Diabetic Therapy Lecture PDF

Question 1

Secretion of insulin is triggered by these 5 things

Answer 1

• glucose
• amino acids
• fatty acids
• ketone bodies
• Epi/norepi

Question 2

Absence of insulin transfers us from a ___ state to a ___ state

Answer 2

anabolic, catabolic (in absence of insulin we see glycogen converted to glucose, gluconeogenesis, and decreased cellular uptake of glucose)

Question 3

Therapeutic uses of insulin (3)

Answer 3

• diabetes mellitus (type 1 all patients and some type 2)
• IV for diabetic ketoacidosis
• treatment of hyperkalemia (pulls K+ intracellularly

Question 4

Why were animal sources of insulin discontinued?

Answer 4

Because they differ slightly from human insulin, antibodies may develop

Question 5

Recombinant human insulin analogs

Answer 5

Bioidentical insulin grown in e coli or yeast that has been slightly modified to have a different time course (either shorter or longer acting)

Question 6

Rapid acting insulin analog time frame compared to regular

Answer 6

5-30 minutes, 30-60 (but have a shorter duration of action in 3-5 hours, are more convenient because can be administered with or just before a meal

Question 7

Metformin (glucophage) function

Answer 7

-Drug of choice for initial treatment of type 2 diabetes, when not A1C goal reached can use additional agents depending on comorbidities (SGL2 inhibitors)

Question 8

If max dose of 2 drugs insufficient to achieve glycemic control, then…

Answer 8

….insulin or another drug can be added

Question 9

Sulfonylureas function

Answer 9

PO drugs derivatives from sulfonamides administered to reduce plasma glucose levels

Question 10

Principal differences between first and 2nd gen sulfonylureas

Answer 10

Second gen are much more potent at lower doses and serious interactions are less common and are therefore widely used and generally superior

Question 11

3 second gen sulfonylureas

Answer 11

• Glipizide (glucotrol)
• glyburide
• glimepiride

Question 12

Sulfonylureas mech of action

Answer 12

Stimulate release of insulin from pancreatic tissues by binding receptor sites on B cell causing depolarization triggering increase in intracelular calcium and thus insulin release (pancreas must be able to produce insulin for them to be effective, with prolonged use agents enhance cellular sensitivity to insulin thru unknown mechanism)

Question 13

Sulfonylureas ADR’s (4)

Answer 13

• Hypoglycemia (tell patients not to skip meals)
• weight gain 5-10 pounds
• hematologic reactions such as lekupenia or thrombocytopenia
• disulfuram like reaction (flushing, palpitations, nausea reported with use when drinking on chlorpropamide ( a gen 1 agent)

Question 14

Metformin mech of action

Answer 14

• lowers blood glucose primarily thru decreasing hepatic gluconeogenesis and secretion of glucagon like peptide
• does not stimulate insulin release from pancreas and does not actively drive down blood glucose levels posing little to any added risk of hypoglycemia when used alone

Question 15

Metformin therapeutic use (4)

Answer 15

• monotherapy in patients whose blood sugar levels are not controlled by diet or exercise alone
• combo therapy with other antidiabetic agents such as sulfonylureas
• PCOS off labeled use
• Cardiovascular reduction in risk of MI

Question 16

Metformin ADR’s (3)

Answer 16

• GI effects
• Decreased B12 and folic acid absorption which can lead to deficiencies (not recommended to supplement with metformin)
• Lactic acidosis in patients with low GFR

Question 17

Acarbose (precose) drug class and mech of action

Answer 17

• alpha glucosidase inhibitor
• oral agent that reversibly inhibits alpha glucosidase, and enzyme present in brush border mucosa of small intestine, slows rate at which complex polysaccharides and sucrose are digested resulting in lower postprandial blood glucose conc

Question 18

Acarbose (precose) ADR (1)

Answer 18

-GI effects due to fermentation of unabsorbed carbohydrate

Question 19

Miglitol (glyset) function

Answer 19

Delays carb conversion of oligosaccharides and complex carbs to glucose decreasing postprandial rise in blood glucose

Question 20

Thiazolidinediones function and mech of action

Answer 20

• Antidiabetic agents that work primarily by decreasing insulin resistance
• Decrease insulin resistance by activating a specific receptor type in the cell nucleus known as PPAR gamma, as a result insulin responsive genes are turned on that hep regulate carbohydrate and lipid metabolism, cellular response to insulin is increased promoting uptake

Question 21

Thiazolidinediones ADR’s (4)

Answer 21

• Uncertain if benefits outweigh risks
• Heart failure
• weight gain
• anemia

Question 22

Rosiglitazone (avandia) drug class, function and ADR’s (3)

Answer 22

• Thiazolidinediones
• Approved for monotherapy or with metformin for treatment of type 2 diabetes
• edema, weight gain, mild anemia

Question 23

Pioglitazone (ACTOS) drug class, function, ADR’s (3)

Answer 23

• Thiazolidinedions
• Approved for monotherapy or with metformin for treatment of diabetes
• Fractures, bladder cancer, hepatotoxicity

Question 24

Metiglinides (Glinides) function

Answer 24

Short acting agents for type 2 diabetes with same mech of action as sulfonylureas, tend to be shorter acting tho and are taken with each meal

Question 25

DPP-4 inhibitors mech of action and therapeutic use (1)

Answer 25

Promote glycemic control by enhancing the actions of incretin hormones, potentiating glucose dependent secretion of insulin and suppress glucagon secretion, produce modest reductions in A1C levels when used as monotherapy -2nd line therapy as add on to metformin

Question 26

Sitagliptin (Januvia) drug class, function, and ADR's (3)

Answer 26

- DDP inhibitor - Approved for PO monotherapy or in combo with other antidiabetic drugs for treatment of type 2 diabetes - URI, headaches, pancreatitis

Question 27

SGLT2 inhibitors mech of action and other benefit

Answer 27

- Block SGLT2 transporters decreasing renal glucose reabsorption and increasing urinary glucose excretion, reducing fasting and prepreandial blood glucose levels - Reduction in SBP reducing CV risk

Question 28

SGLT2 inhibitors ADR's (3)

Answer 28

- frequent mycotic genital and urinary tract infection - fournier gangrene (necrotizing infection of external genitalia, perineum, and perianal region) - acute kidney injury

Question 29

Bromocriptine (cycloset) function, mech of action, and other beneficial use

Answer 29

- Approved as adjunct to diet and exercise to treat type 2 diabetes as monotherapy or in conjunction with metformin - unknown mechanism but dopamine agonist - breast milk production inhibition

Question 30

Glucagon like peptide 1 (GLP1) receptor agonists function and mech of action

Answer 30

- injectable agents administered SC for treatment of type 2 diabetes - Have same physiologic effect as endogenous incretins slowing gastric emptying stimulation of glucose dependent release of insulin and inhibition of postprandial release of glucagon

Question 31

Exenatide drug class and function

Answer 31

- GLP-1 agonist | - type 2 diabetes adjunct to metformin and/or sulfonyurea in pts without adequate glycemic control

Question 32

GLP 1 agonist ADR's (2)

Answer 32

- pancreatitis | - thyroid carcinomas

Question 33

Pramlintide (symlin) drug class and function

Answer 33

- synthetic analog of human amylin (amylin mimetic) - approved for adjunctive treatment for patients with type 1 or 2 diabetes who inject insulin at mealtimes and have failed to achieve glucose control

Question 34

3 frequently used rapid acting insulin analogs

Answer 34

- Aspart - glulisine - lispro (humalog)

Question 35

Lispro (humalog) rapid absorption mech of action

Answer 35

-unlike most insulin, avoids self association to form hexamers unlike most insulins and thus attains more rapid absorption and onset of action (15 min)

Question 36

Air inhaled insulin (Afrezza) function and ADR's (3)

Answer 36

- Inhaled rapid acting dry powder formulation of recombinant human insulin approved for treatment of adults with type 1 or 2 DM - Throat pain, cough, FEV1 decline

Question 37

Regular insulin (humulin R) function

Answer 37

Unmodified crystalline insulin that is short acting soluble insulin, after SC injection forms small hexamers delaying absorption and onset to .5-1 hour, with peak action occurring 2.5-5 hours, and lasting 4-12 hours

Question 38

Regular U-500 insulin function (Humulin)

Answer 38

Normal insulin indicated in patients who require >200 units/day specifically targeting insulin resistant patients with severe type 2 diabetes, exhibits both a bolus and basal effect and can be used as monotherapy in some cases for type 2 diabetics

Question 39

Examples of long acting insulin (3)

Answer 39

- Lantus - levemir - toujeo

Question 40

Lantus function

Answer 40

Long acting peakless insulin analog, mimics basal effects of insulin secreted by healthy pancreas

Question 41

Administration of insulin

Answer 41

Must be given by injection or inhalation because it is degraded in the stomach as a peptide

Question 42

Insulin injection sites

Answer 42

Since absorption varies among sites, it is recommended to make injections in one particular area, but sites should be rotated in that area to help limit lipohypertrophy

Question 43

Complications of insulin therapy (3)

Answer 43

- hypoglycemia (blood glucose <70 mg/dL) - diabetic coma - hypokalemia (can impact heart)

Question 44

Treatment of hypoglycemia in patients (3)

Answer 44

- oral sugar supplements (NOT chocolate or hard piece of candy - aspiration risk if loss of gag reflex or unconscious) - IV dextrose - Glucagon

Question 45

2 causes of diabetic coma that must be determined

Answer 45

- hypoglycemic requiring withholding of insulin | - ketoacidosis which requires insulin