Antidiabetic Drugs 2

Question 1

This drug is effective at reducing fasting plasma glucose and HbA1c

Answer 1

Sulfonylureas

Question 2

This drug stimulates insulin release from B cells: bind to the SUR1 subunit and block the ATP-sensitive K+ channel in the beta cell membrane.

Answer 2

Sulfonylurea

Question 3

Adverse effects of sulfonylureas

Answer 3

• Hypoglycemia

* Weight gain

Question 4

First-generation Sulfonylureas

Answer 4

Chlorpropamide

Question 5

• Longhalf-life.
• Hypoglycemia is common, particularly in elderly patients. Contraindicated in elderly patients.
• Hyperemic flush when alcohol is ingested. Mainly due to inhibition of aldehyde dehydrogenase.

Answer 5

Chlorpropamide

Question 6

____________may potentiate action of vasopressin and elicit an apparent syndrome of inappropriate secretion of ADH (SIADH).

Answer 6

Chlorpropamide

Question 7

Second-generation Sulfonylureas

Answer 7

➢**Glyburide (Glibenclamide)
• Causes hypoglycemia in 20-30% of users.
➢ Glipizide
• Short half-life. Less likely to get cause hypoglycaemia.
• Causes hypoglycemia in 10-15% of users.
➢ Glimepiride
• Approved for once-daily use.
• Causes hypoglycemia in 9-14% of users. Approved for once- daily use.

Question 8

Adverse effects of Second-generation Sulfonylureas

Answer 8

• Hypoglycemia

* Weight gain

Question 9

Insulin Secretagogues: Meglitinides

Answer 9

➢ Repaglinide
• Causes Hypoglycemia
➢ Nateglinide
• Less risk of hypoglycemia.

Question 10

Function and details of meglitinides

Answer 10

• Stimulates insulin release by binding to SUR1 and inhibiting ATP-sensitive K+ channel.
• Not as effective as sulfonylureas in reducing FPG and HbA1C levels.
• In contrast with sulfonylureas, the meglitinides have a rapid onset and short duration of action.
• Are postprandial glucose regulators.
• Must be taken before each meal; if the meal is missed the drug must be omitted.

No sulfur

Question 11

Adverse effects of meglitinides

Answer 11

Weight gain

Hypoglycemia

Question 12

Reduces glucose levels by inhibiting gluconeogenesis; does not cause insulin secretion
Inhibits gluconeogenesis by reducing gene expression of gluconeogenesis enzymes
• At the molecular level, these actions are mediated at least in part by activation of AMP-activated protein kinase (AMPK).

Answer 12

Biguanides - metformin

Question 13

AE OF METFORMIN

Answer 13

• Largely GI : anorexia, nausea, vomiting, abdominal discomfort, diarrhea.
• Long term use may interfere with B12 absorption.
• Small risk of potentially fatal lactic acidosis.
• Contraindicated in patients with renal disease, hepatic disease, hypoxia, or alcoholism.

Question 14

First line in type 2 DM

Answer 14

Metformin

Question 15

• MOA : involves gene regulation
• decrease insulin resistance.
• slow onset and offset
• Less effective than sulfonylureas and Metformin in decreasing FPG and HbA1C levels.

Answer 15

Thiazolidinediones (TZDs)

Question 16

• Decrease insulin resistance.
• Agonists of peroxisome proliferator-
activated receptor- gamma

Answer 16

TZDs-
Pioglitazone
Rosiglitazone

Question 17

The effects on lipids are more favorable and associated with significant improvements in: HDL, TG, LDL particle concentration, and LDL particle size.

Answer 17

Pioglitazone

Question 18

AE OF TZD

Answer 18

• Fluid retention, weight gain and edema.

* Contraindicated in patients with Class III or IV heart failure

Question 19

Why does the FDA require monitoring of liver function with TZD therapy?

Answer 19

Troglitazone was the first thiazolidinedione to be approved. It caused severe hepatic toxicity and was withdrawn.

Question 20

MOA of Acarbose

Answer 20

Reduces post prandial digestion of starch and disaccharides by deferring absorption to distal SI
- decreased postprandial hyperglycemia
• Evokes modest drop in HbA1C and FPG levels.

Question 21

AE of acarbose

Answer 21

• Flatulence,diarrhea,abdominalpain.
• Contraindicated in IBS or any intestinal condition worsened by gas
and distension.
• Acarbose is associated with reversible hepatic enzyme elevation.
• Periodical liver function monitoring is required with acarbose therapy.

Question 22

• Competitive inhibitor of intestinal a-glucosidases
• Blocks SGLT
• blocks cleaving preventing rise in glucose levels

Answer 22

Acarbose

Question 23

• Injectable
• Analog of glucagon-like-polypeptide 1 (GLP-1).
• Derived from the salivary gland of the Gila monster.
• FullagonistathumanGLP-1receptors.
• Resistant to dipeptidyl peptidase IV (DPP-IV).

Answer 23

Incretin Analogs

➢Exenatide

Question 24

MOA of exenatide

Answer 24

• Enhances glucose-dependent insulin secretion.
• Suppresses postprandial glucagon release.
• Slows gastric emptying.
• Decreases appetite.
• May stimulate β-cell proliferation