Chempath MedGems Flashcards
Name a drug used in the treatment of non-acute gout to reduce urate levels by increasing the fractional excretion of uric acid?
Probenecid
What is the mechanism of colchicine?
Inhibits polymerisation of tubulin to reduce migration of neutrophils
What is the mechanism of allopurinol?
Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid
How is the anion gap calculated?
(Na + K) - (Cl + HCO3)
Normally 14-18mmol/L
What are the causes of a raised anion gap?
GOLDMARK
- G: Glycols (ethylene glycol and propylene glycol) [overdose]
- O: Oxoproline [chronic paracetamol use, usually malnourished women]
- L: L-lactate [sepsis]
- D: D-lactate [short bowel syndrome]
- M: Methanol [overdose]
- A: Aspirin [overdose. Initially causes respiratory alkalosis but in moderate/severe overdose causes metabolic acidosis]
- R: Renal failure
- K: Ketoacidosis [DKA, alcoholic, starvation]
What are the causes of a normal aniona gap with metabolic acidosis?
- Addison’s disease
- Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis)
- Chloride gain (Sodium Chloride 0.9% infusion)
- Drugs (acetazolamide)
What condition describes inadequate function of the proximal renal tubules of the kidney and is associated with glucosuria, hypophosphatemia and hyperuricosuria?
Fanconi syndrome
What is Fanconi syndrome?
An inherited or acquired condition where there is almost complete failure of the proximal convoluted tubule in the kidney to reabsorb molecules
What are the classic causes?
- Congenital
- Wilson’s disease (To be even more unhelpful, Wilson’s is also associated with Type 1 Renal Tubular Acidosis)
- Tetracyclines
- Multiple Myeloma
- Lead poisoning
In bile acid synthesis Acyl-CoA cholesterol acyltransferase (ACAT) is the enzyme that converts cholesterol into what?
Cholesterol ester
What is the most potent pharmacological agent at reducing low density lipoprotein concentration in blood?
Evolocumab
(PCKS9 inhibitor)
Lomitapide is a low density lipoprotein lowering drug.
What protein does Lomitapide inhibit?
Microsomal triglyceride transfer protein
(lowers VLDLs which in turn lowers LDLs)
The van den Bergh reaction is used to measure serum bilirubin via fractionation. What kind of bilirubin is measured with the direct reaction?
The direct reaction measures conjugated bilirubin whereas a complete reaction measures total bilirubin.
The indirect reaction refers to the difference between these two and measures unconjugated bilirubin.
What is the eponymous name for psuedohypoparathyroidism?
Albright hereditary osteodystrophy
A 21 year old woman with Borderline Personality Disorder presents to A&E after taking an overdose of medication. Her blood gas shows a metabolic acidosis with respiratory alkalosis. She refuses to tell you what she has taken but does say she has ringing in her ears. What has she most likely overdosed on?
Salicylates
What are the sx of salicyclates overdose?
nausea and vomiting, dizziness and ringing in the ears.
Severe poisoning characteristically causes a respiratory alkalosis with metabolic acidosis.
Why do salicyclates cause respiratory alkalosis?
Salicylates stimulate the respiratory centre causing hyperventilation and inhibit the Krebs cycle resulting in anaerobic metabolism
In de novo purine synthesis, what kind of feedback do guanylic acid (GMP) and adenylic acid (AMP) have on the enzyme PAT?
Negative
Phosphoribosyl pyrophosphate amidotransferase (PAT) is the enzyme responsible for the conversion of PRPP into PRA. This is the rate limiting step in the de novo synthesis of purines. Guanylic acid (GMP) and adenylic acid (AMP) exert negative feedback on PAT.
What are the LFTs in gilbert’s syndrome?
Autosomal dominant
- Raised unconjugated bilirubin
- Normal LFTs
What are the LFTs in NAFLD?
Raised AST and ALT (AST:ALT <1) and increased GGT
Normal bilirubin and albumin
What are the LFTs in paracetamol poisoning?
- AST and ALT >1000 IU/L
- AST and ALT > GGT and ALP
What are the LFTs in alcohol abuse?
- Isolated rise in GGT
- Mild elevations in AST and ALT
What (other than alcohol abuse) can cause isolated raised GGT?
Enzyme-inducing drugs:
- Phenytoin
- Carbamazepine
- Phenobarbitone
What is Dublin-Johnson syndrome?
Autosomal recessive
- Raised conjugated bilirubin (reduced conjugated bilirubin secretion into the bile)
- AST and ALT normal
What is Crigler-Najjar syndrome?
Complete (type 1) or partial (type 2) reduction in UDP glucuronosyl transferase –> unconjucated hyperbilirubinaemia
What are the three stages of alcoholic liver disease?
- Alcoholic statosis
- Alcoholic hepatitis
- Alcholic cirrhosis
GGT, AST and ALT will be elevated (AST:ALT >=2:1)
