Adverse Drug Reactions Flashcards
What is an ADR?
any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment
How can the onset of an ADR be classified?
- Acute= within 60 minutes and presents with bronchoconstriction
- Sub-acute= 1-24 hours and presents with rash, serum sickness
- Latent= >2 days and presents with eczematous eruptions
How can the severity of an ADR be classified?
- Mild: bothersome but requires no change in therapy i.e metallic taste with metronidazole
- Moderate: requires change in therapy, additional treatment, hospitalisation i.e amphotericin induced hypokalemia
- Severe: disabling or life-threatening i.e kidney failure
How can ADRs be classified?
- Type A: Augmented
- Type B: Bizarre
- Type C: Chronic
- Type D: Delayed
- Type E: End of Treatment
- Type F: Failure of Treatment
Describe type A ADRs.
- dose related
- predictable
- easily reversible
- most common
- not usually life threatening
Describe type B ADRs
- idiosyncratic
- unpredictable
- rare
- cause serious illness/death
- unidentified fro months/years
- unrelated to dose
- not readily reversible
What are the predisposing factors relating to ADRs?
- multiple drug therapies
- renal/hepatic impairment
- Race and genetic polymorphisms
- age
- sex
What causes type A reactions?
- Excess pharmacological action
- they may be due to the secondary pharmacology of a drug unrelated to the therapeutic effect
What are the 2 types of type A ADRs?
- augmentation of the primary effect
- secondary effect
Reasons for Type A ADRs
- too high a dose
- pharmaceutical variation
- pharmacokinetic variation
- pharmacodynamics variation
What factors affect pharmacokinetic variation?
Absorption (dose, formulation, GI motility, first pass metabolism)
- distribution
- metabolism (enhanced/impaired)
- elimination (renal disease, reduced GFR)
Describe pharmacogenetics in ADRs.
- a number of drugs are metabolised via acetlyation which is under genetic control
- 1 in 10 have slow metabolism
- prone to drug toxicity
- peripheral neuropathy with isoniazid
How can disease impact ADR?
- renal and hepatic impairment can lead to increased toxicity if drug is not excreted
- Cardiac failure reduces the drug absorption from the gut due to oedema. There is poor renal perfusion and decreased GFR which leads to hepatic congestion.
When are type B ADRs more likely to occur?
-more common with macromolecules such as proteins, vaccines and polypeptides
-patients with asthma or eczema
Presence of particular HLA increases risk
What is the mechanism of type B?
-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
Define idiosyncratic
- inherent abnormal response to a drug
- due to genetic abnormality such as enzyme deficiency or abnormal receptor activity
How can differences in response to a drug be considered?
- genetic
- immunological
Describe an enzyme abnormality
Erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency
-individuals with sex-linked inherited deficiency of this enzyme are susceptible to red cell haemolysis when given drugs such as primaquine or sulphonamides
Describe a receptor abnormality.
malignant hyperthermia with general anaesthetics
Describe hypersensitivity reactions.
- due to antigen-antibody interaction
- first dose acts as the antigen
- body produces the antibody
- subsequent antigen-antibody reaction
Describe type C ADRs.
- related to duration of treatment
- does not occur with a single dose
- semi-predictable
Give examples of Type C reactions.
- Iatrogenic Cushings disease
- Steroid induced osteoporosis
- opiate dependence
- tardive dyskinesia with neuroleptic drugs
- analgesic nephropathy due to paracetamol or NSAIDa
Describe type D reactions.
- adverse effects occur a long time after treatment
- teratogenesis- the children of treated patients
- carcinogenesis- treated patients years after treatment has stopped
Give examples of type D reactions.
- second cancers in those treated with alkylating agents or immunosuppressive agents (cyclophosphamide, alkylating agents)
- craniofacial malformations in children whose mothers were treated with isotretinoin
