Antipruritic treatments pt 2

Question 1

what steroid drug is most implicated in causing cat diabetes?

Answer 1

dexamethasone exhibits greater diabetogenic effects in cats than equipotent doses of prednisolone

Question 2

long acting steroids
- how are they formulated
- recommended use in dogs and cats
- side effects

Answer 2

• These contain insoluble vehicles (acetate, diacetate, acetonide)
• These drugs are not recommended for routine use in the dog
• When necessary, an exception can be made for the use of methylprednisolone acetate in the cat, where it can be used periodically with fewer side effects than in the dog, although side effects can occur that include skin fragility, diabetes and induction of demodicosis
• possibly can contribute to development of congestive heart failure in the cat

Question 3

topical steroids duration of suppression after treatment is stopped:
- betamethasone valerate
- mometasone
- hydrocortisone aceponate

Answer 3

• betamethasone valerate: <4wk
• mometasone: no suppression after 7 days
• hydrocortisone aceponate: no suppression after 70 days

Question 4

what affects potency of topical steroids? forms?

Answer 4

• note that the potency of the steroid is affected by factors other than the type of steroid and its concentration (but these do affect potency too, of course)
• eg. Molecular structure, absorption through the skin and the ability of the drug to leave the vehicle
• ointment > cream > lotion

Question 5

adverse effects linked with potent topical corticosteroid application:

Answer 5

• cutaneous atrophy
• comedones
• superficial follicular cysts
• Iatrogenic Cushing’s Disease

Question 6

hydrocortisone aceponate
- type of drug and properties
-

Answer 6

• diester class drug that allow penetration into the skin without much absorption
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• lipophilic
• Low plasma availability
• Once inside the skin, transformed to deliver increased potency at the site of action with the systemic effects of hydrocortisone
  > significant anti-inflammatory activity
• treat chronically affected areas daily for a week as per label instructions
  > and then maintain on no more than twice weekly application to the same location

Question 7

diprosone vs valisone effect on long-acting steroid potency

Answer 7

• diprosone makes steroid more potent than valisone

Question 8

steroid ointment vs cream vs lotion potency

Answer 8

ointment > cream > lotion

Question 9

allergic otitis steroid therapy

Answer 9

2% Burow’s solution in propylene glycol with 1% hydrocortisone eardrops

Question 10

Allergen-specific immunotherapy (ASIT)
- what is it, benefits
- success depends on?

Answer 10

allergy treatment that entails formulating an injection or sublingual treatment for allergic skin disease.
- one of the few treatments that offer the possible outcome of a long- term remission and is one of the best and safest long-term ways of managing allergies
- The idea is to induce tolerance in the patients to the allergens; this is a slow process, and the owners should be prepared for up to 12 months to assess the response
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Success is dependant on
◦ the validity of the test
> quality control
> timing
◦ Extract formulation

Question 11

when preparing ASIT, considerations to make sure formulation will be effective

Answer 11

• Number of allergens per vial (<12)
• cross-reactivity between allergens
• Mold proteases (can affect pollens – 2 vials?)
• What allergens are in high numbers in the environment during the pet’s allergy “season”
• Potential for anaphylaxis

Question 12

Injectable allergy extract can be formulated in several ways:

Answer 12

Aqueous, Emulsion and Alum precipitated extract are all available, also intralymphatic and sublingual

Question 13

ASIT administration schedule, how it works

Answer 13

The allergens included in the extract are based on the test and the patient history and are administered to the patient using subcutaneous injections starting in lower volumes (and in some cases concentration) - called induction and then in increasing volumes to a maximum dose and frequency (called Maintenance) to induce tolerance in the patient to the allergens.

Question 14

Sublingual immunotherapy (SLIT) pros and cons

Answer 14

Pros:
- used in animals that wont tolerate injections
- no reports of anaphylaxis (compared with injections)
- molds can be included with pollens (extract is stabilized with glycerin)

Cons:
- once to twice daily admin for life if it works - twice daily products may be preferable

Question 15

Oclacitinib - what is it?

Answer 15

It is a non-steroidal small molecule inhibitor of the Jak-Stat signalling pathways that affects Jak 1 and 3 and Erk 1 and 2 but not Stat 3. This leads to anti-inflammatory properties in particular affecting pruritus related to IL- 31
- non-steroidal treatment for allergic skin disease
- same spped of onset as prednisolone
- “apoquel”

Question 16

role of IL-31 in canine allergic skin disease

Answer 16

• pruritic and pro-inflammatory cytokine
• released by Th cells in response to stimulation
• affects sensory nerves > itchyness

Question 17

How do JAK inhibitors work?

Answer 17

normally:
- cytokine binds to cell receptor > JAK activation > STAT phosphorylation > STAT dimerization > to nucleus > RNA polymerase transcription of DNA > leave nucleus > transcription > inflammatory cell function changes

JAK inhibitor stops JAK activation after cytokine binds receptor
> inhibitors only work in cells whose activity is mediated by cytokines that work through JAK

Question 18

Before starting long- term therapy with apoquel:

Answer 18

• CBC
• biochem
• +/- urinalysis and urine culture
• physical and dermatological evaluation
• skin scraping for demodex

Question 19

Oclacitinib (Apoquel) treatment schedule

Answer 19

• Day 0: Begin treatment as
  per label - 0.4 – 0.6 mg/kg PO twice daily for up to 14 days, and then once daily for maintenance therapy.
• MILDLY ITCHY DOGS CAN START SID – pruritus scores at 28d were the same
• may be administered with or without food

Question 20

Oclacitinib (Apoquel) should not be used in what animals?

Answer 20

NOT IN DOGS LESS THAN ONE YEAR – (young dogs: study stopped due to development of pneumonia, demodex)

Question 21

Oclacitinib (Apoquel) - what to warn owner about? what to do if no response?

Answer 21

• warn owner about potential spike in itchiness when dose is decreased to once daily
• if no response and compliant, consider alternative treatment or reassess diagnosis

Question 22

long-term Oclacitinib follow up:

Answer 22

• every 6 - 12 months reassess patient
  > repeat CBC and biochem
  > +/- skin scraping if indicated
  > +/- urinalysis if indicated

Question 23

what is cytopoint?

Answer 23

A caninized IL-31 monoclonal antibody (mAb) treatment
- once monthly injection that is administered subcutaneously and tends to last 4-8 weeks.

Question 24

how are antibody therapies created?

Answer 24

immunize animals with target protein > isolate B-cells from the spleen or lymph node > identify cells that produce antibodies with desired binding properties to target > identify key DNA sequences from the desired antibodies > speciate the antibody > optimize the DNA sequences

Question 25

cytopoint admin, bioavailability, absorption

Answer 25

• subcutaneous injection, therapeutic antibodies are injected into interstitial space.
• There is 50-100% bioavailability
• The therapeutic antibodies move from interstitial space into the bloodstream (and bind to IL-31) by several pathways.
  > They can be transported via lymphatics to blood,
  > absorbed directly into capillaries or
  > absorbed by receptor- mediated cell uptake (endocytosis) and transferred to the blood.

Question 26

cytopoint metabolism and clearance, implications for drug interactions

Answer 26

Clearance mechanisms include:
◦ Binding to target
◦ Anti-mAb antibodies in circulation
◦ Flow out of capillaries into interstitial space, taken up by cells and catabolized
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- Therapeutic antibodies that attach to the FcRn (Fc neonatal receptor) within the endosome are protected from catabolization and are recycled back into the blood or lymph which extends half-life
- Antibodies are catabolized to peptides and amino acids within cells
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These antibodies, therefore, are NOT metabolized by traditional metabolizing enzymes in the kidney or liver. As a result, drug-drug interactions rare. They are not converted into reactive or toxic metabolites. Antibodies are NOT excreted in urine by the kidneys

Question 27

what species is cytopoint for? how many injections

Answer 27

• dogs only - caninized antibody
• Some patients take multiple injections to take effect

Question 28

when should cytopoint be used? treatment schedule based on pruritus timing?

Answer 28

As Cytopoint is specific to only one aspect of allergic skin disease - IL-31 – and there are many mediators that come in to play after, the importance of anti-IL 31 treatment before subsequent inflammation develops has been suggested as a treatment protocol. This “proactive treatment” would suggest that patients be treated on a schedule and not when the pruritus starts to become intolerable

Question 29

When to choose Apoquel over Cytopoint?

Answer 29

• In large dogs, the cost of therapy with CytopointTM is higher that Apoquel.
• Apoquel may have activity against food allergies; effect of Cytopoint on food is currently unclear.
• Apoquel should not be used in dogs < 3Kg or < 1 year old but Cytopoint can be used at all weights and sizes.
• In cases of moderate to marked inflammation, Apoquel has greater anti-inflammatory action compared to Cytopoint.
• Interestingly, in a paper published in December 2018, giant/large dogs had a better success rate with Cytopoint over smaller ones.
• There are no drug interactions with Cytopoint and so it can be considered when age, medical or drug contraindications or concerns preclude the use of other treatments.
• consider cytopoint when compliance could be an issue