Adverse Drug Reactions

Question 1

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

Answer 1

ADR

An appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product

Question 2

Acute

Answer 2

» within 60 minutes» bronchoconstrictio

Question 3

Sub-acute

Answer 3

» 1 to 24 hours» Rash, serum sickness

Question 4

Latent

Answer 4

> 2 days» Eczematous (skin) eruptions

Question 5

Mild

Answer 5

bothersome but requires no change in therapy

» Metallic taste with metronidazole

Question 6

Moderate»

Answer 6

requires change in therapy, additional treatment, hospitalization » Amphotericin induced hypokalemia

Question 7

severe»

Answer 7

disabling or life-threatening» kidney failure

Question 8

Classification of ADRs

Answer 8

ABCDEF

Question 9

normal
but excess response to drug – know the effect of that drug
Dose related - problem - high dose
predictable

Answer 9

Type A - Augmented

Many type A reactions are due to a property of a drug unrelated to the primary effect
- galactorrhoea with domperidone
dry mouth with tricyclic antidepressants
Type A ADRs are Entirely predictable
Dose dependent
Resolve when the drug is reduced or stopped
Recognised before a drug is available

Question 10

diosyncratic and unpredictable

Answer 10

Type B - bizarre

appear out of any where

Question 11

Reasons for Type A ADR

Answer 11

Too high a dose
Pharmaceutical variation Pharmacokinetic variation(mainly) Pharmacodynamic variation (some)
The last two commonly occur as a result of disease

Pharmacokinetic variation (mainly)AbsorptionyDose Formulation
GI motility
First pass metabolism
The majority of ADRs which arise through absorption problems result in therapeutic failure

Distribution,Metabolism,Hepatic enhanced, impaired
Liver disease is particularly important when drugs have a narrow therapeutic index
Elimination -Renal Reduced GFR

Pharmacogenetic-A number of drugs are metabolised via acetylation which is under genetic control
10% of the population are slow metabolisers yprone to drug toxicity
eripheral neuropathy with isoniazid

Altered Pharmacodynamic action
Natural variability in pharmacodynamic response
Disease states can significantly alter response

Question 12

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

Answer 12

Type B - Bizzare

Question 13

Manifests as rash, asthma, serum sickness

Answer 13

Type B - Bizzare

Question 14

Mechanism is immunological

Answer 14

Type B - Bizzare

ImmunologicalyNo relation to the pharmacological action of the drugyDelay between exposure and ADRyNo dose response curveyManifests as rash, asthma, serum sickness

Question 15

Risk Factors of Type B - Bizzare

Answer 15

More common with macromolecules,proteins, vaccines, polypeptides
Patients with history of asthma, eczema,
HLA status - Presence of particular HLA increases risk of a type B reaction

Question 16

Several genetic abnormalities may lead to abnormal and unpredictable responses to drugs
Erythrocyte (G6PD) are susceptible to red cell haemolysis (HA) when given drugs such as primaquine or sulphonamides. Common type of….. reaction

Answer 16

Type B - Bizzare

Question 17

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

Answer 17

Type C - Chronic

Semi-predictable
Iatrogenic Cushings disease
Steroid induced osteoporosis
Opiate dependence
Tardive dyskinesia with neuroleptic drug

Question 18

These adverse effects occur some time after treatment in
The children of treated patients
Or in the treated patients themselves years after treatment has stopped

Answer 18

Type D Delayed Effect

Second cancers in those treated with alkylating agents or immunosuppressive agents
cyclophosphamideyalkylating agents
Craniofacial malformations in children whose mothers were treated with isotretinoin
Suppressed Fertility
Teratogenicity

Question 19

Adverse effects which occur when a drug treatment is stopped especially suddenly.

Answer 19

Type E End of Treatment Effects

Unstable angina and MI when beta blockers are stopped.
Addisonian crisis when long term steroids are suddenly stopped
Withdrawal seizures when anti-epileptics are stopped Alcohol

Rebound Phenomena
Occur when a drug is suddenly withdrawn
Alcohol
Benzodiazepines
beta-blockers - Covert to overt disease when treatment stop - MI
corticosteroid

Question 20

Common
Dose related
Frequently caused by drug interactions
Failure of the OCP when administered with hepatic enzyme inducers/ antibiotics

Answer 20

Failure of therapy Type F

Question 21

Reporting ADR

Answer 21

yellow card scheme

All significant or unusual adverse drug reactions as well as unanticipated or novel events that are suspected to be drug related
All ADRs affecting Black Triangle Drugs/Products

On line reports made for all medicines including vaccines, blood factors and immunoglobulins, herbal medicines and homeopathic remedies, and all medical devices.

Collects information on:
side effects (also known as adverse drug reactions or ADRs)
medical device adverse incidents
defective medicines (those that are not of an acceptable quality)
counterfeit or fake medicines or medical devices

Question 22

ADR present in these areas of the body

Answer 22

Haematologic
CNS 
Dermatologic/Allergic
Metabolic
Cardiovascular
Gastrointestinal
Renal/Genitourinary
Respiratory
Sensory

Question 23

Drugs Commonly Involved

Answer 23

Antibiotics
Antineoplastics*
Anticoagulants
Cardiovascular drugs*
Hypoglycemics
Antihypertensives
NSAID/Analgesics
Diagnostic agents
CNS drugs* 
*account for 69% of fatal ADRs