Diabetes Drugs

Question 1

What is the goal of insulin therapy for pts with T1DM?

Answer 1

Achieve normal glycemic control

Use basal insulin to replace insulin made under fasting conditions, and posprandial insulin for more rapid action

Question 2

Insulin MOA (3 primary organs and its effects)

Answer 2

Liver
Inhibit secretion of glucagon from alpha cells, thus decreasing gluconeogenesis and glycogenolysis

Muscle
Upregulate GLUT4 and increase glucose uptake. Increase protein synthesis and inhibit proteolysis

Adipose
Increase glucose uptake and decrease lipolysis

Question 3

Name the different forms of rapid acting insulin

Answer 3

Insulin aspart
Insulin lispro
Insulin glulisine

Question 4

What is the intermediate acting insulin?

Answer 4

NPH Insulin

Question 5

Name the long acting insulins

Answer 5

Insulin glargine

Insulin detmir

Question 6

Insulin

Administration

Answer 6

SubQ via syringe, pen, or pump

Note: You should change site of administration over time, as insulin promotes lipid storage in adipose cells

Question 7

Compare Conventional Insulin Therapy with Intensive Insulin Therapy

Answer 7

Conventional: Two injections per day containing both NPH insulin and regular insulin
Risk of hyperglycemia at night

Intensive: Once/twice daily basal insulin to lower fasting glucose, with pre-meal bolus of rapid insulin to control postprandial glucose
Needs more patient commitment; higher cost

Question 8

Major symptoms of Hypoglycemia

Answer 8

Mild: Tremor, palpitations, sweating, hunger

Moderate: Headache, mood change, decreased attention, patients may need assistance

Severe: Unresponsive, Unconscious, convulsions, death

Question 9

What is the best treatment for T2DM?

Answer 9

Diet and exercise

Question 10

What is the DOC for patients unable to control T2DM with diet and exercise along?

Answer 10

Metformin

Question 11

Metformin

MOA

Answer 11

Blocks complex 1 in mitochondrial oxidative phosphorylation, leading to an antagonization of adenylate cyclase in the liver (preventing gluconeogenesis). Also causes increased AMP, leading to higher AMPK, causing increased insulin sensitivity, glucose uptake.

Lower plasma glucose and insulin resistance

Question 12

Metformin

Adverse Effects

Answer 12

Mostly well tolerated (some GI effects, potential B12 def)

Major AE: Lactic Acidosis that may be fatal
-Paritcular risk in high risk pt (elderly, renal/hepatic insufficiency)

Question 13

Metformin

Contraindications

Answer 13

Pregnent/lactating women

Renal or hepatic insufficiency

Elderly (risk renal insufficiency)

Anyone at risk for lactic acidosis

Anyone taking iodinated contrast agent for radiography (risk of agent-induced acute renal failure)

Question 14

What are the two Thiazolidinediones?

Answer 14

Pioglitazone

Rosiglitazone

Question 15

Pioglitazone and Rosiglitazone

MOA

Answer 15

Agonist for PPARy
Increases gene transcription of GLUT4 in muscle, increased adiponectin

Increases Insulin SENSITIVITY

Question 16

Pioglitazone and Rosiglitazone

Indications

Answer 16

Used in monotherapy or in combo with metformin, sulfonylureas, or insulin for T2DM

Decreases FASTING blood glucose

Question 17

Pioglitazone and Rosiglitazone

Adverse Effects

Answer 17

Weight gain

Fluid retention and peripheral edema
-Increased risk HEART FAILURE

Increased risk bone fracture

Hepatotoxic

Question 18

Pioglitazone and Rosiglitazone

Contraindications

Answer 18

Liver disease
Heart failure
Pregnancy

Question 19

What two classes of drugs are known as insulin secretagogues? What is each of their durations?

Answer 19

Sulfonylureas (longer acting, primarily affect fasting glucose)

Meglitinides (shorter duration, primarily affect postprandial glucose)

Question 20

What sulfonylurea drugs are commonly used today?

Answer 20

Glipizide
Glimepride
Glyburide

Question 21

Sulfonylurea

MOA

Answer 21

Inhibit Sur1 subunit of the Kir6.2 channel on beta cells. Causes an increase in intracellular K+, stimulatign Ca2+ influx and causing release of insulin-containign granules

Question 22

Sulfonylureas

Indications and Uses

Answer 22

Long duration of glucose lowering effect, primarily affecting fasting plasma glucose

Activity is dependent on function of beta cells, which will likely lose function over time

Question 23

Sulfonylureas

Adverse Effects

Answer 23

Hypoglycemia– seen more in pts with renal or hepatic insufficiency

Weight gain

Question 24

Describe the metabolism of Glipizide, Glyburide, and Glimepride and how that affects their potential uses and toxicites

Answer 24

Glyburide and Glimepride are metabolized in liver to active metabolites, so they may cause increased drug conc and toxicity in renal or hepatic insufficiency

Glipizide is metabolized in liver to an inactive metabolite, so it is safer to use in patients with renal insufficiency

Question 25

Sulfonylureas | Contraindications

Answer 25

Elderly people with renal or liver insufficiency T1DM Pregnant/lactating women Sulfa allergy

Question 26

Sulfonylureas | Drug Interactions

Answer 26

Sulfonylureas are highly protein bound drugs, so it is easy to knock them off with other drugs (salicylates, B blockers, warfarin, fibrates) and cause toxicity

Question 27

Meglitinides | MOA

Answer 27

Bind a different part of Sur1 subunit of the Kir6.2 channel on Beta cells, inhibiting it and causing increase in intracellular K+, then ca2+, then release of insulin granules

Question 28

What is the major difference between meglitinides and Sulfonylureas?

Answer 28

Meglitinides are much more rapid acting and used to affect postprandial blood glucose They are glucose-dependent, whereas sulfonylureas are not

Question 29

Name the two Meglitinides

Answer 29

Repaglinide | Nateglinide

Question 30

Meglitinides | Adverse Effects

Answer 30

Hypoglycemia | Weight gain

Question 31

Meglitinides | Contraindications

Answer 31

Liver disease Pregnancy

Question 32

What is the major difference between Nateglinide and Repaglinide?

Answer 32

Nateglinide does not require dose adjustment in renal insufficiency

Question 33

List the GLP-1 homologs

Answer 33

Exenatide | Liraglutide

Question 34

Describe the Incretin Effect

Answer 34

Oral glucose induces a much better plasma insulin response than IV glucose does because of release of incretins form intestines, which potentiate insulin release at beta cells

Question 35

Exenatide | MOA

Answer 35

Binds GLP-1 receptor on beta cells and potentiates glucose-induced insulin release Suppresses glucagon production Makes periphery more sensitive to insulin

Question 36

What is the advantage of giving exenatide over recombinant GLP-1?

Answer 36

GLP-1 has a very short half life (2 min) because it is rapidly broken down by DPP-IV Exenatide acts longer than GLP1 itself, and exenatide reduces both fasting and postprandial glucose

Question 37

List the DPP-IV Inhibitors

Answer 37

Sitagliptin | Saxagliptin

Question 38

DPP-IV Inhibitors | MOA

Answer 38

Inhibit breakdown of GLP1 by DPP-IV, thus allowing more activity of GLP1

Question 39

Alpha-glucosidase inhibitors | MOA

Answer 39

Reduce postprandial blood glucose by inhibiting the digestion of polysaccharides in the small intestine (inhibit alpha-glucosidase enzyme)

Question 40

Alpha-glucosidase inhibitors | Adverse Effects

Answer 40

May cause GI side effects -- do not use when pt has any GI disorder Do NOT treat any hypoglycemia with complex carbs because the patient won't be able to break them down

Question 41

SGLT2 Inhibitors | MOA

Answer 41

Work to inhibit SGLT2 Na+/Glucose linked transporter protein in the kidney Promotes glucose excretion from kidney by preventing its reabsorption in the PCT

Question 42

SGLT2 Inhibitors | Adverse Effects

Answer 42

Increased risk UTIs Thirst/dehydration Hypotension Hyperkalemia

Question 43

Bromocriptine | MOA

Answer 43

Direct D2 agonist Given in quick release in early morning Decreases gluconeogenesis, lipolysis, and lipogenesis

Question 44

Colesevelam | MOA

Answer 44

Bile acid binding resin that is also used to treat dyslipidemia Prevent bile acid from being reabsorbed in the small intestine. Bile acids can then bind receptors in the colon to stimulate GLP1 secretion and thus potentiate insulin release

Question 45

Pramlintide | MOA

Answer 45

Amylin homolog that inhibits hepatic gluconeogenesis, slows gastric emptying, and lowers glycogenolysis Reduces POSTPRANDIAL glucose excursion

Question 46

Pramlintide | Indications

Answer 46

Used as an adjunct to insulin therapy Increases risk of severe hypoglycemia, so insulin dosage should be lowered before adding pramlintide