skin rash ( ringan),
bronkospasme , hipotensi pd anafilaksis
(mengancam jiwa)
* pasien dg riwayat elergi, punya resiko alami ESO
utk pemakaian obat yg lain
b. Riwayat ESO sebelumnya
* pasien yg alami ESO thd suatu obat punya resiko
yg lebih besar utk alami ESO dr obat lain
c. Terapi polifarmasi
- kemungkinan terjadinya interaksi obat-obat
- interaksi obat terjadi melalui :
* penghambatan atau peningkatan absorpsi
* penurunan aliran darah hepatik
* penghambatan ekskresi renal
 * penghambatan atau stimulasi metab obat
* pendesakan ikatan obat dr ikatan albumin
* efek f.dinamik obat pd jar target

d. Obat dgn indeks terapi sempit

- Resiko ESO yg jauh lebih besar daripada obat
umumnya
- Cth. aminoglikosida (gentamisin), antikoagulan
(heparin,warfarin), anti konvulsan (phenytoin), obat
jantung (digoksin)
e. Kondisi patologik
- Keberadaan obat dlm tbh dipengaruhi kondisi patologik
- Mis gangguan fgs ginjal dan hepar penurunan
metab dan eliminasi obat ESO
f. Genetik
- Berpengaruh thd farmakokinetik dan
farmakodinamika obat respon bervariasi
* orang Inggris rentan thd isoniazide
g. Elderly
h. Pasien kondisi khusus ( kehamilan, pediatrik)
i. Pasien dgn sistem imun tertekan
- diabetes mellitus, HIV, gagal ginjal,sirosis hepatika
j. Pasien dgn gagal organ
 Faktor risiko terjadinya ESO

Reaksi obat ( nonimmune) Reaksi hipersensitivitas (immune)

Wanita Wanita
Penyakit serius Dewasa
Insuffisiensi ginjal HIV
Penyakit hati Concomitant viral infection
Polifarmasi Hipersensitivitas sblmnya thd obat
pencetus asma
HIV Beta blocker
Herpes infection Polimorphisme genetik spesifik
Alkoholism Systemic lupus erythematosus
 Penilaian ADR
Skala Naranjo

NO Question Yes No Do not Score

know
1 Are there previous conclusive reports on this reaction ? +1 0 0
2 Did the adverse event appear after the suspected drug was administered ? +2 -1 0

3 Did the adverse reaction improve when the drug was discontinued or the specific +1 0 0
antagonist was administered ?

4 Did the adverse reaction reappear when the drug was readministered ? +2 -1 0
5 Are there alternative cause (other than the drug) that could on their own have -1 +2 0
caused the reaction?
6 Did the reaction reappear when a placebo was given ? -1 +1 0
7 Was the drug detected in the blood (or other fluids) in concentrations known to +1 0 0
be toxic?
8 Was the reation more severe when the dose was increased, or lesss severe +1 0 0
when the dose was decresed ?
9 Did the patient have a similar reaction to the same or similar drugs in any +1 0 0
previous exposure ?
10 Was the patient confirmed by any objective evidence ? +1 0 0
Score :
9-10 : definitely ADR 5-8 : probable ADR 1-4 : possible ADR < 1 : doubtful
 Pertanyaan saat menilai pasien dgn suspected drug
induced disorders
Is there any history of drug-induced reaction?
1. What were the characteristics of the previous reactions?
2. At what stage during therapy did the current reaction occurred?
3. At the time of reaction, which drugs was the patient taking, when
were they started and what were the doses of each drug?
4. Had the patient been exposed to any of these drugs previously?
5. What are the other medical problems of patients?
6. What were the clinical manifestations of the drug induced reaction
and could these manifestations help to determine that which drug
was responsible for the reaction?
7. Were there any laboratory abnormalities that could be explained by
a drug induced reaction?
8. When the drug was discontinued, did the reaction cease?
Management Plan

If it is non-immune adverse drug reaction

-toxicity, side effects, secondary effect, drug interaction, drug
intolerance, drug idiosyncrasy, pseudoallergic reaction etc:

Modifying dose of drug

Use of alternative drug
Can consider prophylactic regimen
Patient /physician education
 But if immune adverse reaction is suspected after
laboratory tests and diagnosis of drug Hypersensitivity
is confirmed
Avoidance of drug, if possible
Consider desensitization if presumed IgE mediated
Consider prophylactic regimen (if seen to be
effective)
If re-administration of implicated drug is absolutely
contra indicated then it should be stopped
Prudent use of all drugs in future
Patient / physician education
DOCUMENTING ADVERSE DRUG EVENTS
- The purpose of documenting adverse drug events in a
patients chart is to help prevent the recurrence of the
harm.
-The more likely an event is to recur and the more
serious the event, the stronger the case for documentation
-For probable and certain adverse drug reactions are
nearly always appropriate to document in the patient
chart.
-For events that are less likely to recur, it must consider
the seriousness and nature of the event.
-For possible adverse drug reaction merits documentation.
 ALGORITME IDENTIFIKASI ESO
Laporan ESO
( aktif, pasif)

Identifikasi ESO
( pasien, tanda/gejala, RPS/RPD, riwayat obat, waktu terjadinya)

Investigasi obat yg dicurigai

Kesimpulan

Rekomendasi
 Formulir pelaporan ESO

Pelaporan
a.Komite Farmasi dan Terapi
b.Pusat Monitoring Efek Samping Produk Terapetik
(MESPT)
Dokumentasi