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Corticosteroids Flashcards

1
Q

What are the 2 subgroups of corticosteroids?

A

mineralocorticoids Glucocorticoids

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2
Q

What are the major endogenous glucocorticoids? Where are they produced

A

cortisol Cortisone Corticosterone -Produced in the zona fasiculata of the adrenal cortex

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3
Q

Are the endogenous glucocorticoids produced at a constituative or enduced rate?

A

constitutive rate

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4
Q

What is the major mineralocorticoid?

A

aldosterone Produced in the zona glomerulosa Corticosterone converts to aldosterone

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5
Q

What regulates corticosteroid synthesis? Include the pathway for cortisol production

A

Hypothalamic-pituitary adrenal axis - stress elicits neurologic signals that activate the hypothalamus - Hypothalamus releases CRH which causes the anterior pituitary to release ACTH -ACTH stimulates cortisol synthesis

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6
Q

Cortisol synthesis from ACTH

A
  • ACTH activates its receptor in the adrenals Activated ACTH-R initiates cAMP driven events resulting in: 1) receptor mediated uptake of LDL 2) Hydrolysis of cholesterol esters 3) Cholesterol transport into mitochondria 4) Synthesis of progenolone from cholesterol 5) synthesis of cortisol from pregnenolone
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7
Q

ACTH to aldosteronse pathway

A

ACTH-R initiates cAMP driven events resulting: 1) receptor mediated uptake of LDL 2) Hydrolysis of cholesterol esters 3) Cholesterol transport into mitochondria 4) Synthesis of prognenolone from cholesterol 5) synthesis of corticosterone from prognenolone 6) Synthesis of aldosterone from corticosterone in the zona glomerulosa cells

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8
Q

What feedback mechanisms are associated with ACTH?

A

ACTH inhibits its own release from the anterior pituitary. The activated ACTH-R initiates biochemical cascades and gene expression events resulting in the retention of ACTH

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9
Q

How does Cortisol have feedback on the HPA?

A

Cortisol inhibits CRH synthesis at the hypothalamus Cortisol inhibits ACTH release from the AP

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10
Q

Corticosteroids are agonists or antagonists for the cortisol receptor?

A

Agonists for the cortisol receptor

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11
Q

What is a side effect for prolonged corticosteroid drug usage

A

Adrenal atrophy

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12
Q

What can happen with abrupt withdrawal of a corticosteroid?

A

Can lead to adrenal insufficiency

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13
Q

Regulation of Aldosterone release?

A

ACTH Promotes the synthesis of aldosterone in the zona glomerulosa where aldosterone synthetase is present. the release of Aldosterone requires the presence of Angiotensin II

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14
Q

What is transcortin?

A

A plasma proteint that specifically carries corticosteroids to target organs. - carries exogenous and endogenous corticosteroids

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15
Q

Can Corticosteroids interact with their receptor while bound to Transcortin?

A

no- must be released from the transcortin

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16
Q

How is affinity and onset of action associated with transcortin

A

The affinity of a drug for transcortin will determine: - The onset of action - The duration of action

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17
Q

How are corticosteroids metabolized?

A

Transcortin influences hepatic metabolism of corticosteroids. it is not metabolized while bound to transcortin

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18
Q

Receptor selectivity and Physiologic functions of corticosteroids

A
  • All endogenous glucocorticoids and all exogenous glucocorticoids have different affinities for the cortisol receptor. - Aldosterone has its own receptor that it is highly selective for. - some glucocorticoids can bind to and activate the aldosterone receptor. ***Kidney cells have an enzyme that inactivates cortisol thus preventing it from activating the aldosterone receptor
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19
Q

What are reasons for using corticosteroids?

A

Inhibit inflammation Suppress the immune system Replacement therapies

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20
Q

How do corticosteroids inhibit inflammation?

A

Reduce inflammation by activating the expression of lipocortin which is a direct inhibitor of PLA2 The inhibition of inflammation results from a reduction of capillary permeability and exudation

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21
Q

How do corticosteroids suppress the immune system

A
  • suppress inflammation by inhibiting various aspects of cell mediated immunity such as T-cell associated cytokine production and signaling - Corticosteroids also promote the production of macrophage-associated cytokines that are antiinflammatory
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22
Q

Do NSAIDS suppress the immune system?

A

No, they are inhibitors of inflammation at the level of decreasing vascular permeability. Same for anti-histamines.

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23
Q

What are examples of primary conditions where corticosteroid replacement therapy is indicated?

A

Adrenal atrophy Cellular dysfunction Autoimmune disease Lack of normal secretion of corticosteroids

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24
Q

What are examples of secondary conditions where corticosteroid replacement therapy is indicated?

A

Pituitary issues - atrophy - dysfunction - auto immune lack of normal ACTH

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25
What are examples of tertiary conditions where corticosteroid replacement therapy is indicated?
hypothalmic issues - atrophy - dysfunction - Autoimmune disease Lack of normal secretion of CRH
26
What reason would you have for short term use of corticosteroids?
shock
27
What reason would you have for chronic but finite/sporadic use of corticosteroids?
pruritic dermatoses (most common use) allergic respiratory and GI diseases
28
What reasons would you ahve for a chronic life-long use:
Autoimmune diseases Replacement therapy
29
Would you use corticosteroids for corneal ulcers?
no!!! makes them way worse
30
What ophthalmic inflammatory conditions may indicate use of corticosteroids?
retinitis choroiditis Optic neuritis
31
What neurologic conditions indicate the use of corticosteroids?
cervical or lumbar disc disease Vestibular disease Peripheral neuropathies Polymyositis
32
What are some potential side effects of corticosteroid use?
diabetes mellitus cushing's syndrome Hirsutism PU/PD Adrenal insufficiency
33
What are significant side effects associated with corticosteroids?
- increased susceptibility to infection - peptic ulcer - diabetogenesis from increased gluconeogenesis
34
What causes PU/PD in animals that were administered corticosteroids?
Electrolytes vascular tone Glucose
35
What are permanent consequences of corticosteroid usage?
Adrenal insufficiency Diabetes mellitus
36
When would cushings like disease be observed on the timeline of therapy with corticosteroids?
during
37
When would addison's like disease be observed on the timeline of therapy with corticosteroids?
After
38
How is duration of action and length of HPA suppression associated?
the longer the duration of action, the longer the HPA suppression
39
What drug is used for Canine Atopy?
Prednisone Less prevalent side effects with SID Owner compliance is easier
40
what is the approach to therapy when dosing Prednisone in a dog?
3-5 days full dose EOD full dose EOD 1/2 dose e3d then keep tapering until you find a dose that eliminates the symptoms. - antihistamines can be given on the "off" days
41
What is the drug of choice with feline allergic skin diseases? why is this different than in canine patients?
Prednisolone Dogs are able to convert prednisone to prednisolone, but cats lack the ability to convert this.
42
What injectable drug is an option when treating feline allergic skin disease
methylprednisolone (Depo-Medrol) - if the cat is not pillable use this every 6-8 weeks by injection. \*avoid use in obese cats because of the risk of diabetes.
43
What is the relationship between Methylprednisolone and HPA suppression
HPA axis suppression is more likely when compared to oral prednisone
44
Treatment of feline asthma
Prednisolone with a bronchodilator- nebulized or oral
45
Can antihistamines be used in feline asthma?
no
46
What do you do if a feline asthmatic patient is not pillable?
Methylprednisolone every 4-8 weeks by injection (more frequent than for skin)
47
Equine heaves
associated with an allergic reaction to particulates in the straw and hay . Approach treatment the same as feline asthma (horses can't convert prednisone to prednisolone) - nebulizer IV prednisolone in dire situations
48
How do you approach treatment of autoimmune diseases?
Taper much slower. Start on hgih doses until signs abate 2-3 months on alternate day high dose 2-3 months on alternate day low dose - continue to taper as long as the signs are gone Prednisone in dogs Prednisolone in cats
49
when using corticosteroids for a replacement therapy what concerns regarding sparing the HPA axis should you have?
none - The HPA is no longer functional
50
With replacements with corticosteroids, what adjunct therapy would you need to administer?
mineralocorticoids
51
What replacement therapy would you use to replace cortisol?
Fludrocortisone or desoxycorticosterone
52
Describe Triamcinolone
For use in dogs, cats, and horses topical and injectable, but not long-acting \*\*Main advantages are intra-lesional injection and a lack of mineralocorticoid activity. -Can be used subconjunctival in horses instead of daily eye drops.
53
What is triamcinolone used for in dogs
inflammed anal sacs
54
What is the level of HPA suppression in Triamcinolone?
HPA suppression more likely than methylprednisolone
55
Describe the drug Betamethasone
topical for ears, skin, and eye - combined with an antibiotic and/or antifuncal Some systemic absorption so there may be some PU/PD
56
Describe Flumethasone
injectable corticosteroid may be used in racehorses and Greyhounds Very potent, so proceed with caution
57
Describe the drug Mometasone
nasal spray and topical - much less systemic absorption than other topicals. \*very good choice if concerned about side effects, if the patient is on other drugs, or has other conditions. inhibits passage across biomembranes
58
what are drug-drug interactinos with corticosteroids
do not use with digitalis do not use with diuretics that cause hypokalemia (corticosteroids also cause hypokalemia so together can lead to arrhythmias) - these are of most importance for drugs with mineralocorticoid activity do not use NSAIDS
59
Why should combinations of corticosteroids and NSAIDS be avoided?
corticosteroids block PLA2, and prevents NSAIDS from having substrate to bind to. There is no antiinflammatory synergism between the two drugs. - They do compound on their ability to produce side effects. \*\* you will get gastric ulcers if you combine these medications\*\*
60
In what situations would you need to use an anti-adrenal medication
Cushing's disease Adrenal Neoplasia
61
What are the 2 types of anti-adrenal drugs?
adrenolytic Anti-secretion
62
What is an example of an adrenolytic drug?
Mitotane
63
How does Mitotane work?
This drug irreversibly destroys the zona fasciculata and reticularis. 10-14 day treatment followed by weekly treatment as needed. * There is an inducible Addison's disease so life-long glucocorticoid therapy will be required
64
Should you be concerned about the Mitotane reaction with the zona glomerulosa?
No- The zona glomerulosa is spared. this means that Fludrocortisone or desoxycorticosterone supplementation is not indicated
65
What are common side effects for Mitotane use?
hepatotoxicity is a common side effect Enducible Addison's disease
66
What are examples of anti-secretion, anti-adrenal drugs?
trilostane ketoconazole Selegiline D2- Receptor agonists
67
How does the drug Trilostane work?
This drug is considered an anti-secretion, anti-adrenal drug that inhibits 3-B-hydroxysteroid dehydrogenase. This also inhibits sex steroid synthesis leading to reproductive disturbances. Safer therapy than mitotane but the therapy will be life-long
68
How does the drug Ketoconazole work?
this drug is considered an anti-secretion, anti-adrenal drug that inhibits cytochrome P450 system involved in steroidogenesis * Trilostane is preferred due to the increased rate of side effects * hepatotoxicity * Drug-drug interations * Reproductive disturbances
69
How does the drug Selegiline work?
This drug is considered an anti-secretion, anti-adrenal medication that functions by inhibiting ACTH secretion by increasing the dopamine activity at the anterior pituitary. This drug prevents dopamine from reuptake. increased dopamine in the synapse. -Dopamine blocks ACTH release at the AP cell
70
What conditions will the drug Selegiline treat?
This will only work on **ACTH-dependent Cushing's disease of pituitary origin.** * This will not work on Cushing's disease due to ectopic production of ACTH This medication is biochemically converted to amphetamine and methamphetamine so it is also used to treat **canine cognitive dysfunction**
71
What are D2 receptor agonist drugs?
These drugs are anti-adrenal drugs * Bromocriptine * Carbergoline * Pergolide
72
How do D2 Recptor agonists work?
inhibits ACTH secretion by activating dopamine receptors at the anterior pituitary - this will only work on ACTH dependent Cushing's disease
73
What is an anti adrenal medication that is used in an emergency situation
Etomidate- This is a GABA-R agonist used for sedation. This also inhibits 11-B-hydroxylase which is an enzyme present in the cortisol synthesis pathway. - this can be given IV to treat a hypercortisolemic patient that cannot swallow a pill
74
What is a common side effect of Equine Cushing's disease?
Laminitis.
75
What veterinary uses do anabolic steroids have?
Testosterone analogs used to * Rebuild muscle mass * Reverse nephropathy-associated anemia * increase appetite in emaciated animals Strignent availability due to abuse potential
76
What is an alternative medication that could potentially be used instead of anabolic steroids?
Myostatin - this is a regulatory protein that prevents myocyte hypertrophy and hyperplasia. SMAD2,3 inhibits the expression of myogenesis genes
77
What is a potential side effect in humans for myostatin inhibitors?
there is an unknown potential for abuse, but myocardial hypertrophy has been noted in humans with lowered myostatin
78
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Pharmacology (7 decks)

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