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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?

25
which insulin agent is good for maintaining basal levels?
long acting
26
which insulin agent is good for mimicking sleep?
intermediate, NPH
27
what is the most common adverse effect of insulin therapy?
``` hypoglycemia hypersensitivity resistance lipohypertrophy lipoatrophy ```
28
what is the cause of hypoglycemia in insulin therapy?
insulin therapy is too effective
29
what is the treatment for hypoglycemia?
glucose or glucagon
30
what are the symptoms of hypoglycemia?
sympathetic symptoms - irritability, confusion, headache, speech difficulty, blurred vision, tiredness
31
what is the first line agent for type II diabetes?
metformin
32
what are the important points about metformin?
does not produce hypoglycemia | not dependent upon beta cell function
33
what is the MOA of metformin?
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
what are the adverse effects of metformin?
GI disturbances - poor compliance | vitamin B12 deficiency
35
what are the sulfonylurea diabetic agents? what are they used for?
glimepiride glipizide glyburide oral antidiabetic agents
36
what are the meglitinides? what are they used for?
repaglinide nateglinide oral antidiabetic agents
37
what is the MOA of the sulfonylureas and meglitinides?
inhibition of ATP-sensitive potassium channel of B cell, resulting in insulin release
38
what are the adverse effects of the sulfonylureas and meglitinides?
weight gain | hypoglycemia
39
what are the glucosidase inhibitors?
acarbose | miglitol
40
glucosidase inhibitors are contraindicated in what populations?
IBD, GI issues
41
what is the MOA of the glucosidase inhibitors?
inhibition of brush border glucosidase enzyme and subsequent absorption of glucose
42
what are the thiazolidinediones (TZDs)?
pioglitazone | rosiglitazone
43
what is the MOA of the thiazolidinediones (TZDs)?
1. decrease peripheral resistance by activating PPAR gamma | 2. increase peripheral sensitivity by increasing GLUT4 expression in glucose sensitive tissues
44
what are the adverse effects of the thiazolidinediones (TZDs)?
``` peripheral edema hepatotoxicity bone fractures hypoglycemia CV ```
45
what is the amylinomimetic agent?
pramlintide
46
what is the MOA of pramlintide? what type of drug is it?
inhibit glucagon release inhibit gastric emptying anoretic effect amylinomimetic
47
what are the incretin agents?
exenatide | liraglutide
48
what is the MOA of the incretins?
potentiate insulin secretion inhibits glucagon release inhibits gastric emptying anoretic effect
49
what are the dipeptidyl peptidase (DPP) inhibitors?
sitagliptin saxagliptin linagliptin
50
what is the MOA of the dipeptidyl peptidase (DPP) inhibitors?
inhibit incretin degradation
51
what are the adverse effects of the dipeptidyl peptidase (DPP) inhibitors?
``` nasopharyngitis upper respiratory infections headaches acute pancreatitis hemorrhagic or necrotizing pancreatitis ```

Year 2 Pharmacology (70 decks)

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