Endocrine Pharm

Question 1

What is insulin?

Answer 1

• Hormone synthesized by beta cells of pancreas within islets of langerhans
• Proinsulin = insulin precursor

Question 2

Categories of insulin

Answer 2

1. Rapid Acting
2. Short Acting
3. Intermediate Duration
4. Long Duration

Question 3

Rapid Acting Insulin

Answer 3

• Lispro
• Onset 10-20 minutes
• Give if incredibly hyperglycemic
• Need to take RIGHT before eating (tray is in the room)
• Peaks in 30 min - 2.5 hours and lasts 3-6 hours
• Varies based on absorption because given SC
• Commonly used with meals

Question 4

Short Acting Insulin

Answer 4

• Regular insulin
• Onset 30-60 min
• Peak 1-5 hours
• Lasts 6-10 hours
• Should take with meals but not as quickly as rapid acting
• Also helps with hyperkalemia

Question 5

Intermediate Duration Insulin

Answer 5

• NPH
• Works in 1-2 hours
• Peaks 6-14 hours
• Lasts 16-24 hours
• Mimic what pancreas would be doing constantly

Question 6

Long Duration Insulin

Answer 6

• Glargine
• No peak
• Mimic what pancreas would be doing constantly
• Steady
• Works in 70 minutes
• Lasts 24 hours
• Nice because don’t have to take so many times each day

Question 7

What is a common insulin regimen?

Answer 7

Intermediate/long acting and rapid/short acting around meal times

Question 8

Mixing Insulins

Answer 8

• Often use short acting and longer acting simultaneously
• NPH is compatible with regular, lisper, apart, glulisine
• Draw up short acting first

Question 9

Administration of Insulin

Answer 9

• SC injections:

- Syringe and needle, pen injectors, jet injectors, subcutaneous pumps

Question 10

Side effects of insulin

Answer 10

• Hypoglycemia
• Hypokalemia
• Allergic rxn: irritation around injection site

Question 11

Treatment of Hypoglycemia

Answer 11

• IV: Dextrose 50% injection

- IM: Glucagon breaks down glycogen to glucose, works in 10-15 min

Question 12

Metformin (Biguanide)

Answer 12

• Often initial drug of choice for Type 2 DM
• MOA: inhibits glucose production in liver, reduces glucose absorption in gut, sensitizes insulin receptors in target tissues
• DOES NOT STIMULATE INSULIN RELEASE (would not cause hypoglycemia)
• Slowly absorbed from small intestines
• Excreted unchanged in kidneys
• Most common side effects: GI (decreased appetite, n and d)
• Start with low dose and titrate to tolerate effects
• 3-5% of patients will stop using bc GI effects

Question 13

Toxicity and Cautions of Metformin

Answer 13

• Inhibit mitochondrial oxidation of lactic acid = can lead to lacticacidosis (rare but life threatening)
• Caution in patients with poor renal function bc increased risk of lacticacidosis
• Contraindicated within 48 hours of IV contrast admin

Question 14

Sulfonylureas

Answer 14

• First oral anti diabetic available
• MOA: stimulate release of insulin from pancreatic islets (will not work if pancreas doesn’t work)
• Can be used in combination with metformin

Question 15

2 Generations of Sulfonylureas

Answer 15

• First gen: uncommon, not seen anymore

- Second gen: Glipizide = immediate and sustained release

Question 16

AE of Sulfonylureas

Answer 16

• Hypoglycemia: because causes release of insulin from pancreas
• Really eliminated: can be a problem if we have a kidney problem
• Reduce dose in elderly
• Avoid in pregnancy: can cause hypoglycemia in fetus upon birth

Question 17

Thiazolidinediones

Answer 17

• MOA: reduces insulin resistance and decreases glucose production by activating PPAR gamma enzyme
• Usually used in combination with other agents
• Prototype: Pioglitazone

Question 18

Pioglitazone

Answer 18

• Metabolism: CYP2C8 = drug interactions
• AE: most common are resp tract infection, headache, sinusitis, myalgia
• Most important AE: fluid retention (worry about this in heart failure), hypoglycemia

Question 19

Meglitinides

Answer 19

• MOA: stimulate insulin release
• Prototype: Repaglinide
• If don’t respond to sulfonylurea then won’t respond to this
• Metabolized by liver with VERY short half life (important because must give frequently)
• AE: hypoglycemia
• Rapidly absorbed from GI tract so have to eat within 30 minutes

Question 20

Incretin Hormes

Answer 20

• Glucagon-like peptide-1 (GLP-1) and GIP
• Secreted following meal ingestion
• DPP-4 enzyme inactivates GLP-1 and GIP
• GLP-1 and GIP facilitate release of insulin from B cell in pancreas and prevent glucagon release from liver

Question 21

Gliptins: DPP-4 Inhibitors

Answer 21

• Cause GLP-1 and GIP to go to pancreas
• Stimulate insulin release and block glucagon release
• Prototype: Sitagliptin
• AE: Upper resp infection, headache, inflammation in nose and throat
• Serious AE: Hypoglycemia, pancreatitis, hypersensitivity reactions (anaphylaxis and SJS)

Question 22

Incretin Mimetics

Answer 22

• Prototype: Liraglutide
• MOA: analog of human GLP-1 that causes direct activation of GLP-1 Receptors
• Can be used alone or with other things (watch with sulfonylurea to avoid hypoglycemia)
• Administered via SQ injection
• AE: dose-related GI effects and rare cases of pancreatitis