Focus On ADR

Question 1

Adverse DRUG REACTION ADR

Answer 1

Any reaction that is ‘noxious, unintended and occurs at doses normally used in man’, where there is reasonable probability that it is caused by a drug

Question 2

Adverse drug event ADE

Answer 2

Any untoward medical occurrence in someone administered a drug which doesn’t necessarily have a casual relationship with this treatment

Question 3

Allergy is ADR or ADE

Answer 3

A type of ADR
Relatively uncommon e.g affecting 1 in 100 to 1 in 1000

Question 4

Allergy cause:

Answer 4

Immunologically mediated: Immediate (IgE) hypersensitivity or Delayed (IgG) hypersensitivity

Question 5

Allergy is triggered by?

Answer 5

An interaction between the drug and host protein- generating a ‘hapten’ which drives and immune response

Question 6

Sensitisation

Answer 6

A mild allergic reaction could be more sever next time around

Question 7

Side effects

Answer 7

Any effect of a drug that occurs in addition to the intended effect

Question 8

ADR defined in terms of side effect

Answer 8

ADR is any harmful/unpleasant effect that occurs in addition to the intended effect

Question 9

Prostaglandin eye drop : use and side effect

Answer 9

Used to treat glaucoma, a condition of raised pressure inside the eyeball
Side effect= longer eyelashes

Question 10

Why are ADR important?

Answer 10

Major problem in clinical reactive and DD
Represent 7% of acute hospital admissions
Commonest reason for drug withdrawal and failure of new drugs to reach the market

Question 11

Classification of ADRS

Answer 11

A- augumented/dose dependent
B- bizarre
C- continued use
D- delayed onset
E- end of treatment
F- failure of treatment

Question 12

How are ADRs classified?

Answer 12

Depending on time of onset and relationship with dose

Question 13

NAPQI

Answer 13

Highly reactive, oxidises key enzymes, causing cell death (apoptosis)
Can also bind renal cells to cause renal failure

Question 14

Overdose of paracetamol explained=

Answer 14

Phase 2 metabolism = saturated
More in phase 1 = increased NAPQI = hepatotoxic/ nephrotoxic

Question 15

Role of N- acetylcysteine in paracetamol overdose

Answer 15

Replenishes glutathione to mop up excess NAPQI

Question 16

Describe TYPE A ADR

Answer 16

AUGUMENTED
Dose related: will affect everyone if they take enough of the drug

Question 17

Examples of drug causing type A toxicity:

Answer 17

Opiates (morphine, codeine)
Carbon tetrachloride (dry cleaner) =liver necrosis
Acute alcohol ingestion = hepatitis

Question 18

38 year old. Recent diagnosis of epilepsy. Started on carbamazepine. 7 days later develops a fever, sore throat and painful eyes. Then develops painful ulcers in mouth and rash all over body. What TYPE OF ADR IS THIS?

Answer 18

Type B reactions- Bizarre
Not dose related, may occur at therapeutic doses

Question 19

Describe Type B reactions- Bizarre

Answer 19

Unpredictable , ‘idiosyncratic’ e.g allergic reactions
Caused by some unusual characteristic of the patient and the drug in combination
NOt related to PD of drug or metabolite

Question 20

Stevens-Johnson syndrome is a from of what?

Answer 20

Form of allergic reaction = TYPE IV (delayed/ IgG mediated) hypersensitivity

Question 21

Stevens-Johnson syndrome stimulates?

Answer 21

Cytotoxic T cells ( I.e CD8+ T cells) and T helper cells (I.e CD4+ T cells) to initiate autoimmune reactions that attack the skim and mucous membranes

Question 22

Stevens-Johnson syndrome allele is prevalent in?

Answer 22

Han Chinese and Thai people

Question 23

Stevens-Johnson syndrome associated with what allele?

Answer 23

HLA-B*1502 allele, gene variant that codes for the immune system

Question 24

CT Scans measure?

Answer 24

Density - black is not dense
White= very dense I.e bones and sometimes blood shows white is ‘contrast’ dye injected into blood

Question 25

Alcohol metabolism explain

Answer 25

Alcohol dehydrogenase- (transforms ethanol into toxic compound =by product ) acetylaldehyde CYP450- changes in oxidation/ reduction

Question 26

Alcohol liver injury

Answer 26

Fatty change (alcohol steatosis) Hepatitis

Question 27

Alcohol cirrhosis

Answer 27

Destruction and fibrosis with regenerating nodules

Question 28

Scarring of the liver caused by cirrhosis increases?

Answer 28

The pressure in the portal vein, causing fluid to leak into the abdomen

Question 29

Type C reaction - continued use explained

Answer 29

Caused by dose accumulation or long term use

Question 30

Examples of Type C reaction

Answer 30

Steroids- impaired insulin sensitivity, weight gain, reduction in bone density Methotrexate- fibrosis (scarring) of lungs and liver Amiodarone - fibrosis( scarring) of lungs and liver, grey tinge to skin Spironolactone (aldosterone antagonist) - gynaecomastia (breast growth) and reduced libido

Question 31

Type D reaction is?

Answer 31

Delayed onset due to prolonged use in drug which doesn’t tend to accumulate May occur even if drug has been stopped Liver damage may not be apparent until some years after drug is taken

Question 32

Examples of Type D reaction

Answer 32

Tardive dyskinesia (abnormal facial movement) from antipsychotics Hepatocellular carcinoma from alcohol Mesothelioma from asbestos

Question 33

Type E reactions are typically caused by?

Answer 33

End of treatment Typically caused by withdrawal or rebound effects

Question 34

Examples of Type E:

Answer 34

Opiates (recurrence of pain) Benzodiazepines (recurrence of agitation and potentially seizure) Corticosteroids (loss of psychological production of steroids can lead to addisonian crisis)

Question 35

Type F reactions is? Define?

Answer 35

Failure of treatment Unexpected failure o treatment, despite normal dosing Can occur at any stage of treatment

Question 36

The F reactions often involve?

Answer 36

Drug-drug reaction

Question 37

St John’s wort is?

Answer 37

An enzyme inducer- it increases activity of CYP450 enzymes that metabolise contraceptive hormones

Question 38

General principles to treat ADRs-

Answer 38

Look at what clarification of ADR AND report the reaction - yellow card scheme

Question 39

What can increased ADRs?

Answer 39

Co-morbidities Drug interactions Special groups (pregnant women, children and the elderly)

Question 40

General principles to treat ADRs- Augumented

Answer 40

Reduce dose o withhold

Question 41

General principles to treat ADRs- bizarre

Answer 41

Stop drug- depending on severity, often reaction is a ‘absolute contraindication’ May need drugs to treat allergy (antihistamines, steroids, adrenaline)

Question 42

General principles to treat ADRs- continued use

Answer 42

Recognition of potential for this and use drug sparingly/for shortens amount of time if possible If ADR develops, stop drug or reduce dose

Question 43

General principles to treat ADRs- delayed onset

Answer 43

Recognition for potential for this ; balance risks and benefits of drug and discuss with patient

Question 44

General principles to treat ADRs- end of treatment

Answer 44

May need to restart treatment If need to stop this should be done slowly reducing the dose over weeks/months

Question 45

General principles to treat ADRs- failure to treatment

Answer 45

Prevent by clinician and patient being aware of drug-drug interactions and what to avoid Stop any new rugs causing interactions Increase dose of initial drug if safe to do so, or switch to a different treatment