Pharm: Metformin, thiazolidinediones, pramlintide, SGLT-2 inhibitors Flashcards
What is the first line oral agent for the management of type 2 diabetes?
Metformin (think of the student saying metaphors)
What does metformin do?
Decreases hepatic glucose output
Decreases intestinal glucose absorption
Increases peripheral glucose uptake and utilization
Metformin inhibits the enzyme, _________, to decrease hepatic gluconeogensis.
glycerophosphate dehydrogenase (mGDP)- a mitochondrial enzyme responsible for getting molecules into the gluconeogenesis pathway
(think of the girl- whom the METaphOR-weilding boy is trying to woo- who is biting a mitochondria-shaped candy)
Metformin activates __________ to exert its effect.
AMP-activated protein kinase aka AMPK- inhibits gluconeogenesis
(think of the AMPK liver bag)
Besides supressing gluconeogenesis in the liver, how does metformin help control glucose levels?
Increasing insulin sensitivity- facilitates peripheral uptake of glucose
(think of the valentines mailbox by the metformin metaphor boy- welcome INside for INsulin increasing fat and sugar uptake)
What side effects can metformin cause? And which patients do we need to be concerned about?
- lactic acidosis from blocked gluconeogenesis in liver (think of the spilled, spoiled milk).
This needs to be thought of in patients with renal failure, because metformin is just usually excreted unmodified by the kidneys and with kidney disease, metformin builds up (think of the cracked, kidney-shaped tray that the lactic acid is on).
- GI upset (like the green-faced girl about to barf at the metformin boy)
True or False: Metformin causes weight loss.
True. Modest weight reduction- unlike sulfonylureas and meglitinides (just like how metformin metaphor boy is skinny)
What is the suffix for thiadolidinediones?
-glitazone: rosiglitazone, pioglitazone (think of girl reading “ROSes are red” on the GLITter-covered card)
What is the mechanism of thiadolidinediones?
They ligands of peroxisome proliferator activated receptor gamma aka PPAR-gamma (think of the “life of the PPARy on the successful boy’s shirt)- an intracellular receptor that regulates gene transcription and increases glucose uptake and decreases glucose production
What are two of the most important genes regulated by PPARy?
- adiponectin- upregulated (think of his turtleneck)
2. GLUT4- upregulated (like the open GLUT4 mailbox)
Explain the unique relationship between the thiazolidinediones and weight gain.
Thiazodlidinediones lead to increased differentiation of adipocytes, leading to decreased serum triglyceride levels (from increased triglyceride storage) and weight gain
(think of the successful, fat boy eating doughnuts to represent fat storage: -glitazones put extra GLIT in your ZONE)
True or false: thiazolidinediones take days to weeks to become effective.
True. Because it works by increasing gene expression, it takes time.
What big side effect do you need to worry about with the thiazolidinediones (not related to weight gain)?
Peripheral edema from increase fluid retention from increased sodium retention in the renal collecting tubules (like thiazolidinedione boy’s baggy pants)
What patient population do you need to avoid giving thiazolidinediones?
Do not give to patients with CHF (like the baggy heart balloon being crushed by the boy’s chair)
The non-insulin-raising drug that acts on the peroxisome proliferator-activator receptor gamma can cause which side effect that is especially common in older women?
Osteoporosis (think of the boy’s chair, which has a femur-shaped leg that is breaking)
What cells normally secrete amylin?
The pancreatic islet cells that also secrete insulin!
Amylin is secreted with insulin.
What does amylin do?
Decrease glucagon and delay gastric emptying (just like the full, stomach-shaped water cooler and torn glucagon sweetner packets (because glucagon increases blood sugar levels) next to the furious AMY and LyNn who were asked out by the same boy).
What is the amylin analogue called?
Pramlintide- given subcutaneously
Pramlintide can be used to treat the _______ in both types of diabetes.
postprandial glucose spike- hyperglycemia
The two main side effects with pramlintide are __________.
- hypoglycemia (the falling candy jar that AMY is kicking)
2. nausea (Brayden getting sick imagining what will happen to him)
These two drugs work by inhibiting intestinal-brush-border enzyme alpha glucosidase:
acarbose (A-Carb candies) and miglitol (wIgGLer candies by the brush border flag decorations)
Inhibiting alpha glucosidase work to __________.
delay glucose absorption- disaccharides are not converted to monosaccharides (just like the frustrated boy is delayed in eating his A-carb Wiggler gummy worms)
Alpha glucosidase inhibitors control the _____________ spike.
postprandial glucose
What are the main side effects of alpha glucosidase inhibitors?
Diarrhea and flatulence- both related to the massive load of undigested disaccharides that are fermented by gut bacteria (think of the leaky bathroom)
