Diabetes Drugs Flashcards
MOA of Metformin?
Decrease hepatic glucose production Activate hepatic AMP-kinase and inhibit mitochondrial isoform of glycerophosphate dehydrogenase
Benefits of Metformin?
Weight neutral
No hypoglycemia
Possibly fewer CVD events and cancer
What are the common side effects of Metformin?
GI problems: diarrhea (usually but not always transient) abdominal discomfort, nausea, vomiting, anorexia
What are the rare side effects of Metformin?
lactic acidosis
Vitamin B12 deficiency
Glyburide, Glipizide, Glimepiride are what class of drugs?
Oral Sulfonylurea agents (promote insulin secretion)
What is the MAO of oral sulfonylurea agents?
Block K(atp) chennels in pancreatic beta-cells which stimulates insulin and C-peptide secretion
(serum glucose enters beta-cells via Glut2 bidirectional glucose transporters. ^[Glucose] increases glycolysis and produces ATP => ATP DEACTIVATES K+ channels, which depolarize beta cell membrane triggering the opening of voltage gated Ca2+ channels, and Ca2+ mediated excocytosis of insulin and C-peptide. (pre-formed pro-insulin is stored in secretory granules - C-peptide is just part of the pro-insulin molecule)
What are the side effects of Sulfonylurea drugs?
Hypoglycemia
Weight gain
*May adversely affect
ischemic preconditioning
What kind of drugs are Repaglinide and Nateglinide?
Oral meglitinides
What is the MOA of Oral meglitinides?
Same as Sulfonylurea drugs - Block K+(ATP) channels to stimulate insulin and C-peptide secretion
What are advantages/disadvantages of meglitinides vs Sulfonylurea drugs? (i.e. Side effects / dosing)
Both cause hypoglycemia and weight gain but meglitinides (repaglinide, nateglinide) cause less hypoglycemia than the sulfonylurea drugs (glyburide, glipizide, glimepiride)
Drugs that activate PPAR-gamma ?
Thiazolidinediones “-litazone” Pioglitazone Rosiglitazone
PPAR-y = paraxazome proliferator-activated receptor
What is the MAO of Pioglitazone?
activates PPAR-gamma
Decreases insulin resistance
Why do the Rides, Zides, and Glinides cause weight gain?
All increase insulin secretion and activate its endogenous anabolic responses - increase glycogen and triglyceride sysnthesis, decrease lypolysis/ inhibit glucogon release)
What is the consequence activating PPAR-gamma?
decreases insulin resistance
What are the specific benefits and disadvantages of pioglitazone?
Possible decrease in
myocardial infarctions
Increase in bladder cancer
What are the side effects/disadvantages of Thiazolidinediones?
(Pioglitazone Rosiglitazone) sides effects:
Weight gain Edema Congestive heart failure Bone fractures Macular edema
EXPENSIVE!
What is the shared benefit of Pioglitazone and Rosiglitazone?
No hypoglycemia
What is the MOA for Acarbose and Miglitol?
Oral Alpha-Glucosidase (competitive)
Inhibitors
usually oligosaccarides - acarbose may also inhibit pancreatic amylase
What does inhibiting Alpha-Glucosidase do?
Delays carbohydrate
absorption which results in
decreased postprandial
glucose levels
What are the benefits of acarbose and miglitol?
No hypoglycemia Weight neutral Moderate efficacy in lowering postprandial glucose levels
What are the side effects of acarbose and miglitol?
GI symptoms:
flatulence, diarrhea,
abdominal fullness and
discomfort
Dosing issues: Need to take with each
carbohydrate containing
meal
Efficacy issues:
only modest ↓ in A1c
What is the MOA?
Exenatide
Liraglutide
Dulaglutide
Albiglutide
GLP-1 Receptor Agonists
what does a GLP-1 Receptor Agonist do? (4 functions)
Increases glucose-stimulated insulin
secretion,
decreases glucagon secretion,
slows
gastric motility,
increases
satiety
What are the major benefits of GLP-1R agonists?
Promote weight loss
No hypoglycemia
Disadvantages of GLP-1R agonists?
Risk of pancreatitis
GI side effects (nausea,
vomiting, diarrhea)
Hypoglycemia (less than
sulfonylureas)
Caution with renal
insufficiency
Have to inject subcutaneously (Byetta twice daily, Bydureon Albiglutide, Dulaglutide once weekly, Victoza once daily)
C-cell
hyperplasia/medullary
thyroid tumors in animals
Expensive!
What drugs inhibit the metabolism of GLP-1 (glucagon-like-peptide 1)?
the DPP-4 inhibitors
“-gliptins”
What are the benefits of the DDP-4 inhibitors?
Weight neutral
No hypoglycemia
Well-tolerated
What are the side effects of DDP-4 inhibitors?
Risk of pancreatitis
Possible runny nose, URIs,
headache
What is the MOA of these drugs?
Canagliflozin
Dapagliflozin
Empagliflozin
oral SGLT2 Inhibitors (“-gliflozin” - GLucose In FLow cauZes INfections)
What is SGLT2?
Sodium/Glucose cotransporter-2 facilitates re-absorption of glucose and sodium
Inhibition of SGLT2 reduces glucose reabsorption in the kidney;
increases urinary glucose excretion
Side effects of canagliflozin, Dapagliflozin, and Empagliflozin?
Genital mycotic infections, urinary tract infections, hypotension, impaired renal function, hyperkalemia, hypersensitivity, increased LDL-cholesterol
Which drugs share increased risk of pancreatitis?
GLP-1 agonists and DPP4 inhibitors (“tides” and “gliptins”)— both function along same pathway leading to endogenous insulin secretion but GLP-1 agonists are upstream so these drugs are more potent stimulators of insulin
- GLP1/GIP/Glucagon are agonists for GLP1R increases insulin secretion
- DPP4 is enzyme that breaks down GLP1 so blocking DPP4 also increases insulin secretion by activation of GLP1R
Insulin cases the kidney to increase Na+ reabsorption so more insulin (e.g. GLP1R agonists) forces the kidney to work harder
Which class of drugs cases UTI’s and gentical mycoses as a side effect? Why doe they do this?
gliflozin drugs (SGLT-2 inhibitors) - Increased urinary exretion of glucose (from blocked reabsorption) acts as a growth medium for fungi and bacteria
