Metabolism 4 Flashcards
In type 2 diabetes you treat the consequences rather than curing the disease. TRUE OR FALSE?
TRUE
Name the different types of classes of type 2 diabetes oral drugs?
- SFU
- Metformin
- Glinides
- DDP-inhibitors
- A-glucosides
- TZDs
Name the different type of classes of type 2 diabetes parental drugs?
- Insulin
- GLP-4 receptors
Metformin is the standard drug for first in line therapy for most type 2 diabetic patienst. TRUE OR FALSE?
- TRUE
what is the mechanism of action for metformin?
- It reduces heaptic glucose output
- Increases sensitivity to insulin
Metformin causes hypoglycemia. TRUE OR FALSE?
FALSE
what are some ADRs for metformin?
- It causes lactic acidosis
What is AMPK?
- It is a protein kinase
When is AMPK actiavted?
- When there is an increased in intracellular cAMP
AMPK is the cells fuel sensor. TRUE OR FALSE?
TRUE
What does AMPK actiavtes?
- Glucose uptake
- Glycolysis
- Fatty acid oxidation
- Mitochondrial biogenesis
What are the three classes of drugs that stimulate an increase in insulin secretion?
- Sulfonylureas - glucose independent insulin release
- GLP-1 receptor - glucose dependent increase insulin secretion
- DDP-4 inhibitors - which stimulate activity of GLP-1 receptors
How does glucose-stimulated insulin secretion occur ?
- An increase in intracellular glucose leads to increase in ATP levels
- Causes ATP-sensitive K+ channels to close and memebrane depolarises
- Volatge gated Ca+ channels open, ca+ floods into the cell
- Leads to insulin secretion and synthesis
How do sulfonylureas work in causing insulin release?
- SU binds to SUR-1 which is a component of the ATP-sensitive K+channel
- ATP-sensitive K+ channle to close and membrane depolarises
- Volateg agted Ca+ channles to open - ca+ flood in
- Insulin secretion
Give an exmple of a sulfonylurea drug and what are they indicated for?
- Gliclazide - indicated fo type 2 diabetes ont not effective in type 1
Meglinitides are also glucose independent insulin secrettagogues. TRUE OR FALSE?
TRUE
Sulfonylureas and meglinitides are preffered because of the the reduced chances of hypoglycemia? TRUE OR FALSE?
TRue
Sulfonylureas and meglinitides are highyl plasma bound. TRUE OR FLASE?
TRUE
Sulfonylureas and meglinitides do cause hypoglycemia at titrated doses and they cause weight gain. TRUE OR FALSE?
TRUE
Repaglinide is clincally effective and cost effective and is a prefered choice if metformin is not working? TRUE OR FALSE?
TRUE
Should not combine sulfonylureas and meglitinides as they both thave the same mechanism of action. TRUE OR FALSE?
TRUE
what are incretins?
- They are hormones that are secreted from the gut after a meal e.h GLP-1 OR GIP
Incretins include GLP-1 agonist and DPP-4 antagonists and they cause glucose stimulated insulin release. TRUE OR FALSE?
TRUE
Provide an example of a GLP-1 agonist and a DPP4 anatgonist?
- GLP-1 agonist - Exenatide
- DPP4-antagonist - Sitagliptin
How do GLP-1 agonists work?
- They are glucose stimulated insulin release
- They increase secretory machinery
- Increase insulin biosynthesis
- Increase activity of ca+channels
GLP-1 do not cause insulin release in the absence of glucose so risk of hypoglycemia is reduced. TRUE OR FLASE?
TRUE
GLP-1 have a short half life. TRUE OR FLASE?
TRUE
How do DPP-4 inhibitors work?
- They increase the plasma concentration of GLP-1 which increases insulin secretion
DPP-4 inhibitors have good oral bioavailbility. TRUEOR FALSE?
TRUE
GLP-1 agonists, are cleared by proteolytic degradation . TRUE OR FASE?
TRUE
GLP-1 have a short half lives and no oral bioavailbilty so are given as injections. TRUE OR FALSE?
TRUE
GLP-1 agonist cause signifcant weigth loss in some patients. true or flase?
true
DPP-4 inhibitors are considered safe and have reduced risks of hypoglycemia. TRUE OR FALSE?
TRUE
Why is the use of GLP-1 agonists so resticted?
- Costs -they are more expensive
- Conveniece - they are injecetdable whilst DPP-4 are oral
- Side effects - cause vomiting and nausea whic cahave adherence issues
What are TZDs and hwo do they work?
- They are insulin sensitisers - they improve insulin sensitivity by decreasing ectopic fat storage
- They act as ligands to the PPARg transcritpion factor
Give an example of a TZD drug?
- Pioglitazone
TZDs can take several months to work? true or false?
true
How do SGLT2 inhibitors work?
- They increase excretion of glucose through the urine leading to decreased plasma glucose
What are the ADRs of some SGLT2 inhibitors?
- Can cause hypotension and hypovolemia due to increased urination
what is ketone body production driven by?
- Driven by uncrontolled lipolysis
Ketone body is not used as a fuel when glucose level sare high which leads to accumulation of ketone bodies leading to acidifaction of blood. TRUE OR FALSE?
TRUE
Diabetic ketoacidosis usually occurs in type 1 diabetes. true or fkase?
true
Some patients being treated with SGLT2 inhibitors have been seen to have DKA. TRUE OR FALSE?
TRUE
There are different types of insulin with diffrent duration of actions . true or false?
true
hwo do inhibition of glucose uptake work?
- Inhibits a-glucosidase
Inhibition of glucose uptkae are indicated for uncontrolled type 2 diabetes. TRUE OR FLASE?
TRUE