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Year 2 Pharmacology > Insulin and hypoglycemic agents > Flashcards

Insulin and hypoglycemic agents Flashcards

1
Q

what are the positive regulators of insulin release?

A 
glucose 
amino acids 
incretins 
EPI / B2 adrenergic 
vagal
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2
Q

what are the negative regulators of insulin release?

A

NE / a2 adrenergic

amylin

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3
Q

what is the molecular mechanism of insulin release?

A
  1. glucose enters cell
  2. increase ratio of ATP:ADP generated in the cell
  3. ATP sensitive potassium channel closes, causing depolarization - stimulates voltage dependent calcium channel
  4. calcium dependent release of insulin
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4
Q

in which tissues is GLUT4 located?

A

muscle, adipose

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5
Q

which glucose transporter is regulated by insulin?

A

GLUT4

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6
Q

what is the role of GLUT4?

A

insulin mediated uptake of glucose

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7
Q

what are the key signs and symptoms of type I diabetes?

A 
polyuria 
thirst 
blurred vision 
weight loss / polyphagia 
weakness / dizziness 
paresthesias 
level of consciousness
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8
Q

what are the key signs and symptoms of type II diabetes?

A

infections
neuropathy
classic severe insulin deficiency signs
obesity and metabolic syndrome

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9
Q

what are the pharmacokinetics of insulin therapy?

A

diffusion in to peripheral tissue rather than into portal circulation - preferential effects on hepatic metabolic processes is less

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10
Q

what is the main route of administration for insulin?

A

subQ

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11
Q

what is the therapeutic goal of insulin therapy?

A

fasting blood glucose concentrations between 90-120 mg/dL

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12
Q

what are the rapid acting insulin agents?

A

insulin lispro
insulin aspart
insulin glulisine
inhaled insulin

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13
Q

what is the short acting insulin?

A

regular insulin

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14
Q

what is the intermediate acting insulin?

A

NPH

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15
Q

what are the long acting insulin agents?

A

glargine

detemir

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16
Q

what are the key features of the rapid acting insulin agents?

A

amino acid alteration in C-terminal tail of B peptide preventing insulin complex formation

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17
Q

what are the key features of the short acting insulin agent?

A

identical to human insulin, forms complexes

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18
Q

what are the key features of the intermediate acting insulin agent?

A

protamine-insulin complex

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19
Q

what are the key features of the long acting insulin agents?

A

amino acid substitutions that result in precipitate formation at a more neutral pH in the body

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20
Q

what are the kinetics of the rapid acting insulin agents?

A

onset: 10-30 minutes
peak: 30m - 3h
duration: 3-5h

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21
Q

what are the kinetics of the short acting insulin agents?

A

onset: 30-60m
peak: 2.5-5h
duration: 4-12h

22
Q

what are the kinetics of the intermediate acting insulin agents?

A

onset: 1-2h
peak: 4-8h
duration: 10-20h

23
Q

what are the kinetics of the long acting insulin agents?

A

onset: 1-4h
peak: no peak
duration: 12-20h, 22-24h

24
Q

which insulin agent is good for mimicking management of a meal?

A

rapid

25
Q

which insulin agent is good for maintaining basal levels?

A

long acting

26
Q

which insulin agent is good for mimicking sleep?

A

intermediate, NPH

27
Q

what is the most common adverse effect of insulin therapy?

A 
hypoglycemia 
hypersensitivity 
resistance 
lipohypertrophy 
lipoatrophy
28
Q

what is the cause of hypoglycemia in insulin therapy?

A

insulin therapy is too effective

29
Q

what is the treatment for hypoglycemia?

A

glucose or glucagon

30
Q

what are the symptoms of hypoglycemia?

A

sympathetic symptoms - irritability, confusion, headache, speech difficulty, blurred vision, tiredness

31
Q

what is the first line agent for type II diabetes?

A

metformin

32
Q

what are the important points about metformin?

A

does not produce hypoglycemia

not dependent upon beta cell function

33
Q

what is the MOA of metformin?

A
  1. decrease hepatic glucose output
  2. increase peripheral glucose utilization
  3. activation of hepatic enzyme AMP-activated protein kinase (AMPK)

peripheral and hepatic effects

34
Q

what are the adverse effects of metformin?

A

GI disturbances - poor compliance

vitamin B12 deficiency

35
Q

what are the sulfonylurea diabetic agents? what are they used for?

A

glimepiride
glipizide
glyburide

oral antidiabetic agents

36
Q

what are the meglitinides? what are they used for?

A

repaglinide
nateglinide

oral antidiabetic agents

37
Q

what is the MOA of the sulfonylureas and meglitinides?

A

inhibition of ATP-sensitive potassium channel of B cell, resulting in insulin release

38
Q

what are the adverse effects of the sulfonylureas and meglitinides?

A

weight gain

hypoglycemia

39
Q

what are the glucosidase inhibitors?

A

acarbose

miglitol

40
Q

glucosidase inhibitors are contraindicated in what populations?

A

IBD, GI issues

41
Q

what is the MOA of the glucosidase inhibitors?

A

inhibition of brush border glucosidase enzyme and subsequent absorption of glucose

42
Q

what are the thiazolidinediones (TZDs)?

A

pioglitazone

rosiglitazone

43
Q

what is the MOA of the thiazolidinediones (TZDs)?

A
  1. decrease peripheral resistance by activating PPAR gamma

2. increase peripheral sensitivity by increasing GLUT4 expression in glucose sensitive tissues

44
Q

what are the adverse effects of the thiazolidinediones (TZDs)?

A 
peripheral edema 
hepatotoxicity 
bone fractures 
hypoglycemia 
CV
45
Q

what is the amylinomimetic agent?

A

pramlintide

46
Q

what is the MOA of pramlintide? what type of drug is it?

A

inhibit glucagon release
inhibit gastric emptying
anoretic effect

amylinomimetic

47
Q

what are the incretin agents?

A

exenatide

liraglutide

48
Q

what is the MOA of the incretins?

A

potentiate insulin secretion
inhibits glucagon release
inhibits gastric emptying
anoretic effect

49
Q

what are the dipeptidyl peptidase (DPP) inhibitors?

A

sitagliptin
saxagliptin
linagliptin

50
Q

what is the MOA of the dipeptidyl peptidase (DPP) inhibitors?

A

inhibit incretin degradation

51
Q

what are the adverse effects of the dipeptidyl peptidase (DPP) inhibitors?

A 
nasopharyngitis 
upper respiratory infections 
headaches 
acute pancreatitis 
hemorrhagic or necrotizing pancreatitis

Year 2 Pharmacology (70 decks)

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