Pharmacology of Diabetes

Question 1

Patient has T2DM, is hypertensive, overweight and has dyslipidemia. What is the therapeutic objective?

Answer 1

lower glucose
lower BP
weight loss
improve lipid profile

Question 2

What is the first line drug for T2DM?

Answer 2

metformin

Question 3

How do you think the molecular structure of metformin would influence it’s absorption into the blood and distribution to body tissues?

Answer 3

Molecule is charged/highly polar, doesn’t move readily across membranes, poorly absorbed

Question 4

The expression of the organic cation transporter 1 (OCT-1) is highest in tissues: Liver hepatocytes (highest expression), the small intestinal enterocytes and the renal proximal tubules. Why do you think this is relevant to the pharmacokinetics of orally administered metformin?

Answer 4

A lot of glucose is produced in the liver/can get into hepatic portal vein, drug is absorbed from small intestine, metformin can be excreted at renal proximal tubules

Question 5

Why do you think renal impairment could cause problems for diabetic patients on metformin?

Answer 5

Metformin is always in active form and not metabolised in the body, if not excreted, could cause metformin overdose

Question 6

What is the biggest problem with adherence to metformin?

Answer 6

GI side effect profile

Question 7

What practical things could you recommend to a patient struggling to tolerate GI side effects of metformin?

Answer 7

taking it after not before food or could switch to a better tolerated preparation. Sustained release metformin is absorbed slowly so there are fewer GI side effects