10 - Adverse Drug Reaction

Question 0

56) The difference between ADR and side effect?

Answer 0

ADR is always unpleasant or unwanted

Side effect may be beneficial as well as harmful

• Sildenafil (viagra) originally developed to treat angina
• Promethazine (for cold, flu, cough) is the first generation of anti histamine

Question 1

55) What is adverse drug reaction (ADR)?

Answer 1

A response to a drug which is noxious and unintended, an which occurs at doses normally used.

Question 2

57) ADRs can occurs at:

Answer 2

• Supratherapeutic doses
• Standard therapeutic doses
• Subtherapeutic doses (susceptible patients)

Question 3

58) Contributing factors to ADR development:

Answer 3

1. Underlying susceptibility (genetics, physiological)
2. Drug interactions
3. Toxic effect not detected in animal studies

Question 4

59) Types of ADR

Answer 4

1. Direct toxicity
2. Secondary or alternative drug effect
3. Chronic treatment effects
4. Delayed effects
5. End of treatment effects
6. Failure of therapy effects
7. Type B reactions “bizarre”

Question 5

60) Features of direct toxicity type of ADR

Answer 5

1. Dose-related
2. Highly predictable
3. Highly reversible when dose is reduced
4. Sometimes irreversible e.g. drug dependence (opiates)

Question 6

61) Example of direct toxicity type of ADR

Answer 6

1. Warfarin (anticoagulant) -> bleeding/hemorrhage
2. A1-adrenoreceptor antagonist (for hypotension) -> Hypertension
3. Anxiolytics (antianxiety) -> sedation

Question 7

62) Features of secondary or alternative drug effects

Answer 7

• Overdose

- Patient susceptibility for an ADR

Question 8

63) Examples of secondary or alternative drug effect

Answer 8

1. Opiates (analgesics) -> resp. depression, vomiting
2. Aspirin (mild analgesic) -> bleeding
3. Paracetamol (mild analgesic) -> hepatotoxicity
4. Phenytoin (antiepileptic) -> gingival hyperplasia

Question 9

64) Examples of chronic treatment effects (type of ADR):

Answer 9

1. Anti psychotic drugs -> Tardive dyskinesia

2. Glucocorticoid therapy -> Osteoporosis

Question 10

65) Examples of delayed effects (type of ADR):

Answer 10

1. Halothane (anesthetics), flucloxacillin (antibiotic) -> severe liver failure
2. NSAIDs, sulphonamides, penicillin -> skin eruption
3. Drug-induced cancers -> skin cancers and lymphomas following application of tacrolimus (imunosuppressant)

Question 11

66) Example of end of treatment effects (withdrawal syndrome) (type of ADR):

Answer 11

After stopping paroxetine (antidepressant)

1. Headache
2. Anxiety
3. Dizziness
4. Sleep disturbances
5. Gastrointestinal disturbance

Question 12

67) Features of type B reactions

Answer 12

1. Uncommon
2. Occur at normal therapeutic doses
3. Very serious outcomes
4. Closely related to underlying susceptibility
5. Only detected after widespread use of a drug
6. Low incidence, no clear dose-relationship

Question 13

68) Example of type B reactions (type of ADR)

Answer 13

1. Chloramphenicol -> aplastic anaemia

2. Penicillin -> anaphylactic shock

Question 14

69) Stevens-Johnson Syndrome (SJS)…

Answer 14

• Disorder of the immune system
• Can be triggered by infections or drugs
• In some group, drug reaction may be aggravated by genetic factors

Question 15

70) What are the non covalent interactions in necrosis or apoptosis.

Answer 15

1. Reaction between ROS and damage lipid membranes
2. Depletion of glutathione (GSH)
3. Modification of sulphydryl groups (-SH) on enzymes

Question 16

71) Why does liver is vulnerable to ADR (hepatotoxicity)?

Answer 16

Abundance of CYP450 enzyme -> more vulnerable to toxic metabolites they produce

Question 17

72) Why does kidney is vulnerable to ADR (nephrotoxicity) ?

Answer 17

Drugs more concentrated in renal tubular fluid vs plasma -> toxic susceptibility

Question 18

73) Substances that could cause teratogenicity and fetal damage to the embryo/foetus especially when taken during the first trimester of pregnancy

Answer 18

1. Anticonvulsants
2. Vitamin A analogues
3. Alcohol