Treatment of Diabetes - Oral Agents Flashcards
what is the MOA of sulfonylureas
Increase pancreatic Beta-cell insulin secretion by: Closing ATP-sensitive potassium channels -> depolarizes the membrane, -> opening of voltage-gated calcium channels -> influx of calcium into the Beta-cell -> fusion of insulin-containing secretory granules with the cell membrane -> insulin secretion.
Name the 3 Sulfonylureas
glipizide (Glucotrol), glyburide (Diabeta, Micronase), and glimepiride (Amaryl).
The major side effects of sulfonylureas are ______
hypoglycemia and weight gain
nausea and gastrointestinal discomfort.
Sulfonylureas must be used with caution in patients with ________
moderate to severe renal insufficiency or liver disease
Sulfonylureas must not be used in patients with allergy to _____- drugs, and can cause ______ in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency.
sulfa,
hemolytic anemia
what is the MOA of Metformin
acts mainly at the liver to potentiate the suppressive effects of insulin on hepatic glucose production
what are the side effects of Metformin
nausea, vomiting, bloating, and diarrhea
what are the Contraindications to metformin use:
1) congestive heart failure, especially unstable or acute
2) intravascular iodinated contrast media for radiologic studies
3) eGFR <30 mL/min/1.73 m2
4) metabolic acidosis, acute or chronic, including ketoacidosis
what is the “incretin effect”
when glucose is given orally there is a 2-3 fold increase in insulin secretion when compared to IV glucose
what are Two specific gut peptides that account for a substantial proportion of the incretin effect:
glucagon-like peptide-1 (GLP-1) and
glucose-dependent insulinotropic polypeptide or [gastric inhibitory peptide (GIP)]
The actions of GIP and GLP-1 are transduced via G protein-coupled receptors, coupled to _______
adenyl cyclase
GIP receptors are predominantly expressed in ______ cells, while GLP-1 receptors are also expressed in the ________, among other tissues.
pancreatic islet ,
brain and heart
Both GIP and GLP-1 are rapidly inactivated within minutes of appearing in the circulation by an enzyme called _______
dipeptidyl peptidase-4 (DPP-4).
GLP-1 is an incretin produced in enteroendocrine L cells located in the _____ and ______
distal ileum,
colon.
how does GLP-1 control blood glucose ?
mainly by amplifying glucose-stimulated insulin secretion, inhibiting glucagon secretion, and slowing gastric emptying.
GIP is an incretin produced in enteroendocrine K cells in the ______.
duodenum
GIP administration has not been shown to be effective for the treatment of type 2 diabetes. why?
beta-cells in individuals with type 2 diabetes are resistant to the insulin stimulatory action of GIP
Name the GLP-1 agonists
exenatide (Byetta), liraglutide (Victoza), exenatide Qwk (Bydureon), dulaglutide (Trulicity), lixisenatide (Lyxumia
name the DPP-4 inhibitors
sitagliptin (Januvia),
saxagliptin (Onglyza),
linagliptin (Tradjenta),
alogliptin (Nesina)
The use of GLP-1 agonists is not recommended in patients with _______
active pancreatitis, a history of pancreatitis, or pancreatic carcinoma
what are the downsides to GLP-1 agonists
SC injections
Side effects
Expensive
How do DPP-4 inhibitors work
They enhance pancreatic insulin secretion and suppress glucagon secretion, but do not alter gastric emptying or affect appetite
what are the main adverse effects of DPP-4 inhibitors
nasopharyngitis and headache
what are DPP-4 (dipeptidylpeptidase-4) inhibitors ?
they inhibit the enzyme that cleaves incretines
how do Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors work
By inhibiting reabsorption of glucose by the kidneys, increasing glucose excretion, and reduces circulating glucose levels.
Name the 3 Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors
canagliflozin (Invokana),
dapagliflozin (Farxiga),
empagliflozin (Jardiance)
what are The main beneficial effects Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors besides blood glucose lowering?
weight loss and blood pressure lowering.
what are Key adverse effects of Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors
Increased risk for genital and urinary tract infections, hypovolemia,
hypokalemia,
possible effects on bone metabolism (increased fracture risk),
euglycemic diabetic ketoacidosis,
and (for canagliflozin) amputation
Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors should not be used in patients with _______
severe renal disease, end stage renal disease, or patients on dialysis
Thiazolidinediones should not be used in which patients?
individuals with active liver disease, moderate or severe congestive heart failure, or significant cardiovascular risk.
how do Thiazolidinediones work
insulin sensitizers that enhance insulin action, mainly at the level of skeletal muscle and adipose tissue, with a lesser effect to reduce hepatic gluconeogenesis
Name the 2 Thiazolidinediones
rosiglitazone (Avandia) and pioglitazone (Actos)
which individuals should have a stringent a1c target of <6.5%
relatively recent onset of diabetes,
are motivated,
have few or mild complications and/or comorbidities ts.
which individuals should have a less stringent a1c goal of <8%
1) patients with hypoglycemia unawareness,
2) limited life expectancy,
3) advanced microvascular or macrovascular complications,
4) extensive comorbid conditions,
5) those with longstanding diabetes
how often should A1c be checked in diabetic patients
Hemoglobin A1c is drawn at least twice and up to 4 times per year to monitor effectiveness of glycemic control.
when and how often should patients check their blood glucose
at least twice per day at specific time points: fasting, before lunch, before dinner, and at bedtime.
which glucose lowering drugs are the cheapest
metformin and sulfonlyureas at $4/month
