Pharm Exam 3 MOA Only

Question 1

a Glucosidase Inhibitors

Answer 1

• Are carbohydrate analogs that bind reversibly and with much greater affinity than carbs to GS
• Delays the absorption of carbohydrates making it effective in decreasing the after meal glucose spike
• Metabolism occurs within the GI tract
• generally considered to be additive to other antidiabetics

Question 2

Biguanides

Answer 2

• Reduced gluconeogenesis by activating AMPK
• Increase insulin action in muscle and fat through AMPK
• Delayed glucose absorption in the GI tract
• Direct stimulation of glycolysis in tissue with increased removal of glucose from blood
• Reduced plasma glucagon

Question 3

Incretins

Answer 3

• GLP-1 and GIP stimulate insulin release in response to elevated blood glucose
• GLP-1 lowers glucagon secretion, slows gastric emptying and regulates beta cell growth
• DPP-4 inactivates GLP-1 and GIP
• Gliptins inhibit DDP-4
• Incretin Mimetics cannot be broken down by DPP-4
• Incretin effect - Oral glucose is more effective at stimulating insulin release than IV administered because GLP-1 and GIP are secreted in the bowel

Question 4

Insulin

Answer 4

• Mobilizes GLUT-4 transporters on fat and muscle cells
• Increased glycogen synthesis in liver and muscle
• Inhibits gluconeogenesis in the liver
• Muscle it increases the uptake of amino acids for protein synthesis
• Adipose it promotes the synthesis of triglycerides and inhibits lipolysis

Question 5

Meglitinides

Answer 5

• Stimulate the release of insulin
• Bind to beta cells at the SUR-1 receptor
• Opening of the ATP sensitive K channel
• Depolarizes the cell resulting in Ca++ release
• Ca++ initiates exocytosis of insulin
• Relies on functioning beta cells so it is not used in DM1
• Short onset allows it to be used before meals to decrease glucose spike

Question 6

Sulfonylureas

Answer 6

• Stimulate the release of insulin
• Bind to beta cells at the SUR-1 receptor
• Opening of the ATP sensitive K channel
• Depolarizes the cell resulting in Ca++ release
• Ca++ initiates exocytosis of insulin
• Relies on functioning beta cells so it is not used in DM1

Question 7

Thiazolidinediones

Answer 7

• Peroxisome proliferator activated receptor- gamma agonists (PPAR-y)
• PPAR-y receptors are found in the nucleus of muscle, fat and liver cells
• PPAR-y recdeptors are responsible for lipid and protein metabolism, insulin signal transduction, tissue differentiation
• Promote uptake and storage of FFA’s
• Promote expression and translocation of glucose transporters
• Stimulation of adiponectin which increases glucose uptake, inhibits atherosclerosis and endothelial apoptosis, stabilizes plaques

Question 8

Glucagon

Answer 8

• Secretion is controlled by the Sympathetic NS
• Works through cAMP
• Increases glycogenolysis
• Decreased glycogen synthesis
• Increased glycolysis
• Increased ketogenesis

Question 9

Somatostatin analogs

Answer 9

• Acts on the somatostatin Receptors s1-S5
• Secreted by the delta cells
• Reduces secretion of GH. Insulin, Glucagon, Gastrin, VIP and pancreatic enzymes
• Lowers portal BP by vasoconstriction leading to decreased blood flow to the liver

Question 10

GH Antagonists

Answer 10

• Block the action of GH at the liver
• Blocks the release of IGF-1 which works on bone, and soft tissues
• GH is an Insulin antagonist

Question 11

ACTH

Answer 11

• Acts though cAMP activation to produce cortisol in the ZF

Question 12

Thyroid replacements

Answer 12

• Replacement of T4

Question 13

Antithyroids

Answer 13

Thioamides
- Inhibit thyroid perioxidase
- Block iodine oxidation
- Block the coupling of iodinated tyrosines
- Inhibit peripheral iodination of T3 and T4
- Do not block the uptake of iodine
Radioactive Iodine 131I
- Destroys the thyroid gland through radiation

Question 14

Steroids as Immune Modifiers

Answer 14

• Decreasing the number of white blood cells
• reduce the function of macrophages and lymphocytes
• Reduced function on phospholipase A2 resulting in reduced mediators of inflamation

Question 15

B Cell biologics

Answer 15

• Either destroy the B Cell or decrease its function
• Blockage of CD20 results in apoptosis
• Blocking of the cytokines which stimulate B Cell activity will decrease the function of B Cells
• CD20 is expressed only of B Cells

Question 16

T Cell Biologics

Answer 16

• CD3 is expressed on all T cells, targeting it will nonspecifically inhibit all T cells
• CD25 is the IL-2 receptor. Decreased IL-2 leads to decreased inflammation.
• Expressed on Treg cells which suppress Autoreactive T cells so the benefit must out weigh the cost
• CTLA-4 is a costimulator of T cells, its inhibition will decrease the activation of T cells

Question 17

Mixed Biologics

Answer 17

• CD52 located on both T and B cells. Targeting of it by mAbs results in prolonged T and B cell Depletion.
• IL6 - Receptor. Targeting this does not destroy lymphocytes but can inhibit them

Question 18

TNF-a

Answer 18

• Reduces the inflammatory process and releases cytotoxic agents

Question 19

Antimetabolites

Answer 19

• Act in several ways but the end result is reduced DNA and RNA synthesis
• T and B cells are highly sensitive because they must produce their own (de novo) purines

Question 20

Calcineurin Inhibitors

Answer 20

• Act on T cells
• Calcineurin binds to NFAT to dephosporalate it which allows it to bind to T cell DNA resulting in production of IL-2 which matures the T cell
• Calcineurin inhibitors prevent this process

Question 21

mTOR Inhibitors

Answer 21

• Binds to FKBP-12 in the cytoplasm, this complex then inhibits mTOR
• Impede VGEF
• Block the action of IL-2

Question 22

Glatiramoids

Answer 22

• Binds to MHC class II

- Induces T helper 2 suppressive cells