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Principles of Disease 16 > Adverse Drug Reactions > Flashcards

Adverse Drug Reactions Flashcards

1
Q

Define an adverse drug reaction

A

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

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2
Q

Describe an acute reaction

A

Occurs within 60 mins

E.g. broncoconstriction

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3
Q

Describe a sub-acute reaction

A

Occurs within 1-24hrs after exposure

E..g. rash, serum sickness

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4
Q

Describe a latent reaction

A

Occurs >2days later e.g. eczematous eruptions

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5
Q

How can you classify reaction severity?

A

• Mild - bothersome but requires no
change in therapy e.g. metallic taste with metronidazole
• Moderate - requires change in therapy,
additional treatment, or hospitalization e.g. amphotericin induced hypokalemia
• Severe- disabling or life-threatening e.g. kidney failure

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6
Q

How are ADRs classified?

A 
Type A 	Augmented
	Type B	Bizarre
	Type C	Chronic
	Type D	Delayed
	Type E	End of treatment   
	Type F	Failure of treatment
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7
Q

Describe type A ADRs

A

Dose related response, with the side effects usually predictable but augmented. In some cases, the reactions are not necessarily related to the drugs pharmacological effect e.g.dry mouth and tricyclic antidepressants. Effects are usually reversible upon removal of the drug.

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8
Q

What are some reasons type A ADRs occur?

A 
Too high a dose 
Pharmaceutical variation 
Pharmacokinetic variation 
Pharmacodynamic variation 
The last two commonly occur as a result of disease
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9
Q

What are some predisposing factors for ADRs?

A

Multiple Drug Therapy - Incidence of ADRs increase exponentially with the number of medicaments
Age - Elderly and neonates
Sex - ADRs more common in women
Intercurrent Disease - Renal and hepatic impairment
Race and Genetic Polymorphisms

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10
Q

Describe type B ADRs

A 
"Bizarre effects",  idiosyncratic and unprediactableBizarre 
Unpredictable 
Rare 
Cause serious illness or death 
Unidentified for months or years 
Unrelated to the dose
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11
Q

What is a exaggerated type A ADR associated with bat blockers?

A

Brachycardia

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12
Q

What is an exaggerated type A ADR associated with sulphonylureas and insulin?

A

Hypoglycaemia

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13
Q

What is a secondary type A ADR associated with sironalactone?

A

Gynaecomastia

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14
Q

What is a secondary type A ADR associated with beta blockers?

A

Bronchospasm

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15
Q

What factors affect absorption and cause pharmacokinetic variation?

A

Dose
Formulation
GI motility
First pass metabolism

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16
Q

What % of the general population are slow acetylators?

A

10%

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17
Q

Describe some diseases that can cause pharmacokinetic variation

A

Renal and hepatic impairment - If a drug is excreted by the kidneys toxic levels may build up

Cardiac Failure - Reduce drug absorption from the gut due to oedema. Poor renal perfusion and decreased GFR. Hepatic congestion

18
Q

What is the main cause of type A ADRs?

A

Pharmacokinetic variation

19
Q

What are some important factors in type B ADRs?

A

More common with macromolecules
- Proteins
- Vaccines
- Polypeptides
Patients with history of asthma, eczema etc.
HLA status
Presence of particular HLA increases risk of a type B reaction

20
Q

Describe a type B ADR caused by pharmacokinetic variation

A

Erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency
Individuals with sex linked inherited deficiency of this enzyme are susceptible to red cell haemolysis when given drugs such as primaquine or sulphonamides

21
Q

What drugs make patients with a certain genetic disorder susceptible to red cell haemolysis?

A

Erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency
Individuals with sex linked inherited deficiency of this enzyme are susceptible to red cell haemolysis when given drugs such as primaquine or sulphonamides

22
Q

Describe a type C ADR

A

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
Iatrogenic Cushings disease from steroid use
Steroid induced osteoporosis
Opiate dependence
Tardive dyskinesia with neuroleptic drugs
NSAIDs causing analgesic nephropathy and duodenal ulcers

23
Q

What is a type C ADR associated with long term steroid use?

A

Cushings syndrome

24
Q

What is a type C ADR associated with steroid use?

A

Osteoporosis

25
Q

What is a type C ADR associated with NSAID use?

A

duodenal ulcers and analgesic nephropathy

26
Q

What is a type D ADR?

A

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.
  • Teratogenesis, secondary cancers, reduced fertility
27
Q

What drug causes type D ADR craniofacial malformations?

A

Isotretanoin

28
Q

What are type E reactions?

A

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

29
Q

What type E reaction is associated with the fast withdrawal of steroids following long term use?

A

Addisonian crisis (adrenal crisis) - severe adrenal deficiency caused by insufficient cortisol levels

30
Q

What type E reaction is associated with the removal of beta blockers?

A

Unstable angina and MI

31
Q

What type E reaction is associated with the withdrawal of anti-epileptics?

A

Seizures

32
Q

What type E reactions are associated with alcohol withdrawal?

A

Seizure activity which can lead to hypoxic damage

33
Q

Which drugs can cause rebound pneumonia on withdrawal?

A

Alcohol
Benzodiazepines
Beta-blockers
Corticosteroid

34
Q

What frequently causes type F failure of treatment ADRs?

A

Drug interactions and dose

35
Q

What risk factors are associated with ADRs?

A 
Age (children and elderly) 
Multiple medications – increases exponentially with each additional drug 
Multiple co-morbid conditions 
Inappropriate medication prescribing, use, or monitoring 
End-organ dysfunction 
Altered physiology 
Prior history of ADRs 
Extent (dose) and duration of exposure 
Genetic predispositio
36
Q

How are ADRs reported?

A

Yellow card system to MHRA

37
Q

What % of inpatients experience ADRs?

A

10-20%

38
Q

What % of hospital deaths are due to ADRs?

A

0.25-3%

39
Q

What is an enzyme abnormality that can cause type B reactions?

A

G6P-dehydrogenase deficiency

40
Q

What is a receptor abnormality that can cause type B reactions?

A

Malignant hyperthermia with general anaesthetics due to mutations in ryanodine receptors

41
Q

Name some teratogenic agents

A 
Cytotoxics
Vitamin A
Antithyroid drugs
Steroids
Oral anticoagulants

Principles of Disease 16 (37 decks)

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