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Clinical Pharmacology > SA Endocrine 3 > Flashcards

SA Endocrine 3 Flashcards

1
Q

Anterior Pituitary (Adenohypophysis) hormones

A
  • LH, FSH, GH, TSH, Prolactin

- ACTH (Pars distalis)

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2
Q

Posterior Pituitary (Neurohypophysis) Hormones

A
  • ADH, oxytocin
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3
Q

Pars intermedia Hormones

A
  • Small avascular zone

- Some ACTH production

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4
Q

Which part of the adrenal gland takes up the most space?

A
  • Zona fasciulata (75%)
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5
Q

Where are cortisol receptors found?

A
  • Most cells in the body
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6
Q

Functions of cortisol

A
  • Gluconeogenesis
  • Anti-inflammatory
  • Immunosuppressive
  • Stimulation of erythropoiesis
  • Maintenance of vascular tone and resistance
  • Appropriate response to stress
  • More
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7
Q

Corticotropin Releasing Hormone Origin and feedback

A
  • Hypothalamus

- Negative feedback by cortisol

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8
Q

ACTH release and negative feedback

A
  • ACTH released by pituitary (anterior pituitary)

- Negative feedback by cortisol

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9
Q

Function of aldosterone

A
  • Blood volume regulation
  • Secretion of potassium from kidneys and resorption of sodium from the kidneys
  • Regulated by RAAS
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10
Q

Cushing’s (Hyperadrenocorticism overview)

A
  • Usually benign mass develops in pituitary gland or adrenal gland
  • Pituitary mass produces excessive amounts of ACTH that stimulate the adrenal to produce excessive cortisol
  • OR an adrenal mass secretes excessive amounts of cortisol
  • If only 1 adrenal gland has a mass, then the other gland will atrophy and stop producing cortisol
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11
Q

Synthetic Adrenocorticotropic Hormone (ACTH-cosyntropin) Indication

A
  • Used in ACTH Stim Test
  • Evaluates maximal response of the adrenal glands to ACTH (adrenocortical reserve)
  • Used for diagnosis of hyperadrenocorticism, hypoadrenocorticism, and iatrogenic Cushing’s
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12
Q

What is the maximum dose of ACTH-Cosyntropin that you can give?

A
  • Maximum per dog is 250 µg
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13
Q

Route of ACTH-cosyntropin

A
  • Parenterally (IV)

- Inactivated by gut enzymes

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14
Q

Adverse effects of ACTH-cosyntropin

A

Possible hypersensitivity

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15
Q

Cost of ACTH-cosyntropin

A
  • Expensive
  • Generic more affordable
  • Comes lyophilized and is reconstituted with sterile water
  • Only good for 24 hours but aliquots can be frozen for up to 6 months
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16
Q

Dexamethasone Drug class (as diagnostic drug for Hyperadrenocorticism)

A
  • Synthetic glucocorticoid with minimal mineralocorticoid activity
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17
Q

Dexamethasone Indication

A
  • Dexamethasone Suppression test

- Used to diagnose and differentiate between pituitary and adrenal dependent Cushing’s

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18
Q

Adverse effects of dexamethasone

A
  • Single low dose for the Dexamethasone suppression test not expected to have significant side effects
  • Possible: PU/PD/PP, GI ulceration, insulin resistance (cats especially)
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19
Q

How much more potent is dexamethasone than prednisone?

A
  • 8-10x (though I think we learned 7x by Dr. Slovak)
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20
Q

Drug interactions of Dexamethasone

A
  • Do not give with concurrent NSAIDs due to increased risk of GI ulceration
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21
Q

Why do you use dexamethasone instead of prednisone for dexamethasone test?

A
  • It does not interfere with cortisol assays, whereas prednisone does
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22
Q

Trilostane (Vetoryl) drug class

A
  • Synthetic steroid analog
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23
Q

Trilostane (Vetoryl) MOA

A
  • Competitive enzyme inhibitor that blocks formation of cortisol
  • Also some effect on aldosterone and androgen synthesis
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24
Q

Trilostane (Vetoryl) dosing overview

A
  • Typically start BID or SID PO (dose need varies by patient; BID better for diabetics)
  • Dose in the morning if you’re going to test 1x a day
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25
Q

Trilostane (Vetoryl) Monitoring

A
  • Monitor ACTH stim tests in 2 weeks and 4 weeks

- Do not make dose increases before 4 weeks

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26
Q

Adverse effects of Trilostane (Vetoryl)

A
  • Idiosyncratic adrenal necrosis**
  • Electrolyte abnormalities - hyperkalemia, hyponatremia
  • Reversible Addisonian state (GI signs 1st, lethargy, hypovolemia)
  • Caution in animals with renal or hepatic impairment
  • Do not use in pregnant animals
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27
Q

Drug interactions with Trilostane (Vetoryl)

A
  • Ketoconazole and mitotane may potentiate the effects

- ACE inhibitors, Potassium sparing diuretics (spironolactone) may increase risk of hyperkalemia

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28
Q

Trilostane formulation

A
  • Capsules only - dosing can be tricky

- Do NOT use compounded drug as 1 study found it was very inconsistent in terms of actual capsule content

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29
Q

Price of Trilostane

A

$$$$$

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30
Q

Mitotane drug class

A
  • Chemotherapeutic agent
31
Q

MOA of Mitotane

A
  • Adrenolytic/adrenal cytotoxic

- Mainly zona fasciculata and reticularis, but 6-10% will have zona glomerulosa destruction

32
Q

High dose Mitotane

A
  • Generally not recommended
  • Can be used to essentially kill the adrenal glands and create an Addisonian patient
  • In some cases easier to manage than a Cushinoid
  • High rate of complications and potential death
33
Q

Low to moderate dose Mitotane

A
  • Preferred method
34
Q

Induction phase Low to Moderate Dose Mitotane

A
  1. Lower dose for 7-10 days
    - Monitor closely for adverse effect (appetite, lethargy, GI signs)
    - If they occur, STOP the drug and recheck an ACTH stim
35
Q

What do you want to test at the end of the Induction phase for Mitotane?

A
  • Check ACTH stim tests at day 10 and then every 5-10 days until baseline and post ACTH stim cortisols are between 1-5 µg/dL (ideally >2)
36
Q

Maintenance phase of low to moderate dose Mitotane

A
  • 35-50 mg/kg per week divided into 2-3 doses

- Monitor for adverse effects

37
Q

What should you do if adverse effects are reported with mitotane

A
  • STOP IT and
  • Recheck and ACTH stim
  • Supplement with dexamethasone as needed to keep the dog safe until it can be evaluated
38
Q

Adverse effects of Mitotane

A
  • Addisonian state (GI signs, lethargy)
  • Liver changes - congestion, centrilobular atrophy, fatty degeneration)
  • Caution in animals with diabetes, renal or hepatic impairment, and in pregnant animals
39
Q

Drug interactions with mitotane

A
  • Phenobarbital - reduces mitotane efficacy and mitotane increases its metabolism
  • Spironolactone - blocks action of mitotane
40
Q

Lab work considerations of mitotane

A
  • May reduce serum total T4 concentrations (not free T4)
41
Q

Mitotane dosing recommendations

A
  • Give with food, as fat improves absorption
42
Q

Ketoconazole drug class

A
  • Azole antifungal
43
Q

Ketoconazole MOA

A
  • Inhibits steroid biosynthesis

- Interferes with the imidazole ring and cytochrome P450 enzyme systems

44
Q

Ketoconazole recommendation for treatment of Hyperadrenocorticism

A
  • Not recommended

- Not considered very effective, and effect is variable

45
Q

Ketoconazole Adverse effects

A
  • GI signs
  • Hepatotoxicity
  • Thrombocytopenia
  • Suppression of sex hormone production and infertility in males
46
Q

Drug interactions of ketoconazole

A
  • MANY!

- May potentiate the effects of other anti-cortisol drugs (trilostane, mitotane)

47
Q

Oral bioavailability of ketoconazole

A
  • Variable in dogs

- needs acidic environment

48
Q

Selegiline drug class

A
  • Monoamine oxidase inhibitor (MAO)
49
Q

Selegiline MOA

A
  • Dopamine inhibits ACTH release from pars intermedia of the pituitary
  • MAO metabolizes dopamine
  • By inhibiting MAO, dopamine concentrations in the pars intermedia are increased thus increasing inhibition of ACTH
50
Q

Selegiline general recommendations

A
  • NOT RECOMMENDED
  • Not considered very effective, as the majority of dogs with Cushing’s have lesions in the pars distalis
  • In this region ACTH release is independent of dopamine
  • Therefore selegiline does not affect ACTH secretion and thus cortisol
  • The increased dopamine may make them happier and can help with cognitive dysfunction
51
Q

Dosing for Selegiline

A
  • Dosing in the morning with food
52
Q

Adverse effects of Selegiline

A
  • GI, restlessness, lethargy, salivation
53
Q

Drug interactions of Selegiline

A
  • MANY!

- Always check before starting

54
Q

Metyrapone MOA

A
  • Enzyme inhibitor that blocks formation of cortisol
55
Q

Metyrapone Indication

A
  • Possible treatment for feline Cushing’s

- Used for short term stabilization prior to adrenalectomy

56
Q

When should you see effects with Metyrapone?

A
  • Generally within 5 days
57
Q

Adverse effects of Metyrapone?

A
  • Well tolerated
58
Q

Hypoadrenocorticism overview

A
  • Suspected immune-mediated destruction of the adrenal cortex (zona glomerulosa and/or zona fasciulata)
  • Loss of sufficient production of cortisol and usually aldosterone
59
Q

Synthetic ACTH used for diagnosis of hypoadrenocorticism

A
  • Same procedure as with Cushing’s

- Interpretation if baseline and post cortisol value <2 µg/dL is diagnostic for Addison’s disease

60
Q

Prednisone drug class

A
  • Glucocorticoid
61
Q

Prednisone MOA

A
  • Direct hormone supplementation
62
Q

Physiologic dose of Prednisone for Addisonian patients (KNOW THIS)

A
  • 0.15-0.3 mg/kg/day

- Double during stressful or exciting events

63
Q

Adverse effects of physiologic pred dose

A
  • Should be minimal to non-existent at proper dose as you’re just replacing what should normally be there
  • If steroid side effects are seen, the dose may need to be decreased
64
Q

Prednisone and cortisol testing

A
  • It will be detected as cortisol on an assay

- Wait at least 24 hours after a prednisone dose to perform cortisol testing

65
Q

DOCP (desoxycorticosterone pivalate) Drug class

A
  • Long acting mineralocorticoid with no glucocorticoid activity
66
Q

Dosing and frequency of DOCP

A
  • IM or SQ once every 25-30 days

- Dose and frequency vary by patient and are adjusted based on electrolytes

67
Q

Adverse effects of DOCP

A
  • Contraindicated with CHF, severe renal disease, edema
  • Irritation at the injection site
  • GI signs, hypersensitivity reactions, PU/PD
68
Q

Drug interactions of DOCP

A
  • Potassium depleting diuretics (furosemide) - can develop hypokalemia, counteracts DOCP effects by increasing Na loss
69
Q

Do you usually give DOCP with atypical Addisonian patients?

A
  • No, not generally if there aren’t electrolyte abnormalities
70
Q

Cost of DOCP

A

$$$

- 100-150/month

71
Q

Fludrocortisone Drug Class

A
  • Aldosterone Replacement

- Mineralocorticoid with some glucocorticoid effects

72
Q

Adverse effects of Fludrocortisone

A
  • PU/PD, hypertension, edema, hypokalemia
73
Q

Drug interactions

A
  • Potassium depleting diuretics (Furosemide)
  • Can develop hypokalemia
  • Counteracts effects by increasing Na loss
74
Q

Other considerations of fludrocortisone

A
  • Some dogs may not require pred or require a lower dose because of glucocorticoid activity of Florinef
  • Still need to supplement additional glucocorticoids duirng stress
  • Not generally given in dogs with atypical Addison’s
  • Expensive in larger dogs

Clinical Pharmacology (7 decks)

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