Chapter 39 (PART 2) : Pancreatic hormones and antidiabetic drugs

What type of diabetes are oral antidiabetic drugs used for?

type 2 diabetes (B cells work but receptors don’t)

When are oral antidiabetics approved for treatment?

when diet and exercise have not achieved target glycemic control

True or False:

Oral antidiabetic drugs can wither be used as a monotherapy or concurrently with other antidiabetic drugs, including insulin

True

What class of oral hypoglycemic drugs is being described:

enter or act on beta cells and cause the release of insulin (increase release of insulin and amylin)

secretagogues

True or False:

Secretagogues should be used in type 1 diabetes

False, it should not

What do sulfonylureas do?

stimulate insulin release → reduce fasting plasma glucose

ex. Glipizide (Glucotrol)

What do non-sulfonylureas (aka. meglitinides) do?

• stimulate insulin secretion

• quicker onset of action than sulfonylureas

• bind to SUR receptors and do the same thing but different chemical structure

ex. Repaglinide (Prandin)

True or False:

Secretagogues are contraindicated in type 1 diabetes, patients with liver or kidney disease, and pregnancy

True

True or False:

Glucose absorption inhibitors alter insulin secretion and blood glucose levels.

False, they do not alter insulin secretion or blood glucose levels.

What is the MOA of glucose absorption inhibitors?

• interrupt carb digestion from diet (inhibit key enzymes → glycoside hydrolase)

• glucose absorption delayed or less but not eliminated

• keep blood glucose levels from peaking after meals

• for type 1 or type 2

Ex. Miglitol (Glyset)

What drugs are being described:

antihyperglycemic drugs that keep blood glucose levels from rising too fast

biguanides

What is the MOA of biguanides?

• decrease blood glucose levels after meals by decreasing liver glucose production and intestinal glucose absorption

• also appears to enhance glucose use by other tissues in the body

• mainly for type 2

When are biguanides contraindicated?

alcohol use increases the action of biguanides on lactic acid metabolism (more lactic acid made)

What is the MOA of insulin sensitizers?

• enhance peripheral cell response to insulin (thus mainly for type 2)

• allow glucose to be used more efficiently (can bind better)

• decrease insulin resistance and increase insulin sensitivity of fat, skeletal muscle, and liver cells (activate nuclear receptors inside cells that regulate insulin activity)

• leads to decreased circulating levels of glucose

Ex. Pioglitazone (Actos)

When are insulin sensitizers contraindicated?

in patients with CHF (congestive heart failure)

What does the gut hormone GLP-1 do?

stimulates the release of insulin from B cells

What enzyme metabolizes the gut hormone GLP-1?

dipeptidyl peptidase-4 (DPP-4)

What is the MOA of DPP-4 inhibitors?

inhibits DPP-4 in the intestine causing:

• stimulation of insulin secretion

• decreased glucagon secretion

What is the MOA of SGLT-2 inhibitors?

acts at kidneys; inhibition of glucose reabsorption in the nephron, leaving excess glucose in urine to be excreted → decreasing blood glucose levels

• used in type 1

Ex. Canagliflozin (Invokana)

What are SGLT-1 and SGLT-2 ?

glucose transporters