Diabetes Flashcards
What are the diagnostic criteria for Diabetes (3)? Or..?
Fasting plasma glucose >/= 126
2 hr plasma glucose >/= 200
HbA1c >/= 6.5%
…or random plasma glucose >200 and symptoms of hyperglycemia
Differences between Type I and Type II?
insulin-dependent, juvenile onset, 10%, prone to ketoacidosis, HLA association, obesity uncommon (Type I). BOTH cause vascular complications
What does insulin cause in liver/skeletal muscle?
absorption of glucose-> storage as glycogen
What does insulin cause fat cells to do?
absorption of lipids-> storage as trigylcerides
How does insulin work (4)?
1) insulin binds to alpha subunits of the insulin receptor
2) this stimulates the tyrosine kinase activity of the beta subunits.
3) glucose transport proteins are then activated and translocated from the cytoplasms to the cell membrane
4) this stimulates glucose entry into the cell
What is the long-acting insulin preparation?
Glargine
What is the intermediate-acting insulin prep?
NPH
What are the short-acting insulin preparations (3)?
Aspart, Lispro, Regular (slightly later onset and longer-acting than the other two)
How can insulin be delivered?
syringes, refillable/prefilled pens, insulin pumps
What are the complications of insulin preparations (4)?
hypoglycemia (relieved by glucose), ketoacidosis, insulin allergy, lipodystrophy at injection site
What are the main pathophysiological defects in Type II DM that lead to hyperglycemia (6)?
-decreased peripheral glucose uptake
-increased hepatic glucose production
-increased pancreatic glucagon secretion
-decreased pancreatic insulin secretion
-decreased incretin effect—^
+gut carbohydrate delivery and absorption
What is the Sulphonylurea (SFU) to know?
Glyburide (2nd generation)
How do the SFUs (Glyburide) work (3)?
1) induce insulin release from pancreas (closing K+-ATP channels)
2) reduce serum glucagon levels
3) potentiate action of insulin on its target tissues
What are the adverse drug reactions of SFUs (Glyburide) (5)?
severe hypoglycemia, weight gain, nausea, vomiting, hypersensitivity reactions
What are the indications for SFUs (Glyburide)?
T2D patients failed to achieve glycemic control with diet and life-style modifications; may be used in patients with kidney disease
What is the first choice therapy for Type II DM?
Metformin
What type of drug is Metformin?
Biguanide
What is Metformin’s mode of action (3)?
1) decreases hepatic glucose production
2) increases insulin action on peripheral muscle and fat tissues
3) non-insulin-dependent effects, no effect on release of GH or glucagon
What’s the significance of non-insulin-dependent effects of Metformin?
no hypoglycemia and no weight gain!
What are the adverse drug reactions of Metformin?
nausea, diarrhea
What are the contraindications for Metformin (5+)?
contraindicated in patients with renal impairment, hepatic diseases, heart problems, acidosis, blood infection, etc.
What are the Thiazolidinediones (TZDs)?
Rosiglitazone, Pioglitazone
What is the mode of action of TZDs (3)?
1) agonists for nuclear peroxisome proliferator-activated receptor-y and activate insulin responsive genes that regulate carbohydrate and lipid metabolism
2) promote glucose uptake to muscles/fat and decrease hepatic glucose production
3) require insulin presence for action
What are the adverse drug reactions of TZDs (3) and specific notes about two drugs?
- 1st year liver function monitoring, edema and weight gain
- Rosiglitazone: FDA restricted access, risk of heart attack/MI
- Pioglitazone: common usage in the US
What are indications for TZDs?
good for overweight/obese patients
What is an additional consideration for TZDs?
slow onset to affect blood glucose
What is the alpha-Glucosidase inhibitor?
Acarbose
What is the mode of action of a-Glucosidase inhibitors (Acarbose) (2)?
delays carbohydrate digestion and slows glucose absorption in the gut. no effect on insulin release
What are the adverse drug reactions of Acarbose (5)?
dose-related malabsorption, flatulence, nausea, diarrhea, no weight gain!
What are the two main gut incretins and what do they do?
- GIP: glucose-dependent insulinotropic polypeptide
- GLP-1: glucagon-like peptide-1; post-meal level diminished in T2D patients
- Incretin, GLP-1 stimulates insulin release and inhibits glucagon release—>lowering of blood glucose
What is the GLP-1 analog or “incretin mimetic”?
Exenatide
Which enzyme inactivates/degrades GLP-1 incretin?
DPP-4
Which drug is the DPP-4 inhibitor and how is it administered? What does it do?
Sitagliptin, oral, blocks DPP-4–>stops degradation of GLP-1and therefore decreases glucose
What is the mode of action of Exenatide (5)?
1) induces insulin release (glucose-dependent)
2) reduces post-meal glucagon and hence hepatic glucose production
3) slows stomach emptying
4) promotes satiety and inhibits appetite
5) preserves beta cell mass
How is Exenatide administered?
injected twice daily 1 hr pre-meal or extended release once weekly
What are the adverse drug reactions to Exenatide?
nausea, vomiting, headache
Who should not be given Exenatide?
avoid in patients with severe kidney and GI problems
What is the mode of action of Sitagliptin)?
inhibits degradation of incretins thus increasing GLP-1.
How is Sitagliptin administered?
orally (once daily)
What are the adverse drug reactions of Sitagliptin?
headache, risk of infections
Who should you cautiously use Sitagliptin with?
caution in kidney problems and potential contraindications
What does a coleopterist study?
beetles (wow, cool)
What is the proposed treatment algorithm for type II DM?
non-pharm therapy (diet, weight loss, exercise)->monotherapy (Metformin)->glycemic goals not acheived->combo therapy (SFU+metformin or SFU+TZD)->metformin+TZD+?->glycemic goals not achieved->insulin
What are the drugs to know (11)?
- Insulin preps: Lispro/Aspart, NPH, regular, Glargine
- Anti-diabetics: Glyburide (SFUs), Metformin (Biguanides), Pioglitazone/Rosiglitazone (TZDs), Acarbose (a-glucosidase inhibitors), Exenatide (GLP-1 analog), Sitaglitpin (DPP-4 inhibitors)
