Insuline and oral antidiabetic agents

Question 1

what affects rate of absorption of insulin

Answer 1

-insulin forms dimers and hexamers in concentrated solutions but these are absorbed slowly when injected subcutaneously. Monomers are absorbed much faster.

Question 2

insulin lispro

Answer 2

• rapid acting insulin

- modification of the amino acid squence (B28/B29) that promotes absorption by preventing self-association

Question 3

insulin aspart

Answer 3

• rapid acting insulin

- modification of the amino acid sequence (B28 substitution) that promotes absorption by preventing self association

Question 4

insulin glulisine

Answer 4

• rapid acting insulin

- modification of the amino acid sequence (B3 and B29 changed( that promotes absorption by preventing self-association

Question 5

NPH insulin

Answer 5

-wild type amino acid sequence (cloudy suspension with protamine added to give a `1:6 molar ratio to insulin). under these conditions basically all the protamine and insuline are in a complex, slows absorption

Question 6

insulin glargine

Answer 6

-modification of the amino acid sequence (A21 changed, B31/32) to make insulin soluble at acidic pH but precipitates at neutral pH thus slowing down absorption

Question 7

insulin detemir

Answer 7

-modification of the amino acid sequence (C terminal Thr B chain was deleted and myristic acid attached to new C terminal Lys) that increases self-aggregation and binding to albumin

Question 8

inhalable insulin

Answer 8

• regular human insulin
• peaks 12-15 mins, basal in 3 h
• slower than SQ rapid acting, but faster than regular

Question 9

amylin

Answer 9

• can improve effectiveness of insulin therapy, approved for Type 1 DM
• hormone made in the B cells in pancreas that acts upon the alpha cells to inhibit glucagon secretion. CNS-mediated anorectic effect
  drug: pramlintide

Question 10

adverse reactions to insulin therapy

Answer 10

• hypoglycemia
• lipodystrophy at site of injection
• cough for inhalable insulin, contraindicated in smokers and COPD
• allergy and resistance

Question 11

sulfonylureas

Answer 11

• increase insulin secretion by decreasing K efflux from B cells in the panreas
• tolbutamide, chorpropramide (1st gen)
• glipizide, glyburide, glimepride (2nd gen, more potent)

Question 12

SE of sulfonylureas

Answer 12

• hypoglycemia

- sulfonylurea resistance/tachyphylaxis

Question 13

meglitinides

Answer 13

• like sulfonylureas they prevent K efflux from B cells, ultimately leading to increase insulin secretion
• chemically unrelated to sulfonylureas
• binding affinity of meglitinides for K channels is higher than sulfonylureas
  name: repaglinide

Question 14

repaglinide use and SE

Answer 14

-more potent than second gen sulfonylureas but of shorter duration
-used mostly for control of postprandial glucose
-meglitinide
SE: hypoglycemia, use cautiously with renal/liver insuff

Question 15

D-phenylalanine analog

Answer 15

• chemically unrelated to meglitinides or sulfonylureas, but stimulates insulin secretion by the same mechanism
• nateglinide
• faster than meglitinide, but less sustained

Question 16

SE of nateglinide, bonus feature

Answer 16

• hypoglycemia

- safe for use in reduced renal function

Question 17

biguanides

Answer 17

-inactivate mitochondrial glycerophosphate dehydrogenase, antagonize actions of glucagon and activate AMP-activated protein kinase
-takes place in liver and leads to reduction in gluconeogenesis and hepatic glucose output
1st line for DM II

Question 18

metformin, type of drug, SE

Answer 18

• biguanide

- GI discomfort, lactic acidosis, B12 deficiency

Question 19

thiazolidinediones

Answer 19

• agonists for PPAR-gamma, increase insulin sensitivity in target tissues (liver, fat, muscle)
  name: pioglitazone and rosiglitazone

Question 20

SE of pioglitazone and rosiglitazone

Answer 20

• increase risk of CV disease
• fluid retention and edema
• wgt gain
• liver toxicity and bladder cancer

Question 21

alpha-glucosidase inhibitors

Answer 21

• alpha glucosidase receptors in intestine absorb CHO, drug reduces intestinal absorption of CHO
  names: acarbose, miglitol

Question 22

SE of acarbose, miglitol

Answer 22

• flatulence, diarrhea, abd pain

- not really effective solo

Question 23

incretins

Answer 23

• hormones secreted after a meal that increase insulin and decrease glucagon release
• exenatide, liraglutide (SQ inj)
• sitagliptin, saxagliptin (oral)

Question 24

SE of exenatide and liraglutide

Answer 24

• nausea, anorexia, h/a, diarrhea, pancreatitis

- incretin agonists

Question 25

SE of sitagliptin and saxagliptin

Answer 25

• oral incretin agonists

- h/a, increased infections, pancreatitis

Question 26

pramlintide use & SE

Answer 26

-useful in DM II alone
-given with insulin in type I DM
SE: hypoglycemia, N/V, anorexia

Question 27

canaglifozin, MOA & SE

Answer 27

-inhibit glucose reabsorption thus promoting glucose excretion in urine via glucose/sodium cotransporter inhibition
SE: UTI, increased urination

Question 28

empaglifozin

Answer 28

-inhibit glucose reabsorption thus promoting glucose excretion in urine via glucose/sodium cotransporter inhibition
SE: UTI, increased urination

Question 29

1st line rx of DM II

Answer 29

-weight loss, exercise, metformin

Question 30

2nd line rx of DM II

Answer 30

-metformin + another agent

Question 31

3rd line rx of DM II

Answer 31

-metformin + 2 agents

Question 32

4th line rx of DM II

Answer 32

-metformin and insulin and non-insulin agents

Question 33

other drugs that can affect insulin release

Answer 33

• Ca channel blockers (decrease insulin release)
• adrenergic agents (agonists increase insulin & output of glucose from liver, antagonists decrease)
  glucocorticosteroids: increase glucose, resistance
• progestins, estrogens, etc.