DM Oral Agents

Question 1

What is the mechanism of action of sulfonylureas?

Answer 1

Block K channels on beta cells causing an increased release of stored insulin. The drugs also cause hepatic, adipose, and muscle cells to take in more insulin.

Question 2

What must be true of a patient’s physiology for them to be eligible to be prescribed a sulfonylurea?

Answer 2

Their pancreas must be able to make insulin.

Question 3

Describe sulfonylureas with regard to their clearance from the body and plasma protein binding.

Answer 3

They are generally cleared renally and are highly plasma protein bound.

Question 4

Differentiate first generation sulfonylureas from second generation and list examples of each.

Answer 4

1st: long half life - Exs: Acetohexamide, Chlorpropamide, Tolazamide, Tolbutamide
2nd: short half life - Exs: Glimepride, Glipizide, Glyburide. 2nd and 3rd generation drugs can be co-administered with insulin.

Question 5

How often are sulfonylureas usually given?

Answer 5

QD, some BID.

Question 6

What is the mechanism of action of biguanides and what must be present for them to be effective?

Answer 6

They reduce hepatic glucose production. Only effective in the presence of insulin.

Question 7

List examples of biguanides. State which was pulled from the market and why.

Answer 7

Metformin and phenformin. Phenformin pulled from market bc it caused lactic acidosis.

Question 8

How is metformin usually dosed and what is the main instruction with its administration?

Answer 8

500 mg, PO, BID - take with food bc it can cause GI distress.

Question 9

What side effect of metformin is beneficial in T2D?

Answer 9

weight loss

Question 10

List 2 adverse effects of metformin.

Answer 10

N/V, and dysphagia

Question 11

In what type of patients is metformin administration a primary concern?

Answer 11

Patients that have renal disease - increased risk of lactic acidosis. Patients must have creatinine clearance (CrCl) measured > 30 ml/day and it should not be started if CrCl < 45 ml/day

Question 12

What is the formula to determine creatinine clearance in males and in females?

Answer 12

CrCl = [(140 - age) * weight in kg] / [72 * serum creat.]

In females multiply answer by 0.8

Question 13

What is the normal creatine clearance in a healthy indivisual? At what level should renally cleared drugs be adjusted?

Answer 13

Normal = 100 ml/day

Adjust drugs if CrCl < 50 ml/day

Question 14

Other than the primary concern, in what other conditions is metformin admin a caution?

Answer 14

hepatic dysfunction, shock, pregnancy, when contrast dyes must be administered.

Question 15

What is the mechanism of action of thiazolidineediones?

Answer 15

reduce peripheral insulin resistance.

Question 16

In what patients are thiazolidineediones contraindicated and why?

Answer 16

Contraindicated in heart and hepatic failure s/p causing edema and weight gain.

Question 17

What is the mechanism of action of Meglitinides?

Answer 17

Short acting secretagogues (increase insulin secretion) that act similar to sulfonylureas.

Question 18

List 2 examples of meglitinides.

Answer 18

Repaglinide and Nateglinide

Question 19

What is the mechanism of action of Exenatide?

Answer 19

Functional analogue of GLP-1 –> increases insulin secretion and delays gastric emptying (inc satiety).

Question 20

What other drug is used in conjunction with exenatide?

Answer 20

Insulin

Question 21

What are the adverse effects of exenatide?

Answer 21

weight loss, N/V, maybe pancreatitis

Question 22

How is exenatide dosed?

Answer 22

5-10 mcg SC, BID prior to AM and PM meals. There is also an extended release option given SC q week.

Question 23

Give examples of some GLP-1 agonists other than exenatide.

Answer 23

qd: Liraglutide
q week: albiglutide, dulaglutide
PO: semaglutide

Question 24

What is the black box warning associated with long acting (q week) GLP-1 agonsists?

Answer 24

Increased risk of thyroid C-cell tumors

Question 25

What is the mechanism of dipetidylpeptidase-4 (DPP-4) inhibitors compared to exenatide?

Answer 25

DPP-4 chews up GLP-1. So by inhibiting DPP-4, you increase the activity of GLP-1 acting similar to the GLP-1 agonists.

Question 26

What are examples of DPP-4 inhibitors and what is the new warning with these drugs?

Answer 26

Exs: vidagliptin, sitagliptin, saxagliptan, alogliptin
Warning: heart failure

Question 27

What is the mechanism of action of acarbose and miglitol?

Answer 27

alpha-glucosidase inhibitor reducing the digestion of complex carbohydrates in the gut.

Question 28

How are acarbose and miglitol dosed?

Answer 28

25 - 100 mg PO, TID

Question 29

How is toxicity of acarbose and miglitol treated?

Answer 29

Glucose as opposed to sucrose.

Question 30

What is the mechanism of action of pramlinitide?

Answer 30

Synthetic amylin analogue with longer 1/2 life - works like a GLP-1 agonist (inc insulin secretion and delays gastric emptying)

Question 31

How is pramlinitide administered?

Answer 31

15 mcg SC prior to large meals - co administered with insulin.

Question 32

What are adverse effects of pramlinitide?

Answer 32

weight loss, N/V

Question 33

What is the mechanism of action of canaglifozin?

Answer 33

SGPT-2 inhibitor. SGPT-2 is an enzyme in the kidney that promotes reabsorption of GLC. If reabsorption of GLC is inhibited, more GLC stays in the urine and BGL decreases.

Question 34

What blood monitoring must be done when canaglifozin is prescribed?

Answer 34

CrCl, and serum K.

Question 35

What are adverse effects of canaglifozin?

Answer 35

Polyuria, polydipsia, yeast infections, UTI, balanitis (inflammation of penile foreskin), inc LDL, osteopenia/fractures (possibly some Ca wasting)

Question 36

What comorbidity may benefit from canaglifozin?

Answer 36

Heart failure

Question 37

How is canaglifozin dosed?

Answer 37

100 mg PO, qd before first daily meal (T2D only)

Question 38

What is the treatment of DKA?

Answer 38

Insulin gtt at 0.5-10 u/hr to decrease BGL by 100 per hour. Also admin phosphate and potassium.