Pharmacology of Diabetes

Question 1

What are the 7 steps of pharmacology?

Answer 1

Identify the patients problem
Specify therapeutic objective
Select drug
Discuss choice 
Write a correct prescription
Counsel the patient on appropriate use
Make arrangements for follow up

Question 2

What is the patients problem?

Answer 2

Elevated HbA1c

Hypertensive

Dyslipidaemia (low HDL and high LDL)

Obesity

Overall –> metabolic syndrome

Question 3

What is the therapeutic objective for this patient?

Answer 3

Weight loss

Lower blood glucose to normal range

Manage hypertension to within normal range

Manage lipid profile

Question 4

What would be the first treatment for someone with type 2 diabetes?

Answer 4

In this case you could begin with giving lifestyle advice to see if the diabetes can be controlled without medication

Weight loss can be very impactful in resolving diabetes

Question 5

How does metformin move across membranes?

Answer 5

Cation transporter 1

OCT-1

Question 6

Where is the expression of OCT-1 highest?

Answer 6

Highest in the

Liver hepatocytes
Small intestinal enterocytes
Renal proximal tubules

Question 7

Why is OCT-1 present in the gut?

Answer 7

Enterocytes - Route into bloodstream for metformin
Can access the hepatic portal vein
ABSORPTION

Question 8

Why is OCT-1 present in the liver?

Answer 8

Liver hepatocytes - Acts on the liver to produce effect (lower production of glucose)
DISTRIBUTION

Question 9

Why is OCT-1 present in the renal proximal tubule?

Answer 9

For excretion to prevent drug accumulation

EXCRETION

Question 10

Why is metformin unusual?

Answer 10

Barely metabolised at all
Most drugs the drugs that is excreted is very different to the one that was taken

The liver would want to make a drug more polar so it is easier to excrete but metformin is already highly polar

Question 11

What would you do if after initial metformin treatment no significant improvement has been made?

Answer 11

Ask about lifestyle changes and why she may be struggling to lose weight?

Ask about compliance with medication?

Consider dual therapy of metformin with another drug (first intensification)

Question 12

How would you choose which drug to use for dual therapy?

Answer 12

Not just on mechanism of drug but think about the effects on the PATIENT

Exclude drugs that cause weight gain as the patient is obese

Exclude SGLT-2 as it increases glucose lost in urine - should not be given to someone with recurrent UTIs

Consider cost (DPP-4 inhibitors are 30x more expensive than pioglitazone)

Question 13

What are the side effects of DPP-4 inhibitors?

Answer 13

Upper respiratory tract infections

Question 14

What are the side effects of Pioglitazone?

Answer 14

Increased incidence of heart failure

Question 15

What are the side effects of Sulphonylurea?

Answer 15

Weight gain a likely side effect

Question 16

What are the side effects of SLGT-2 inhibitor?

Answer 16

Urogenital infections due to increased glucose load

Question 17

Where does SGLT-2 inhibitors act?

Answer 17

Sodium glucose co-transporter-2 in the PCT

Question 18

What is the action of SGLT-2 inhibitors?

Answer 18

Decreased glucose reabsorption

Question 19

Where do sulphonylurase work?

Answer 19

ATP sensitive K+ channels on pancreatic beta cells

Question 20

What is the action of sulphonylurase?

Answer 20

Insulin secretion

Question 21

Where is the action of DPP-4 inhibitors?

Answer 21

Dipeptidyl peptidase 4 on the vascular endothelium

Question 22

What is the action of DPP-4 inhibitors?

Answer 22

Increased plasma incretin levels

Question 23

Where does Metformin act?

Answer 23

AMP activated protein kinase in the hepatocyte mitochondria

Question 24

What is the mechanism of action of Metformin?

Answer 24

Decreased gluconeogenesis