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Clinical Pharmacology > SA Endocrine > Flashcards

SA Endocrine Flashcards

1
Q

Steroid hormones Action

A
  • Diffuse through cell membranes and work directly on the nucleus to regulate gene expression and resulting protein synthesis
  • Relatively stable
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2
Q

Steroid hormone Examples

A
  • Aldosterone
  • Cortisol
  • Androgens
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3
Q

Peptide hormones Action

A
  • Interact with cell membrane receptors and work through 2nd messenger systems
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4
Q

Fragility of peptide hormones

A
  • Shorter acting

- More difficult to measure in blood

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5
Q

Peptide hormone examples

A
  • Thyroxine
  • Insulin
  • ACTH
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6
Q

What proportion of the pancreas is endocrine?

A
  • 2-3% of pancreatic mass
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7
Q

Insulin secretion style

A
  • Pulsatile
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8
Q

Insulin is released in response to what?

A
  • High blood glucose levels
  • Some amino acids
  • Intestinal hormones
  • Parasympathetic stimulation
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9
Q

Insulin release is inhibited by what?

A
  • Somatostatin
  • Sympathetic nervous system
  • Fasting
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10
Q

Is insulin catabolic or anabolic?

A
  • Anabolic hormone
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11
Q

Insulin stimulates what?

A
  1. Glycogen synthesis
  2. Lipogenesis
  3. Protein synthesis and storage
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12
Q

Insulin inhibits what?

A
  1. Glycogenolysis
  2. Lipolysis
  3. Protein catabolism
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13
Q

Where are insulin receptors found?

A
  • Most cells in the body
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14
Q

What will up or down-regulate insulin receptors?

A
  • Levels of circulating insulin
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15
Q

Diabetogenic hormones

A
  1. Glucagon
  2. Growth hormone
  3. Cortisol
  4. Epinephrine and norepinephrine
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16
Q

Diabetes mellitus in dogs

A
  • Combination of factors leads to irreversible beta cell destruction and lack of insulin production
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17
Q

Diabetes mellitus in cats

A
  • Combination of factors (including amyloid deposition) leads to either irreversible beta cell loss or more commonly significant insulin resistance and beta cell dysfunction which can be reversible
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18
Q

Acarbose Class

A
  • Alpha-glucosidase inhibitor
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19
Q

Acarbose MOA

A
  • Slows post-prandial glucose absorption
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20
Q

Acarbose indications

A
  • Cats that won’t eat a low carbohydrate diet
  • Dogs with poor glycemic control for which a cause cannot be found or treated
  • Not generally recommended for use, especially as a sole therapy
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21
Q

Adverse effects of Acarbose

A
  • Dose dependent
  • Up to 35% of patients
  • Hypoglycemia only when used with other hypoglycemic agents (insulin)
  • Dogs: diarrhea and weight loss
  • Cats: flatulence and soft stool/diarrhea
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22
Q

Contraindications and cautions with Acarbose

A
  • Caution with kidney or liver disease

- Contraindicated with underweight animals, DKA, IBD/intestinal malabsorptive disease

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23
Q

Acarbose Drug interactions

A
  • Hypoglycemic agents - may cause hypoglycemia

- Hyperglycemic agents (e.g. corticosteroids) as they may reduce or negate the effect

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24
Q

Other considerations with acarbose

A
  • Not considered effective in cats with advanced kidney disease, especially with poor appetites and on low protein diets
  • Not effective in animals fed ad libitum
  • May see two weeks to see peak effect
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25
Q

Glipizide class

A
  • Sulfonylurea antidiabetic agent
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26
Q

Glipizide MOA

A
  • Stimulates beta cell secretion of insulin

- Must have functional beta cells for this drug to work

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27
Q

Indications for use of Glipizide

A
  • Only considered useful in cats with non-insulin dependent diabetes (type II)
  • 20-30% of cats
  • If insulin cannot be given or very small doses of insulin are needed to control the DM
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28
Q

Contraindications of Glipizide

A
  • DKA, acidosis, severe trauma/infection, surgery
  • Caution with untreated adrenal or pituitary insufficiency, thyroid impairment, kidney or liver disease, vomiting, fever, malnourishment
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29
Q

Adverse effects of Glipizide

A
  • GI signs: seen in 15% of cats
  • Hypoglycemia - rare, more likely when given with other hypoglycemic agents (insulin)
  • Increased amyloid deposition which can worsen beta cell function
  • Elevated liver enzymes and jaundice (8%), which should be monitored every 1-2 weeks initially
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30
Q

Drug interactions of Glipizide

A
  • Many! Either reduce or potentiate the effects

- Always check before starting

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31
Q

How long until you see an effect with glipizide?

A
  • May take 1-2 months to see effect
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32
Q

Route of administration of acarbose and glipizide

A
  • Oral
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33
Q

What are some of the drawbacks for oral hypoglycemic therapy in general?

A
  • In general, oral hypoglycemic agents are not recommended for use
  • Response to therapy is minimal: must select patients properly.
  • 15% good response (some develop resistance over time)
  • 15% partial response
  • Cats will have a better chance of going into remission if treated with insulin therapy instead
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34
Q

Insulin types

A
  • Human, porcine, and bovine (only compounded)
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35
Q

Canine insulin similarity to pig, human, and bovine insulin

A
  • Canine insulin = porcine insulin
  • 1 amino acid different than human
  • 3 amino acids different from bovine
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36
Q

Feline insulin similarity to pig, human, and bovine insulin

A
  • 1 amino acid different from bovine
  • 3 amino acids different from porcine
  • 4 amino acids different from human
  • However they tend to do well with this
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37
Q

What are the four formulations of insulin and the routes?

A
  • Regular (IV, IM, OR SC)
  • NPH (SC only, never IV)
  • PZI (SC only)
  • Lente/Ultralente (SC only)
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38
Q

Regular insulin

A
  • Recombinant human insulin with no chemical modification
  • Onset and duration basically the same as endogenous insulin (short onset)
  • IV, IM, or SC

ONLY ONE WE CAN GIVE IV

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39
Q

NPH Insulin

A
  • Combined with protein (protamine) to delay absorption after SC administration
  • Administered SC (never IV)
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40
Q

PZI Insulin

A
  • Combined with protamine and zinc
  • Greater delay in absorption than NPH after SC
  • Administer SC (never IV)
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41
Q

Lente/Ultralente Insulin

A
  • Insulin molecules combined into crystals of various sizes

- Small crystals (semi-lente) or large crystals (ultra-lente)

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42
Q

Difference between semi-lente and ultralente for absorption

A
  • Smaller crystals delay absorption for a short time

- Larger crystals result in longer delay

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43
Q

Lente combination

A
  • Lente is combo of 30% semi-lente crystals and 70% lente crystals
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44
Q

Lente route

A
  • SC
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45
Q

Synthetic insulins/insulin analogs

A
  • Basically human insulins
  • Chemical modification of human insulin structures
  • Amino acids added, substituted, modified
  • Altered structure slows absorption and degradation
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46
Q

Adverse effects of insulin in general

A
  • HYPOGLYCEMIA
  • Somogyi effect (insulin induced hyperglycemia)
  • Injection site reactions
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47
Q

Drug interactions with insulin

A
  • Many! May potentiate or decrease hypoglycemic effects

- Always check Plumbs before starting

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48
Q

Humulin R/Novalin R

A
  • Recombinant Human Insulin

- Insulin of choice for DKA, hyperkalemia

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49
Q

Duration of Humulin R/Novalin R

A
  • Short acting
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50
Q

Route of Humulin R/Novalin R

A
  • Can be given IV or IM
51
Q

Indications for Humulin R/Novalin R

A
  • DKA
  • Urethral obstruction with high potassium
  • In those cats they often give with dextrose to drive potassium into the cells
52
Q

Considerations for Humulin R/Novalin R

A
  • Refrigerate

- Do not shake bottle but role gently to mix

53
Q

Vetsulin

A
  • Porcine Lente Insulin
54
Q

Vetsulin indication

A
  • Insulin of choice for dogs
55
Q

Vetsulin duration of action

A
  • Generally about 12 hours
56
Q

What type of syringe do you use with vetsulin?

A

U-40!

57
Q

Dosing frequency and route for Vetsulin

A
  • BID

- SC with meals

58
Q

Other considerations for vetsulin

A
  • Refrigerate

- Shake thoroughly before drawing up**** (THE ONLY ONE YOU SHAKE)

59
Q

Novolin-N, Humulin-N

A
  • NPH insulin, human recombinant
60
Q

Indication for Novolin-N, Humulin-N

A
  • Commonly used insulin for dogs if Vetsulin is not an option
61
Q

Duration of Novolin-N, Humulin-N

A
  • Intermediate acting
62
Q

Dose frequency and Route for Novolin-N and Humulin-N

A
  • BID
  • SC with meals
  • Use U-100 syringes
63
Q

Novolin-N and Humulin-N other considerations

A
  • Refrigerate

- Do not shake the bottle - roll gently to mix

64
Q

Levemir/Detemir

A
  • Human recombinant insulin analog
65
Q

Indication for levemir/detemir

A
  • More potent - canine insulin receptors 4x more sensitive to detemir than humans
66
Q

Duration of detemir/levemir

A
  • Intermediate acting
67
Q

Dose frequency and route of Detemir/Levemir

A
  • U-100 syringes

- BID SC with meals

68
Q

Other considerations for detemir/levemir

A
  • Not generally used for cats
  • Do not shake the bottle - roll gently to mix
  • Refrigerate
69
Q

Glargine/Lantus

A
  • Human recombinant, insulin analog
70
Q

Glargine/lantus Indication

A
  • You use this a LOT with cats; insulin of choice for cats
71
Q

Duration of action of glargine/lantus

A
  • Potentially long acting (12-24hr)

- Usually start BID and some can go to SID

72
Q

Dose frequency and route of glargine/lantus

A
  • BID
  • SC with meals
  • Use U-100 syringes
73
Q

Other considerations for Glargine/Lantus

A
  • Vials good for up to 6 months in refrigerator
  • Pens good for 1 month unrefrigerated
  • Do not shake the bottle - roll gently to mix
74
Q

Glargine/Lantus Bonus for cats

A
  • Can put them into remission potentially
75
Q

ProZinc

A
  • PZI insulin, Human recombinant
76
Q

ProZinc Indication

A
  • Often 2nd line choice after glargine for cats

- FDA approved for cats

77
Q

ProZinc Dose Frequency and syringe type

A
  • U40
  • BID
  • SC with meals
78
Q

Other considerations for ProZinc

A
  • Refrigerate
  • Do not shake the bottle
  • Roll gently to mix
79
Q

Treatment overview for Hypercalcemia

A
  • 1st: address and treat underlying cause if possible

- 2nd: provide non-specific therapy if no cause is found or can be treated

80
Q

Physiologic saline Diuresis overview

A
  • Non-specific
  • Fast and easy to do
  • Corrects dehydration, improves GFR, and improves hypercalcemia
81
Q

MOA of Physiologic Saline Diuresis

A
  • Corrects dehydration if present
  • Dehydration reduces GFR
  • Causes hemoconcentration which increases relative calcium plasma concentrations
  • Also decreases renal tubular calcium reabsorption as more calcium is excreted or lost
82
Q

Considerations for physiologic Saline Diuresis and Rate of action

A
  • Give IV or SC

- Fast acting

83
Q

Furosemide for Hypercalcemia Site of action

A
  • Loop of Henle
84
Q

Furosemide for Hypercalcemia MOA

A
  • Inhibits Na+/K+/2Cl- symporter

- Inhibits calcium reabsorption in the thick ascending limb of Loop of Henle

85
Q

Furosemide for Hypercalcemia Dose requirements

A
  • Animal must be hydrated/volume expanded prior to use
86
Q

Furosemide for Hypercalcemia Rate of action

A
  • VERY fast acting
87
Q

Glucocorticoids for hypercalcemia

A
  • Prednisone/Prednisolone

- Dexamethasone

88
Q

Glucocorticoids MOA

A
  • Reduce bone resorption of calcium
  • Increase renal calcium excretion
  • Decrease intestinal absorption of calcium
  • Cytotoxic to neoplastic lymphocytes (USE for lymphoma)
89
Q

Other considerations for glucocorticoids

A
  • Delay use of this drug until a diagnosis of lymphoma has been established or ruled out
  • Not very effective in patients with primary hyperparathyroidism or non-hematologic neoplasias
  • Depending on underlying cause may be fast acting
90
Q

Alendronate or Pamidronate, Zoledronate drug type

A
  • Bisphosphonates

- Alendronate is oral and the other two are injectable

91
Q

MOA of Alendronate or Pamidronate, Zoledronate

A
  • Inhibits osteoclast activity and bone resorption

- Promotes apoptosis and inhibits osteoclastogenesis, angiogenesis, and cancer cell proliferation

92
Q

Speed of Alendronate or Pamidronate, Zoledronate

A
  • Generally slow acting
93
Q

Alendronate Dose Intervals

A
  • For dog is SID

- For cat is once a week

94
Q

Adverse effects of Alendronate

A
  • GI signs

- Esophagitis

95
Q

Considerations for Alendronate

A
  • Fast 12 hrs before and 2 hrs after as food reduces absorption
  • Esophagitis: follow with water, butter the lips (cat), exercise for 30 min after (dogs)
96
Q

Pamidronate Dosing and route

A
  • IV diluted and given as CRI every 5-28 days
97
Q

Pamidronate Adverse effects

A
  • Electrolyte abnormalities (hypomagnesemia)

- Renal toxicity

98
Q

Considerations for pamidromate

A
  • Give over 2-4 hours to reduce renal effects
99
Q

Zoledronate dosing

A
  • Dilute and give as IV CRI over 15 min every 28 days
100
Q

Zoledronate adverse effects

A
  • Possible renal toxicity, but lower potential than with pamidronate
101
Q

Calcitonin origin

A
  • Salmon
102
Q

Calcitonin MOA

A
  • Inhibits osteoclastic bone resorption

- Reduces tubular reabsorption and promotes excretion of calcium, phosphorus, and other electrolytes

103
Q

Calcitonin usage in general

A
  • Not recommended
  • Dogs only
  • SC 2-3x a day
104
Q

Adverse effects of Calcitonin

A
  • GI, hypersensitivity
105
Q

Drug interactions with Calcitonin

A
  • Pamidronate

- No benefit and may worsen outcomes in dogs

106
Q

Other Considerations of Calcitonin

A
  • Very short duration of action, poor efficacy, expensive, development of resistance
107
Q

Hypocalcemia emergency treatment

A
  • Calcium gluconate 10% solution

- Calcium salt

108
Q

MOA of Calcium gluconate

A
  • Direct replacement
109
Q

Dosing instructions for Calcium Gluconate

A
  • Based on elemental calcium (contains 9.3 mg/mL)
  • SQ - dilute in equal volumes of saline
  • Must administer very slowly!!! ****
110
Q

Adverse effects of calcium gluconate 10% solution

A
  • Hypotension
  • Cardiac arrhythmias or arrest
  • SQ or IM administration could result in mild to severe tissue reactions
111
Q

Other considerations of calcium gluconate

A
  • Always check the formulation being used and dose off of elemental calcium content
  • monitor patients with an ECG during administration
112
Q

Chronic hypocalcemia cause

A
  • Most common cause is hypoparathyroidism

- lack of PTH production

113
Q

Absence of PTH

A
  • Vitamin D is not activated in kidneys

- Intestinal absorption, bone release, and renal retention of calcium are reduced

114
Q
  • Chronic hypocalcemia general principles
A
  • Generally combines a direct calcium supplement and vitamin D supplement
115
Q

Calcium carbonate

A
  • Tums
116
Q

MOA calcium carbonate

A
  • Direct replacement of calcium

- Also binds dietary phosphate

117
Q

Route of calcium carbonate

A
  • orally
118
Q

Considerations with Calcium Carbonate

A
  • Give with food
119
Q

Calcitriol

A
  • 1,25 dihydroxy vitamin D
  • Activated vitamin D
  • You need calcitriol to get oral calcium
120
Q

MOA of calcitriol

A
  • Vitamin D analog - direct replacement
121
Q

Indications of use for calcitriol

A
  • Hypoparathyroidism

- Renal secondary hyperparathyroidism (decreased renal activation of Vitamin D)

122
Q

Adverse effects of calcitriol

A
  • Hypercalcemia
  • Tissue mineralization
  • DO NOT give in hyperphosphatemic animals or those with Ca/Phos products >70 (Ca x Phos)
  • Development of calcium oxalate uroliths
123
Q

Other considerations of calcitriol

A
  • Combine with oral calcium supplementations to reduce dose needs

Clinical Pharmacology (7 decks)

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