Pharmacovigilance 3 Flashcards
What are some causes of adverse drug reactions?
- Inherent Drug Characteristics
- Active ingredients
- Excipients, formulation - Quality Problems
- Contamination with toxic heavy metals
- Counterfeits, substandard products - Adulteration
- with potent medicinal ingredients, analogs of potent medicinal ingredients - Substitution of ingredients
- Drug-drug interactions, drug-food interactions
- Long term exposure; high doses
- Individual susceptibility
- e.g. HLA-B 1501 allele predisposes to severe skin reactions with carbamazepine
- HLA-B5801 allele predisposes to allopurinol induced serious cutaneous adverse reactions (SCAR) - In-use issues
Occurrences that most likely signify a drug association
- SJS
- TEN
- Agranulocytosis
- Acute dystonias
- Drug-induced liver injury (if confounders properly excluded)
- Cushing’s syndrome (if endogeneous causes excluded)
A diagnosis of ADR is arrived after excluding all possible causes.
SJS / TEN characteristics and presentation
- Most serious form of adverse skin reactions
- Essentially drug-induced, esp for TEN
- Other causes are infections (e.g.viral, bacterial, fungal)
- Mortality rates are close to half for TEN
Presentation:
- Severe mucosal erosions (eyes, oropharynx, genitalia, anus)
- Widespread erythematous macules
- Epidermal detachment
SJS: < 10% epidermal detachment of total BSA
TEN: > 30% epidermal detachment
Transitional SJS-TEN: 10-30% epidermal detachment
Diagnosis of Drug-Induced Liver Toxicity
- History of ingestion of drugs, including complementary medicines, within 12 months of onset of illness :
- Exclusion of viral serology e.g. anti-HAV IgM, anti-HCV IgM
- -vemetabolic screen (autoimmune disorders or diseases that causes liver injury) e.g. Antinuclear Antibody Test (ANA), ceruloplasmin, antimitochondrialantibody (AMA)
- Daily alcohol intake < 20 g
- Absence of biliary or focal liver pathology on ultrasound or CT scan of abdomen
What are the main clinical symptoms of cushing syndrome?
- Weight gain, increased appetite, insomnia can occur quite quickly
- ‘Cushing’ appearance takes weeks to months to develop (moon face, buffalo hump, truncal weight gain, thinning of skin, purplish striae)
What are the possible causes of cushing syndrome?
- Adrenal Tumour
- Cushing Disease –pituitary tumour(too much ACTH), common cause
- Ectopic ACTH-producing Tumoureglung tumour
- Exogenous Source
- most common cause
Pharmacovigilance on COVID-19 vaccine Anaphylaxis:
- prevalence
- demographics of local cases
- 0.86 per 100,000 administered doses
- predominantly female, 42 years old, with past history of allergies, on their first dose.
Vaccine recipients should be observed for at least _______ after vaccination for sign of allergic reactions.
30 minutes
Toxic heavy metal permissible limits for complementary medicines
Arsenic - 5ppm
Cadmium - 0.3ppm
Lead - 10ppm
Mercury - 0.5ppm
Mercury poisoning
- MOA
- Clinical symptoms
MOA:
- Inhibits formation of melanin by competing with copper in the action of the enzyme tyrosinase
Symptoms:
- Facial burns, skin discolouring, neurological toxicities, kidney toxicity
Complementary health products that cause ADRs
A. Virility products
- Sildenafil, vardenafil, tadalafil and their analogues are modified in a way to escape detection.
B. Anti-inflammatory products
- Dexamethasone, NSAIDs
C. Slimming Products
- Sibutramine and its analogues
Illegal aphrodisiacs abnormal lab findings and treatment
Lab findings:
- reduced blood sugar (hypoglycaemia)
- increased plasma insulin levels
- increased serum C-peptide levels
Treatment:
- Dextrose 10% infusion 2h - 126h
What are insulinomas and their diagnosis?
- beta- cells secrete insulin in response to increase in blood sugar –> lower blood sugar to normal
- Tumour of pancreas increases excessive amts of insulin
- Secretion of insulin by insulinomas not properly regulated by glucose and tumours continue to secrete insulin causing glucose levels decrease further than normal
Diagnosis:
- hypoglycaemia
- increased insulin, proinsulin and C-peptide levels
- tumour localised with abdominal imaging (either CT abdomen or MRI pancreas)
Findings for commonly added ingredient glibenclamide
- illegal doses were twice as high as the maximum dose
- resulted in: dangerously low blood sugar, recurring for days, dizziness, cold sweat, loss of consciousness, coma, death
Future challenges
- Opportunities in Genomic Era
- Emergence of Complementary Medicines
- Registries for Biological Products and Gene Therapy
- Forging Closer Ties with International Counterparts
- MaximisingIT Tools for Signal Detection & Communication
