k-31 efek non terapi2010.ppt

8/10/2019 K-31 Efek Non Terapi2010.ppt

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Efek Non Terapi

(Adverse Drug Reaction)

School of Medicine

Universitas Sumatera Utara

2010

Hasanul Arifin, Tri Widyawati


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All substances are poisons; there is

none which is not a poison; the right

dose differentiates a poison and aremedy.

Key Principle of Pharmacology

Paracelsus (1493-1541)

No drug has a single action.


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1956 Talidomid obat yang sangat aman

5 tahun kemudian

8000 bayi di 46 negara cacat

Medicines Control Agency (MCA) : Inggris

Food and Drug Administration (FDA) : AS

Badan Pengawas Obat dan Makanan (Badan POM) : Indonesia

Mengevaluasi obat baru yang belum / sudah beredar di masyarakat


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Drugs removed from or restricted

in Europe an USA

Terfenadine (1998)

Mibefradil (1998)

Astemizole (1999)

Grepafloxacin (1999)

Cisapride (2000)

Cerivastatin (2001)

Troglitazone (Rezulin) (2000)

Rofecoxib (Vioxx) (2004)


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ADRs are important

USA :

- Over 2 million serious ADRs/year

- 100.000 deaths/year from ADRs

- ADRs are fourth leading cause of death

more than lung disease, Diabetes, AIDS, and accidents

- 3-5% are preventable in-hospital ADRs due to drug interactions(Lazarou J et al.JAMA.1998; 279(15):1200-1205. Gurwitz JH et al.Am.J.Med.2000;109(2):87-94.)

Only heart disease, cancer, and stroke kill more Americans than

ADRs

The number of deaths from ADRs is three times the number of

deaths from people killed by automobile accidents


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Adverse drug reactions may lead to

complications:

Prevents optimal drug use in some patients

Necessitates supportive care

Significantly complicates treatment

Decreases patients quality of life

Results in temporary or permanent harm,

disability, or death


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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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Who might get an ADR?

Anyone who takes a medicine

Differential diagnosis should include the

possibility of an ADR if the patient is takingany form of medication


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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

Uncommon but well recognised ADRs

Achilles tendonitis caused by quinolone antibiotics

Visual field defects with vigabatrin


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What should raise

our suspicion of an ADR?

A symptom :

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 notdeliberately rechallenge!)


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Classification


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ADR

PREDICTABLE

Perpanjangan respons

farmakologik

UNPREDICTABLE

Penyebab

imunologik

(alergi dan

hipersensitifitas)

Cytotoksisitas Defek genetik

Tipe I Tipe II Tipe III Tipe IV


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Type I reaction (IgE-mediated) Anaphylaxis from lactam antibiotic

Type II reaction (cytotoxic) Hemolytic anemia from penicillin

Type III reaction (immune complex) Serum sickness from anti-thymocyte

globulin

Type IV reaction (delayed, cell-mediated) Contact dermatitis from topical

antihistamine

Specific T-cell activation Morbilliform rash from sulfonamides

Immunologic and Nonimmunologic

Drug Reactions

Immunologic


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Pharmacologic side effect Dry mouth from antihistamines

Secondary pharmacologic side effect Thrush while taking antibiotics

Drug toxicity Hepatotoxicity from methotrexate

Drug-drug interactions Seizure from theophylline while taking erythromycin

Drug overdose Seizure from excessive lidocaine (Xylocaine)


Drug Reactions

Non Immunologic Predictable


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Pseudoallergic Anaphylactoid reaction after radiocontrast media

Idiosyncratic Hemolytic anemia in a patient with G6PD deficiencyafter primaquine therapy

Intolerance Tinnitus after a single, small dose of aspirin


Drug Reactions

Non ImmunologicUnPredictable


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Obat Efek yang mungkin

Gol ACE inhibitor Gagal ginjal pada janin dan neonatus

Obat antitiroid Hipertirodisme pada janin

Benzodiazepin Ketergantungan obat pada janin

Barbiturat Ketregantungan Obat

AINS Konstriksi pada ductus arterious

Tetrasiklin Pewarnaan gigi, hambatan pertumbuhan tulang

Warfarin Pendarahan dalam otak jantung

Penggunaan Obat bagi yang menyusui juga perlu mendapat perhatian

untuk meminimal ROTD

Obat Efek yang mungkin

Tetrasiklin Resiko perwarnaan gigi

Karbimazol Hipotiroidisme

Benzodiazepin Letargia

Aspirin Resiko sindroma reye

Barbiturat Mengantuk


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PREDICTABLE UNPREDICTABLE

Synonyms Augmented, toxic, quantitative, dose-related Bizarre, allergic, idiosyncratic, or

drug intolerance, qualitative, dose-

independent

Mechanism Predictable, understood Usually poorly understood

Site 1.Same site of primary drug action2.Another site for primary & secondary action

Unrelated to the site of action

Incidence High (70%) Low(30%)

Morbidity Mild Severe

Mortality Low High

Causes

Phseutic availab. at site of absorption : quantity &

release of dosage form

Decomposition products, additives,

excepients, etc

Phkinetic level at site of action due to abnormalities of

ADME

Liberation of an abnormal

metabolite

Phdynamic 1.Enhanced organ or tissue responsiveness

due to enhanced number or sensitivity of

receptors

2.Homeostatic imbalance

3.Disease state

1. Genetic

2. Immunologic

3. Neoplastic

4. Teratologic

Reproducibility Reproducible Not reproducible

Treatment Adjust the dose Stop treatment


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Risk Factors for Developing an

ADR

Multiple drug therapy Over the counter medications

Alcohol

Drugs of abuse

Number of drugs

Age

- Very young Very old

Pregnancy

Risk to fetal development (first trimester, phenytoin) Co-morbidity/chronic diseasescan alter a drugs

absorption, distribution, metabolism or elimination

Hereditary factorsslow acetylators

Have a history of allergy or a previous reaction to drugs


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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

asthmaticbronchospasm

Drug use in an inappropriate clinical indication ormedically unnecessary

antibiotics for a viral infection


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Prevention of ADRs

Avoid inappropriate in the context of clinical condition

Use right dose, route, frequency, based on patient variables

Elicit medication history; consider untoward incidents

Elicit history of allergies (in patients with allergic disease)

Rule out drug interactions

Adopt right tehnique, eg. Slow iv injection of Aminophylline

Carry out appropriate monitoring (eg. PT with warfarin, Li level)


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DOKTER

APOTEKER

PERAWAT

PASIEN

Pemantauan pasien

Pengurangan dosis

Pemantauan kadar serum

Pemantauan kerja farmakologi

PENCEGAHAN ROTD


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Evaluation and Management of Drug Reaction

Medical history: symptoms, detailed

medication list, temporal sequence

Physical examination

Clinical laboratory data

Is a drug reaction likely?Yes No

Other etiology likely

Evaluate and treat other

causes of symptoms.

Is there a suspicion of

drug-induced hypersensitivity/

immunologic reaction?

Immune mechanism

IgE-mediated

Cytotoxic

Immune complex

Delayed, cell-mediated

Other immune mechanism

Nonimmune mechanism

Pharmacologic side effect

Drug toxicity

Drug-drug interactions

Drug overdose

Pseudoallergic

Idiosyncratic

Intolerance

Evaluate with appropriateconfirmatory tests.

Are tests supportive of

immune drug reaction?

Diagnosis of drug

hypersensitivity/

immunologicreaction confirmed

Management Consider desensitization (IgE) or

graded challenge (non-IgE) before

administration, as appropriate.*

Anaphylactic reactions require prompt

emergency treatment.

Avoid drug if possible.

Consider prophylactic regimen before

administration (if shown to be effective).

Prudent use of drugs in future Patient education

Does test have high

negative predictive

value?

Yes

NoNo

Yes

Administer drug with observation.


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Remember

All health-care professionals have a

responsibility to inform colleagues

about clinically important adversedrug reactions that they detect, even

if a well-recognised or causal link is

uncertain.

Edwards IR and Aronson JK. Adverse drug reactions: definitions, diagnosis, and

management. Lancet 2000; 356: 1255-59


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k-31 efek non terapi2010.ppt

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