Ch 57: Drugs for Diabetes Mellitus

Question 1

In addition to affecting carbohydrate metabolism, insulin deficiency disrupts metabolism of…

Answer 1

…proteins and lipids as well.

p. 667

Question 2

What are the possible triggers for immune-mediated destruction of pancreatic beta cells?

Answer 2

Genetic, environmental, and infectious,

p. 668

Question 3

What are the target tissues of insulin?

Answer 3

liver, muscle, and adipose tissue

p. 668

Question 4

Insulin resistance appears to result from 3 causes:

reduced _______ of _______ to its receptors, reduced receptor _______, and reduced receptor ______________.

Answer 4

binding of insulin,
numbers,
responsiveness
(p. 668)

Question 5

What is the cause of microvascular damage in diabetics?

Answer 5

Thickening of the basement membrane, causing blood flow in these narrow vessels to fall.
(p. 669)

Question 6

Diabetic nephropathy is characterized by…

Answer 6

…proteinuria, reduced glomerular filtration, and increased BP.
(p. 669)

Question 7

Diabetic gastroparesis affects __% to __% of patients with long-standing diabetes.

Answer 7

20% - 30%

p. 669

Question 8

Meglitinides, aka glinides, have the same mechanism of action as _____________, which is…

Answer 8

sulfonylureas; stimulation of pancreatic insulin release.

p. 688

Question 9

What 2 drugs are meglitinides (glinides)?

Answer 9

repaglinide and nateglinide

p. 688

Question 10

What type of drug is metformin?

Answer 10

a biguanide

Question 11

What is the mechanism of action of metformin?

Answer 11

To decrease glucose production by the liver and increase tissue response to insulin.

Question 12

What are the major adverse effects of metformin?

Answer 12

GI symptoms: decreased appetite, nausea, diarrhea, and rarely lactic acidosis

(p. 685)

Question 13

Metformin is a good drug for patients who…

Answer 13

…skip meals.

Question 14

How is metformin metabolized?

Answer 14

It is not metabolized. It is excreted unchanged by the kidneys.

(p. 684)

Question 15

Metformin is contraindicated in….

Answer 15

….patients with renal insufficiency, and patients with severe heart failure or alcoholism, both of whom are already predisposed to lactic acidosis.

(p. 686)

Question 16

Sulfonylureas act primarily by…

Answer 16

…stimulating the release of insulin from pancreatic islets.
They bind with and block ATP-sensitive potassium channels in the cell membraine. As a result, the membrane depolarizes, thereby permitting influx of calcium, which in turn causes insulin release.

(p. 687)

Question 17

Name the 3 second generation sulfonylureas.

Answer 17

glipizide
glyburide (long-acting)
glimepiride

(p. 687)

Question 18

Regardless of what the glucose level is – high, normal, or low, sulfonylureas will…..

Answer 18

….make it go lower.

p. 687

Question 19

Sulfonylureas are contraindicated in….

Answer 19

….impaired renal or liver function.

p. 687

Question 20

The first first-generation sulfonylurea was linked to an increased risk of…

Answer 20

….morality from sudden cardiac death.

Question 21

In regards to prescribing of meglitinides, patients who do not respond to sulfonylureas will….

Answer 21

….not respond to meglitinides either.

Question 22

What is different about the meglitidines compared to sulfonylureas?

Answer 22

They are more short-acting, and are taken with each meal (15 min prior).

(p. 688)

Question 23

What is the advantage of using meglitinides in patients with renal disease?

Answer 23

They are metabolized by the liver and excreted in the bile, therefore they are safe to use in patients with impaired renal function.

Question 24

Because of possible hypoglycemia, it is imperative that patients on meglitinides…..

Answer 24

….eat no later than 30 minutes after taking the drug.

p. 688

Question 25

What drugs belong to the thiazolidinediones (TZD)?

Answer 25

pioglitazone
rosiglitazone

(p. 688)

Question 26

What is the mechanism of action of thiazolidinediones?

Answer 26

Activation of a specific receptor type in the cell nucleus, knows as peroxisome proliferator-activated receptor gamma (PPAR gamma). By activating PPAR gamma, TZDs turn on insulin-responsive genes that help regulate carbohydrate and lipid metabolism.
Overall, they increase glucose uptake by skeletal muscle and adipose tissue and decrease glucose production by the liver.

(p. 689)

Question 27

pioglitazone (Actos) and in particular, rosiglitazone (Avandia) are associated with…

Answer 27

….myocardial infarction and sudden cardiac death.

p. 689

Question 28

What are the side effects of the TZDs?

Answer 28

retention of fluid resulting in edema and weight gain, increased risk of fractures

Question 29

What drugs are alpha-glucosidase inhibitors?

Answer 29

acarbose (Precose)

miglitol (Glycet)

Question 30

What is the mechanism of action of alpha-glucosidase inhibitors?

Answer 30

Alpha-glucosidase is an enzyme located on the brush border of cells that line the intestine. These drugs inhibit this enzyme, and thereby slow digestion of carbohydrates, which reduces the postprandial rise in blood glucose.

(p. 690)

Question 31

Alpha-glucosidase inhibitors should be administered with….

Answer 31

….the first bite of each meal.

Question 32

What are the common adverse effects of the alpha glucosidase inhibitors?

Answer 32

Flatulence, cramps, abdominal dissension, borborygmus, and diarrhea.
With long term therapy, these drugs can cause liver dysfunction.

(p. 690)

Question 33

Which drugs are considered GLP-1 receptor antagonists?

glucagon-like peptide-1

Answer 33

exenatide (Byetta)
liraglutide (Victoza)
dulaglutide (Trulicity)
albiglutide (Tanzeum)

Question 34

What is the mechanism of action of the GLP-1 receptor antagonists?

Answer 34

These drugs are considered incretin mimetics. Incretin mimetics activate receptors for GLP-1, and thereby cause the same effects as endogenous incretins. That is, they slow gastric emptying, stimulate glucose–dependent release of insulin, inhibit postprandial release of glucagon, and suppress appetite.

(p. 692)

Question 35

What is the black box warning for the GLP-1 receptor antagonists?

Answer 35

increased risk for medullary thyroid carcinoma

Question 36

What is the recommended dosing for the GLP-1 receptor antagonists?

Answer 36

Injected BEFORE a meal. Some of them are daily, some are BID.

Question 37

Which drug class do you NOT want to combine with the GLP-1 receptor antagonists?

Answer 37

Dipeptidyl peptidase-4 (DPP-4) inhibitors (also called gliptins)

Question 38

What form do the DPP-4 inhibitors come in, and name three of these drugs.

Answer 38

oral
saxagliptin (Onglyza)
sitagliptin (Januvia)
linagliptin (Tradjenta)

Question 39

What are some of the more serious adverse effects of DPP-4 inhibitors (gliptins)?

Answer 39

pancreatitis, including fatal necrotizing and hemorrhagic pancreatitis

hypersensitivity reactions such as Stevens-Johnson syndrome, anaphylaxis, etc.

(p. 690)

Question 40

What does SGLT stand for?

Answer 40

sodium-glucose co-transporter

Question 41

What is the mechanism of action of the SGLT-2 inhibitors?

Answer 41

SGLT-2 is a high capacity, low-affinity transporter expressed chiefly in the kidney that accounts for approximately 90% of glucose reabsorption in the kidney. SGLT-2 inhibitors have been shown to block the reabsorption of filtered glucose, leading to glucosuria. This mechanism of action has proven clinically useful in patients with type II diabetes in terms of improving glycemic control. In addition, the glucosuria associated with SGLT-2 inhibition is associated with caloric loss, thus providing a potential benefit of weight loss.

(p. 691)

Question 42

Name 3 drugs that are SGLT-2 inhibitors.

Answer 42

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

Question 43

SGLT-2 inhibitors are contraindicated in….

Answer 43

….moderate renal insufficiency.

Question 44

What are the adverse effects of SGLT-2 inhibitors?

Answer 44

female genital fungal infections, vaginitis, urinary tract infections, and increased urination sometimes resulting in dehydration.