LEC 9 Pharmacovigilance lll

Question 1

Causes of ADR (8)

Answer 1

1. Inherent drug characteristics
2. Quality problems
   - counterfeits
   - contamination with THM
3. Adulteration
   - with potent medicinal ingredients or their analogues
4. Substitution of ingredients
5. DDI & FDI
6. Long term exposure / high dose
7. Individual susceptibility
   - genetics
8. In-use issues
   - ReNu lens solution

Question 2

Reactions that most likely signify a drug association (6)

Answer 2

• SJS
• TEN
• agranulocytosis
• acute dystonias
• drug induced liver injury
• cushing syndrome

Question 3

SJS causes

Answer 3

• drug induced

- infections

Question 4

Liver toxicity causes (4)

Answer 4

• viral diseases
• drug induced liver toxicity (DILI)
• autoimmune disorders
• daily alcohol intake >20g

Question 5

DILI

Answer 5

Drug Induced Liver Injury

Question 6

Diagnosis of DILI (5)

Answer 6

1. Exclude viral serology
   eg anti-HAV lgM, anti-HCV lgM
2. Negative metabolic screen
   - autoimmune disease
3. Daily alcohol intake <20g
4. Absence of biliary or focal liver pathology on U/S or CT scan of abdomen
5. History of ingestion of drugs / CPM within 12months of onset

Question 7

Cushing Syndrome

Answer 7

Hormonal disorder resulting from long term exposure of high doses of steroids

• weight gain
• insomnia
• increased BP & blood glucose
• decreased immunity
• bone loss
• cataracts
• cushing appearance

Question 8

Cushing appearance (5)

Answer 8

• moon face
• buffalo hump
• truncal weight gain
• skin thinning
• purplish striae

Question 9

Causes of Cushing syndrome (4)

Answer 9

1. Adrenal tumours
2. Cushing disease (pituitary tumour)
   - common cause
3. Ectopic ACTH-producing tumour
   eg lung tumour
4. Exogeneous source
   eg drugs
   - MOST common cause

Question 10

Pharmacovigilance of COVID-19 vaccination

Answer 10

• anaphylaxis

- median time for onset of anaphylaxis is 30min

Question 11

Why cannot observe patients receiving COVID-19 vaccination for 20min only instead of 30min?

Answer 11

• anaphylaxis occurs after 20min for all age group except 60-69y/o (meaning 60-69y/o median time for anaphylaxis is less than 20min)
• a reduction from 30min to 20min would result in only 1/3 of anaphylaxis cases being detected instead of 2/3 (30min)

Question 12

THM

Answer 12

Toxic Heavy Metals

• lead
• arsenic
• mercury
• cadmium

Question 13

THM contamination limits for complementary medicines

Answer 13

1. Lead 10ppm
2. Arsenic 5ppm
3. Mercury 0.5ppm
4. Cadmium 0.3ppm

LAMC

Question 14

Lead poisoning signs & symptoms (4)

Answer 14

• anemia with basophilic stippling (red spots on RBC)
• burton’s line (black gum line)
• abdominal pain
• elevated blood lead levels

Question 15

Mercury poisoning signs & symptoms (4)

Answer 15

Inhibit formation of melanin by competing with copper on tyrosinase

• facial burns
• skin discoloration
• neurological toxicities
• kidney toxicities

Question 16

Complementary Health Products prone to adulterations (3)

Answer 16

1. Virility products
   - sildenafil
   - vardenafil
   - tadalafil
   - gibenclamide
2. Slimming products
   - sibutramine
3. Anti-inflammatory products
   - dexamethasone
   - NSAIDs

Question 17

Illegal aphrodisiacs

Answer 17

Adulterated products to treat sexual dysfunction

Question 18

Signs & symptoms of hypoglycemia (7)

Answer 18

• dizziness
• cold sweat
• loss of consciousness
• increased plasma insulin
• increased serum C-peptide
• decreased blood sugar level
• elevated blood/urine level of gibenclamide & its metabolites

Question 19

Cause of insulinomas (1)

Answer 19

Pancreatic tumours
- insulin secretion not properly regulated by glucose but the tumours secrete excessive insulin, resulting in glucose levels to decrease further

Question 20

Relationship between proinsulin, insulin & C-peptides (3)

Answer 20

Proinsulin = Insulin + C-peptides

• cleavage of proinsulin produce insulin & C-peptides which are stored in beta cells
• when insulin is required, insulin & C-peptides are released into bloodstream in equal amounts
• hence C-peptides is useful as a marker of insulin

Question 21

Complications of hypoglycemia

Answer 21

• coma

- death

Question 22

Future of pharmacovigilance (5)

Answer 22

1. Opportunities in genomic era
2. Emergence of Complementary Medicines
3. Registries for biological products & gene therapy
4. Forging closer ties with international counterparts
   - international data for pharmacovigilance
5. Maximising IT tools for signal detection & communication

Question 23

Examples of Quality Problems leading to ADR (2)

Answer 23

1. Counterfeit products
   - Eyemo
2. Contaminated products with THM
   - Endopile (indian traditional medicine)

Question 24

Examples of Adulterated products leading to ADR (3)

Answer 24

1. Illegal aphrodisiacs
   - gibenclamide
   - sildenafil
   - vardenafil
   - tadalafil
2. Slimming products
   - sibutramine
3. Anti-inflammatory products
   - dexamethasone
   - NSAIDs

Question 25

Example of In-use Issues leading to ADR (1)

Answer 25

ReNu contact lens solution

Question 26

In-use Issues (4)

Answer 26

- GMP compliance - passed product testings - no counterfeit products - problem arise due to poor patient hygiene/habits which reduces margin of efficacy

Question 27

Anaphylaxis definition

Answer 27

- rare but potentially life-threatening systemic hypersensitivity reaction

Question 28

SJS / TEN presentation (3)

Answer 28

- severe mucosal erosions - epidermal detachment - widespread erythematous macules

Question 29

Can you get anaphylaxis on 2nd dose even though 1st dose don't have?

Answer 29

Yes, it is possible

Question 30

Reporting of ADE relating to CPM

Answer 30

- include batch number as mostly are due to batch issues

Question 31

Example of substitution of products (1)

Answer 31

- Travacalm by Pan Pharmaceuticals with hyoscine

Question 32

Why companies use analogues of therapeutic compounds in adulterated products?

Answer 32

- to avoid lab detections as their structures are slightly different

Question 33

Causes of hypoglycemia (3)

Answer 33

- insulinomas (pancreatic tumours) - drug-induced hypoglycemia - autoimmune insulin syndrome

Question 34

Diagnosis of illegal aphrodisiacs containing hypoglycemic agents (5)

Answer 34

- normal imaging of pancreas (rule out insulinomas) - blood glucose level low - high blood levels of insulin, C-peptide - blood/urine tests positive for gibenclamide - sampled drug tests positive for gibenclamide