Treatment of Diabetes - Oral Agents

Question 1

what is the MOA of sulfonylureas

Answer 1

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.

Question 2

Name the 3 Sulfonylureas

Answer 2

glipizide (Glucotrol), glyburide (Diabeta, Micronase), and glimepiride (Amaryl).

Question 3

The major side effects of sulfonylureas are ______

Answer 3

hypoglycemia and weight gain

nausea and gastrointestinal discomfort.

Question 4

Sulfonylureas must be used with caution in patients with ________

Answer 4

moderate to severe renal insufficiency or liver disease

Question 5

Sulfonylureas must not be used in patients with allergy to _____- drugs, and can cause ______ in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

Answer 5

sulfa,

hemolytic anemia

Question 6

what is the MOA of Metformin

Answer 6

acts mainly at the liver to potentiate the suppressive effects of insulin on hepatic glucose production

Question 7

what are the side effects of Metformin

Answer 7

nausea, vomiting, bloating, and diarrhea

Question 8

what are the Contraindications to metformin use:

Answer 8

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

Question 9

what is the “incretin effect”

Answer 9

when glucose is given orally there is a 2-3 fold increase in insulin secretion when compared to IV glucose

Question 10

what are Two specific gut peptides that account for a substantial proportion of the incretin effect:

Answer 10

glucagon-like peptide-1 (GLP-1) and

glucose-dependent insulinotropic polypeptide or [gastric inhibitory peptide (GIP)]

Question 11

The actions of GIP and GLP-1 are transduced via G protein-coupled receptors, coupled to _______

Answer 11

adenyl cyclase

Question 12

GIP receptors are predominantly expressed in ______ cells, while GLP-1 receptors are also expressed in the ________, among other tissues.

Answer 12

pancreatic islet ,

brain and heart

Question 13

Both GIP and GLP-1 are rapidly inactivated within minutes of appearing in the circulation by an enzyme called _______

Answer 13

dipeptidyl peptidase-4 (DPP-4).

Question 14

GLP-1 is an incretin produced in enteroendocrine L cells located in the _____ and ______

Answer 14

distal ileum,

colon.

Question 15

how does GLP-1 control blood glucose ?

Answer 15

mainly by amplifying glucose-stimulated insulin secretion, inhibiting glucagon secretion, and slowing gastric emptying.

Question 16

GIP is an incretin produced in enteroendocrine K cells in the ______.

Answer 16

duodenum

Question 17

GIP administration has not been shown to be effective for the treatment of type 2 diabetes. why?

Answer 17

beta-cells in individuals with type 2 diabetes are resistant to the insulin stimulatory action of GIP

Question 18

Name the GLP-1 agonists

Answer 18

exenatide (Byetta), 
liraglutide (Victoza), 
exenatide Qwk (Bydureon), 
dulaglutide (Trulicity), 
lixisenatide (Lyxumia

Question 19

name the DPP-4 inhibitors

Answer 19

sitagliptin (Januvia),
saxagliptin (Onglyza),
linagliptin (Tradjenta),
alogliptin (Nesina)

Question 20

The use of GLP-1 agonists is not recommended in patients with _______

Answer 20

active pancreatitis, a history of pancreatitis, or pancreatic carcinoma

Question 21

what are the downsides to GLP-1 agonists

Answer 21

SC injections
Side effects
Expensive

Question 22

How do DPP-4 inhibitors work

Answer 22

They enhance pancreatic insulin secretion and suppress glucagon secretion, but do not alter gastric emptying or affect appetite

Question 23

what are the main adverse effects of DPP-4 inhibitors

Answer 23

nasopharyngitis and headache

Question 24

what are DPP-4 (dipeptidylpeptidase-4) inhibitors ?

Answer 24

they inhibit the enzyme that cleaves incretines

Question 25

how do Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors work

Answer 25

By inhibiting reabsorption of glucose by the kidneys, increasing glucose excretion, and reduces circulating glucose levels.

Question 26

Name the 3 Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors

Answer 26

canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance)

Question 27

what are The main beneficial effects Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors besides blood glucose lowering?

Answer 27

weight loss and blood pressure lowering.

Question 28

what are Key adverse effects of Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors

Answer 28

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

Question 29

Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors should not be used in patients with _______

Answer 29

severe renal disease, end stage renal disease, or patients on dialysis

Question 30

Thiazolidinediones should not be used in which patients?

Answer 30

individuals with active liver disease, moderate or severe congestive heart failure, or significant cardiovascular risk.

Question 31

how do Thiazolidinediones work

Answer 31

insulin sensitizers that enhance insulin action, mainly at the level of skeletal muscle and adipose tissue, with a lesser effect to reduce hepatic gluconeogenesis

Question 32

Name the 2 Thiazolidinediones

Answer 32

rosiglitazone (Avandia) and pioglitazone (Actos)

Question 33

which individuals should have a stringent a1c target of <6.5%

Answer 33

relatively recent onset of diabetes, are motivated, have few or mild complications and/or comorbidities ts.

Question 34

which individuals should have a less stringent a1c goal of <8%

Answer 34

1) patients with hypoglycemia unawareness, 2) limited life expectancy, 3) advanced microvascular or macrovascular complications, 4) extensive comorbid conditions, 5) those with longstanding diabetes

Question 35

how often should A1c be checked in diabetic patients

Answer 35

Hemoglobin A1c is drawn at least twice and up to 4 times per year to monitor effectiveness of glycemic control.

Question 36

when and how often should patients check their blood glucose

Answer 36

at least twice per day at specific time points: fasting, before lunch, before dinner, and at bedtime.

Question 37

which glucose lowering drugs are the cheapest

Answer 37

metformin and sulfonlyureas at $4/month