Week 1 - Pharmacological Management of DM Flashcards
How can diabetes mellitus be diagnosed (lab criteria)?
Any one of the following criteria can diagnose diabetes: FBG > 7 A1c > 6.5 OGTT 2hr > 11 Random PG >11
What are microvascular complications of DM?
Retinopathy
Nephropathy
Neuropathy
What are macrovascular complications of DM?
Stroke, HTN, Peripheral vascular disease, foot problems
What is the ideal HbA1c level?
4 - 6 %
What is the best way for measuring obesity? Why?
Waist circumference - better than BMI at correlating to cardiac outcomes.
What is the best method for preventing diabetes?
Exercise!
Briefly, how should diabetes be monitored?
HbA1c every 3 months
SMBG (slef-monitoring blood glc)
What are some oral hypoglycemic agents?
- Insulin
- Insulin secretagogues (ex. sulfonylureas)
- Biguanides
- Alpha-glucosidase inhibitors
- thiazolidinediones
- Incretins
- SGLT2 Inhibitors
What is a class within insulin secreteagogues? What is the mechanism of insulin secretagogue action?
Sulfonylureas
- binds to receptor on beta cell
- causes K+ channel to close
- get more depolarization and action potential firing
- Ca++ enters cell
- Insulin granules get secreted
By approximately how much do sulfonylureas reduce the HbA1c?
1 - 2 %
How are sulfonylureas metabolized/excreted?
Metabolized in liver
Excreted via kidneys (60-70%)
What are some side effects of sulfonylureas?
weight gain, hypoglycemia
Name some sulfonylureas.
Which is associated with less hypoglycemia?
Glyburide
Gliclazide
Glimepiride (a/w less hypoglycemia)
What is the mechanism of action of Meglitinides?
- Bind K+ channel on beta cells
- stimulate APs and insulin release
How are meglitinides metabolized/excreted?
metabolized in liver; excreted in feces (90%)
Name some examples of Meglitinides.
Repaglinide
Nateglinide
What is the mechanism of action of Alpha-Glucosidase Inhibitors?
- competitively inhibits pancreatic alpha-amylase & intestinal membrane-bound alpha-glucosidase.
- decreases conversion of CHO to monosaccharides
- (ie. delays carb metabolism and mellows the glc spike)
By approximately how much do alpha-glucosidase inhibitors lower the HbA1c?
0.4 - 1 %
Give an example of an alpha-glucosidase inhibitor.
Acarbose
What are the side effects of alpha-glucosidase inhibitors?
GI upset; hypoglycemia;
does NOT affect weight
What is the mechanism by which Biguanides act?
- reduce insulin sensitivity
- reduce hepatic gluconeogenesis
- increase insulin-stimulated glc transport at muscle
- decrease FA oxidation
What’s the difference between sulfonylureas and meglitinides?
Meglitinides have a weaker binding affinity
By approximately how much do biguanides reduce the HbA1c?
1-2%
What are the side effects of biguanides?
- diarrhea, N/V, bloating, flatulence, metallic taste
- does NOT affect weight
How do Thiazolidinediones work?
- what is the mecahnism in different organs?
Increase responsiveness and efficiency of beta cells.
- Liver: decrease insulin resistance & decrease glc/fat production
- Muscle/Fat: decrease insulin resistance
- Pancreas: decrease demand for insulin secretion & increase insulin content in beta cell
What are some side effects of Thiazoladinediones?
Weight gain, fluid retention, CHF
What are some examples of thiazolidinediones?
Rosiglitazone
Pioglitazone
Where is GLP secreted and was are its actions?
GLP is secreted from L cells in the intestine & colon.
- stimulates insulin/reduces glucagon secretion
- slows gastric emptying & reduces food intake
Long term: increases beta cell mass & function
What is DPP-4?
How is this used as a drug target?
DPP-4 is a protein that inactivates GLP-1.
DPP-4 inhibitors increase endogenous GLP and lead to glucagon-like action.
What is the mechanism of action of SGLT-2 inhibitor?
Blocks the Na+/Glc transporter in the proximal tubule of the kidney to prevent glc reabsorption, thus lowering blood glucose.
What are some side effects of SGLT-2 inhibitors?
- increased risk of urogenital mycotic infections
- increased LDL
- weight loss
What are prototypical SGLT-2 Inhibitors?
“-gliflozins”
Dapaglifozin, Canaglifozin, Empaglifozen
What are some types of short-acting insulin?
Insulin Regular
lispro, glulisine, aspart
What are some types of intermediate/long-acting insulin?
NPH, glargine, detemir
What are some major issues with insulin?
- hypoglycemia
- weight gain
- variable kinetics/compatibility
- need to adjust with renal dysfunction
What drug should treatment of Type 2 DM start with?
Metformin
What can be done to monitor for/prevent macrovascular disease?
- Treat dyslipidemia
- Monitor for CAD and CVD (statin therapy?)
May use anti-platelet tx for secondary prevention
What can be done to monitor for/prevent microvascular disease?
- Annual eye exams
- Monitor for proteinuria
- Regular foot exams
- Sexual hx for ED
- Evaluate gastric emptying
