Chempath MedGems

Question 1

Name a drug used in the treatment of non-acute gout to reduce urate levels by increasing the fractional excretion of uric acid?

Answer 1

Probenecid

Question 2

What is the mechanism of colchicine?

Answer 2

Inhibits polymerisation of tubulin to reduce migration of neutrophils

Question 3

What is the mechanism of allopurinol?

Answer 3

Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid

Question 4

How is the anion gap calculated?

Answer 4

(Na + K) - (Cl + HCO3)

Normally 14-18mmol/L

Question 5

What are the causes of a raised anion gap?

Answer 5

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]

Question 6

What are the causes of a normal aniona gap with metabolic acidosis?

Answer 6

• Addison’s disease
• Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis)
• Chloride gain (Sodium Chloride 0.9% infusion)
• Drugs (acetazolamide)

Question 7

What condition describes inadequate function of the proximal renal tubules of the kidney and is associated with glucosuria, hypophosphatemia and hyperuricosuria?

Answer 7

Fanconi syndrome

Question 8

What is Fanconi syndrome?

Answer 8

An inherited or acquired condition where there is almost complete failure of the proximal convoluted tubule in the kidney to reabsorb molecules

Question 9

What are the classic causes?

Answer 9

• 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

Question 10

In bile acid synthesis Acyl-CoA cholesterol acyltransferase (ACAT) is the enzyme that converts cholesterol into what?

Answer 10

Cholesterol ester

Question 11

What is the most potent pharmacological agent at reducing low density lipoprotein concentration in blood?

Answer 11

Evolocumab
(PCKS9 inhibitor)

Question 12

Lomitapide is a low density lipoprotein lowering drug.

What protein does Lomitapide inhibit?

Answer 12

Microsomal triglyceride transfer protein

(lowers VLDLs which in turn lowers LDLs)

Question 13

The van den Bergh reaction is used to measure serum bilirubin via fractionation. What kind of bilirubin is measured with the direct reaction?

Answer 13

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.

Question 14

What is the eponymous name for psuedohypoparathyroidism?

Answer 14

Albright hereditary osteodystrophy

Question 15

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?

Answer 15

Salicylates

Question 16

What are the sx of salicyclates overdose?

Answer 16

nausea and vomiting, dizziness and ringing in the ears.

Severe poisoning characteristically causes a respiratory alkalosis with metabolic acidosis.

Question 17

Why do salicyclates cause respiratory alkalosis?

Answer 17

Salicylates stimulate the respiratory centre causing hyperventilation and inhibit the Krebs cycle resulting in anaerobic metabolism

Question 18

In de novo purine synthesis, what kind of feedback do guanylic acid (GMP) and adenylic acid (AMP) have on the enzyme PAT?

Answer 18

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.

Question 19

What are the LFTs in gilbert’s syndrome?

Answer 19

Autosomal dominant

• Raised unconjugated bilirubin
• Normal LFTs

Question 20

What are the LFTs in NAFLD?

Answer 20

Raised AST and ALT (AST:ALT <1) and increased GGT

Normal bilirubin and albumin

Question 21

What are the LFTs in paracetamol poisoning?

Answer 21

• AST and ALT >1000 IU/L
• AST and ALT > GGT and ALP

Question 22

What are the LFTs in alcohol abuse?

Answer 22

• Isolated rise in GGT
• Mild elevations in AST and ALT

Question 23

What (other than alcohol abuse) can cause isolated raised GGT?

Answer 23

Enzyme-inducing drugs:
- Phenytoin
- Carbamazepine
- Phenobarbitone

Question 24

What is Dublin-Johnson syndrome?

Answer 24

Autosomal recessive

• Raised conjugated bilirubin (reduced conjugated bilirubin secretion into the bile)
• AST and ALT normal

Question 25

What is Crigler-Najjar syndrome?

Answer 25

Complete (type 1) or partial (type 2) reduction in UDP glucuronosyl transferase –> unconjucated hyperbilirubinaemia

Question 26

What are the three stages of alcoholic liver disease?

Answer 26

1. Alcoholic statosis
2. Alcoholic hepatitis
3. Alcholic cirrhosis

GGT, AST and ALT will be elevated (AST:ALT >=2:1)