k10 adverse drug reaction
Post on 10-May-2017
225 Views
Preview:
TRANSCRIPT
14032012 Adverse Drug Reaction
Dr.Datten Bangun MSc,SpFK&
Dr.Zulkarnain Rangkuty,MS
Dept.Farmakologi & TherapeutikFak.Kedokteran USU
M E D A N
All Drugs are Dangerous
No Drugs are Dangerous if used properly
How dangerous a drug is depends on the skill of the prescriber
The most dangerous drugs have the greatest potential for benefit
Some drugs are dangerous in acute poisoning but not when used therapeutically
Some drugs have a low therapeutic ratio
Some drugs have a low incidence of horrendous effects
Some adverse effects can be predicted if you know the pharmacology (Type A); some are not (Type B)
Some adverse effects occur after a delay or after stopping
BADGOOD
RISK BENEFIT
When prescribing drugs a doctor must assess risk to benefit ratio in the individual patient by
•Choosing an appropriate class of drug then an appropriate individual agent
•Is it effective ?
•What are the chances of adverse effect ?
•Are there features in this patient which affect choice eg other drugs, organ failure, aged
•Tailoring the dose
•Considering duration of treatment
The Risk to Benefit Ratio
Adverse Drug Reaction
• Response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis and therapy (WHO)
• Unwanted or harmful reaction experienced after the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to drug
Type of adverse reactions
• Type A (Augmented)• Type B (Bizarre)• Type C (Chronic)• Type D (Delayed)• Type E (End of use)• Type F (Therapeutic failure)• Type G (Genetic/genomic)
CLASSIFICATION OF ADRS• Type A (Augmented ) reactions
– Reactions which can be predicted from the known pharmacology of the drug
– Dose dependent, can be alleviated by a dose reduction
– E.g. Bleeding with anticoagulants, bradycardia with beta blockers, headache with nitrates, postural hypotension with prazosin
CLASSIFICATION OF ADRS
• Type B (Bizarre) reactions– Cannot be predicted from the
pharmacology of the drug– Not dose dependent, host dependent
factors important in pre-disposition– E.g. anaphylaxis with penicillin,
anticonvulsant hypersensitivity
• Type C (Chemical) reactions– Biological characteristics can be predicted from the
chemical structure of the drug/metabolite– E.g. paracetamol hepatotoxicity
• Type D (Delayed) reactions– Occur after many years of treatment. Can be due to
accumulation– E.g. Secondary tumours after treatment with
chemotherapy, teratogenic effects of phenytoin taken during pregnancy, analgesic nephropathy, tardive dyskinesia with antipsychotic agents,
– Genital Ca after dietilstilbesterol in pregnant woman
CLASSIFICATION OF ADRS
CLASSIFICATION OF ADRS
• Type E ( End of treatment) reactions– Occur on withdrawal especially when drug
is stopped abruptly– E.g. withdrawal seizures on stopping
phenytoin, adrenocortical insufficiency on withdrawal of steroids
Type A Type B
Associated with the pharmacology of the product
Predictable
Dose related
Common
Serious
1. Type I hypersensitivity (Anaphylactic type)
Immediate hypersensitivity reaction, resulting from release of pharmacologically active mediators.
2. Type II Hypersensitivity
Cytolytic or cytotoxic reactions (1) Mechanism:① Complement-dependent reactionsTransfusion reactionsErythroblastosis fetal Autoimmune hemolytic anemiaCertain drug reactions
3. Type Hypersensitivity Ⅲ(Immune complex-mediated)
(1) Reaction types(1) Reaction types ① Arthus reaction ② serum sickness ③ Collagen diseases
4. Type HypersensitivityⅣ (Cell-Mediated )
Delayed hypersensitivity reaction (1) TissueTissue reactionreaction: Consist of
parenchymal destruction associated with perivascular lymphocytic and macrophage reaction.
②Antibody-dependent cell-mediated cytotoxicit (ADCC).
May be relevant to: Graft rejection The destruction of targets too large to be
phagocytosed, such as parasites or tumor cells.
4. Type HypersensitivityⅣ (Cell-Mediated )
③Antibody-mediated cellular dysfunction
Myasthenia gravis: muscle weakness
Graves’ disease:Graves’ disease: hyperthyroidism
Preventing ADRs cont’d
• Age, hepatic and renal disease may impair clearance of drugs so smaller doses may be needed. Genetic factors may also predispose to certain ADRs
• Prescribe as few drugs as possible and give clear instructions
• Where possible use familiar drugs. With new drugs be particularly alert for ADRs and unexpected event.
• If serious ADRs are liable to occur warn the patient
Prevention of Adverse Drug reactions
• Never use any drug unless there is good indication. If the patient is pregnant do not use the drug unless the need is imperative.
• Allergy and idiosyncrasy are important causes of ADRs. Ask if the patient had previous reactions.
• Ask if the patient is already taking other drugs including self medication
Preventing ADRs cont’d
• Age, hepatic and renal disease may impair clearance of drugs so smaller doses may be needed. Genetic factors may also predispose to certain ADRs
• Prescribe as few drugs as possible and give clear instructions
• Where possible use familiar drugs. With new drugs be particularly alert for ADRs and unexpected event.
• If serious ADRs are liable to occur warn the patient
teratogenic
Teratogenicity is based on…
• Substance ----thalidomide• Dose relatedness,length of exposure• Time course --1st semester• Susceptibility
Type AType A Type BType B
PharmacologicaPharmacologically predictablelly predictable
Yes Yes NoNo
Dose Dose dependentdependent
Yes Yes NoNo
IncidenceIncidence HighHigh LowLow
MorbidityMorbidity HighHigh LowLow
MortalityMortality LowLow HighHigh
ManagementManagement Dosage Dosage adjustmentadjustment
STOPSTOP
• Type A ADRs – intrinsic to the drug effects• Type B ADRs - idiosyncratic
Mechanisms of non dose-related (Type B) ADR
• Pharmacodynamic causes-target organs – genetic, immunologic,
neoplastic or teratogenic
Erythrocyte glucose-6-phosphate (G6PD) deficiency
• Sex-linked inherited deficiency • Weakened red cell membrane • Hemolysis from primaquine, sulfonamides,
sulfones and nitrofurantoin• African type-mild, Mediterranean type-
severe
Drugs that should be avoided with G6PD deficiency
• Dapsone• Niridazole• Methylene blue (methylthioninium Cl) • Primaquine• Quinolones (ciprofloxacin, nalidixic acid,
norfloxacin, ofloxacin)• Sulfonamides (Cotrimoxazole)
Malignant hyperthermia
• Rapid rise in body temperature (at least 2 C per hour)
• Associated with anesthetics and muscle relaxants (succinylcholine)
• Stiffness of skeletal muscle, hyperventilation, acidosis, hyperkalemia, increased activity of sympathetic NS outcome?Associated with a sudden release of intracellular ionized Ca
Antidote: Dantrolene
Predisposing factors
• Multiple drug therapy• Age1.Elderly- hypnotics, diuretics, NSAIDS, anti-
hypertensives, psychotropics, digoxin2.Adults- polypharmacy3.Children- antiepileptics, cytotoxic agents,
anesthetic gases, antibiotics (associated with hepatic failure), Na valproate
Predisposing factors
• Age4. Neonates- chloramphenicol, morphine,
antiarrhythmicsReye’s syndrome - ?Hepatotoxicity – Na valproate
Predisposing factors
• Gender- Females have 1.5-1.7 folds of developing ADR
than males- Women are prone to develop blood
dyscrasias with phenylbutazone & chloramphenicol
- Histaminoid reactions with neuromuscular blocking drugs
Prevention of Adverse Drug reactions
• Never use any drug unless there is good indication. If the patient is pregnant do not use the drug unless the need is imperative.
• Allergy and idiosyncrasy are important causes of ADRs. Ask if the patient had previous reactions.
• Ask if the patient is already taking other drugs including self medication
Preventing ADRs cont’d
• Age, hepatic and renal disease may impair clearance of drugs so smaller doses may be needed. Genetic factors may also predispose to certain ADRs
• Prescribe as few drugs as possible and give clear instructions
• Where possible use familiar drugs. With new drugs be particularly alert for ADRs and unexpected event.
• If serious ADRs are liable to occur warn the patient
Drug administered
Pt develops a new condition/symptoms
Drug suspected?
Yes
Check literature
Documented ?– (for the product or similar class of products)
Yes
Highly suggestive of ADR
Not documented in literature
Drug continued Drug discontinued
Worsening of symptoms Symptoms improve (+ve dechallenge)
Drug restarted
Symptoms recur(+ve rechallenge)
Any other possible causes?• Concomitant therapy• Underlying conditions
top related