Diabetes Case Drugs

Question 1

Metformin

Answer 1

Biguanide antihyperglycaemic agent

MOA-
- Inhibits mitochondrial complex 1 in liver
- Preventing mitochondrial ATP synthesis and therefore, promoting AMPK activation
- AMPK phosphorylates acetyl CoA
- Promotes hepatic fat oxidation: Reduced hepatic fat store increases liver sensitivity to glucose, Increases anaerobic glucose metabolism in enterocytes (gut) -> increased net glucose uptake, Increases glucose uptake and utilisation in skeletal muscle

Dosage-
500mg three times a day with a meal, max 2g a day

Side effects-
- GI bloating
- Decreased appetite and weight loss
- Lactic acidosis (rare but caution in renal + hepatic disease patients) due to reduced drug elimination - inhibition of gluconeogenesis by blocking pyruvate carboxylase, the first step of gluconeogenesis
- Long term use may interfere with vitamin B12 absorption

Question 2

Atorvastatin

Answer 2

HMG-CoA reductase inhibitor

MOA-
- Inhibits HMG-CoA reductase in hepatocytes which catalyses conversion of HMG-CoA to mevalonic acid which is needed in cholesterol, LDL and VLDL production
- Inhibits production of cholesterol in the liver by up-regulating hepatic LDL receptors to increase hepatic uptake of LDL
- Lower abnormal cholesterol and triglycerides levels, increases HDL cholesterol conc
- This decreases the amount of plaque deposited on arterial walls

Use-
- Reduce levels of LDL and VLDL - ‘bad’ cholesterol in the blood to protect endothelial lining in arteries (prescribed to reduce cardiovascular risk)

Dosage-
- Usual dose 10 mg once daily; increased if necessary up to 80 mg once daily

Side effects-
- Myopathy (rare)
- GI discomfort, constipation, diarrhea, vomiting, nausea
- Headaches