adverse drug reactions Flashcards
Adverse Drug Reactions =
Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment
Adverse Drug Reactions =
Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment
Onset of event (ADR)
Acute
- within 60 minutes
- bronchoconstriction
Sub-acute
- 1 to 24 hours
- Rash, serum sickness
Latent
- 2 days
- Eczematous eruptionsSeverity of reaction (ADR)
Mild
- bothersome but requires no change in therapy
- Metallic taste with metronidazole
Moderate
- requires change in therapy, additional treatment or
hospitalization
- Amphotericin induced hypokalemia
Severe
- disabling or life-threatening
- kidney failureClassification of ADRs
Type A Augmented Type B Bizarre Type C Chronic Type D Delayed Type E End of treatment Type F Failure of treatment
Type A ADRs
Augmented pharmacologic effects
- Dose related
- Predictable
Type B ADRs
Bizarre effects
- Idiosyncratic and unpredictable
Predisposing Factors to ADR
Multiple Drug Therapy
- Incidence of ADRs increase exponentially with the
number of medicaments
Inter-current Disease
- Renal and hepatic impairment
Race and Genetic Polymorphisms
Age
- Elderly and neonates
Sex
- ADRs more common in womenType A Reactions
They are due to excess pharmacological action
- bradycardia with beta-blockers
- hypoglycaemia with sulphonylureas or insulin
Easily reversible on reducing the dose or stopping the drug
They are the most common of all ADRS accounting for 80% of all ADRs
Not usually life threatening
Reasons for Type A ADRs due to disease
Pharmacokinetic variation
Pharmacodynamic variation
Pharmacokinetic Variation
- The majority of ADRs which arise through absorption problems result in therapeutic failure
- Liver disease is particularly important when drugs have a narrow therapeutic index
Pharmacogenetic
A number of drugs are metabolised via acetylation which is under genetic control
- 10% of the population are slow metabolisers
- prone to drug toxicity
- peripheral neuropathy with isoniazid
Disease and ADRs
Renal and hepatic impairment
- If a drug is excreted by the kidneys toxic drug levels
may build up
Cardiac Failure
- Reduce drug absorption from the gut due to oedema
- Poor renal perfusion and decreased GFR
- Hepatic congestion
Most type A ADRs are
pharmacokinetic in nature
Type B ADRs
Bizarre Unpredictable Rare Cause serious illness or death Unidentified for months or years Unrelated to the dose Not readily reversed
Type B ADRs mechanism
Idiosyncratic
Drug allergy or hypersensitivity
- Immunological
- No relation to the pharmacological action of the drug
- Delay between exposure and ADR
- No dose response curve
- Manifests as rash, asthma, serum sickness
Type B ADRs Important Factors
More common with macromolecules
- proteins
- vaccines
- polypeptides
Patients with history of asthma, excema,
HLA status
- Presence of particular HLA increases risk of a type B
reactionIdiosyncratic is the
Inherent abnormal response to a drug
Due to genetic abnormality such as enzyme deficiency
Or abnormal receptor activity.
Pharmacogenetic
Differences in response to drugs may be considered as:
Genetic
Immunological
Type C Chronic/Long Term Effects
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
- Iatrogenic Cushings disease
- Steroid induced osteoporosis
- Opiate dependence
- Tardive dyskinesia with neuroleptic drugs
- Analgesic nephropathy due to paracetamol or NSAIDs
Type D Delayed Effects
These adverse effects occur a long time after treatment
- Teratogenesis
- Carcinogenesis
- The children of treated patients-teratogenesis
- Carcinogenesis in treated patients years after treatment has stopped.
Type D Delayed Effects
Craniofacial malformations in
children whose mothers were treated with isotretinoin
Due to maternal medication use during 1st trimester of pregnancy
All drugs should be avoided during
pregnancy unless they are safe or the benefit outweighs potential risk
teratogenic Agents
isotretinoin Cytotoxics Vitamin A Antithyroid drugs Steroids Oral nticoagulants
Type E End of Treatment Effects
Adverse effects which occur when a drug treatment is stopped especially suddenly following long-term use
Type E End of Treatment Effects
Unstable angina and MI when
beta blockers are stopped.
Type E End of Treatment Effects
Addisonian crisis when
Long term steroids are suddenly stopped
Type E End of Treatment Effects
Withdrawal seizures when
anti-epileptics are stopped
Rebound Phenomena Occur when
drug is suddenly withdrawn
- Alcohol
- Benzodiazepines
- beta-blockers
- corticosteroids
Type F ADRs
Failure of therapy
Common
Dose related
Frequently caused by drug interactions
Failure of the OCP when administered with hepatic enzyme inducers/ antibiotics
most at risk of ADRs?
Age (children and elderly)
Multiple medications
Multiple co-morbid conditions
Inappropriate medication prescribing, use, or monitoring
60% of ADRs and ADEs are
preventable, although some effects cannot be avoided (e.g. nausea in chemo treatment for cancer)
Report ADRs using
Yellow Card Scheme
