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Flashcards in Adverse Drug Reactions Deck (24):

What is an adverse drug reaction?

Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment


Common drugs involved:

- Antibiotics
- Antineoplastics
- Anticoagulants
- Cardiovascular drugs
- Hypoglycaemics
- Antihypertensives
- NSAID/Analgesics
- Diagnostic agents
- CNS drugs (neuro and psych)


Body systems commonly involved:

- Haematologic
- Dermatologic/allergic
- Metabolic
- Cardiovascular
- Gastrointestinal
- Renal/genitourinary
- Respiratory
- Sensory


ADR risk factors

- Age
- Multiple medications
- Multiple co-morbid conditions
- Inappropritate medication prescribing use or monitoring
- End-organ dysfunction
- Altered physiology
- Prior history of ADRs
- Extent (dose) and duration of exposure
- Genetic predisposition


Frequency of ADRs

- 10-20% of all inpatients suffer an adverse drug reaction
- 6.5% of hospital admissions occur as a result of an ADR
- 4th leading cause of death


Classification of onset of ADRs

- Acute: within 60 minutes, bronchoconstriction
- Sub-acute: 1 to 24 hours. Rash, serum sickness
- Latent: >2 days. Eczematous eruptions


Classification of severity of ADRs

- Mild: bothersome but requires no change in therapy
- Moderate: requires change in therapy, additional treatment, hospitalisation
- Severe: Disabling or life-threatening, kidney failure


Type A ADR

- Augmented
- Dose related
- Predictable can often be unrelated to primary effect
- Resolve when the drug is reduced or stopped
- Recognised before a drug is available


Type B ADR

- Bizarre
- Idiosyncratic
- Unpredictable
- Rare
- Cause serious illness or death
- Unidentified for months or years
- Unrelated to dose


Type C

- Chronic/long term effects
- Related to duration of treatment as well as dose.
- Semi-predictable
- Doesn't occur with one dose


Type D

- Delayed
- Adverse effects occur after some time e.g. children of treated patients or treated patients years after treatment


Type E

- End of treatment effects
- Adverse effects when drug is stopped suddenly


Type F

- Failure of treatment
- Common
- Dose related
- Frequently cause by drug interactions
- Failure of Oral Contraceptives when administered with hepatic enzyme inducers/antibiotics


Examples of Type A ADR

- Galactorrhoea with domperidone
- Dry mouth with tricyclic antidepressants


Reasons for Type A ADRs

- Too high a dose
- Pharmaceutical variation
2 main ones:
- Pharmacokinetic (ADME)
- Pharmacodynamic variation

- Pharmacogenetic. 10% population slow metabolisers, can be prone to drug toxicity
- Disease: renal, hepatic, cardiac failure (oedomas in gut, decreased GFR, hepatic congestion)


Factors that affect Type B reactions

- More common with macromolecules: protein, vaccine, polypeptides
- Patients with a history of asthma, eczema
- Presence of certain HLAs


Immunological mechanisms of Type B

- No relation to the pharmacological action of the drug
- Delay between exposure and ADR
- No response curve
- Manifests as rash, asthma, serum sickness
- Idiosyncratic: inherent abnormal response, abnormal receptor activity


Pharmacogenetic mechanisms of Type B

- Genetic
- Examples of genetic: enzyme abnormality. Erthythrocyte glucose-6-phosphate deydrogenase (G6PD) deficiency
- Susceptible to red cell haemolysis when given drugs such as primaquine and sulphonamides
- Receptor abnormality malignant hyperthermia with general anaesthetics

Also get immunological


Examples of Type C reactions

- Iatrogen Cushings disease
- Steroid induced osteoporosis
- Opiate dependence
- Analgesic neuropathy due to paracemtaol or NSAIDS


Examples of Type D reactions

- Teratogenesis: Craniofacial malformation in children with mothers who have been treated with isotretinoin
- Carcinogenesis: those treated with alkylating agents or immunosuppressive agents such as cyclophosphamide


Examples of Type E reactions

- Unstable angina and MI when beta blockers are stopped
- Addisonian crisis when long term steroids suddenly stopped e.g. hypopituitism if you come off steroids and your adrenals are suppressed
- Withdrawal seizures when antiepileptics are stopped


Rebound phenomena

- Alcohol
- Benzodiazepines
- Beta blockers
- Corticosteroids


Diagnosis steps of ADR:

1. Differential diagnosis
2. Medication history (past and present)
3. Assess time of onset and dose relationship
4. Laboratory investigation: plasma concentration measurement and allergy tests


How to report ADRs

- Yellow Cards
Collect info on:
- Side effects
- Medical device adverse incidents
- Defective medicines
- Counterfeit or fake medicines or medical devices