What ion regulates the two forming steps of insulin?
calcium
Stimulating what receptors will inhibit insulin release?
alpha 2 adrenergic
Stimulating what receptors will cause in a release of insulin?
beta 2 adrenergic receptors and vagal nerves
What is the primary stimulatory factor that releases insulin?
glucose
What neurotransmitter is found in beta cells in pancreas and is released along with insulin?
serotonin
What type of impairment has a more detrimental effect on insulin levels-- kidney or liver?
kidney
what is the most commonly used clinical marker utilized to screen for diabetes?
Hemoglobin A1C
This is a yellow fluorescent AGE that is formed when arginine groups in proteins react with methylglyoxal that has built up inside cells during hyperglycemia?
Arg-pyrimidine
____ insulin differs from human by substitution of 1 different AA?
porcine
_____ insulin differs from human by substitution of 2 different AAs?
bovine
What is the normal range of glucose when fasted?
70-130 mg/dl
What drugs can cause hypoglycemia?
ethanol
beta adrenergic receptor antagonists
salicylates
What drugs can cause hyperglycemia?
epinephrine
glucocorts
oral contraceptives
phenytoin
clonidine
calcium channel blockers
diuretics
These drugs stimulate the release of insulin from beta cells by binding to and blocking an ATP-ase sensitive K+ channel, which causes depolarization and an increase in intracellular calcium which leads to release of insulin?
sulfonylureas
These drugs may also decrease the hepatic clearance of insulin?
sulfonylureas
Are first gen or second gen sulfonylureas 100 times more potent?
second gen
The dosage must be individualized for these oral hypoglycemic agents?
sulfonylureas
Name the four first gen sulfonylureas.
Tolazamide (Tolinase)
Chlorpropamide (Diabinese)
Tolbutamide (Orinase)
Acetohexamide (Dymelor)
Which first gen sulfonylurea has no active metabolites?
Tolbutamide
Which first gen sulfonylurea has the longest serum half life of 36 hours and is therefore the longest acting?
Chlorpropamide
List first gen sulfonylureas in order of increasing half lives starting with the shortest half life.
Tolbutamide
Acetohexamide (6-8)
Tolazamide (7)
Chlorpropamide
Name the two second gen sulfonylureas.
Glipizide
Glyburide
Which second gen sulfonylurea has no active metabolites?
glipizide
Name the third gen sulfonylurea.
glimepiride (Amaryl)
What is the half life of glimepiride?
9 hours
What are the addtl MOAs of glimepiride?
appears to translocate GLUT4 to the cell surface -- insulin like activity
may bind to a different protein than the usual sulfonylurea receptor on the beta cell
What is the indication for sulfonylureas?
control glucose in Type 2 when diet and exercise do not work
What is the pKa of sulfonylureas?
5
What is the most common side effect of the sulfonylureas?
hypoglycemia
lots of DIs
What is the indication for the thiazolidinediones?
for Type 2
alone or in combo with sulfonylurea or insulin
These drugs could cause hepatic failure?
thiazolidinediones
Monitor transaminase levels before and after starting therapy with these drugs?
thiazolidinediones
Name the two thiazolidinediones.
rosiglitazone (Avandia)
pioglitazone (Actos)
Which thiazolid is metabolized by 2C8 (and to a lesser extent by 2C9)?
rosiglitazone
Which thiazolid is metabolized by 3A4?
pioglitazone
These drugs increase the activity of nuclear receptor PPAR gamma that regulates genes responsible for the control of glucose and insulin metabolism in adipose, liver and skeletal muscle tissues, which increases tissue sensitivity?
thiazolids
These drugs need to be taken with additional BC other than OCs?
thiazolids (mainly pioglitazone)
These drugs are contraindicated in patients at risk for heart failure?
thiazolids
What is a common side effect when taking thiazolids?
edema
This drug is a non-sulfonylurea analog of glyburide?
repaglinide (Prandin)
What enzyme metabolizes Prandin?
3A4
this drug is for Type 2 w/ diet and exercise and can be used in combo with a thiazolid?
prandin
This drug stimulates the release of insulin in beta cells by binding to and blocking an ATPase sensitive K+ channel, which causes depolarization and an increase in intracellular calcium, which leads to release of insulin? May also decrease hepatic clearance of insulin and is a miscellaneous non-sulf?
Prandin
This drug can decrease vit B12 and folate absorption?
metformin
This drug's half life is only 1.3-4.5 hours?
metformin
This drug has no protein binding and no metabolism with rapid renal excretion?
metformin
You should STOP taking this drug if you have an MI or septicemia?
metformin
Metformin
Glucophage
Nateglinide
Starlix
T/F: metformin causes insulin release in the pancreas.
false
This drug is for Type 2 with diet and exercise and can be used in combo with a sulfonylurea?
metformin
Acarbose
Precose
Repaglinide
Prandin
Pioglitazone
Actos
Rosiglitazone
Avandia
Glimepiride
Amaryl
Glyburide
DiaBeta
Micronase
Glynase PresTab
Glipizide
Glucotrol
Tolazamide
Tolinase
Tolbutamide
Orinase
Chlorpropamide
Diabinese
Acetohexamide
Dymelor
This drug decreases hepatic gluconeogenesis and intestinal glucose absorption, increases peripheral tissue insulin sensititivity, and does NOT cause insulin release in the pancreas?
metformin
This drug is a D-phenylglycine and is unrelated to the sulfonylureas?
Starlix
Miglitol
Glyset
What enzymes metabolize Starlix?
2C9 = 70%
3A4 = 30%
This drug is highly selective with low affinity for heart and skeletal muscle potassium channels and has 98% albumin binding?
Starlix
Which drug should you take w/ the first bite of every meal TID?
Acarbose
This drug decreases carb absorption by competitively inhibiting teh intestinal enzyme alpha glucosidase? Also prevents protonation of glycosidic bond in the saccharides.
Acarbose
Which one has minimal systemic absorption -- acarbose or miglitol?
acarbose
Which one has rapid and complete systemic absorption -- acarbose or miglitol?
miglitol
At what dose of acarbose can we see an elevated serum transaminase?
>100mg
Name two alpha-glucosidase inhibitors.
acarbose (Precose)
miglitol (Glyset)
What is a common adverse side effect of using alpha glucosidase inhibitors to treat Type 2 diabetes?
pneumatosis cystoides intestinalis
Which drug could reduce Hemoglobin A1C that Sreejayan is studying?
chromium picolinate
Metaglip combo
glipizide + metformin
Avandamet combo
rosiglitazone + metformin
Glucovance combo
glyburide + metformin
Avandaryl combo
rosiglitazone + glimepiride
ACTOplus met combo
pioglitazone + metformin
PrandiMet combo
Prandin (repag) + metformin
Insulin glulisine
Apidra
Insulin Detemir
Levemir
Insulin Glargine
Lantus
Insulin aspart
Novolog
Insulin lispro
Humalog
What are the two long acting insulins?
lantus
levemir
This insulin product is developed in saccharomyces cerevisiae and is followed by chemical modification with a fatty acid?
levemir
This long acting insulin forms microprecipitates in subQ tissue which prolongs its duration from 18 to 26 hours?
lantus
This insulin product is produced in E. coli?
apidra
Take this rapid acting insulin 5-10 min before a meal?
novolog
Take this rapid acting insulin 15 min before meals or immediately after eating?
humalog
What is the duration for both humalog and novolog?
3-5 hours
Name the recombinant/chemically modified insulins.
apidra- rapid
novolog- rapid
humalog- rapid
lantus- long
levemir- long
Exenatide
Byetta
Pramlintide acetate
Symlin
This NME recombinant/synthetic insulin is an incretin mimetic or glucagon-like peptide -1 receptor agonist that binds the GLP1 receptor on beta cells causing insulin synthesis and excretion?
Byetta
This NME recombinant/synthetic insulin is a synthetic analog of human amylin (which is a neuroendocrine hormone made by beta cells that contribute to post prandial glucose control)?
Symlin
Duetact combo
Pioglitazone + Glimepiride
This is a rapid acting insulin product for inhalation that failed?
Exubera
What are incretins?
peptide hormones released from the gut in response to ingestion of carbs
What are the 2 MOAs of incretins?
regulate rate of nutrient transit in the GI tract (esp stomach emptying)
enhance glucose, stimulate insulin secretion from the pancreas when glucose levels are high
T/F: IV insulin causes the release of incretins
false
This drug could cause acute pancreatitis and the FDA also warns of acute renal failure and insufficiency?
Byetta
This drug was originally identified in the Heloderm suspectum lizard (Gila monster) and has 39 amino acids?
Byetta
Why is the action of incretins so short (short half life)?
because of rapid metabolism by DPP-IV
This drug has a black box warning for risk of thyroid C-cell tumors?
Victoza
Inject this drug SubQ every day any time of the day independent of meals?
victoza
Victoza
Iiraglutide
What is the MOA of Victoza?
mimics incretin or GLP-1 as an adjunct to diet and exercise
Sitagliptin phosphate
Januvia
This drug is a DPP-IV inhibitor so it prolongs the biological levels of natural incretins GLP-1 and GIP, thereby increasing insulin release and decreasing glucagon release?
Januvia
Does Januvia inhibit any CYP enzymes?
no
T/F: Januvia is a substrate for PGP
true
You need to modify the dosage of this drug if patient has moderate to end-stage renal failure b/c it is excreted via active tubular secretion as unchanged drug via organic cation transporters (OCT)?
Januvia
Janumet Combo
Januvia + metformin
Juvisyns combo
Januvia + simvastatin
Saxagliptin
Onglyza
What is the MOA of Onglyza?
DPP-IV inhibitor
How is Onglyza metabolized?
3A4 and 3A5 to an active metabolite
What is an adverse effect of Januvia?
cleaving other peptides like neuropeptides, cytokines, chemokines
What is an adverse effect of Onglyza?
decreased Lymphocyte countsd = UTI and URI
hypoglycemia
urticaria
acute pancreatitis
headache
Linagliptin
Tradjenta
What is the newest DPP-IV inhibitor (2011)?
Tradjenta
Do not use this new drug in Type 1 patients or patients with diabetic ketoacidosis or with insulin?
Tradjenta
This drug is a mild inducer and mild inhibitor of 3A4, and a substrate for PGP? (new)
Tradjenta
Old drug but new indication?
Cycloset
This drug is a dopamine receptor agonist, so it can increase dopamine levels early in the day and improve metabolism problems related to diabetes Type 2?
Cycloset
bromocriptine mesylate
Cycloset
This drug was also marketed as Parlodel for Parkinson's and hyperprolactinemia?
Cycloset
becaplermin
Regranex
colesevelam hcl
Welchol
this drug comes from human derived platelet growth factor?
Regranex
Use this drug with extreme caution in patients with any known malignancy?
Regranex
This is a 0.1% topical gel used to treat lower extremity diabetic neuropathic ulcers assuming that adequate blood supply is present?
Regranex
Who cannot use Regranex?
anyone with a known neoplasm at the site of administration
How do you calculate the dose for Regranex?
length of gel in inches- (ulcer length) x (ulcer width) x 0.6
This is a bile acid sequesterant used as an adjunct to diet and exercise to improve glycemic control in adults with Type 2 DM?