Drugs Used in Diabetes

Question 1

Pathology behind Type 1 DM?

Answer 1

loss of pancreatic B cells > absolute dependence on insulin

Question 2

Pathology behind Type 2 diabetes?

Answer 2

decreased response to insulin

Question 3

Which type of diabetes is ketoacidosis prone?

Answer 3

Type 1 DM

Question 4

Name some basal insulin forms.

Answer 4

glargine, determir, degludac

Question 5

Name some meal time insulin medications.

Answer 5

lispro, regular, aspart, glulisine

Question 6

What are some factors/drugs that can increase insulin release?

Answer 6

increased by glucose, sulfonylureas, M-agonists, B2 agonists

Question 7

What are some factors that can decrease insulin release?

Answer 7

a2 agonists

Question 8

What are the symptoms associated with diabetic ketoacidosis?

Answer 8

polyuria, polydipsia, nausea, fatigue, dehydration, Kussmaul breathing, “fruity” breath

Question 9

What is the best treatment for diabetic ketoacidosis?

Answer 9

regular insulin IV, fluid and electrolyte replacement

Question 10

Do most basal forms of insulin have a peak?

Answer 10

no

Question 11

MOA of glargine.

Answer 11

insulin binds to the transmembrane receptors which activate tyrosine kinase to phosphorylate tissue-specific substrates

Question 12

What is the DOC for Type II diabetes?

Answer 12

metformin

Question 13

Does metformin cause hypoglycemia or weight gain?

Answer 13

no

Question 14

MOA metformin.

Answer 14

may involve inc. tissue sensitivity to insulin and/or dec hepatic gluconeogenesis

Question 15

Indications for metformin.

Answer 15

mono therapy or combinations for treatment of Type II DM

Question 16

S/E metformin use?

Answer 16

possible lactic acidosis, GI distress

Question 17

Name a drug class that metformin has synergistic activity with?

Answer 17

sulfonylureas

Question 18

Acarbose MOA.

Answer 18

inhibits a-glucosidase in brush borders of SI > dec formation of absorbable carbs > dec postprandial glucose > dec demand for insulin

Question 19

What are the S/E of acarbose?

Answer 19

GI discomfort, flatulence, diarrhea; recent concern over potential hepatotoxicity

Question 20

What is a way to tell if diabetic medication has potential to cause hypoglycemia vs if it doesn’t?

Answer 20

If the target in the diabetes medication is glucose > there is not a risk of hypoglycemia;

If the target in the diabetes medication is insulin; then it has potential to cause hypoglycemia

Question 21

What is the MOA of sulfonylureas? How do they affect glucagon release?

Answer 21

• Normally K+ efflux in pancreatic B cells maintains hyper-polarization of membranes; insulin is release only when depolarization occurs
• Acute action of sulfonylureas is to block K+ channels> depolarization > insulin release
• dec glucagon release
• inc. insulin receptor sensitivity

Question 22

Glucagon is released from what pancreatic cells?

Answer 22

alpha cells

Question 23

How does glucose act as an insulinogen?

Answer 23

glucose increases intracellular ATP > closure of K+ channels > membrane depolarization> inc Ca2+ influx > insulin release

Question 24

Repaglinide MOA?

Answer 24

stimulates insulin release from pancreatic beta cells

Question 25

Indications for repaglinide.

Answer 25

adjunctive use in Type 2 diabetes - administer just before meals due to short half-life

Question 26

Which GLUT type usually bring glucose into the Beta pancreatic cell?

Answer 26

GLUT 2

Question 27

Indications for 1st generation sulfonylureas?

Answer 27

they were discontinued because had long t1/2 which increased the risk for hypoglycemia

Question 28

What are the second generation sulfonylureas?

Answer 28

glipizide, glyburide

Question 29

Would you decrease doses of glipizide in hepatic or renal dysfunction? (Which one would you decrease it in?)

Answer 29

hepatic dysfujnction

Question 30

Would you decrease the dose of glyburide in hepatic or renal dysfunction?

Answer 30

dec dose in renal dysfunction

Question 31

S/E of sulfonylurea use?

Answer 31

Hypoglycemia weight gain

Question 32

What are some important adverse drug interactions to consider when using sulfonylureas?

Answer 32

inc. hypoglycemia with use of cimetidine, insulin, salicylates, sulfonamides, have A/E with first generation sulfonylureas.

Question 33

Symptoms of hypoglycemia.

Answer 33

lip/tongue tingling, lethargy, confusion, sweats, tremors, tachycardia, coma, seizures

Question 34

What is the best treatment for hypoglycemia?

Answer 34

oral glucose (or eat some candy), IV dextrose if unconscious, or glucagon (IM or inhalation)

Question 35

What is the MOA of the thiazolidinediones?

Answer 35

* bind to nuclear peroxisome proliferator activating receptors (PPARy) involved in transcription of genes responsible for insulin regulation * sensitization of tissue to insulin, * plus dec hepatic gluconeogenesis and triglycerides * and inc. insulin receptor numbers

Question 36

Name the TZD drugs? What is the suffix to remember them?

Answer 36

"glitazones" pioglitazone rosiglitazone

Question 37

Is PPARy also implicated in the MOA for fibrates?

Answer 37

PPARa so alpha type is the difference

Question 38

S/E of using TZDs?

Answer 38

less hypoglycemia than sulfonylureas, but weight gain and edema have been reported

Question 39

Be able to reproduce a table on the modes of action of drugs covered in this chapter and the organs implicated in their MOA?

Answer 39

Question 40

MOA Exenatide?

Answer 40

GLP1 is an incretin released from the SI. It augments glucose-dependent insulin secretion. This drug is a long acting GLP-1 receptor full agonist

Question 41

Indications for Exenatide.

Answer 41

used in combination with other agents in Type 2 diabetes

Question 42

S/E of exenatide?

Answer 42

nausea, hypoglycemia when used with oral sulfonylureas

Question 43

MOA of the gliptins? Name a drug in this group?

Answer 43

sitagliptin MOA: inhibits dipetidyl peptidase (DPP-4) thereby inhibiting inactivation of GLP-1

Question 44

Pramlintide MOA.

Answer 44

a synthetic version of amylin that slows rate at which food is absorbed from intestines. Decrease glucose production and decreases appetite

Question 45

Indication for pramlintide?

Answer 45

type 1 and type 2 diabetes

Question 46

What is the suffix for the SGLT -2 inhibtors? Name a drug in this class.

Answer 46

"gliflozins" canagliflozin

Question 47

GLP-1 agonist common suffix and drug names in this class?

Answer 47

"glutides" liraglutide, exenatide

Question 48

MOA canagliflozin.

Answer 48

blocks SGLT-2 in the proximal tubule, increasing glucose excretion

Question 49

S/E of the SGLT-2 inhibitors?

Answer 49

UTIs

Question 50

SGLT-2 stands for what?

Answer 50

sodium-glucose cotransporter 2

Question 51

Drugs to think of when thinking of diabetic nephropathy treatment?

Answer 51

ACE, ARBs

Question 52

Drugs to think of when thinking of treating diabetic neuropathy symptoms?

Answer 52

TCAs (to a lesser degree), gabapentin

Question 53

Drugs to think of when thinking of gastroparesis related to diabetes?

Answer 53

metoclopramide, erythromycin (macrolide; macrolides stimulate motilin receptors)