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. Long Acting (24 hrs activity)
6.1. Insulin Glargine
7. Biguanides
7.1. Metformin
7.1.1. Use
7.1.1.1. Reduces insulin resistane in Type II
7.1.2. Admin/PK
7.1.2.1. Ineffective in the absense of insulin
7.1.2.1.1. Must take with food
7.1.2.2. Excreted in urine
7.1.2.3. 1/2 life = 2 hrs
7.1.3. Decreases risk of Type II D in pts with insulin resistance
7.1.3.1. Not as effective as lifestyle changes!!!
7.1.4. MOA
7.1.4.1. Improves glucose uptake in M and fat celss
7.1.4.2. Reduces hepatic glucose production - Major Action!!!
7.1.4.3. Ultimately decreases serum insulin and glucose levels
7.1.4.3.1. Decreases both fasting and postprandial hyperglycemia
7.1.5. SE
7.1.5.1. Positives
7.1.5.1.1. No risk of hypoglycemia
7.1.5.1.2. Prevent macrovascular complications
7.1.5.1.3. Decreased TG, total and LDL-C
7.1.5.1.4. Not stimulating any insulin release from pancreas
7.1.5.1.5. Cheap!!!
7.1.5.2. Negative
7.1.5.2.1. NVD (pretty common)
7.1.5.2.2. Metallic taste
7.1.5.2.3. Lactic acidosis (rare)
7.1.6. Decreases VLDL synthesis
7.1.7. CI
7.1.7.1. Pt predisposed to lactic acidosis
7.1.7.1.1. Renal Dz, Hepatic Dz, or alcoholics
7.1.7.1.2. Hx of LA
7.1.7.1.3. Decreased tissue perfusion or hemodynamic instability
7.1.7.1.4. Discontinue prior to
7.2. Weight loss or stabilization
8. Type II Diabetes causes
8.1. Insulin resistance
8.1.1. Failure of liver to decrease glucose production
8.1.2. Impaired glucose uptake in muscle and fat cells
8.1.3. Drugs that work here:
8.1.3.1. Metformin
8.1.3.2. TZDs
8.2. reduced GLP-1
8.2.1. Drugs that work here:
8.2.1.1. Incretins
8.3. Pancreatic Beta cell dysfuntion
8.3.1. reduced insulin secretion
8.3.1.1. Drugs that work here:
8.3.1.1.1. Sulfonylureas
8.3.1.1.2. Meglitinides
8.3.2. Reduced amylin secretion
8.3.2.1. Drugs that work here:
8.3.2.1.1. Pramlintide
9. Glucagon
9.1. Use
9.1.1. Tx hypoglycemia
9.2. MOA
9.2.1. Made by alpha cells in pancreas; stimulate liver into GNG and glycogenolysis
9.3. Admin
9.3.1. SQ injection
10. Insulin
10.1. Rapid Acting (4 hrs activity)
10.1.1. Insulin Lispro
10.2. Short Acting
10.2.1. Regular Humulin R
10.3. Intermediate Acting
10.3.1. NPH Humulin N
10.4. Use
10.4.1. Pt often on > 1 type
10.4.1.1. Ex - 1 LA dose/day for basal levels + RA injection before every meal to handle addition carb load
10.4.2. Insulin pump
10.4.2.1. maintains basal raid + gives a meal bolus
10.4.2.2. Only use RA insulin
10.4.3. Injection
10.5. SE
10.5.1. Lipohypertrophy
10.5.1.1. Occurs when you give the injection in the same spot
10.5.2. Hypoglycemia
10.5.2.1. Sx of activated sympathetics
10.5.2.2. Sx of brain not getting enough glucose
11. alpha-glucosidase inhibitors
11.1. Acarbose
11.2. Miglitol
11.3. MOA
11.3.1. Reversible inhibition of NZ on brush border that breaks down disaccharides into glucose
11.3.1.1. Slows absorption of glucose from gut
11.3.1.1.1. Reduces postprand insulin spike
11.3.1.1.2. No effect on fasting glucose levels
11.4. Use
11.4.1. Type II DM
11.4.2. Reduces risk of Type II DM in pts with impaired glucose tolerance
11.5. SE
11.5.1. Flatulence, bloating, abdominal discomfort
11.5.2. Diarrhea
11.5.3. Elevated liver NZs