Adverse Drug Reactions Flashcards
Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment
ADR
An appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product
Acute
» within 60 minutes» bronchoconstrictio
Sub-acute
» 1 to 24 hours» Rash, serum sickness
Latent
> 2 days» Eczematous (skin) eruptions
Mild
bothersome but requires no change in therapy
» Metallic taste with metronidazole
Moderate»
requires change in therapy, additional treatment, hospitalization » Amphotericin induced hypokalemia
severe»
disabling or life-threatening» kidney failure
Classification of ADRs
ABCDEF
normal
but excess response to drug – know the effect of that drug
Dose related - problem - high dose
predictable
Type A - Augmented
Many type A reactions are due to a property of a drug unrelated to the primary effect
- galactorrhoea with domperidone
dry mouth with tricyclic antidepressants
Type A ADRs are Entirely predictable
Dose dependent
Resolve when the drug is reduced or stopped
Recognised before a drug is available
diosyncratic and unpredictable
Type B - bizarre
appear out of any where
Reasons for Type A ADR
Too high a dose
Pharmaceutical variation Pharmacokinetic variation(mainly) Pharmacodynamic variation (some)
The last two commonly occur as a result of disease
Pharmacokinetic variation (mainly)AbsorptionyDose Formulation
GI motility
First pass metabolism
The majority of ADRs which arise through absorption problems result in therapeutic failure
Distribution,Metabolism,Hepatic enhanced, impaired
Liver disease is particularly important when drugs have a narrow therapeutic index
Elimination -Renal Reduced GFR
Pharmacogenetic-A number of drugs are metabolised via acetylation which is under genetic control
10% of the population are slow metabolisers yprone to drug toxicity
eripheral neuropathy with isoniazid
Altered Pharmacodynamic action
Natural variability in pharmacodynamic response
Disease states can significantly alter response
Bizarre Unpredictable Rare Cause serious illness or death Unidentified for months or years Unrelated to the dose
Type B - Bizzare
Manifests as rash, asthma, serum sickness
Type B - Bizzare
Mechanism is immunological
Type B - Bizzare
ImmunologicalyNo relation to the pharmacological action of the drugyDelay between exposure and ADRyNo dose response curveyManifests as rash, asthma, serum sickness
Risk Factors of Type B - Bizzare
More common with macromolecules,proteins, vaccines, polypeptides
Patients with history of asthma, eczema,
HLA status - Presence of particular HLA increases risk of a type B reaction
Several genetic abnormalities may lead to abnormal and unpredictable responses to drugs
Erythrocyte (G6PD) are susceptible to red cell haemolysis (HA) when given drugs such as primaquine or sulphonamides. Common type of….. reaction
Type B - Bizzare
This type of ADR is related to the duration of treatment as well as the dose and does not occur with a single dose
Semi predictable
Type C - Chronic
Semi-predictable Iatrogenic Cushings disease Steroid induced osteoporosis Opiate dependence Tardive dyskinesia with neuroleptic drug
These adverse effects occur some time after treatment in
The children of treated patients
Or in the treated patients themselves years after treatment has stopped
Type D Delayed Effect
Second cancers in those treated with alkylating agents or immunosuppressive agents
cyclophosphamideyalkylating agents
Craniofacial malformations in children whose mothers were treated with isotretinoin
Suppressed Fertility
Teratogenicity
Adverse effects which occur when a drug treatment is stopped especially suddenly.
Type E End of Treatment Effects
Unstable angina and MI when beta blockers are stopped.
Addisonian crisis when long term steroids are suddenly stopped
Withdrawal seizures when anti-epileptics are stopped Alcohol
Rebound Phenomena Occur when a drug is suddenly withdrawn Alcohol Benzodiazepines beta-blockers - Covert to overt disease when treatment stop - MI corticosteroid
Common
Dose related
Frequently caused by drug interactions
Failure of the OCP when administered with hepatic enzyme inducers/ antibiotics
Failure of therapy Type F
Reporting ADR
yellow card scheme
All significant or unusual adverse drug reactions as well as unanticipated or novel events that are suspected to be drug related
All ADRs affecting Black Triangle Drugs/Products
On line reports made for all medicines including vaccines, blood factors and immunoglobulins, herbal medicines and homeopathic remedies, and all medical devices.
Collects information on:
side effects (also known as adverse drug reactions or ADRs)
medical device adverse incidents
defective medicines (those that are not of an acceptable quality)
counterfeit or fake medicines or medical devices
ADR present in these areas of the body
Haematologic CNS Dermatologic/Allergic Metabolic Cardiovascular Gastrointestinal Renal/Genitourinary Respiratory Sensory
Drugs Commonly Involved
Antibiotics Antineoplastics* Anticoagulants Cardiovascular drugs* Hypoglycemics Antihypertensives NSAID/Analgesics Diagnostic agents CNS drugs* *account for 69% of fatal ADRs
