1. Sulfonylureas
1.1. Glimepiride
1.2. Glipizide
1.3. Glyburide
1.4. MOA
1.4.1. Antagonized K channel on pancreatic beta cell
1.4.1.1. Cause cell depolarization and allows efflux of Ca
1.4.1.1.1. Increased insulin release
1.4.2. Increases AMOUNT, not FREQUENCY of pulsatilue release of insulin
1.4.2.1. No effect on basal insulin levels!
1.4.3. Minor effect: Subsequently decreases glucagon release (b/c of increased insulin release)
1.4.3.1. Possibly enhance by increased release of SMSTN w/ insulin
1.5. Use
1.5.1. Type II DM
1.5.2. Take 1/day
1.6. SE
1.6.1. Hypoglycemia
1.6.1.1. Both basal and postprandial
1.6.2. Weight gain
1.6.2.1. d/t high insulin levels
1.6.3. NV
1.6.4. Allergic skin rxns
1.6.5. Cholestatic jaundice
1.6.6. TCP, leukopenia, hemolytic anemia
1.6.7. Hyponatremia and SIADH
2. Meglitinides
2.1. Repaglinide
2.2. Nateglinide
2.3. MOA
2.3.1. Similar to Sulfonylreas
2.3.1.1. binds different site on the K channel
2.4. PK
2.4.1. Fast onset of action (15-30 min)
2.4.2. Short duration of action
2.4.2.1. Repa>Nate
2.4.3. Take before meal to control postprandial glycemia
2.5. Use
2.5.1. Type II DM
2.6. SE
2.6.1. Hypoglycemia
3. Thiazolidinediones (TZDs)
3.1. Pioglitazone
3.2. Rosiglitazone
3.3. MOA
3.3.1. Stimulate PPAR-gamma (intracellular receptor that increases transcription of GLUT-4)
3.3.1.1. Found in fat and some muscle tissue
3.3.2. Increases glucose uptake in M and fat tissue
3.3.3. Decreased levels of free TGs
3.3.4. Inhibit GNG
3.4. Use
3.4.1. Type II D
3.4.2. Taken one/day, with food
3.4.2.1. Requires presence of insulin to work
3.4.2.1.1. GLUT-4 is an insulin sensitive receptor
3.5. SE
3.5.1. Weight gain
3.5.1.1. PPAR activation
3.5.1.1.1. collecting tubules
3.5.1.1.2. Differentiation of pre-adipocytes into mature adipose cells
3.5.2. Fluid retention
3.5.2.1. CI in pts with > Stage III CHF or acutely decompensated
3.5.3. Bone fracture
3.5.3.1. PPAR activated diverts stromal cells from osteoblasts to adipocyte lineage
3.5.3.1.1. fat deposition in bone
3.5.4. Anemia
3.5.5. Hepatotoxicity
3.5.6. Increased risk of CV events
4. Amylin analog
4.1. Primlintide
4.2. Use
4.2.1. Type I & II DM who inject insulin at meal times
4.2.2. SQ injection
4.3. MOA
4.3.1. Released w/ insulin from beta cells
4.3.1.1. Increases satiety
4.3.1.2. Delays gastric emptying
4.3.1.3. Inhibits glucagon release
4.3.2. Reduces postprandial glucose spike
4.4. SE
4.4.1. NVA
4.4.2. Headache
4.4.3. Hypoglycemia when combined w/ insulin
5. Incretin (GLP-1) mimetics
5.1. GLP-1 agonist
5.1.1. Exanatide
5.1.2. Liraglutide
5.1.3. Admin - SQ injection
5.1.4. SE
5.1.4.1. Hypoglycemia
5.1.4.2. Pruritis, urtecaria, rash
5.1.4.3. Acute pancreatitis
5.1.4.4. Lira ONLY - risk of thyroid Ca
5.1.4.4.1. Black box warning!!!
5.2. DPP-IV inhibitors
5.2.1. Sitagliptin
5.2.2. Saxagliptin
5.2.3. Admin - oral
5.2.4. SE
5.2.4.1. Hypoglycemia
5.2.4.2. Allergic rxns
5.2.4.2.1. Stevens-Johnson Syndrome
5.2.4.2.2. angioedema
5.2.4.2.3. anaphyllaxis
5.3. MOA
5.3.1. GLP-1 is secreted by L-cells in ileum
5.3.1.1. Slows gastric emptying in stomach
5.3.1.1.1. Reduces postprandial spike in blood glucose levels
5.3.1.2. Promotes sense of satiety in brain
5.3.1.3. Increases glu-stimulated insulin and decreases glucagon secretion in pancreas
5.3.1.3.1. If target glu-stimulated insulin release, less chance of hypoglycemia
5.3.2. DPP-IV is the NZ that metabolizes GLP-1
5.3.2.1. GLP-1 1/2 life in circulation = 1-2 minutes
5.4. Use
5.4.1. Type II DM
6. Not stimulating any insulin release from pancreas
7. No effect on fasting glucose levels
8. maintains basal raid + gives a meal bolus
9. Biguanides
9.1. Metformin
9.1.1. Use
9.1.1.1. Reduces insulin resistane in Type II
9.1.1.2. Decreases risk of Type II D in pts with insulin resistance
9.1.1.2.1. Not as effective as lifestyle changes!!!
9.1.2. Admin/PK
9.1.2.1. Ineffective in the absense of insulin
9.1.2.1.1. Must take with food
9.1.2.2. Excreted in urine
9.1.2.3. 1/2 life = 2 hrs
9.1.3. MOA
9.1.3.1. Improves glucose uptake in M and fat celss
9.1.3.2. Reduces hepatic glucose production - Major Action!!!
9.1.3.3. Ultimately decreases serum insulin and glucose levels
9.1.3.3.1. Decreases both fasting and postprandial hyperglycemia
9.1.4. SE
9.1.4.1. Positives
9.1.4.1.1. No risk of hypoglycemia
9.1.4.1.2. Weight loss or stabilization
9.1.4.1.3. Prevent macrovascular complications
9.1.4.1.4. Decreased TG, total and LDL-C
9.1.4.1.5. Cheap!!!
9.1.4.2. Negative
9.1.4.2.1. NVD (pretty common)
9.1.4.2.2. Metallic taste
9.1.4.2.3. Lactic acidosis (rare)
9.1.5. CI
9.1.5.1. Pt predisposed to lactic acidosis
9.1.5.1.1. Renal Dz, Hepatic Dz, or alcoholics
9.1.5.1.2. Hx of LA
9.1.5.1.3. Decreased tissue perfusion or hemodynamic instability
9.1.5.1.4. Discontinue prior to
10. Type II Diabetes causes
10.1. Insulin resistance
10.1.1. Failure of liver to decrease glucose production
10.1.2. Impaired glucose uptake in muscle and fat cells
10.1.3. Drugs that work here:
10.1.3.1. Metformin
10.1.3.2. TZDs
10.2. reduced GLP-1
10.2.1. Drugs that work here:
10.2.1.1. Incretins
10.3. Pancreatic Beta cell dysfuntion
10.3.1. reduced insulin secretion
10.3.1.1. Drugs that work here:
10.3.1.1.1. Sulfonylureas
10.3.1.1.2. Meglitinides
10.3.2. Reduced amylin secretion
10.3.2.1. Drugs that work here:
10.3.2.1.1. Pramlintide
11. Glucagon
11.1. Use
11.1.1. Tx hypoglycemia
11.2. MOA
11.2.1. Made by alpha cells in pancreas; stimulate liver into GNG and glycogenolysis
11.3. Admin
11.3.1. SQ injection
12. Insulin
12.1. Rapid Acting (4 hrs activity)
12.1.1. Insulin Lispro
12.2. Short Acting
12.2.1. Regular Humulin R
12.3. Intermediate Acting
12.3.1. NPH Humulin N
12.4. Long Acting (24 hrs activity)
12.4.1. Insulin Glargine
12.5. Use
12.5.1. Pt often on > 1 type
12.5.1.1. Ex - 1 LA dose/day for basal levels + RA injection before every meal to handle addition carb load
12.5.2. Insulin pump
12.5.2.1. Only use RA insulin
12.5.3. Injection
12.6. SE
12.6.1. Lipohypertrophy
12.6.1.1. Occurs when you give the injection in the same spot
12.6.2. Hypoglycemia
12.6.2.1. Sx of activated sympathetics
12.6.2.2. Sx of brain not getting enough glucose
13. alpha-glucosidase inhibitors
13.1. Acarbose
13.2. Miglitol
13.3. MOA
13.3.1. Reversible inhibition of NZ on brush border that breaks down disaccharides into glucose
13.3.1.1. Slows absorption of glucose from gut
13.3.1.1.1. Reduces postprand insulin spike
13.4. Use
13.4.1. Type II DM
13.4.2. Reduces risk of Type II DM in pts with impaired glucose tolerance
13.5. SE
13.5.1. Flatulence, bloating, abdominal discomfort
13.5.2. Diarrhea
13.5.3. Elevated liver NZs