Adverse Drug reactions Flashcards
Define adverse drug reactions
Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment.
How frequent are adverse reactions and consequences ?
- 4th leading cause of death
- 60% of ADRs are preventable
- primary care ADRs leads to hospital admission
- secondary care ADRs lead to longer hospital stay
What causes avoidable ADRs and what is their frequency?
- non-steroidal drugs
- anti-inflammatory drugs
- anti coagulants
- antiplatelets
-they cause a third of admissions
What are the top 5 contributors to adverse drug reactions?
- surgery
- medication errors
- medical errors (nonsurgical)
- patient falls
- nosocomial infections
What is the classification of onset of adverse drug reactions?
- Acute
- Sub acute
- Latent
In what cases are ADRs not preventable?
nausea in chemo treatment for cancer
What is the classification of acute ADRs?
- occurs within 60 minutes
- bronchoconsitrction
What is the classification of sub-acute ADRs?
- 1-24 hours
- rash, serum sickness
What is the classification of latent ADRs?
- 2 days
- excematous eruptions
Classification of severity of ADRs?
-Mild
-Moderate
Severe
Classification of mild ADRs?
- Bothers some but requires no change in therapy
- Metallic taste with metronidazole
Classification of moderate ADRs?
- Requires change in therapy, additional treatment or hospitalization
- Diuretic induced hypokalemia
Classification of severe ADRs?
- Disabling or life-threatening
- Kidney failure
How do we classify the different types of ADRs?
Type A- Augmented Type B- Bizarre - Idiosyncratic and unpredictable Type C-Chronic Type D- Delayed Type E- End of treatment Type F- Failure of treatment
What are predisposing factors for ADRs?
- multiple drug therapy
- inter-current disease (renal and hepatic impairment)
- race and genetic polymorphisms
- age (elderly and neonates)
- sex
What gender is ADRs most common in and why?
Women due to different liver functions and pharmacokinetics
Describe Type A ADRs
- Augmented response to the pharmacological actions of a drug
- Dose dependent
- Entirely Predictable
- not usually life threatening
What are the 2 types of ADRs?
o Augmentation of the primary effect
o Secondary effect
Examples of Type A ADRs.
- Due to excess pharmacological action
o Bradycardia with beta-blockers
o Hypoglycaemia with sulphonylureas or insulin
Describe the secondary effect of type A ADRs
- Due to the secondary pharmacology of a drug unrelated to the therapeutic effect.
- Still rationalizable form the known pharmacology of the drug.
Examples of secondary effect of Type A ADRs
- Galactorrhoea with domperidone
- Dry mouth with tricyclic antidepressants
Causes for Type A ADRs?
- Too high a dose
- Pharmaceutical variation
o Pharmacokinetic variation
Absorption
• Dose
• Formulation
• GI motility
• First pass metabolism
o Pharmacodynamic variation
Describe Type B ADRs.
- Bizarre, unpredictable, rare, cause serious illness or death
- Unidentified for months or years
- Unrelated to the dose or concentration
- Not readily reversed
What factors increase the chances of Type B ADRs?
- More common with macromolecules
o Proteins
o Vaccines
o Polypeptides - Patients with history of asthma, excema
- HLA status
o Presence of particular HLA increases risk of a Type B reaction
What are the mechanisms of type B ADRs?
- Idiosyncratic
- Drug allergy or hypersensitivity
Describe the idiosyncratic mechanism of Type B ADRs.
- inherent abnormal response to a drug
- occurs due to genetic abnormality to a drug or abnormal receptor activity
Describe the drug allergy or hypersensitivity mechanisms of Type B ADRs.
How does it manifest?
- immunological
- has no relation to the pharmacological action of the drug
- delay been exposure and ADR
- manifests as rash, asthma, serum sickness
Describe Type C Chronic ADRs.
- Related to the duration of treatments and the dose
- Does not occur with a single dose
- semi predictable
Examples of tYPE C chronic disease
o Latrogenic Cushings disease
o Opiate dependence
o Steroid induced osteoporosis
Describe Type D Delayed ADRs
- adverse effects occur a long time after treatment
- teratogenesis
- carcinogenesis
What is teratogenesis?
seen in type d delayed ADRs
o Children of treated patients
o Abnormal congenital malformations in the fetus following in utero exposure due to maternal medication use during 1st trimester of pregnancy
Example of teratogenesis?
o Craniofacial malformaitons in childrens whose mothers were treated with isotretinoin
What are teratogenic agents?
Cytotoxics
Vitamin A
Antithyroid drugs
Steroids
How to prevent teratogensis
o All drugs should be avoided during pregnancy unless they are safe or the benefit out-weigh potential risk.
What is carcinogenesis in Type D ADRs?
o In treated patients years after treatment has stopped
What is Type E End of treatment ADRs?
- Occurs when a drug treatment is stopped especially suddenly following long term use
Examples of Type E End of treatment ADRs?
o Unstable angina and MI - when beta blockers are stopped
o Alcohol
o Withdrawal seizures when anti-epileptics are stopped
o Addisonian crisis when long term steroids are suddenly stopped
When does rebound phenomena occur?
When a drug is suddenly withdrawn.
- Alcohols
- Benzodiazepines
- Beta-blockers
- Corticosteroids
What is Type F ADRs?
- Failure of therapy
- Frequently caused by drug interactions
- Common
- Dose related
- Most worrying- failure of the OCP when administered with hepatic enzyme inducers/antibiotics
How do we diagnosis ADRs?
- Differential diagnosis- be suspicious
- Medication history (past and present)
- Assess time of onset and dose relationship
- Laboratory investigations
o Plasma concentration measurement
o Allergy tests
Who is most at risk of ADRs?
- Age (children and elderly)
- Multiple medications
- Multiple co-morbid conditions
- Inappropiate medication prescribing, use or monitoring
- End-organ dysfunction
- Altered physiology
- Prior history of ADRs
- Extent (dose) and duration of exposure
- Genetic predisposition
What are drugs commonly involved?
Drugs that we are very used to.
- Antibiotics
- Painkillers- NSAID, Opiates
- Cardiovascular drugs
- Hypogycemics
Surveilance methods for ADRs
Anecdotal reporting
Most common is using yellow card scheme
