Non-insulin diabetes pharm - Lowwang Flashcards
What class of medication increases insulin secretion (secretagogues)?
What is the MOA?
Sulfonylureas.
Blockage of an ATP sensitive K+ channel on the B cell leading to depolarization, Ca influx, and vesicle fusion resulting in insulin release.
What are the side effects of the sulfonylureas?
hypoglycemia and weight gain.
glyburide
sulfonylureas
glimepiride
sulfonylureas
glipizide
sulfonylureas
What are some contraindications to the sulfonylureas?
Liver/kidney disease G6PD deficiency (sulfa-containing drug--> hemolytic anemia)
What is the MOA of metformin?
Suppresses hepatic glucose production by potentiating the effects of insulin.
Contraindications to metformin use include:
1) congestive heart failure, especially unstable or acute
2) radiologic studies
3) renal impairment
4) metabolic acidosis, acute or chronic, including ketoacidosis
Metformin is the only drug in the class of _____.
Biguanines
Thiazolidinediones (TDZs) work in what fashion?
tl;dr Regulation of transcription factors by PPAR-gamma binding enhance insulin action.
Thiazolidinediones activate nuclear peroxisome proliferator-activated receptor (PPAR) gamma. They are true insulin sensitizers that enhance insulin action.
Binding of a thiazolidinedione (TZD) to a PPAR-γ receptor leads to ….regulation of the transcription of genes involved in adipocyte differentiation, and glucose and lipid metabolism.
What are the contraindications of TDZs?
HEART FAILURE, probably due to water retention (weight gain)
Femur fractures
Bladder cancer if taken >1yr
Liver disease
What is the incretin effect?
Oral glucose ingestion increases insulin release beyond IV administration of insulin.
What two hormones create the incretin effect?
How?
GLP-1, GIP
Act through G-protein receptors.
These peptides are important for the integrated control of gut motility, satiety and postprandial islet hormone responses. Rapidly inactivated by DPP-4.
GLP-1 controls blood glucose mainly by
Amplifying insulin secretion in response to po glucose
Inhibiting glucagon secretion
Decreasing gastric emptying
Signalling satiety to the brain.
GLP-1 is an incretin produced in the____ and ____.
Distal ileum and colon
GIP is an incretin produced in enteroendocrine K cells in the _____.
duodenum
GIP is secreted after nutrient ingestion and enhances glucose-dependent insulin secretion. β-cells in individuals with type 2 diabetes are (resistant or sensitive) to the insulin stimulatory action of GIP.
resistant
What is the prototypical GLP-1 agonist?
exenatide. It is resistant to cleavage by DPP-4, making it much more potent than endogenous GLP-1
Pros of exenatide?
Lower A1c
BID administration
Weight loss
Cons of exenatide?
subcutaneous injection
nausea
$$$$
Name three GLP-1 agonists aside from exenatide?
Liraglutide (may be better than exenatide)
albiglutide
dulaglutide
Name 4 DPP-4 (dipeptidylpeptidase-4) inhibitors
-gliptins
saxagliptin
sitagliptin
linagliptin
alogliptin
What are pros of the DPP-4 inhibitors?
po administration (TID)
lower fasting glucose
weight neutral
What is the MOA of DPP-4 inhibitors?
INhibit DPP-4, obviously. But they increase pancreatic secretion of insulin and decrease glucagon release.
What are the cons/side effects of DPP-4 inhibitors?
Nasopharyngitis
Headache
Name the Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors.
Canagliflozin
dapagliflozin
empagliflozin
How does Canagliflozin work?
Block glucose reuptake by the renal tubule.
What are the pros of the SGLT-2 inhibitors?
po, BID
weight loss
lower BP
What are the cons of the SGLT-2 inhibitors?
UIs
hypovolemia
hypokalemia
CONTRAINDICATED in RENAL DISEASE
What are some pros of metformin?
Cheap
can be taken with other diabetes meds
What are some cons of metformin?
must titrate up to dose
GLP-1 is GLUCOSE DEPENDENT!
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