Repro-Endo: Pancreas

Question 1

Insulin

Answer 1

• Self-administered Subcu / IV (emergency)
• Supplies Insulin for DM-1 or resistance DM-2, DKA
• Leading to decreased Plasma Glucose
• Tx: DM-1, DM-2, DKA, Insulin comes in Short, Intermediate, and Long-acting forms
• SE: Hypoglycemia, Hypokalemia (K⁺ shift into intracellular compartment)

Question 2

Ultrashort-acting Insulin Drugs?

Answer 2

• Bind Insulin receptor (Tyrosine Kinase Activity)
• Onset: 20 minutes
• Duration: 4 hours
• Tx: DM1, DM2, GDM (post-prandial glucose ctrl)
• Synthetic Insulin - Lysine and Proline at end of β-chain
• Does not dimerize upon injection –> 30 min. prior food
• SE: Hypoglycemia, Rare Hypersensitivity rxn
• Lispro
• Aspart
• Glulisine

Question 3

Rapid Acting Insulin Drug?

Answer 3

• Onset: 1 hour
• Duration: 6 - 8 hours
• Tx: DM1, DM2, GDM, DKA (IV), Hyperkalemia (+ glucose) and Stress Hyperglycemia
• Does Not dimerize upon SubQ inj.–> 30 delay
• Regular Insulin
• Only type of Insulin given IV

Question 4

Intermediate-acting Insulin Drugs?

Answer 4

• Onset: 2 - 4 hours
• Duration: 10 - 18 hours
• Tx: DM1, DM2, GDM
• Insulin and Zinc to react w/ Protamine (basic protein)
• -> Protamine-Insulin-Zinc
• -> Slow Release
• NPH (Neutral Protamine Hagedorn)
• Lente
• Most widely used type of Insulin

Question 5

Long-acting Insulin Drugs?

Answer 5

• Tx: DM1, DM2, GDM
• Glargine: 12 hours –> 24 hours
• Protamine Zinc: 14 - 24 hours –> 36 hours
• 3 Amino acid difference (2 Arg & Asp)
• Glargine (soluble in the vial pH 4.0 to precipitate upon injection (at neutral pH)
• Ultralente: 18 - 24 hours –> 36 hours
• Detemir (Levemir)
• Establishes Basal Insulin Level

Question 6

Sulfonylureas

Answer 6

• Closes K+ channels on β-cells and K+ efflux
• -> Leading to Depolarization
• -> Ca²⁺ influx –> Insulin Release
• -> Decreased Glucagon release from α-cells and **Increased tissue sensitivity to Insulin
• -> Increased Glucose Uptake (peripheral)**
• Tx: DM-2 (reqs. 30% B-cell function)
• 1st Gen: Tolbutamide
• 2nd Gen: Glyburide, Glipizide
• SE: Risk of Hypoglycemia a/w Renal Failure, Weight gain, IV hypersensitivity rxn, Hypoglycemia w/ Cimetidine, Insulin Salicylates, Sulfonamides

Question 7

Biguanides

(Metformin)

Answer 7

• Inhibit Gluconeogenesis in Liver
• Decrease Hepatic Glucose production (Liver)
• Inscrease Peripheral Insulin sensitivity
• Mechanism unknown
• Decrease Postprandial glucose levels w/out weight gain or Hypoglycemia (euglycemic)
• Tx: Obese diabetic, synergistic w/ Sulfonylureas in pts. w/ Renal failure, Can be used in Pts. w/out Islet function
• Contraindicated in Pts. w/ Renal Impairment
• SE: Lactic acidosis (rare), GI distress, avoid IV contrast

Question 8

α-glucosidase inhibitors

(Acarbose, Miglitol)

Answer 8

• α-glycosidase inhibitor
• -> Decreased carbohydrate absorption from GI tract
• -> inhibits Sucrose –> Glucose
• *–> Decreased Insulin demand**
• -> Delayed sugar hydrolysis and glucose absorption
• -> Decreased Postprandial Hyperglycemia
• Tx: DM-2
• SE: Hypoglycemic –> Glucose tablets or Food intake
• SE: GI disturbances: Flatulence, Diarrhea, Abdominal Discomfort

Question 9

Glitazones / Thiazolidinediones

(Rosiglitazone, Pioglitazone)

Answer 9

• **Decreases Insulin resistance
• -> Enhances Efficacy of Insulin in the Liver, Muscle, Fat**
• Binds nuclear Peroxisome Proliferator-activated Receptor (PPARγ) to control Transcritpion of Insulin-responsive genes
• -> Insulin sensitization and decreased Hepatic gluconeogenesis and **Insulin receptor upregulation
• -> Translocation of Glucose Transporter in Muscle and Adipose tissue**
• Tx: DM-2 in the Absence of Liver Disease, CHF or Coronary artery disease
• SE: Weight gain, Edema (peripheral or macular), Liver function abnormalities

Question 10

Repaglinide

Answer 10

• Oral Hypoglycemic
• Works like Sulfonylureas by stimulating release of Insulin from the Pancreas
• Tx: DM-2
• SE: Hypoglycemia, Weight gain

Question 11

First generation Sulfonylureas Drugs and SEs?

Answer 11

• Tolbutamide
• Chlorpropamide
• SE 1st Gen: Disulfiram-like effects

Question 12

2nd Generation Sulfonylureas Drugs and SEs?

Answer 12

• Glyburide
• Glimepiride
• Glipizide
• SE 2nd Gen: Hypoglycemia

Question 13

Glitazone / Thiazolidinediones Drugs?

Answer 13

• Pioglitazone
• Rosiglitazone

Question 14

α-glucosidase inhibitor drugs?

Answer 14

• Acarbose
• Miglitol

Question 15

Amylin analogs?

Answer 15

• Pramlintide
• Decrease Gastric emptying
• Decrease Glucagon
• Tx: DM1, DM2
• SE: Hypoglycemia, Nausea, Diarrhea

Question 16

GLP-1 analogs?

Answer 16

• Exenatide
• Liraglutide
• Increased Insulin
• Decreased Glucagon release
• Tx: DM2
• SE: Nausea, Vomiting, Pancreatitis

Question 17

DPP-4 inhibitors?

Answer 17

• Linagliptin
• Saxagliptin
• Sitagliptin
• Increased Insulin
• Decreased Glucagon release
• Tx: DM2
• SE: Mild urinary or Respiratory Infections

Question 18

Sitagliptin phosphate?

(DPP-4)

Answer 18

• Orally active inhibitor of the ‘Dipeptidyl peptidase-4’ (DPP-4) enzyme, the enzyme that breaks down Endogenous **Glucagon-like peptide-1 (GLP-1)
• ->**Increase of Endogenous GLP-1
• -> Stimulates Insulin release and Inhibits Glucagon release
• Sitagliptin amplifies the action of GLP-1
• Saxagliptin is a new version that acts the same way

Question 19

SGLT2 Inhibitor

(Canagliflozin)

Answer 19

• SGLT2 (Sodium-glucose cotransporter 2) inhibitor
• -> reduces the reabsorption of Glucose in the Proximal tubule
• -> Loss of Glucsoe and Water in Urine
• SE: Genital mycotic infections (men and women), UTIs, Diuretic effects