Oral Hypoglycemics Flashcards
What are the 3 possible modes of actions for oral hypoglycemics?
5 oral hypoglycemic agents
Sulfonyl
Overview
The name is derived from what 2 structural features?
Why are sulfonylureas weak acids?
Features of sulfonlyl
Like other weak acids they are?
How many generations of them?
- Weak acids protein bound
- 1,2,3
- 1 and 2 are similar 3 is very different
Sulf MOA
4 first gen Sulfonylureas
Tolbutamide (gen?)
What metabolite is formed?
What does this mean for its activity?
Tolazamide (Gen?)
Metabolism?
Metablized Tolazamide vs. Tolbutamide
Which one has the longer DOA and why?
Chlopropamide (gen?)
What block metabolism of the carboxylic acid?
What does this do?
What does the n-propyl chain of chlorpropamide do?
So what does this mean for the drug?
Acetohexamide (gen)
What group is rapidly reduced?
Acetohexamide metabolite and DOA
What first generation sulf provides the core for second gen?
Acetohexamide
2nd gen
What features do they all share?
Are second generations more potent than first?
These 2nd gen agents undergo similar biotranformations but its important to note that the metabolites?
Second gen sulfs 2
Glipizide and Glyburide
Glipizide
Structural featurs and DOA
3 things we need to know
Glyburide Structural features and DOA
SAR of 1st and second gen
What must be on the urea nitrogen?
SAR 1st and 2nd
Where must substitution be present?
SAR 1st and 2nd
For second gen what appears to be important?
3rd Gen
Structural features similar to?
What is the chief example
What 2 good things does this drug have?
3rd gen
Where is binding?
How does it exert its hypoglycemic effects?
What is Glimepiride less likely to produce?
Notes on Glimepiride
Glimiperide
DOA
Structural features
Glimepiride
Metabolism?
Enzymes?
What metabolite has activity and what one doesnt?
Problems with sulfs 4
Meglitinides Given example?
Difference compared to other hypoglycemics?
Potency?
What is it free of?
Meglitinides MOA?
Sites of binding?
Repaglinide
Metabolism
how is it metabolized?
Nateglinide?
MOA?
Like repaglinide free of?
Biguanides
Goats rue
Galegine
What by itself was know to lower sugar?
Example shown?
Metformin
MOA?
What is it dependent on?
has no effect on what three things?
3 important components of Metformins Action
- Inhibits
- Increases
- Increase
- Overall metformin increases?
Metformin doesnt induce?
Protein binding and metabolism?
Elimination where?
Drug is active in pts that dont have?
DOA?
A glucosidase Is
MOA
To be absorbed from the GI tract what has to happen with carbs?
Actual A-Glucosidase I MOA
A-glucosidase Inhibitors MOA
What to Type II pts have that make this type of drug useful?
A-GI notes
What do they not cause?
What is the main SE? Think about where its working
3 A-GIs
Acarbose
Why is it poorly absorbed?
Acarbose
What unit is important for activity?
What type of drug?
Miglitol and Voglibose
What is a key part of its structure?
What about it compared to Acarbose?
Thiazolidine
Glitazones
What functionality do they have?
NO
Metabolic path of troglitazone
What enzymes metabolize it?
What metabolite may have toxicity? what is the toxicity?
Glitazone MOA
What does it do? What does it target?
What are they called?
What do glitazones bind to?
Glitazone MOA
What is the main action of this drug? What does it increase?
What are these drugs dependent on?
Pioglitazone and Rosiglitazone both undergo?
Pioglitazone
Metabolic pathway
Rosiglitazone pathway
Big picture
