Exam 7: Diabetes Flashcards
Thiazolidinediones uses
Type 2 diabetes
Pioglitazone is only one commonly prescribed
Taken daily in combo with other drugs for diabetes
Effects are mediated by gene expression, so it may take 1-3 months to see benefits
Name 1 alpha-glucosidase inhibitor
Acarbose
Acarbose
Alpha-glucosidase inhibitor
Used for type 2 DM, pre diabetes
Slowly titration up to desired dose
Inhibits enzymes that break down complex carbs
Delays and spreads out absorption of glucose after meals
Minimally absorbed
If a patient on Acarbose gets hypoglycemic, they need to get glucose or dextrose, not sucrose which requires alpha-glucosidase to be broken down
Acarbose adverse effects
GI disturbances
Flatulence, diarrhea, abdominal pain
Side effects get less prominent over time due to up regulation of alpha-glucosidases in the distal small intestines
Acarbose contraindications
IBD
Renal impairment
Other GI problems
Which bile acid sequesterant can be used in treatment of DM?
Colesevelam
Pramlintide
Amylin analog, acts on receptor in hindbrain
Suppresses Glucagon release, delays gastric emptying….
Can cause nausea, weight loss, hypoglycemia.
Adjunct to insulin therapy, must be injected separately
Lowers amount of insulin need, mealtime insulin doses should be reduced by about 50%
Pramlintide contraindications
Gastroparesis or any other GI motility disorder
GLP-1 agonist
Exenatide
Exenatide
Synthetic exenidin 4, an incretin
Glucagon like peptide 1 receptor agonist
Therapy for type DM
Causes increased insulin synthesis and secretion in a glucose dependent manner (as opposed to sulfonureas). Less likely to cause hypoglycemia
Also causes delayed gastric emptying and decreased appetite
Also suppresses post prandial glucagon release
Rapidly absorbed after injection
GI disturbances are a common side effect
Liraglutide
GLP1 agonist
Like Exenatide, but is more slowly absorbed. It also binds to albumin, slowing its metabolism
Black box warning, not for use in patients with family history of medullary cancer or multiple endocrine neoplasia type 2
GLP1 agonist adverse effects
GI disturbances Weight loss Hypoglycemia maybe Pancreatitis Can alter pharmacokinetics of drugs that require Rapid GI absorption
GLP1 contraindication
Pancreatitis
DPP-4 inhibitors
Sitagliptin
Other gliptins
Sitagliptin
DPP-4 inhibitor
Increases levels of circulating incretins
Can be taken orally
Result in increased insulin, decreased glucagon release after meals
DPP-4 adverse effects
Increased risk of infection Headache Hypoglycemia when combined with a sulfonurea Hyper sensitivities Pancreatitis
Saxagliptin
DPP-4 inhibitor that is a prodrug, doses need to be adjusted with CYP inhibitors
SGLT2 inhibitors
Canagliflozin
Other flozins
Canagliflozin
SGLT2 inhibitor
Decreased glucose reabsorption in kidneys
Increase risk of genital mycotic infections, UTIs
Contraindication = severe renal impairment
Glucagon
Peptide produced by pancreatic alpha cells
Used for emergency treatment of severe hypoglycemia when patient is unconscious and intravenous glucose isn’t feasible
Also treats beta blocker overdose
Binds to G protein receptor, increases cAMP
Raises blood glucose (glycogenolysis)
Can cause nausea, vomiting, hypertension, tachycardia
Contraindications for Thiazolidinediones
Pregnancy
Hepatic impairment (periodic liver function tests required)
Heart failure
Sulfonureas Mechanism
Increase secretion of endogenous insulin
Inhibit K ATP channels in pancreatic Beta cell membranes
Name 1 Sulfonurea
Glyburide
Glyburide
Sulfonurea
3 Side effects of Sulfonureas (glyburide)
Hypoglycemia, weight gain, sulfa allergy
Contraindications for Sulfonureas (glyburide)
Hepatic or renal impairment could compromise metabolism or excretion of the drug
Pregnant/breastfeeding women (teratogenic)
Patients especially susceptible to hypoglycemia (elderly, acute cardiovascular disease)
Clinical Uses of Sulfonureas
Glyburide
Used to treat DM type II.
They get less effective as pancreatic beta cells lose function
Widely used, often with metformin, thiazolidones.
Name one Meglitinide
Repaglinide
Repaglinide
Meglinitide
Like sulfonureas, increases endogenous insulin secretion by inhibiting K ATP channels
May cause hypoglycemia, weight gain
Use with caution in patents with renal/hepatic impairment
Nateglinide may be safer for those with renal/hepatic impairment
Meglinitide Uses/Advantages
(Repaglinide, nateglinide)
Treats DM type II
Pre-prandial delivery because they are more rapidly acting than sulfonureas.
Safe for those with sulfa allergies
Name two Thiazolidinedione
Pioglitazone
Rosiglitazone
Thiazolidinedione Mechanism
Increase insulin sensitivity in tissues by being Peroxisome proliferator-activated receptor gamma (PPARγ) agonists
These are nuclear receptors that regulate genes involved in glucose and lipid metabolism
What are the two most common side effects of Thiazolidinedione?
Weight gain and edema (edema may lead to CHF)
May also increase risk of osteoporosis in women.
Pioglitazone may increase risk of bladder cancer
