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Pharmacology 2 > Glucose Metabolism > Flashcards

Glucose Metabolism Flashcards

1
Q

What are the 4 cell types in the islets of langerhans?

A

Alpha cells
Beta cells
Delta cells
F cells

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2
Q

Where is insulin produced?

A

Beta cells

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3
Q

Where is glucagon produced?

A

Alpha cells

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4
Q

Where is somatostatin produced?

A

Delta cells

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5
Q

Where is pancreatic polypeptide produced?

A

F cells

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6
Q

T/F: Insulin AA sequence is preserved across species?

A

True

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7
Q

What 4 things stimulate insulin secretion?

A

Rise in blood glucose
GI hormones
AA and fatty acids in GIT
Vagal (catecholamines on B2 receptors)

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8
Q

What 3 things inhibit insulin secretion?

A

Decrease in blood glucose
Somatostatin
Catecholamines (a2 or I3 receptors)

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9
Q

What are the 4 effects of insulin?

A

Storage and building (glycogenesis, lipogenesis, protein synthesis)
Inhibits glycogenolysis, gluconeogenesis, lipolysis
Stimulates uptake of K into cells
Anabolic

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10
Q

What 3 organs metabolize insulin?

A

Liver
Kidneys
Muscle

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11
Q

What causes hypoglycemia?

A

Too much insulin

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12
Q

What are 5 differentials for hypoglycemia?

A 
Artifact
Unable to make glucose
Excessive consumption
Exogenous hypoglycemic agents**
Endogenous hypoglycemic agents**

**care most about these

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13
Q

How can hypoglycemia be an artifact?

A

If blood sample sits out for more that 30 minutes, RBCs consume the glucose in the sample.

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14
Q

What are two causes of excessive consumption of glucose?

A

Sepsis

Extreme exertion

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15
Q

What is an example of an exogenous hypoglycemic agent?

A

Insulin overdose

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16
Q

What is an example of endogenous hypoglycemic agent? (4 things)

A

Xylitol toxicity
Insulinoma
Extrapancreatic neoplasia
Islet cell hyperplasia

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17
Q

What 2 things do you consider if hypoglycemia does not involve insulin?

A

Give dextrose

Treat underlying disease

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18
Q

What 2 things do you consider if hypoglycemia involves insulin?

A

If iatrogenic: stop insulin and give supportive care

If endogenous: treat hypoglycemia, then treat underlying disease

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19
Q

What are the main 3 pharmacologic therapies for hypoglycemia?

A

Replacement
Diet
Anti-hypoglycemic agents

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20
Q

What two things can you use to replace glucose?

A

Glucagon (not commonly used)

Dextrose

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21
Q

What 2 things must you consider when using dextrose?

A

Hyperosmolality/irritation

Rising glucose stimulates insulin secretion

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22
Q

What is the acute dose of dextrose?

A

1mL/kg of 50%, diluted 1:4

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23
Q

What is the maintenance dose of dextrose?

A

2.5-5% dextrose IV

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24
Q

Using dietary management, what do you use to treat acute hypoglycemia?

A

Karo syrup/corn syrup

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25
Q

Using dietary management, what 4 things do you use to treat hypoglycemia?

A

Frequent, small meals
Complex carbs
Easily digestible
Moderate fat and protein

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26
Q

What 4 pharmacologic agents can you use to treat hypoglycemia?

A

Glucocorticoids
Diazoxide
Streptozotocin
Somatostatin

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27
Q

What is the goal of hypoglycemia therapy?

A

To eliminate/minimize clinical signs associated with hypoglycemia

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28
Q

What are the two glucocorticoids used?

A

Predisone

Prednisolone

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29
Q

How do glucocorticoids treat hypoglycemia? (3 things)

A

Increase gluconeogenesis
Decrease glucose uptake into tissue
Stimulate glucagon secretion

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30
Q

Where are glucocorticoids metabolised?

A

Liver

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31
Q

What two things can impair glucocorticoid metabolism?

A

Cirrhosis

Shunt

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32
Q

What is important to know about glucocorticoid side effects?

A

They are proportional to the dose (low dose = mild, higher doses = worse)

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33
Q

When would you use Diazoxide?

A

If glucocorticoids and diet are no longer working

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34
Q

What are the two most common side effects of Diazoxide?

A

Hypersalivation

Anorexia, V&D

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35
Q

What are 4 less common side effects of Diazoxide?

A

Tachycardia
Hematologic changes
Diabetes
Fluid retention

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36
Q

How does Diazoxide treat hypoglycemia?

A

Activates K+ channels in islet cells and switches off voltage-gated Ca2+ channels to inhibit release of insulin

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37
Q

What are two other effects of Diazoxide?

A

Increases glycogenolysis in the liver

Inhibits tissue uptake of glucose

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38
Q

T\F: Diazoxide alters the synthesis of insulin and treats the neoplasia.

A

False. Diazoxide does not alter the synthesis of insulin or treat the neoplasia

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39
Q

How does somatostatin help treat hypoglycemia?

A

Inhibits the release of insulin, glucagon, GH, CCK, Secretin, Gastrin, VIP

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40
Q

What is Octreotide?

A

A somatostatin analogue

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41
Q

What is Octreotide used for? (4 things)

A

Insulinomas
Gastrinomas
Chylothorax
Acromegaly

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42
Q

How does Streptozotocin help with hypoglycemia?

A

Selectively destroys beta cells

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43
Q

T/F: Stretozotocin has a wide therapeutic index.

A

False. Streptozotocin has a very narrow safety margin

44
Q

What causes hyperglycemia?

A

Too little insulin

45
Q

What are the two differentials for hyperglycemia?

A

Physiologic hyperglycemia

Diabetes mellitus

46
Q

What is Type 1 Diabetes Mellitus?

A

Insulin Dependent (IDDM) = absolute deficiency of insulin

47
Q

What is Type 2 Diabetes Mellitus?

A

Non-Insuline Dependent (NIDDM) = Relative insulin deficiency and resistance

48
Q

What species do you not generally see Type 2 Diabetes in?

A

Dogs

49
Q

What species can you see Type 2 diabetes in?

A

Cats

Horses

50
Q

What 3 things does insulin stimulate?

A

Glycogenesis
Lipogenesis
Protein synthesis

51
Q

What 3 things does insulin inhibit?

A

Glycogenolysis
Gluconeogenesis
Lipolysis

52
Q

What does lack of insulin cause in the cells?

A

Cellular starvation

53
Q

What does cellular starvation entail?

A

Decreased tissue use of glucose
Stimulation of liver glycogenolysis
Proteolysis > AAs > gluconeogenesis
Lipolysis > FFAs > ketoacidosis > hepatic lipidosis

54
Q

What are the 4 cardinal signs of diabetes?

A

Catabolism (muscle/weight loss)
Accumulation of glucose in the blood (exceeds renal tubular absorption)
Glucose in urine (see osmotic diuresis… PU/PD)
Polyphagia (lack of glucose entering “satiety center”)

55
Q

What are the 4 goals of hyperglycemia therapy?

A

Reduce hyperglycemia
Reverse Catabolic effects
Reverse ketosis
Control clinical signs

56
Q

Why do you aim to maintain a hyperglycemic patient in a mild hyperglycemic state instead of a normoglycemic state?

A

Risk causing hypoglycemia becaues animal can’t grab a snack like we can.

57
Q

What are the three main treatments for diabetes mellitus?

A

General management
Diet
Pharmacological management

58
Q

What are 2 forms of general diabetes management?

A

Weight management

Exercise

59
Q

How do we manage diabetes mellitus in dogs using diet?

A

Use high fiber diet

60
Q

How do we manage diabetes mellitus in cats using diet?

A

Use low carb diet

61
Q

T/F: Acarbose is a hypoglycemia agent.

A

False, Acarbose is NOT a hypoglycemic agent

62
Q

How does Acarbose work to treat hyperglycemia?

A

Inhibits alpha amylases and brush border oligo/disaccharides to reduce postprandial hyperglycemia after CHO intake

63
Q

What side effects can you see with Acarbose? (2 things)

A

Diarrhea

Weight loss

64
Q

What are the three classes of oral hypoglycemics?

A

Sulfonylureas
Biguanides
Thiazolidinediones

65
Q

Which oral hypoglycemics are secretagogues?

A

Sulfonylureas

66
Q

Which oral hypoglycemics are sensitizers?

A

Biguanides

Thiazolidinediones

67
Q

What is the most commonly used sulfonylurea?

A

Glipizide

68
Q

How does glipizide stimulate insulin secretion?

A

Blocks potassium channels and increases Ca2+

69
Q

On top of stimulating insulin secretion, what else does Glipizide do?

A

Increases sensitivity of tissues to circulating insulin

70
Q

What does glipizide require to be functional for it to work?

A

Beta cells

71
Q

How do biguanides (metformin) help treat hyperglycemia?

A

Inhibit hepatic glycogenolysis and increase peripheral glucose utilization

72
Q

Does metformin affect insulin secretion?

A

No

73
Q

How do thiazolidinediones (Rosiglitazone) help treat hyperglycemia?

A 
PPARy agonists (receptor that regulates FA storage and glucose metabolism)
Controls glucose production, transport and utilization
74
Q

What side effects can you see with Rosiglitazone?

A

Hepatic and cardiovascular side effects

75
Q

What 4 questions do you ask yourself when deciding between insulin or glipizide?

A

Which will be more effective? (Type 2 or Type 2? Dog or cat?)
Which one is safer? (neither is safer)
Which is easier to give? (Tablet vs. injection)
Which needs less monitoring?

76
Q

What type of diabetes are oral hypoglycemics only useful in?

A

Type 2 (NIDDM)

77
Q

How effective are oral hypoglycemics?

A

~20-30% of cats

78
Q

What are 4 major side effects of oral hypoglycemics?

A

Hypoglycemia
Vomiting
Elevated liver enzymes
May accelerate loss of beta cells

79
Q

What are the 5 different types of insulin?

A 
Recombinant human (incl. Prozinc*)
Synthetic insulin
Purified porcine (incl. Caninsulin*)
Purified bovine
Bovine-porcine

*approved for use in animals

80
Q

What concentration are veterinary approved products available in?

A

40IU/mL

81
Q

What concentration are human products available in?

A

100IU/mL

82
Q

What 5 things must you remember about handling insulin?

A 
Refrigerate
Roll gently to reconstitute
Don't dilute
Use appropriate syringe
Pay attention to expiration date
83
Q

What are short-acting insulins mmost commonly used for?

A

Diabetic ketoacidosis (DKA) management in hospitla (CRI)

84
Q

Why are short-acting insulins not sent home?

A

Duration is too short

85
Q

What is the duration of intermediate-acting insulins?

A

~4-24 hours

86
Q

T/F: Caninsulin falls under intermediate-acting insulin category.

A

True

87
Q

What must be considered in cats with intermediate-acting insulins?

A

May not provide adequate duration.

88
Q

What are 3 examples of long-acting insulin?

A

Protamine zinc
Glargine
Detemir

89
Q

What is the reason for adding Protamine or Zinc to insulins?

A

Delays absorption and extends clinical effect

90
Q

What is the duration of long-acting insulins?

A

6-28 hours

91
Q

What does glargine cause?

A

pH causes microprecipitates

92
Q

What is the insulin dose for dogs?

A

0.25-0.5IU/kg BID

93
Q

What is the insulin dose for cats?

A

1IU/cat BID

94
Q

What is the exception to the general insulin dose and why?

A

Detemir, because canine receptors are 4x more sensitive than human receptors (Detemir has human dose on bottle)

95
Q

What is the does of Detemir for dogs?

A

0.1-0.2 IU/kg BID

96
Q

What do you monitor when treating with insulin?

A

Blood glucose
Fructosamine
Clinical signs

97
Q

How do you monitor blood glucose?

A

Glucose curve

98
Q

What does fructosamine give you?

A

Idea of “average” glucose level

99
Q

What is a “healthy” DKA?

A

Animal is eating. Can be managed like a normal diabetic, but with close monitoring.

100
Q

What is a “sick” DKA?

A

Animal is not eating

101
Q

How do you handle a “sick” DKA? (3 things)

A

Correct fluids/electrolytes/acid-base
Supplement K+
IV CRI of insulin to start

102
Q

What is the goal with treating a “sick” DKA?

A

To reverse metabolic situation

103
Q

What do you do with a hyperosmolar nonketotic diabetic? (2 things)

A

Treat like a DKA, but bring glucose down VERY SLOWLY

Can start on fluids (no insulin) initially

104
Q

What is insulin resistance?

A

Hyperglycemia despite insulin dose of 2.2IU/kg or greater

105
Q

Can concurrent disease cause insulin resistance?

A

Yes

106
Q

Can insulin autoantibodies cause insulin resistance?

A

Yes.

107
Q

What is the Somogyi response?

A

An over dose problem where significant drop in blood glucose triggers a glucagon/epinephrine response = overswing.

Pharmacology 2 (9 decks)

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