Dx of ADR and Case Studies Flashcards
Causes of ADRs
- Inherent drug characteristics (API, excipients)
- Quality problems (Contamination, substandard, counterfeits)
- Adulteration (potent API/analogues)
- Substitution of Ingredients
- DDI, D-food interactions
- Long term exposure/high dose
- Individual susceptibility
- In-use issues like non-adherence
What are some occurrences that most likely signify a drug association
- SJS
- TEN
- Agranulocytosis
- Acute Dystonias
- DILI (if other causes excluded)
- Cushing’s syndrome (if endogenous causes excluded)
How is ADR diagnosed?
When possible causes are excluded
Distinguish between SJS and TEN
Use percentage epidermal detachment of total BSA
- SJS: <10%
- TEN > 30%
- Transitional SJS-TEN: 10-30%
Most common ADR of drug that causes withdrawal worldwide?
DILI
What do Dx of DILI include (repeated from PV deck)
- Hx of ingestion of drug (incl. CAM) within 12 months of onset of illness
- Exclude viral causes
- Exclude autoimmune
- Daily alcohol intake <20g
- Absence of biliary/focal liver pathology on ultrasound/CT scan of abdomen
Causes of Cushing Syndrome to exclude to confirm drug induced cushing syndrome?
- Adrenal Tumour
- Cushing Disease (too much ACTH)
- Ectopic ACTH-producing tumour (e.g. lung tumour)
- Exogenous source (e.g. unknown injection)
Toxic Heavy Metals Limit for Complementary Medicines
- As 5ppm
- Cd 0.3ppm
- Pb 10ppm
- Hg 0.5ppm
- Cu: Removed from list
What is the MoA of Mercury, and what is its adverse effects?
Inhibits formation of melanin by competing with Cu in action of tyrosinase enzyme. Forms inorganic salts easily absorbed through skin
Adverse effects: Facial burns, skin discolouring, neurotoxicity, renal toxicity
In the case studies for Pan Pharmceuticals what did the assay with the product Travacalm show?
10 fold variation in hyoscine, which can cause serious ADR like delirium
How did Slim10 enter the market?
They showed good batches for approval, then adulterated subsequent batches
What was Slim10 Adulterated with?
- Fenfluramine (trace amts)
- Thyroxine medications (must add thyroid lysing agent before it can be detected)
- Nitrosofenfluramine (Hepatotoxic analogue of fenfluramine)
What kind of Signs and sx manifested in patients who took Slim10?
Hyperthyroidism
What was the adulterant in some aphrodisiacs? (E.g. Power1 walnut, Counterfeit Cialis, etc.), and what was the AE that manifested in patients who took it?
Glibenclamide (about 40-100mg/tab, while therapeutic dose is 2.5-20mg OD)
AE: Neuroglycopenia
What was used as a marker of insulin for patients who presented with Neuroglycopenia after taking adulterated aphrodisiacs?
C-peptide
