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Clinical Pharmacology > SA Endocrine 3 > Flashcards

SA Endocrine 3 Flashcards

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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
Trilostane (Vetoryl) Monitoring
- Monitor ACTH stim tests in 2 weeks and 4 weeks | - Do not make dose increases before 4 weeks
26
Adverse effects of Trilostane (Vetoryl)
- 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
27
Drug interactions with Trilostane (Vetoryl)
- Ketoconazole and mitotane may potentiate the effects | - ACE inhibitors, Potassium sparing diuretics (spironolactone) may increase risk of hyperkalemia
28
Trilostane formulation
- 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
29
Price of Trilostane
$$$$$
30
Mitotane drug class
- Chemotherapeutic agent
31
MOA of Mitotane
- Adrenolytic/adrenal cytotoxic | - Mainly zona fasciculata and reticularis, but 6-10% will have zona glomerulosa destruction
32
High dose Mitotane
- 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
Low to moderate dose Mitotane
- Preferred method
34
Induction phase Low to Moderate Dose Mitotane
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
What do you want to test at the end of the Induction phase for Mitotane?
- 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
Maintenance phase of low to moderate dose Mitotane
- 35-50 mg/kg per week divided into 2-3 doses | - Monitor for adverse effects
37
What should you do if adverse effects are reported with mitotane
- STOP IT and - Recheck and ACTH stim - Supplement with dexamethasone as needed to keep the dog safe until it can be evaluated
38
Adverse effects of Mitotane
- 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
Drug interactions with mitotane
- Phenobarbital - reduces mitotane efficacy and mitotane increases its metabolism - Spironolactone - blocks action of mitotane
40
Lab work considerations of mitotane
- May reduce serum total T4 concentrations (not free T4)
41
Mitotane dosing recommendations
- Give with food, as fat improves absorption
42
Ketoconazole drug class
- Azole antifungal
43
Ketoconazole MOA
- Inhibits steroid biosynthesis | - Interferes with the imidazole ring and cytochrome P450 enzyme systems
44
Ketoconazole recommendation for treatment of Hyperadrenocorticism
- Not recommended | - Not considered very effective, and effect is variable
45
Ketoconazole Adverse effects
- GI signs - Hepatotoxicity - Thrombocytopenia - Suppression of sex hormone production and infertility in males
46
Drug interactions of ketoconazole
- MANY! | - May potentiate the effects of other anti-cortisol drugs (trilostane, mitotane)
47
Oral bioavailability of ketoconazole
- Variable in dogs | - needs acidic environment
48
Selegiline drug class
- Monoamine oxidase inhibitor (MAO)
49
Selegiline MOA
- 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
Selegiline general recommendations
- 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
Dosing for Selegiline
- Dosing in the morning with food
52
Adverse effects of Selegiline
- GI, restlessness, lethargy, salivation
53
Drug interactions of Selegiline
- MANY! | - Always check before starting
54
Metyrapone MOA
- Enzyme inhibitor that blocks formation of cortisol
55
Metyrapone Indication
- Possible treatment for feline Cushing's | - Used for short term stabilization prior to adrenalectomy
56
When should you see effects with Metyrapone?
- Generally within 5 days
57
Adverse effects of Metyrapone?
- Well tolerated
58
Hypoadrenocorticism overview
- Suspected immune-mediated destruction of the adrenal cortex (zona glomerulosa and/or zona fasciulata) - Loss of sufficient production of cortisol and usually aldosterone
59
Synthetic ACTH used for diagnosis of hypoadrenocorticism
- Same procedure as with Cushing's | - Interpretation if baseline and post cortisol value <2 µg/dL is diagnostic for Addison's disease
60
Prednisone drug class
- Glucocorticoid
61
Prednisone MOA
- Direct hormone supplementation
62
Physiologic dose of Prednisone for Addisonian patients (KNOW THIS)
- 0.15-0.3 mg/kg/day | - Double during stressful or exciting events
63
Adverse effects of physiologic pred dose
- 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
Prednisone and cortisol testing
- It will be detected as cortisol on an assay | - Wait at least 24 hours after a prednisone dose to perform cortisol testing
65
DOCP (desoxycorticosterone pivalate) Drug class
- Long acting mineralocorticoid with no glucocorticoid activity
66
Dosing and frequency of DOCP
- IM or SQ once every 25-30 days | - Dose and frequency vary by patient and are adjusted based on electrolytes
67
Adverse effects of DOCP
- Contraindicated with CHF, severe renal disease, edema - Irritation at the injection site - GI signs, hypersensitivity reactions, PU/PD
68
Drug interactions of DOCP
- Potassium depleting diuretics (furosemide) - can develop hypokalemia, counteracts DOCP effects by increasing Na loss
69
Do you usually give DOCP with atypical Addisonian patients?
- No, not generally if there aren't electrolyte abnormalities
70
Cost of DOCP
$$$ | - 100-150/month
71
Fludrocortisone Drug Class
- Aldosterone Replacement | - Mineralocorticoid with some glucocorticoid effects
72
Adverse effects of Fludrocortisone
- PU/PD, hypertension, edema, hypokalemia
73
Drug interactions
- Potassium depleting diuretics (Furosemide) - Can develop hypokalemia - Counteracts effects by increasing Na loss
74
Other considerations of fludrocortisone
- 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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