LEC 9 Pharmacovigilance lll Flashcards
Causes of ADR (8)
- Inherent drug characteristics
- Quality problems
- counterfeits
- contamination with THM - Adulteration
- with potent medicinal ingredients or their analogues - Substitution of ingredients
- DDI & FDI
- Long term exposure / high dose
- Individual susceptibility
- genetics - In-use issues
- ReNu lens solution
Reactions that most likely signify a drug association (6)
- SJS
- TEN
- agranulocytosis
- acute dystonias
- drug induced liver injury
- cushing syndrome
SJS causes
- drug induced
- infections
Liver toxicity causes (4)
- viral diseases
- drug induced liver toxicity (DILI)
- autoimmune disorders
- daily alcohol intake >20g
DILI
Drug Induced Liver Injury
Diagnosis of DILI (5)
- Exclude viral serology
eg anti-HAV lgM, anti-HCV lgM - Negative metabolic screen
- autoimmune disease - Daily alcohol intake <20g
- Absence of biliary or focal liver pathology on U/S or CT scan of abdomen
- History of ingestion of drugs / CPM within 12months of onset
Cushing Syndrome
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
Cushing appearance (5)
- moon face
- buffalo hump
- truncal weight gain
- skin thinning
- purplish striae
Causes of Cushing syndrome (4)
- Adrenal tumours
- Cushing disease (pituitary tumour)
- common cause - Ectopic ACTH-producing tumour
eg lung tumour - Exogeneous source
eg drugs
- MOST common cause
Pharmacovigilance of COVID-19 vaccination
- anaphylaxis
- median time for onset of anaphylaxis is 30min
Why cannot observe patients receiving COVID-19 vaccination for 20min only instead of 30min?
- 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)
THM
Toxic Heavy Metals
- lead
- arsenic
- mercury
- cadmium
THM contamination limits for complementary medicines
- Lead 10ppm
- Arsenic 5ppm
- Mercury 0.5ppm
- Cadmium 0.3ppm
LAMC
Lead poisoning signs & symptoms (4)
- anemia with basophilic stippling (red spots on RBC)
- burton’s line (black gum line)
- abdominal pain
- elevated blood lead levels
Mercury poisoning signs & symptoms (4)
Inhibit formation of melanin by competing with copper on tyrosinase
- facial burns
- skin discoloration
- neurological toxicities
- kidney toxicities
Complementary Health Products prone to adulterations (3)
- Virility products
- sildenafil
- vardenafil
- tadalafil
- gibenclamide - Slimming products
- sibutramine - Anti-inflammatory products
- dexamethasone
- NSAIDs
Illegal aphrodisiacs
Adulterated products to treat sexual dysfunction
Signs & symptoms of hypoglycemia (7)
- 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
Cause of insulinomas (1)
Pancreatic tumours
- insulin secretion not properly regulated by glucose but the tumours secrete excessive insulin, resulting in glucose levels to decrease further
Relationship between proinsulin, insulin & C-peptides (3)
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
Complications of hypoglycemia
- coma
- death
Future of pharmacovigilance (5)
- Opportunities in genomic era
- Emergence of Complementary Medicines
- Registries for biological products & gene therapy
- Forging closer ties with international counterparts
- international data for pharmacovigilance - Maximising IT tools for signal detection & communication
Examples of Quality Problems leading to ADR (2)
- Counterfeit products
- Eyemo - Contaminated products with THM
- Endopile (indian traditional medicine)
Examples of Adulterated products leading to ADR (3)
- Illegal aphrodisiacs
- gibenclamide
- sildenafil
- vardenafil
- tadalafil - Slimming products
- sibutramine - Anti-inflammatory products
- dexamethasone
- NSAIDs
Example of In-use Issues leading to ADR (1)
ReNu contact lens solution
In-use Issues (4)
- GMP compliance
- passed product testings
- no counterfeit products
- problem arise due to poor patient hygiene/habits which reduces margin of efficacy
Anaphylaxis definition
- rare but potentially life-threatening systemic hypersensitivity reaction
SJS / TEN presentation (3)
- severe mucosal erosions
- epidermal detachment
- widespread erythematous macules
Can you get anaphylaxis on 2nd dose even though 1st dose don’t have?
Yes, it is possible
Reporting of ADE relating to CPM
- include batch number as mostly are due to batch issues
Example of substitution of products (1)
- Travacalm by Pan Pharmaceuticals with hyoscine
Why companies use analogues of therapeutic compounds in adulterated products?
- to avoid lab detections as their structures are slightly different
Causes of hypoglycemia (3)
- insulinomas (pancreatic tumours)
- drug-induced hypoglycemia
- autoimmune insulin syndrome
Diagnosis of illegal aphrodisiacs containing hypoglycemic agents (5)
- 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
