Adverse Drug Reactions Flashcards
what is an adverse drug reaction?
any response to a drug which is noxious/harmful, unintended and occurs at doses used in man for prophylaxis (preventing), diagnosis or treatment, relates to intervention of the use of the medical product
what is an acute onset of adverse drug reaction?
- occurs within 60 minutes
- bronchoconstriction (constriction of airway)
what is a sub-acute onset of adverse drug reaction?
- occurs from 1-24 hours
- rash, serum sickness
what is a latent onset of adverse drug reaction?
- after >2 days
- eczematous eruptions
what 3 categories can an onset of adverse drug reactions be split into?
- acute
- sub-acute
- latent
what 3 categories can severity of adverse drug reaction be split into?
- mild
- moderate
- severe
what is mild severity of drug reaction?
- bothersome but requires no change in therapy
e. g. metallic taste with metronidazole
what is moderate severity of drug reaction?
- requires change in therapy and additional treatment
- hospitalisation
(e. g. amphotericin induced hypokalemia)
what is severe severity of a drug reaction?
- disabling or life threatening
e. g. kidney failure
What is type A ADR?
augmented;
- dose related
- predictable
what is type B ADR?
bizarre;
- idiosyncratic (distinct, individual) and unpredictable
- also included Types C,D and E
what is type C ADR?
Chronic
what is type D ADR?
Delayed
what is type E ADR?
End of treatment
what is type F ADR?
failure of treatment
what are the 5 main predisposing factors to ADRs?
- multiple drug therapy
- age (elderly and neonates)
- sex (more common in women)
- intercurrent disease (e.g. renal or hepatic impairment)
- race and genetic polymorphisms
what are properties of Type A (augmented) reactions?
- normal response
- predictable and dose dependant
- due to excess pharmacological action
(e. g. bradycardia with beta blockers) - can be due to property of drug
- resolve when drug is reduced/stopped
- recognised before a drug is available
what are the reasons for Type A ADRs?
-pharmacokinetic variation
-pharmacodynamic variation
-too high a dose
-pharmaceutical variation
(pharmacological variation occurs as a result of disease)
what is absorption of a drug highly dependent on in pharmacokinetic variation? (5)
- dose
- formulation
- GI motility
- first pass metabolism
- therapeutic failure
- distribution
- metabolism (hepatic; either enhanced or impaired)
- elimination (renal)
what is especially important to consider if a drug has a narrow therapeutic index?
liver function (or disease)
what is pharmacogenetic factor?
- under genetic control; such as acetylation which is used for metabolism of many drugs
- prone to drug toxicity
what 3 disease especially have a huge role in ADRs and need to be monitored?
- renal impairment (build up of toxins if less excretion)
- hepatic impairment (toxin build up if no metabolism)
- cardiac failure (if oedema from circulation, then no drug reabsorption)
what is meant by pharmacodynamic variation?
- natural variability in response
- disease states can alter response significantly
what are the properties of type B (bizarre) ADRs?
- bizarre and unpredictable
- rare
- cause serious illness or death
- unidentified for months or years
- unrelated to the dose
- can be stopped by medicine/ stopper drug
- delay between exposure and ADR
what is the main mechanism involved in type B ADRs?
- immunological (no relation to the pharmacological action of the drug)
- no dose response curve
what can type B ADRs manifest as? (3)
- rash
- asthma
- serum sickness
which 3 factors put people at a greater risk of a Type B reaction?
- More common with macromolecules
- proteins
- vaccines
- polypeptides - patients with history of asthma or eczema
- HLA status (presence of particular human leukocyte antigens increases risk of a type B reaction)
pharmacogenetic differences in response to a Type B ADR may be considered as what 2 things?
- genetic
2. immunological
what are properties of a Type C ADR?
- related to duration of treatment as well as the dose
- doesn’t occur with a single dose
- semi-predictable
what are properties of a Type D ADR?
- occur sometime after the treatment
- occur in children of treated patients
- occur in treated patients themselves years after treatment has stopped
- second cancers in those treated with alkylating agents and cyclophosphamide or immunosuppressive agents
what is a famous Type D (Delayed) effect ADR?
Thalidomide disaster; congenital malformations in the foetus due to maternal medication
what are properties of Type E (end of treatment) ADR?
- adverse effects occur when a drug is stopped especially suddenly
what are common examples of Type E ADRs?
- unstable angina or myocardial infarction when beta blockers are stopped
- Addisonian crisis when long termsteroids are stopped
- withdrawal seizures when anti-epileptics are stopped
- alcohol withdrawal leading to seizures
what drugs are common to have a rebound phenomena? (sudden withdrawal of a drug)
- alcohol
- benzodiazepines
- beta-blockers
- corticosteroids
What are the 4 steps to an ADR diagnosis?
- differential diagnosis
- medication history
- assess time of onset and dose relationship
- laboratory investigations (plasma concentration measurement, allergy tests)
what medication is commonly involved in ADRs?
- antibiotics
- antineoplastics (chemo)
- anticoagulants
- cardiovascular drugs
- hypoglycemics
- antihypersensives
- NSAID/analgesics
- Diagnostic agents
- CNS drugs
what body systems are commonly involved in ADRs?
- haematologic
- CNS
- Dermatologic/ allergic
- metabolic
- cardiovascular
- gastrointestinal
- renal/genitourinary
- respiratory
- sensory
what are the main ADR risk factors? (9)
- age (children and elderly)
- multiple medications
- multiple co-morbid conditions
- inappropriate medication prescribing use or monitoring
- altered physiology
- end-organ dysfunction
- prior history of ADRs
- extent (dose) and duration of exposure
- genetic predisposition
what is used to report, record and monitor ADRs?
Yellow Card scheme
(online reports made on medicines, blood factors, immunoglobulins, herbal medicines, medical devices, homeopathic remedies)
