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Pharmacology II > Therapeutic Approaches to Diabetes > Flashcards

Therapeutic Approaches to Diabetes Flashcards

1
Q

primary energy source for all tissues?

A

Glucose

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2
Q

Uptake of blood glucose for energy utilization is in which two tissues?

A

Skeletal muscle

Brain

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3
Q

Uptake of blood glucose for energy storage is in which tissues?

A

Liver

Adipose

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4
Q

Blood glucose excretion is in which tissue?

A

Kidney

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5
Q

What happens to glucose in a calorie deficit? (2)

A 
Glycogen breakdown (glycogenolysis)
Glucose synthesis (gluconeogenesis)
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6
Q

Blood glucose:
variable or non-variable?
wide or narrow range?

A

Variable

Narrow range

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7
Q

What tissue is critical for glucose homeostasis?

A

Pancreas

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8
Q

The pancreatic islet of langerhans contains which two cells? They release which hormone/substance and under what condition (high or low glucose)

A

alpha : glucagon at low blood glucose levels

beta : insulin at high blood glucose levels

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9
Q

Primary target or alpha cells? (1)

A

hepatocytes

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10
Q

Primary target for beta cells? (3)

A

Liver
Fat
Skeletal muscle

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11
Q

Insulin is what type of hormone?

A

Anabolic polypeptide

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12
Q

Insulin is cleaved by intracellular ______ to generate which two chains? They remain linked by what?

A

proteases
A chain and B chain
Linked by 2 disulfide bridges

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13
Q

4 steps leading to glucose-stimulated insulin secretion (GSIS)

A
  1. Glucose enters via GLUT2 and is metabolized, elevates [ATP]
  2. Elevated ATP inhibits ATP-sensitive K+ channels
  3. Depolarization and opening and voltage-gated Ca2+ channel
  4. Increased intracellular Ca2+ results in exocytic secretion of insulin from storage vesicles into the blood
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14
Q

GLUT2 only transports glucose under what condition?

A

low affinity

>6mM

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15
Q

Blood insulin levels parallel _______ levels

A

blood glucose

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16
Q

Diabetes Mellitus causes what? (2)

What does DIABETES and MELLITUS reference to in this disease?

A

Rapid weight loss
Excessive urination
Diabetes : copious amounts of urine production
Mellitus: sweet taste or smell of urine produced

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17
Q

Diabetes Mellitus disorders are all characterized by what?

A

high blood glucose

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18
Q

Two primary causes of diabetes mellitus?

A

Inadequate insulin secretion

Impairment of insulin action

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19
Q

type I diabetes is the most or least common type of diabetes?
It is the destruction of what?
there is reduced/absence of ________

A

Least common
Pancreatic beta cells
insulin secretion

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20
Q

Type II diabetes is the most or least common type of diabetes?
The tissues are ______ to insulin
Advanced stages associated with __________ insulin secretion

A

Most common
resistant
insufficient

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21
Q 
Type I diabetes is the loss of insulin production and GSIS : 
\_\_\_\_\_\_ glucose uptake
\_\_\_\_\_\_ glucose storage
Failure to inhibit \_\_\_\_\_ production
Low or high levels of blood glucose?
A

Reduced
Reduced
Glucose production
Elevated blood glucose

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22
Q

Acute effects of Type I and Type II diabetes? (5)

A 
Excessive urine production
Extreme thirst/hunger
Rapid HR
Nausea, dizziness, confusion
Weakness, shaking, fainting
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23
Q

Chronic Complications of Type I and Type II diabetes? (8)

A
  1. Weight loss
  2. Damage to blood vessels in eyes
  3. Damage to blood vessels in extremities
  4. Kidney damage
  5. Peripheral nerve damage
  6. Hyperlipidemia
  7. Hypertension
  8. CV disease
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24
Q

Treatments of Type I diabetes? (2)

Even with good management of hyperglycemia, is there still risk of chronic complications?

A

Diet
Insulin replacement
Yes

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25
Q

Type II diabetes is characterized by insulin resistance by the tissues:
____ glucose uptake and energy storage
____ liver glucose synthesis and release
Chronic _______

A

Reduced
Increased
Hyperglycemia

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26
Q

Lifestyle changes to treat Type II diabetes? (3)

A

Diet
Exercise
Weight loss

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27
Q

6 drugs to treat type II diabetes?

A 
Metformin
Insulin secretagogues
Incretin agents
Gliflozins
Thiazolidinediones
Insulin
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28
Q

4 types of insulin/insulin analogues?

A

Regular insulin
Insulin ispro
NPH insulin
Insulin Glargine

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29
Q

2 insulin secretagogues?

A

Glyburide (sulfonylurea)

Rapaglinide (meglitinide)

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30
Q

2 Incretin agents?

A

Sitagliptin

Exetanide

31
Q

2 Gliflozins?

A

Dapagliflozin

Canagliflozin

32
Q

2 Thiazolidinediones?

A

Avandia (rosiglitazone)

Actos (pioglitazone)

33
Q

Insulin replacement therapy is always required in type ____ diabetes

A

I

34
Q

When is Insulin replacement therapy only used on type II diabetics?
Most common in severe cases where what happens?

A

When other therapies fail to provide adequate blood glucose control
Chronic hyperglycemia leads to beta cell destruction and impaired insulin secretion

35
Q

Only mode of insulin administration?

A

Injection

36
Q

Insulin pharmacokinetics are primarily determined by what?

A

absorption

37
Q

Steps of pharmacokinetics of insulin injection/absorption? (3)

A
  1. Injection creates subcutaneous depot of insulin at injection site
  2. Natural insulin molecules self-associate to form hexamers
  3. Hexamer dissociation for absorption
38
Q

Rate of insulin absorption determines what? (3)

A

Onset of action
Peak activity
Duration of action

39
Q

Slow insulin absorption:
Slow/long onset of action?
Slow/long duration?

A

Slow

Long

40
Q

Rapid insulin absorption:
Slow/long onset of action?
Slow/long duration?

A

Rapid

Short

41
Q

Natural insulin:
What configuration?
slow, normal or rapid absorption?
Onset is how long? peak? duration?

A 
•Hexamer
“Normal” absorption
• Onset: 30 min
• Peak: 2 hr
• Duration: 6-8 hr
42
Q

Insulin Lispro:
What configuration?
slow, normal or rapid absorption?
Onset is how long? peak? duration?

A 
Dimers
Rapid
15min
30min
4hr
43
Q

Insulin analogues are amino acid substitutions. These substitutions affect what? (3)

A

Quaternary structure
Crystallization properties
Solubility

44
Q

Which has slower absorption between the following:
Dimer vs. Hexamer
Crystallization High vs. Low
Solubility High vs. Low

A

Hexamer
High
Low

45
Q

NPH : rapid, short, intermediate or long PK?

A

Intermediate

46
Q

Glargine : rapid, short, intermediate or long PK?

A

Long

47
Q

Example of GSIS replacement drug that will induce rapid/regular acting insulin?
What do these mimic?

A

Lispro

Mimics beta cell release of insulin in response to nutrient load

48
Q

Example of basal insulin replacement drug that will induce intermediate/long acting insulin?
This provides constant ____ levels
Important to prevent _____ release from liver during fasting

A

NPH
Insulin
glucose release

49
Q

The dosage of GSIS/basal replacement depends on what? (2)

If not, there is risk for what disease?

A

Carb intake and physical activity

Risk for hypoglycemia

50
Q

Insulin infusion devices:

which two manually monitor glucose?

A

Traditional Insulin Replacement

Insulin Infusion Pump

51
Q

Insulin infusion devices:

Which one requires manual injection?

A

Traditional insulin replacement

52
Q

Insulin Infusion devices:

Which two have automated delivery?

A

Insulin Infusion Pump

Artificial Pancreas

53
Q

Insulin Infusion devices:

Which one has automated glucose monitoring?

A

Artificial Pancreas

54
Q

Most common and severe adverse effect associated with insulin replacement therapy?

A

Hypoglycemia

55
Q

Common causes of hypoglycemia? (3)

What is the treatment for acute hypoglycemia?

A

Inadequate carb intake, unusual physical activity, insulin dose too large

Treatment : glucose

56
Q

What is the most common adverse effect of insulin replacement therapy? Why?

A

Weight gain

Because insulin is an anabolic hormone and promotes energy storage

57
Q

What is the drug of choice for type II diabetes?

A

Metformin

58
Q

Metformin activates which enzyme? This increases insulin sensitivity in which tissues?
What effect does this have?

A

AMP-dependent kinase (AMPK)
Liver, Fat, Skeletal muscle
Decreases basal and post-prandial blood glucose

59
Q

Most common adverse effect of metformin?
Most severe?
Has low risk for ________

A

GI irritation
Lactic acidosis
Hypoglycemia

60
Q

MOA of insulin secretagogues? (4)

A
  1. Inhibits ATP-sensitive K+ channels in pancreatic B-cells
  2. Cell depolarization
  3. Opening of voltage-sensitive Ca2+ channels
  4. Exocytic insulin secretion
    (Compensates for insulin resistance)
61
Q

Two insulin secretagogues?

A

Sulfonylureas

Meglitinides

62
Q

Incretins regulate the release of what? (2)

A

Pancreatic insulin and glucagon

63
Q

MOA of glucose before administration of incretins?

*remember it acts of a-cells and B-cells

A

After oral intake:

  1. Release of GLP-1 from GIT into bloodstream
  2. GLP-1 acts on receptors on a cells or B cells
  3. a cells : decrease in glucagon, decreased glucose production in liver
  4. B cells: Increase in insulin, increased glucose uptake in fat and muscle
64
Q

Dose GLP-1 promote BASAL or GLUCOSE-STIMULATED insulin secretion?

A

Glucose-stimulated

65
Q

Temporal and Contextual control of GLP-1?

A

Temporal : released from intestine in response to glucose ingestion, degraded by DDP-4
Contextual : insulin release only when glucose is >4mmol

66
Q

What degrades GLP-1?

A

DPP-4 : Dipeptidyl peptidase-4

67
Q

What type of incretin agents can reduce GLP-1 degradation?

Example?

A

DPP-4 inhibitors

Ex : Sitagliptin

68
Q

What is the effect of DPP-4 Inhibitors AND Incretin Mimetics on pancreatic GSIS insulin release and glucagon release?

A

Increases pancreatic GSIS insulin release

Reduces glucagon release

69
Q

DPP-4 inhibitors and Incretin Mimetics are used in combination with what drugs? (2)

A

Metformin

Secretagogues

70
Q

What type of incretin agents can activate pancreas GLP-1 receptors?
Example?

A

Incretin mimetics

Ex : Exenatide

71
Q

Administration of:
DPP-4 inhibitors?
Incretin mimetics?

A

DPP : oral

Mimetics : subcutaneous injection

72
Q

Major role of Gliflozins?

Two examples of this drug?

A

Inhibits Renal Glucose Reabsorption
Dapagliflozin
Canagliflozin

73
Q

MOA of gliflozins?

Effects under normoglycemic conditions and hyperglycemic conditions?

A

Inhibition of sodium-glucose transporter linked transporter 2 (SGLT2)

  • Normoglycemic : almost all glucose filtered at glomerulus is reabsorbed from renal proximal tubule by SGLT2
  • Hyperglycemic: SGLT2 can be saturated leading to glucose excretion in urine

Pharmacology II (21 decks)

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