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Pharmacology II > Lecture 1: Drugs Affecting Glucose Metabolism > Flashcards

Lecture 1: Drugs Affecting Glucose Metabolism Flashcards

1
Q

What is the normal glucose range for a dog

A

76-119

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2
Q

What is the normal glucose range for cat

A

60-120

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3
Q

What is normal glucose range for cow

A

40-100

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4
Q

What is normal glucose range for horse

A

62-134

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5
Q

What is the role of the liver in glucose regulation

A

Stores glucose as glycogen when BG high, releases glucose when BG low

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6
Q

What are the 4 diabetogenic/glucose releasing hormones

A
  1. Glucagon
  2. Catecholamines
  3. Cortisol
  4. Growth hormone
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7
Q

What is the 1 anti-diabetic hormone

A

Insulin

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8
Q

What are some clinical signs of DM

A

PU/PD, weight loss, polyphasic, cataracts in dogs, neuropathy in cats

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9
Q

What causes PU/PD in DM

A

Glucose in the urine- osmotic effect

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10
Q

What is the value indicating glucosuria in dogs and cats

A

Dogs: 180-220mg/dL
Cats: 250-290 mg/dL

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11
Q

What percent of dogs develop cataracts with type 1

A

80%

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12
Q

What is the cause of type I DM

A

90% loss of functioning beta cells

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13
Q

What are the 3 potential etiologies of type I DM

A
  1. Autoimmune
  2. Genetics
  3. Acute/severe pancreatitis
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14
Q

What is the reason behind type II DM

A

Insulin resistant tissues

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15
Q

What are some ways tissues become insulin resistant

A
  1. Anti-insulin antibodies- block receptor
  2. Anti-insulin receptor antibodies or down regulation
  3. Problems with downstream signaling
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16
Q

What are some causes of mild or fluctuating insulin resistance

A

Obesity, hyperlipidemia, hyperthyroid cats, hypothyroid dogs, chronic inflammation, renal, hepatic or cardiac insufficiency

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17
Q

What are some causes of severe persistent insulin resistance

A
  1. Diestrus induced increase in GH
  2. Cushing
  3. Diabetogenic drugs- progestins and glucocorticoids
  4. Acromegaly- pituitary tumor-releasing GH—> release glucose
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18
Q

Is impaired insulin secretion reversible or irreversible

A

Irreversible

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19
Q

Is insulin resistance reversible or irreversible

A

Reversible

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20
Q

___is secreted every time insulin is secreted and is toxic to Beta cells, therefore reduces insulin secretion

A

Amyloids

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21
Q

What does remission of type II DM in cats look like

A
  1. Return to euglycemia in absence of insulin tx
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22
Q

How can acromegaly lead to type II DM

A

Pituitary tumor secreting GH which increases the amount of glucose released from liver

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23
Q

What are the two methods to inhibit GH secretion

A
  1. Decrease levels of GH-RH (harder)
  2. Increase levels of GH-IH (easier)
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24
Q

What is octreotide indicated for and how does it work

A

Indications: acromegaly-causing type II DM, insulinomas

PD:
- acromegaly human somatostatin analog (GH-IH) that decreases circulating GH and therefore glucose

  • insulinomas: inhibit insulin gene expression
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25
Q

Which is more effective in cats: short acting octreotide or long acting

A

Long acting

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26
Q

What is a major concern in horses with type 2 DM

A

Laminitis

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27
Q

Which class of insulin is the endogenous molecule: short, intermediate or long acting

A

Short

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28
Q

When is short acting insulin used

A

For emergencies

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29
Q

How is short acting insulin administered

A

IV

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30
Q

How long does short acting insulin last

A

1-4hrs

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31
Q

What class of insulin is Novolin-R

A

Short acting

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32
Q

How long does intermediate acting insulin last

A

8-18hrs

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33
Q

How is intermediate acting insulin administered and what must you do for each administration

A

administered SQ, must rotate spots to avoid lipodystropic reactions

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34
Q

How long do long acting insulins last

A

12-24hrs

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35
Q

What is the dose for the veterinary use insulin

A

40U/mL

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36
Q

What are some adverse reactions for insulin use

A

Hypoglycemia, local or systemic immune reactions

37
Q

What is the dose for the human use insulin

A

100U/mL

38
Q

What species is porcine insulin zinc suspension used in and is it extra label or labeled

A

Labeled for cats and dogs

39
Q

What class of insulin is porcine insulin zinc and what mechanism does it use to be so

A

Intermediate acting insulin- zinc slows absorption, allows for 2 peaks of activity

40
Q

T or F: dogs have a high % chance of having an immune reaction to porcine insulin zinc

A

False, porcine insulin has the same amino acid sequence as dogs

41
Q

What species is neutral protamine hagedorn insulin used in, and is it extra label or labeled

A

Extra-label for dogs

42
Q

What class of insulin is neutral protamine hagedorn and what mechanism does it use for rate of absorption

A

Intermediate acting insulin- protamine slows absorption

43
Q

How many peaks of activity does neutral protamine hagedorn insulin have

A

Single peak at 8.5hrs

44
Q

T or F: dogs have no immune reaction to neutral protamine hagedorn insulin

A

False, human recombinant insulin so ~5% of dogs have immune reactions

45
Q

What species is protamine zinc insulin used for and is it extra label or labeled

A

Labeled for cats

46
Q

What class of insulin is protamine zinc and what is the mechanism of absorption

A

Long acting insulin- uses protamine to slow absorption

47
Q

Which insulin drug is a mixed source insulin 90% beef and 10% pork and results in insulin antibody production in ~45% of dogs, also promotes insulin resistance

A

Protamine zinc insulin

48
Q

What class of insulin is glargine insulin

A

Long acting insulin

49
Q

What is the mechanism of action of glargine insulin

A

Acidic solution is neutralized when injected SQ which causes microprecipitates to form that dissolve at a constant rate- hence the long acting

50
Q

Can you dilute an entire bottle of glargine insulin and store for later use

A

No! Precipitates will fall out of solution and then you won’t be injecting any insulin

51
Q

What class of insulin is detemir insulin

A

Long acting insulin

52
Q

What is the mechanism of action of detemir insulin

A

Forms microprecipitates following injection, has increased plasma protein binding which both contribute to long acting effect

53
Q

Can you dilute an entire bottle of detemir solution and store for usage at later date

A

Yes, does not precipitate when dilated

54
Q

Which insulins have the greatest likelihood of getting a cat into remission

A
  1. Detemir
  2. Glargine
55
Q

What are the treatment goals of a diabetic patient

A
  1. Eliminate clinical signs
  2. Prevent short term complications- hypoglycemia, DKA
  3. Good QOL
    4, postpone/prevent cataracts in dogs
56
Q

T or F: the biggest treatment goal for a diabetic patient is to maintain plasma glucose levels in a normal range

A

False!

57
Q

Keeping insulin levels <300mg/dL requires >___ insulin in dogs or cats

A

1.5U/mL

58
Q

When adjusting insulin levels you must be conservative because of ____

A

Hypoglycemia-can be fatal
Hyperglycemia- rarely fatal

59
Q

What is the polyol pathway useful at indicating

A

Hyperglycemia

60
Q

Describe the polyol pathway

A

Glucose in blood—> sorbitol—> fructuose

Sorbitol—> glycation of protein NH2 groups—> fructosamine and HbA1C

Fructose—> glycolysis

61
Q

What symptoms are found in patients with increase polyol pathway/hyperglycemic

A
  1. Decrease BF
  2. Neuropathy
  3. Cataracts- decrease glycogen
62
Q

What causes DKA

A

Prolonged, uncontrolled hyperglycemia

63
Q

In DKA if the body is unable to utilize glucose, what forms and what is the result

A

Ketone bodies, resulting in metabolic acidosis

64
Q

What are some signs of DKA

A

Lethargy, depression, coma, dehydration, unkempt, muscle wasting, hepatomegaly, plantigrade cats, cataracts in dogs, acetone on breath

65
Q

What is the treatment protocol for DKA

A
  1. Hydrate-0.9% saline, add glucose to prevent hypoglycemia post insulin
  2. Administer short acting insulin (CRI-preferred or IM)
  3. Correct electrolyte imbalances
  4. Correct acidosis
66
Q

Are DKA patients at risk of become hypokalemia or hyperkalemic and why

A

Hypokalemic because prolonged PU leads to wasting of K+ by renal tubules

67
Q

How does insulin affect the Na+/K+ pump

A

Increases activity leading to uptake of K+

68
Q

In DKA patients what must you monitor their heart for and why

A

Arrhythmias due to mass movement of K+ from the blood into the cell

69
Q

What is bexagliflozin and velagliflozin labeled for

A

Type II DM cats that have never been given insulin

70
Q

How does bexagliflozin and velaglifozin work

A

Inhibit SGLA2 which resorbs glucose from proximal tubule—> decreases circulating glucose levels

71
Q

What are the adverse effects of bexagliflozin and velagliflozin

A

Hypoglycemia, DKA, UTI, anorexia, increased USG and fPL, PU/PD, vomiting, diarrhea, lethargy, anorexia, death

72
Q

What are some contraindications of bexagliflozin and velagliflozin

A

Anorexia, lethargy, dehydration, liver or kidney insufficiency, pancreatitis

73
Q

What is kinostat indicated for

A

Prevention of cataracts in diabetic dogs

74
Q

How does kinostat work

A

Kinostat blocks aldose reductase which is responsible for converting glucose to sorbitol in polyol pathway so blocks glycation of NH2 proteins which is what leads to glycation of collagen in the lens that causes cataracts

75
Q

What is glipizide indicated for

A

Extra label for type II cats, especially if owners don’t want to given injections

76
Q

What is the mechanism of action of glipizide

A

Blocks ATP dependent K+ channels, therefore convincing cell it is in high glucose state, so it will increase beta cell secretion of insulin

77
Q

What are some adverse effects of glipizide

A

Promotes formation of toxin amyloid fibers that kill beta cells, reduces remission likelihood, hypoglycemia

78
Q

What is metformin indicated for

A

Type II DM in cats (not great), horses

Extra label

79
Q

How does metformin work

A

Reduces glucose by increasing glucose uptake by the liver and inhibiting gluconeogenesis by opposing glucagon

80
Q

What are some adverse effects of metformin

A

Overdose can cause lactic acidosis, one trial showed 20% of cats died

81
Q

What is one benefit of metformin/what adverse effect does it not cause that most insulins do cause

A

Hypoglycemia

82
Q

What is considered hypoglycemic in dogs

A

<70mg/dL
<60mg/dL- indicating of underlying pathology

83
Q

What can cause hypoglycemia

A
  1. Insulin overdose
  2. Diabetogenic hormones- catecholamines secondary to Addison
  3. Sepsis- bacteria like glucose
  4. Malnutrition in neonates or toy breeds
  5. Liver pathologies
  6. Cancer- hepatic, leiomyosarcomes, insulinomas
84
Q

What are some signs of hypoglycemia

A

Lethargy, depression, head tilt, seizures, coma

85
Q

What are some treatment options at home for hypoglycemia

A
  1. D/c insulin until hyperglycemia, add karo syrup to gums
86
Q

What are some treatment options at hospital for hypoglycemia

A

IV fluids containing dextrose and adjust insulin

87
Q

T or F: dogs can become refractory to octreotide

A

True (can move to diazoxide)

88
Q

What is diazoxide indicated for

A

Insulinomas in dogs and ferrets

89
Q

What is the mechanism of action of diazoxide

A

Opens K+ channels in beta cells, causing hyperpolarization, inhibits insulin release

Pharmacology II (18 decks)

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