Pharmacology of Insulin and Oral Hypoglycemics Flashcards Preview

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Flashcards in Pharmacology of Insulin and Oral Hypoglycemics Deck (58):
1

What is the function of pancreatic polypeptide and from what cell type in the pancreas is it released?

- self-regulates pancreatic secretions and comes from F cells.

2

What is the function of ghrelin and from what cell type is it secreted?

- stimulates growth hormone release and comes from Epsilon cells.

3

What is the role of somatostatin and from what cell type is it secreted?

- inhibitor of secretory cells, and comes from delta cells.

4

What is the normal, prediabetic, and DM levels, respectively for fasting blood glucose?

- normal= less than 100
- prediabetes= 100-125
- DM= greater than 126

5

What is the normal, prediabetic, and DM levels, respectively for 2-hr postload blood glucose?

- normal= less than 140
- prediabetes= 140-199
- DM= greater than 200

6

What is the normal, prediabetic, and DM levels, respectively for hemoglobin A1c %?

- normal= less than 5.6
- prediabetes= 5.7-6.4
- DM= greater than 6.5

7

What type of insulin do you want to give for PRANDIAL situations (after a meal)?

- short and fast acting

8

How is insulin synthesized?

- in pancreatic Beta cells as proinsulin (A, B, and C chains), which will be packaged into secretory granules with trypsin-like proteolysis, which will cleave proinsulin into C-PEPTIDE and INSULIN (A and B chains connected via 2 disulfide bonds).

9

Does C-peptide or insulin have a longer half-life?

- C-peptide

10

Does loss of disulfide linkage of insulin result in loss of function?

- YES

11

**** What stimulates insulin release?

- increased blood GLUCOSE (also B-adrenergic stimulation, vagal stimulation, and glucagon-like peptide 1; GLP-1), which is taken into the pancreatic beta cell via GLUT2 transporter, INCREASING ATP and CLOSING K+ channels, thus depolarizing the cell and OPENING CALCIUM channels= exocytosis of INSULIN :)

12

What drugs will stimulate insulin release?

- SULFONYLUREAS
- meGLITINIDE
- nateGLINIDE
- isoproterenol
- acetylcholine

13

What will inhibit insulin release?

- somatostatin
- leptin
- alpha-sympathetics

14

What drugs will inhibit insulin release?

- diazoxide
- pheytoin
- vinblastine
- colchicine

15

*** What intracellular enzyme is linked to the extracellular insulin receptor?

- TYROSINE KINASE= phosphorylates insulin receptor substrates (IRS), leading to upregulation of GLUT4 transporters on adipose and skeletal muscle tissue and thus entry of glucose into the tissues. This leads to protein, fat, and glycogen synthesis (as well as growth and gene expression).

16

What electrolyte must you monitor when giving insulin?

- K+ because it will also be taken into the cells (can lead to hypokalemia).

17

What are the sources of insulin?

- human and analog insulin (only human used in U.S.)
- Porcine
- Bovine

18

*** What are the RAPID-acting (less than 4 hrs) insulin agents?

- lispro
- aspart
- glulisine
- new= afrezza (inhaled)
*subcutaneously just before a meal.

19

*** What is the SHORT-acting (5-8 hrs) insulin agent?

- regular insulin
*subcutaneously 1 hr before meal.

20

*** What is the INTERMEDIATE-acting (4-12 hrs) insulin agent?

- neutral protamine hagedorn (NPH) insulin
*subcutaneously mixed with rapid or short-acting.

21

*** What are the LONG-acting (12 or 24 hours) insulin agents?

- detmir
- glargine
*subcutaneously background insulin replacement.

22

Can intermediate or long acting agents ever be used intravenously?

- NEVER

23

For what use is rapid-acting insulin (lispro, aspart, or glulisine) used?

- IV for uncomplicated ketoacidosis

24

For what use is short-acting insulin (regular insulin) used?

- IV for ketoacidosis, surgery, or acute infections (most common).

25

What is the goal mean blood glucose for insulin therapy?

- less than 154 mg/dL or HbA1c less than 7%
*standard therapy= twice daily injections.

26

What are the symptoms of hypoglycemia (ADR of insulin)?

- headache, anxiety, tachycardia, confusion, vertigo, diaphoresis, shaky, blurred vision, fatigue...

27

What is lipodystrophy?

- abnormal or degenerative conditions of the body's adipose tissue due to hypersensitivity to insulin injections.

28

**** What are the anti-diabetic type II drugs?

- secretagogues; increased insulin secretion= SULFONYLUREAS, meGLITINIDES, D-phenylalanine derivatives.
- DPP-IV inhibitory; increased insulin secretion= sitaGLIPTIN
- METFORMIN and THIZOLIDINEDIONES= increased insulin sensitivity at peripheral tissues
- alpha-glucosidase inhibitors= reduce glucose absorption from GI system.
- SGLT-2 inhibitor; reduced glucose reabsorption at proximal convoluted tubule of kidney= dapagliFLOZIN
- decreased gastric emptying= AMYLIN (PRAMLINTIDE)

29

**** What is the mechanism of action for SULFONYLUREAS?

- stimulation of insulin release by blocking ATP-sensitive K+ channels, leading to depolarization, Ca2+ influx, and thus insulin exocytosis.
*given P.O. and metabolized by liver.

30

**** What are the 3 sulfonylureas used?

1. GLYBURIDE
2. GLIPIZIDE
3. GLIMEPIRIDE

31

What are some ADRs of sulfonylureas?

- weight gain, hyperinsulinemia, hypoglycemia

32

What sulfonylurea is safe to use in pregnancy?

- GLYBURIDE

33

*** What is the mechanism of action of the insulin secretagogues (-GLITINIDES)?

- similar to sulfonylureas= increased insulin secretion from pancreatic beta-cells
*good for POSTPRANDIAL glucose regulators.

34

*** What is INCRETIN (-GLUTIDES)?

- glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) released from gut after a meal to inhibit glucagon release, stimulate satiety, decrease gastric motility, and increase insulin secretion.
*given S.C. (ex. albiGLUTIDE is given once every 5 days)

35

*** What is the mechanism of action of the DPP-4 inhibitors (-GLIPTINS)?

- prolong GLP-1 effects, thus increasing insulin release to meals and reducing secretion of glucagon.
- however, unlike incretin, these do not cause satiety.
*given P.O.

36

What is an ADR of INCRETIN and DPP-4 inhibitors?

- pancreatitis

37

**** What is the mechanism of action of METFORMIN?

- insulin sensitizer via activation of AMP-stimulated protein kinase= reduction of hepatic gluconeogenesis, slows intestinal absorption of sugars, improves peripheral glucose uptake (increased insulin sensitivity), and reduces plasma glucagon.
*initial drugs of choice for T2DM (given P.O.)

38

Does metformin cause weight gain?

- NO (unlike insulin, secretagogues, or thiazolidinediones)
*remember metformin does NOT stimulate insulin.

39

Can metformin cause hypoglycemia?

- RARELY :)

40

How is metformin metabolized?

- it's NOT. It is excreted in the urine.

41

*** What is the main ADR of metformin?

- LACTIC ACIDOSIS (esp. those with renal disease or alcoholics).

42

*** What are the thiazolidinediones (TZDs) and their MOA?

- rosiGLITAZONE
- pioGLITZAONE
- activates nuclear receptor peroxisome proliferatory-activated receptor-y (PPAR-y), which decreases lipolysis, decreases free fatty acids, increases glucose uptake, and decreases hepatic gluconeogenesis.
*NOT 1st line.

43

What are the ADRs of thiazolidinediones (TZDs; -GLITAZONES)?

- fluid retention (so don't use in heart failure).
- osteopenia

44

**** What are the alpha-glucosidase inhibitors?

- ACARBOS and MIGLITOL (oral) taken with a meal.
- inhibit alpha-glucosidase in the GI brush border, delaying digestion and absorption of carbohydrates resulting in LOWER POSTPRANDIAL glucose levels.
*minimal effects on fasting glucose.

45

What are the contraindications for alpha-glucosidase inhibitors (ACARBOS and MIGLITOL)?

- inflammatory bowel disease
- colonic ulceration
- intestinal obstruction

46

Can you use SUCROSE to treat a pt suffering from a hypoglycemic attack being treated with combination therapy (with alpha-glucosidase inhibitors)?

- NO because sucrose must be digested by alpha-glucosidase

47

What are the SGLT2 inhibitors?

- canagliFLOZIN and dapagliFLOZIN (oral).
- inhibit Na+-glucose transporter 2 (SGLT2) in kidney, thus preventing reabsorption of glucose from the PCT in the kidney, leading to osmotic diuresis.

48

What are the ADRs of SGLT2 inhibitors?

- female genital mycotic infections
- UTI
- hypotension

49

*** What is AMYLIN (pramlintide)?

- delays gastric emptying without affecting absorption, decreases postprandial glucagon secretion, improves satiety, and reduces postprandial glucose levels.
*used S.C. as adjunct to mealtime insulin therapy (but not used in the same syringe)

50

What is bromocriptine?

- dopamine agonist (D2 receptor), which lowers HbA1c slightly.

51

What is colesevelam?

- bile acid sequestrant, which lowers HbA1c slightly.

52

**** What is glucagon?

- hormone secreted by alpha-cells of the pancreas, which activates Gs protein-coupled receptors leading to increased glycogenolysis, gluconeogenesis, and ketogenesis.
- also stimulates release of insulin, catecholamines, and calcitonin.

53

What will glucagon do to the heart?

- inotropic and chronotropic effects (without use of the beta receptors).

54

What does glucagon do to GI smooth muscle?

- relaxation

55

**** A 13 y/o boy with T1DM is brought to the ED. Lab findings include severe hyperglycemia, ketoacidosis, and blood pH of 7.15. What agent should be administered?
A. regular insulin
B. glyburide
C. insulin glargine
D. NPH insulin
E. tolbutamide

- A. regular insulin

56

**** A 24 y/o woman with T1DM wishes to try tight control of her diabetes to improve her long-term prognosis. Which regimen is most appropriate?
A. morning injections of mixed insulin lispro and insulin aspart.
B. evening injections of mixed regular insulin and insulin glargine.
C. morning and evening injections of regular insulin, supplemented by small amounts of NPH insulin at mealtimes.
D. morning injections of insulin glargine, supplemented by small amounts of insulin lispro at mealtimes.
E. morning injections of NPH insulin and evening injection of regular insulin.

D. morning injections of insulin glargine, supplemented by small amounts of insulin lispro at mealtimes.

57

**** Which drug promotes the release of endogenous insulin?
A. acarbose
B. canagliflozin
C. glipizide
D. metformin
E. miglitol
F. pioglitzaone

C. glipizide

58

**** Which of the following drugs is most likely to cause hypoglycemia when used as monotherapy for T2DM?
A. acarbose
B. canagliflozin
C. glyburide
D. metformin
E. miglitol
F. rosiglitzazone

C. glyburide