Block 9 Drugs - Insulin and Oral Hypoglycemics

Question 1

Insulin - standard crystalline insulin

Answer 1

MOA: Binds InsR

Recruits glucose transporters to PM to stimulate glucose uptake into cells

USE: Treatment of Type 1 & 2 diabetes to maintain normoglycemia

S/E: Hypoglycemia

Unique: Administered from 30-45 min prior to meal time

Question 2

Lispro insulin

Answer 2

MOA: Rapid acting insulin preparation

USE: Treatement of Type 1 diabetes/hyperglycemia

S/E: Hypoglycemia

Unique: Administered from 0-15 min prior to meal time

Question 3

Insulin aspart

Answer 3

MOA: Rapid acting insulin preparation

USE: Treatment of Type 1 diabetes/hyperglycemia

S/E: hypoglycemia

Question 4

NPH insulin

Answer 4

MOA: Slow release at SQ injection depot

Forms a microprecipitate

(Intermediate-acting insulin)

USE: Neutral protamine Hagedom (NPH)/Isophane insulin

S/E: Hypoglycemia

CI: SubQ injection only

Unique: Peak action of 6-12 hours; duration of 18-24 hours

Question 5

Glargine insulin

Lantus®, Toujeo®

Answer 5

MOA: Structurally modified insulin prep with low solubility at neutral pH

Slow release, long-acting

USE: Type 1 diabetes as a basal, once daily injection

S/E: Hypoglycemia

Unique: Due to low pH of solution it causes injection site pain

Question 6

Detemir insulin

Levemir®

Answer 6

MOA: Fatty acid acylated insulin at Lys29 causing slow absorption from sc space

USE: Type 1 diabetes as a basal, once daily injection

Neutral pH

S/E: Hypoglycemia

Unique: Less weight gain in type 2 patients than NPH-insulin

Question 7

Degludec insulin

Tresiba®

Answer 7

MOA: Fatty acid acylated insulin at Lys29 with a linker, causing slow absorption from sc space

USE: Type 1 diabetes as a basal, once daily injection

Neutral pH

S/E: Less potential for hypoglycemia

CI: Ultra-long lasting

Unique: Linker addition enables formation of multi-hexamers to prolong effects

Question 8

Octreotide

Sandostatin®

Answer 8

MOA: Activates somatostatin receptors blocking voltage-gated Ca²⁺ channels

Somatostatin Analog

USE: Acromegaly - inhibits GH secretion

Pancreatic islets inhibits insulin and glucagon secretion

S/E: GI effects: diarrhea, constipation, gas, nausea

Unique: Used to treat diarrhea caused by carcinoid tumors

Question 9

Tolbutamide

Answer 9

MOA: Insulin secretagogue

Activates sulfonylurea-R

Oral Hypoglycemic

USE: Hyperglycemia in Type 2 diabetes

S/E: Hypoglycemia

Skin sensitization

Cardivasc mortality

CI: Avoid alcohol

Unique:

1^st gen sulfonylurea - lower potency and greater toxicity than 2^nd gen - rarely prescribed

Question 10

Glipizide

Answer 10

MOA: Insulin secretagogue

Activates sulfonylureaR

Oral hypoglycemic

USE: Hyperglycemia in Type 2 diabetes

S/E: Hypoglycemia

Skin rash

Weight gain

CI: Avoid alcohol

Unique: 2^nd generation sulfonylurea; admin 30 min before meal

Question 11

Glimepride

Answer 11

MOA: Insulin secretagogue

Activates sulfonylurea-R

Oral Hypoglycemic

USE: Hyperglycemia in Type 2 diabetes

S/E: Hypoglycemia

Skin rash

Weight gain

CI: Avoid alcohol

Unique: 2^nd generation sulfonylurea; admin. 30 min before meal

Question 12

Repaglinide

Answer 12

MOA: Meglitinide

Insulin secretagogue

Closes ATP-dependent K⁺ channels

USE: Hyperglycemia of Type 2 diabetes

S/E: Less weight gain than sulfonylureas

CI: Gemfibrozil, clarithromycin, ketoconazole

MAOIs prolong hypoglycemic effect due to CYPC28 & CYP3A4 interactions

Unique: Fast acting, short duration; admin 30 min prior up to meal

Question 13

Metformin

Answer 13

MOA: Biguanide

Multiple MOA’s - increases target cell sensitivity to insulin and glucose uptake

USE: Type 2 diabetes

Useful in patients with refractory obesity

S/E: GI distrubances

CI: Avoid in renal or hepatic impairment

Lactic Acidosis

Alcohol Abuse

CHF

Unique: No significant hypoglycemia (non-insulinotropic); Reduces cardiac risk factors

Question 14

Exenatide

Byetta®

Answer 14

MOA: GLP-1 agonist

Exendin-4

Protease-resistant; increases insulin, decreased glucagon secretion; slows gastric emptying

Synthetic Incretin

USE: Type 2 diabetes glycemic control

S/E: GI disturbances

Hypoglycemia when co-admin. w/ sulfonylurea

Question 15

Sitagliptin

Januvia ®

Answer 15

MOA: Dipeptidyl peptidase-4 (DPP-4) inhibitor

USE: Type 2 diabetes

Elevates GLP-1 and GIP levels

S/E: Respiratory infection

Cold symptoms

Headache

CI: Increase cancer growth (?)

Unique: Available in combination with metformin

Question 16

Acarbose

Precose ®

Answer 16

MOA: α-glucosidase inhibitor

dose-dependent delay or inhibition of carbohydrate absorption

Intestinal disacch inhibitor

USE: Type 2 diabetes

S/E: GI disturbances, diarrhea, stomach discomfort

Question 17

Canagliflozin

Invokana ®

Answer 17

MOA: Sodium0glucose co-transporter-2 (SGLT2) inhibitor

Blocks proximal tubule filtered glucose reabsorption

USE: Type 2 diabetes

S/E: UTI

Hypoglycemia when co-admin with insulin or insulin secretagogue

Weight loss

Dehydration

Hypotension

CI: Should not be used inpatients with renal disease

Hypoglycemia when used with insulin secretagogue

Question 18

Pioglitazone

Actos®

Answer 18

MOA: Thiazolidinedione

Activates PPAR-γ

Reduces insulin resistance - lowers blood glucose by improving target cell response to insulin

USE: Type 2 diabetes - blood sugar control

Only effective in presence of insulin (endogenous)

CI: Hepatotoxic

Broken bones

CHF/MI warnings

Macular edema

Should NOT be taken with CYP2C8 inhibitors

Unique: Long term use linked to bladder cancer

Question 19

Diazoxide

Proglycem®

Answer 19

MOA: Prevents closing of ATP-sensitive K⁺ channels

Hyperpolarizing cells and inhibiting insulin secretion

Hyperglycemia agent

USE: Hyperinsulinemic hypoglycemia caused by inoperable islet adenoma or carcinoma

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI)

S/E: Non-ketotic hyperosmolar coma

CI: Heart failure due to fluid retention

Caution with gouty patients

May cause abnormal facial features in children with >4 yrs treatment

Unique: Has an effect opposite to that of sulfonylureas