Ch 57 Drugs for Diabetes

Question 1

Diabetes is characterized by __

Answer 1

sustained hyperglycemia.

Question 2

Initial metabolic changes of Diabetes involve __

Answer 2

glucose and other carbohydrates.

If the disease progresses, metabolism of fats and proteins changes as well.

Question 3

Diabetes has two major forms:

Answer 3

type 1 diabetes and type 2 diabetes

Question 4

Symptoms of type 1 diabetes result from a complete absence of ___.

Answer 4

insulin.

The underlying cause is autoimmune destruction of pancreatic beta cells.

Question 5

Early in the disease process, symptoms of type 2 diabetes result mainly from cellular resistance to __.

Answer 5

insulin’s actions, not from insulin deficiency.

However, later in the disease process, insulin deficiency develops.

Question 6

Type 1 diabetes and type 2 diabetes share the same longterm complications:

Answer 6

heart disease, stroke, blindness, renal failure, neuropathy, lower limb amputations, erectile dysfunction, and gastroparesis, among others

Question 7

Diabetes is diagnosed if:

Answer 7

(1) hemoglobin A1C is 6.5% or higher;
(2) fasting plasma glucose is 126 mg/dL or higher;
(3) an oral glucose tolerance test (OGTT) results in a blood glucose of 200 mg/dL or higher;
(4) or the patient presents with classic symptoms of hyperglycemia and has a random plasma glucose of 200 mg/dL or higher.

Question 8

With both type 1 and type 2 diabetes, the goal of treatment is to (2).

Answer 8

manage the symptoms of hyperglycemia and reduce long-term complications, including death.

Question 9

Type 1 diabetes is treated primarily with ___.

Answer 9

insulin replacement.

Question 10

Type 2 diabetes is treated with:

Answer 10

oral anti-diabetic drugs or, if needed, with insulin or non-insulin injectable drugs, but always in conjunction with diet modification and exercise.

Question 11

In the past, drugs for type 2 diabetes were started only
after a program of diet modification and exercise had failed to yield glycemic control. Today, drugs (usually metformin) are started __.

Answer 11

immediately after diagnosis, but always in conjunction with diet modification and exercise.

Question 12

In type 1 diabetes, __ can markedly reduce long-term complications, as demonstrated in the Diabetes Control and Complications Trial (DCCT).

Answer 12

tight glycemic control

Question 13

In type 2 diabetes, tight glycemic control can decrease :

Answer 13

microvascular complications,

but not necessarily macrovascular complications or mortality, as shown in the ACCORD, ADVANCE, and VADT trials.

Question 14

Tight glycemic control increases the risk of

Answer 14

severe hypoglycemia and weight gain, and possibly the risk of death.

Question 15

For patients with type 1 diabetes and for patients with type 2 diabetes who use insulin, __ is the standard method for day-to-day monitoring of therapy.

Answer 15

self-monitoring of blood glucose (SMBG)

The premeal target is 80 to 130 mg/dL, and the peak postmeal target is 180 mg/dL or lower for many patients.

Question 16

For patients with type 1 or type 2 diabetes, hemoglobin

A1C should be measured every __.

Answer 16

3 to 6 months to assess long-term glycemic control.

Question 17

Insulin is an anabolic hormone. That is, it promotes:

Answer 17

conservation of energy and buildup of energy stores.

Question 18

Insulin has two basic effects: it

Answer 18

(1) stimulates cellular uptake of glucose, amino acids, and potassium; and
(2) promotes synthesis of complex organic molecules (glycogen, proteins, triglycerides).

Question 19

Insulin deficiency puts the body into a catabolic mode. As a result:

Answer 19

glycogen is converted to glucose, proteins are degraded to amino acids, and fats are converted to glycerol (glycerin) and free fatty acids.

Question 20

Insulin deficiency promotes hyperglycemia by increasing

Answer 20

glycogenolysis and gluconeogenesis and by decreasing glucose utilization.

Question 21

Multiple insulin products are used in the United States:

Answer 21

regular human insulin (injectable and inhaled forms), NPH insulin, and several human insulin analogs: insulin lispro,
insulin aspart, insulin glulisine, insulin detemir, insulin
glargine, and insulin degludec.

Question 22

All insulins used in the United States are produced by

Answer 22

recombinant DNA technology.

Question 23

Insulin lispro, insulin aspart, insulin glulisine, and regular insulin, when administered via inhalation, have a __.

Answer 23

very rapid onset and short duration.

Question 24

Regular insulin, when used subQ, has a __.

Answer 24

moderately rapid onset and short duration.

Question 25

NPH insulin has an

Answer 25

intermediate duration of action

Question 26

(2) have a prolonged duration, with no definite “peak” in either blood levels or hypoglycemic effects. Some patients may still require twice-daily administration with these products.

Answer 26

Insulin glargine (U-100) and insulin detemir

Question 27

(2) have a very long duration of action, with a duration of effect in excess of 24 hours.

Answer 27

Insulin glargine (U-300) and insulin degludec

Question 28

All insulins can be administered subQ, and four

preparations— (4) — can be administered IV as well.

Answer 28

regular, aspart, lispro, and glulisine insulin

Question 29

One insulin preparation—___—is a suspension.

Answer 29

NPH insulin

It looks cloudy and should be agitated before being drawn into a syringe. All other insulins are solutions. They look clear and do not require agitation.

Question 30

SMBG is an essential component of intensive ___.

Answer 30

insulin therapy.

Question 31

The most important and common adverse effect of insulin therapy is ___.

Answer 31

hypoglycemia (blood glucose below 70 mg/dL), which occurs whenever insulin levels exceed insulin needs.

Symptoms include tachycardia, palpitations, sweating, headache, confusion, drowsiness, and fatigue. If hypoglycemia is severe, convulsions, coma, and death may follow.

Question 32

___ can delay awareness of hypoglycemia by masking hypoglycemia-induced signs that are caused by
activation of the sympathetic nervous system (e.g., tachycardia, palpitations).

Answer 32

Beta blockers

In addition, beta blockers inhibit the breakdown of glycogen to glucose and can thereby impede glucose replenishment.

Question 33

Insulin-induced hypoglycemia can be treated with (3).

Answer 33

a fast acting oral sugar (e.g., glucose tablets, orange juice, sugar cubes), IV glucose, or parenteral glucagon.

Oral sucrose— aka table sugar—acts slowly and will barely work at all in patients taking acarbose, a drug that prevents intestinal conversion of sucrose into glucose and fructose.

Question 34

__ decreases glucose production by the liver and increases glucose uptake by muscle and adipose tissue.

Answer 34

Metformin (a biguanide)

Question 35

The major adverse effects of metformin are __. Metformin does not cause hypoglycemia when used alone.

Answer 35

GI disturbances: decreased appetite, nausea, and diarrhea

Question 36

Very rarely, metformin causes ___.

Answer 36

lactic acidosis, which can be fatal.

The risk of lactic acidosis is increased by renal impairment, which decreases metformin excretion and thereby causes levels to rise rapidly.

Metformin is therefore dosed based on renal function.

Question 37

Sulfonylureas stimulate release of __.

Answer 37

insulin from the pancreas.

Question 38

The major adverse effects of sulfonylureas are (2).

Answer 38

hypoglycemia and weight gain

Question 39

Pioglitazone, a thiazolidinedione (glitazone) for type 2

diabetes, increases:

Answer 39

insulin sensitivity of target cells and thereby increases glucose uptake by muscle and adipose tissue and decreases glucose production by the liver.

Question 40

Thiazolidinediones promote water retention and can thereby increase the risk of __.

Answer 40

heart failure.

In addition, pioglitazone can cause liver damage, bladder cancer, and fractures, and can cause ovulation in anovulatory premenopausal women, thereby posing a risk of unintended pregnancy

Question 41

(2) for type 2 diabetes, inhibit digestion and absorption of carbohydrates and thereby reduce the postprandial rise in blood glucose. To be effective, these agents must be taken with every meal.

Answer 41

Acarbose and miglitol (alpha-glucosidase inhibitors)

Question 42

The major adverse effects of alpha-glucosidase inhibitors are __.

Answer 42

GI disturbances: flatulence, cramps, and abdominal distention.

Question 43

DPP-4 inhibitors are oral medications that __.

Answer 43

lower A1C by about 0.5%.

These agents are generally well tolerated and augment the effects of natural incretin hormones.

Question 44

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors lower blood sugar by __.

Answer 44

increasing excretion of glucose via the urine.

SGLT-2 inhibitors can increase the risk of genitourinary infections.

Question 45

(2) have been shown in large cardiovascular outcome trials to prevent cardiovascular events in at-risk patients.

Answer 45

Canagliflozin and empagliflozin (both SGLT-2 inhibitors)

Question 46

Incretin mimetics are injectable agents for the treatment

of type 2 diabetes. These drugs (3).

Answer 46

delay gastric emptying, suppress glucagon release, and stimulate glucose-dependent release of insulin.

There are currently six products available within this drug class: exenatide, exenatide ER, liraglutide, lixisenatide, albiglutide, and dulaglutide.

Question 47

Incretin mimetics pose a risk of hypoglycemia in patients taking a __.

Answer 47

sulfonylurea, but not in those taking metformin.

Nausea is common.

Question 48

Pramlintide, an amylin mimetic, is injected subQ before

meals to __.

Answer 48

enhance the effects of mealtime insulin in patients with type 1 or type 2 diabetes.

The drug delays gastric emptying and suppresses glucagon release and thereby helps reduce postprandial hyperglycemia.

Question 49

The combination of pramlintide plus insulin poses a risk of __.

Answer 49

severe hypoglycemia. Nausea is common.

Question 50

Fixed-dose injectable combination products containing a basal insulin with a GLP-1 receptor agonist are available.
Currently available agents are:

Answer 50

Soliqua 100/33 (insulin glargine, lixisenatide) and Xultophy 100/3.6 (insulin degludec, liraglutide).