Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

VETM 443 Pharmacology > Glucocorticoids/Antiallergic Pharmacology > Flashcards

Glucocorticoids/Antiallergic Pharmacology Flashcards

1
Q

Where are mineralocorticoids and glucocorticoids produced

A

zona glomerulosa produces mineralocorticoids like aldosterone

zona fasciculata produces glucocorticoids like cortisol and corticosterone

These layers of the adrenal gland are physically close together and so disorders usually affect both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Explain the HPA axis

A

It controls cortisol and corticosterone release

stimuli = stress

  1. hypothalamus releases corticotropin releasing hormone
  2. anterior pituitary releases ACTH from propriomelanocortin (POMC)
  3. acts on adrenal gland which releases cortisol

There is negative feedback from
- ACTH acting on the anterior pituitary
- cortisol acting on the hypothalamus and anterior pituitary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How do exogenous corticoids affect the HPA axis

A

They cause negative feedback which results in atrophy of the adrenal gland

Must wean off slowly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is aldosterone produced

A

RAAS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is addisons disease? What are the main abnormalities?

A

hypoadrenocorticism

lack of aldosterone

hyponatremia and hyperkalemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain steroidogenesis

A
  1. cholesterol
  2. pregnenolone
  3. progesterone
    - makes cortisol
  4. corticosterone
  5. aldosterone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where are glucocorticoid receptors and what occurs after activation?

A

In the cytoplasm of cells

Once bound they will translocate to the nucleus and bind glucocorticoid response elements = gene transcription
- can also interact with other transcription factors to affect gene expression

takes time

There are fast effects
- inhibiting arachidonic acid release from damaged cells
- inhibiting lymphocyte activation through altering Ca channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are 2 main features of a stress leukogram

A

neutrophilia and lymphopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List 9 effects of glucocortioids

A

anti-inflammatory

immunosuppressive

vasoconstriction

positive inotrope

postiive chronotrope

bronchodilator

catabolic (increased glucose production from amino acids)

fluid homeostasis

neuroprotective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What mechanisms do glucocorticoids use to have a immunosuppressive/anti-inflammatory effect

A

only at supratherapeutic doses

causes eosinophilia/lymphopenia/neutrophilia
- appear like stress leukogram
- induce lymphoid apoptosis

inhibit arachidonic acid production

reduce histamine production

all along with the same adverse effects as NSAID but stronger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What mechanisms give glucocorticoids catabolic effects

A

increase lipolysis

increase gluconeogenesis (glucose from amino acids)
- only in monogastrics
- ruminants will not be impacted by this

increase blood glucose and antagonize insulin

inhibit bone formation and enhance bone loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do glucocorticoids maintain fluid homeostasis

A

Increase salt and water retention by targeting Na transporter in the kidney and inhibiting ADH release

result in PU/PD
- loss of renal medullary concentration gradient
- increased plasma volume

all glucocorticoids have some mineralocorticoid effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What mechanisms do glucocorticoids use to have an effect on the vasculo-respiratory system? What species should this be noted in, why?

A

reduce vasopermeability and increase vasoconstriction

increase the number and sensitivity of beta adrenergic receptors
- beta 2 agonist impacts are enhanced (bronchodilation)

chronic glucocorticoid use in cats increase the risk of CHF due to increased blood volume and hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do glucocorticoids have a neuroprotective effect

A

Protect against hypoxic/ischemic damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the consequences of glucocorticoid deficiency

A

hypotension

hypoglycemia

anorexia/weight loss

vomit/diarrhea

muscular weakness

increased stress

reduced ability to maintain endothelial integrity and vascular tone

potentially hyponatremia and polyuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the 3 main structures of glucocorticoids and how do they impact the effect

A

steroid structure + side chains

glucocorticoid esters

free ester = short, routinely used, PO

phosphate/succinate = short, rapid onset, IV/IM

acetate/acetonide = long acting (poorly soluble) when IV
- topical
- interarticular in horses
- intralesional in dogs
- most risk of HPA suppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What 4 factors can the structure of the glucocorticoid have an effect on

A

pharmacokinetics (duration in the body/absorption)

active (metabolite vs actual drug)

selectivity for receptor

potency = affinity for receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

List 4 commonly used glucocorticoid drugs

A

prednisone

prednisolone

dexamethasone

fluticasone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the routes of administration you may use for glucocorticoids

A

IV
IM
SC
PO
local
inhale
topical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Compare prednisone and prednisolone

A

prednisone is the non active form of prednisolone

metabolism by CYP450 is needed to turn predisone to prednisolone
- therefore predisone cannot be used topically or by cats or horses

The dose given of either is equivalent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

In what animals must you use prednisolone

A

cats and horses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

In what animals is dexamethasone used

A

small and large animals

common in large animals because it is higher potency and so you need less

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In what animals is fluticasone used and how is it administered?

A

small animals and horses

inhale

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the adverse effects of glucocorticoids

A

immunosuppression
- stress leukogram
- increased infection risk

GI ulcers

increased liver enzymes/steroid hepatopathy
- glucocorticoid inducible increased ALP
- secondary liver enzyme increase due to glycogen accumulation

PU/PD (inconvenient for owners)

iatrogenic hyperadrenococrticism
HPA axis suppression
polyphagia
reduced wound healing
behaviour change
muscle atrophy
induce birth (if late parturition)
hyperglycemia
insulin resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does cat vs dog dosing of glucocorticoids compare

A

cats usually need higher dose because they have fewer receptors and lower affinity than dogs

usually have less adverse effects compared to dogs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are 4 common uses of glucocorticoids

A

physiologic replacement therapy (tx hypoadrenocorticism)

anti-inflammation/anti-allergic

immunosuppressive (tx autoimmune dz)
- higher dose and for many months

chronic palliative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How much endogenous glucocorticoids are produced daily? How does this influence their replacement dose?

A

1mg/kg endogenous per day

usually replacement dose is less because the drugs are more potent

ex. dogs, prednisone = 0.1/0.2mg/kg/d

timing of administration is not important
- not influenced by circadian rhythm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Which glucocorticoids are commonly used to treat allergy in small and large animals

A

small
- prednisone/prednisolone

large
- dexamethasone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

When would you use glucocorticoids for chronic palliative care

A

chronic inflammation like OA that is non responsive to NSAID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Are glucocorticoids used for treating septic shock

A

sometimes - not good evidence

may be helpful in patients with critical illness related corticosteroid insufficiency

but also cause immunosuppression

only if not responsive to medical management (abx/fluid/vasopressin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What should you consider before giving glucocorticoids

A

dont give with NSAID

careful if combining with K wasting diuretic

suppress HPA axis

not curative - will control clinical signs

32
Q

How and when to taper glucocorticoids

A

After 2 weeks of therapy

can usually reduce dose to every other day
- except if replacing the physiologic amount

taper even with the use of chronic topical
- to prevent rebound inflammation
- ex. equine recurrent uveitis

33
Q

What 3 diseases indicate the use of glucocorticoids (non-replacement)

A

atopic dermatitis
- pruritis/alopecia
- use for anti-inflam effects

IMHA
- lethargy/anemia/icterus
- use for immunosuppressive effects

lymphoma
- large LN/v/d/dyspnea
- immunosuppressive effects (induce lymphocyte apoptosis)
- palliative

34
Q

What 4 conditions are contraindications for glucocorticoid use

A

systemic fungal disease

laminitis

concurrent infection

corneal ulcer

35
Q

What is ciclesonide’s mechanism of action? How is it administered

A

inhaled

It is a prodrug that is converted to desisobutyryl-ciclesonide in the lungs (has higher affinity for receptors)

It has similar effect as PO dexamethasone with less impact on HPA/adverse

36
Q

What is a soft drug? Give an example

A

ciclesonide

low adverse effects
low bioavailability if PO
increased clearance = less exposure to active metabolite

soft mist of small particles = higher efficacy

37
Q

What is the pathogenesis of hyperadrenocorticism

A

increased secretion of glucocorticoids

either
adrenal dependent = increased cortisol = adrenal neoplasia

pituitary dependent = increased ACTH = adenoma
- more common (dog/horse)

38
Q

What 2 mechanisms are used to treat hyperadrenocorticism

A

suppress ACTH
- target pituitary

suppress cortisol
- target adrenal

39
Q

Provide 2 examples for hyperadrenocorticism drugs that target the pituitary and adrenal

A

pituitary
- selegine
- pergolide mesylate

adrenal
- trilostane
- mitotane

40
Q

What is the mechanism of action of trilostane

A

blocks pregnenolone conversion to progesterone by inhibiting 3beta hydroxysteroid dehydrogenase
- target adrenal

70% effective
most commonly used

41
Q

What are the adverse effects associated with trilostane

A

vomit
diarrhea
anorexia
lethargy
can have mineralocorticoid disruption

42
Q

What is the mechanism of action of mitotane

A

blocks conversion of cholesterol to pregnenolone and pregnenolone to progesterone by inhibiting CYP450 side chain cleavage enzymes
- target adrenal

43
Q

What are the adverse effects of mitotane

A

severe progressive necrosis of the zona fasciculata and reticularis
- high doses can cause destruction and lifelong monitoring/supplementation

addisonian crisis

44
Q

What are the common adverse effects of hypoadrenocorticism

A

lethargy
vomit
diarrhea
anorexia
weakness
hyponatremia
hyperkalemia

45
Q

What is the mechanism of action of selegine

A

dopamine agonist results in feedback inhibition of ACTH

monoamine oxidase inhibitor (caution with SSRI = seratonin syndrome)

46
Q

When is selegine used

A

in dogs
usually after theyve tried trilostane and mitotane

47
Q

What is the mechanism of action of pergolide mesylate

A

dopamine agonist resulting in feedback inhibition of ACTH

inhibit production of POMC-derived hormones

48
Q

When is pergolide mesylate used

A

PPID horse
standard tx

49
Q

What is hypoadrenocorticism

A

immune mediated reduction of gluco and mineralocorticoids

50
Q

What is the standard treatment for hypoadrenocorticism

A

mineralocorticoid then glucocorticoid if needed

51
Q

List 3 potential treatment options for hypoadrenocorticism

A

desoxycorticosterone pivalate
- mineralocorticoid replacement

fludrocortisone acetate
- mineralo and glucocorticoid replacement

dexamethasone
- glucocorticoid replacement

52
Q

How is desoxycorticosterone pivalate administered

A

usually 1 injection lasts 25d

titrate to lowest dose

may need to add glucocorticoid supplementation too

53
Q

How is fludrocortisone acetate administered

A

PO q24h

54
Q

How is dexamethasone used for treating hypoadrenocorticism

A

glucocorticoid replacement

acute use
- use pred long term

less reactivity with cortisol assays so you can use it before diagnostic testing

55
Q

What are the 2 main mechanisms of atopic dermatitis

A

associated with a skin barrier defect

mast cell degranulation
- Th2 cells trigger B cell release of IgE
- sensitize mast cells
- histamine release
- vasodilation/vascular leak/smooth muscle spasm
- anaphylaxis if systemic

cytokine dystregulation
- IL31 = pruritis - due to Th2
- also IFNy/TNFa - due to Th1

56
Q

List 2 examples of antihistamines

A

diphenhydramine (benadryl)

hydoxyzine

minimal effect

57
Q

What are the adverse effects associated with H1 antagonist

A

antihistamines

mild
- CNS depression/drowsy
- GI
- anticholinergic
- drug interactions - synergistic with omega 3 and 6, may interact with ketoconazole

58
Q

When are antihistamines contraindicated

A

Dont give with other CNS depressants or monoamine oxidase inhibitors

59
Q

Explain the JAK-STAT pathway

A

JAK =janus kinase
STAT = signal transducer and activator of transcription

JAK binds cytokine receptor and phosphorylates tyrosine residue
- will phosphorylate STAT
- result in gene transcription

many types of JAK with many functions

60
Q

What is the mechanism of action of oclacitinib? What is the brand name?

A

apoquel

It is a JAK 1 inhibitor

It blocks IL (IL31) associated B cell IgE production

61
Q

How is oclacitinib administered

A

PO BID for 2 weeks

then

SID

62
Q

What is oclacitinib mainly used for

A

canine atopic dermatitis

63
Q

What contraindications are there for oclacitinib

A

dont give if the animal has an active infection

not labelled for animals <12mo

but safe long term

64
Q

What are the pharmacokinetics of oclacitinib

A

it is rapidly absorbed and reached T max in 1h

it has minimal binding to CYP450 so there are few drug interactions

65
Q

What are the adverse effects associated with oclacitinib

A

GI - vomit/diarrhea/anorexia

immunosuppression and increased risk of secondary infection
- otitis
- UTI
-pyoderma

worsen pre-existing tumors

66
Q

What is the mechanism of action of cyclosporine

A

It is immunosuppressive

inhibits calcineurin in T cells resulting in reduced cytokine (IL2, 4) transcription

It binds RBC

67
Q

What are the pharmocokinetic properties of cyclosporine

A

it is large and lipophilic

more absorption if it is ultramicronized
- absorbed in small intestine

binds RBC - use whole blood for monitoring

CYP450 metabolism

biliary excretion

68
Q

How is cyclosporine administered

A

PO 1-2h after meal

69
Q

What is cyclosporine primarily used for

A

atopic dermatitis in dogs after other treatments have failed
- because strong immunosuppressant and expensive

also IBD cats/lupus/perianal fistula

70
Q

What are 2 brand name cyclosporine products

A

atopica
- ultramicronized

sandimmune
- not ultramicronized
- not absorbed as well as atopica

71
Q

What are the adverse effects associated with cyclosporine

A

GI upset
- common but usually decreases over time

drug interactions (lots)
- if giving with ketoconazole (a CYP450 inhibitor) it will reduce the amount of cyclosporine you need

gingival hyperplasia

hypertrichosis

diabetes mellitus

papillomatosis

neoplasia risk after long term use

rare = hepatotoxic/thromboembolism

72
Q

What is the brand name for Lokivetmab? What is its mechanism of action

A

cytopoint

monoclonal Ig against IL31

73
Q

How is lokivetmab administered

A

dogs

SC q3-4 weeks

74
Q

How is lokivetmab metabolized

A

It uses protein degradation pathway

does not use conjugation/CYP450
- not affected by liver or kidney disease

long half life - max effect is 3d post injection

75
Q

What are the adverse effects of lokivetmab

A

very safe

can use in pregnant and lactating
- unlike librela (frunevetmab)

VETM 443 Pharmacology (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions