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Dermatology > Unit 2: Atopy Pharmacology > Flashcards

Unit 2: Atopy Pharmacology Flashcards

1
Q

Atopy is AKA as _____ _____.

A

atopic dermatitis

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2
Q

What is atopy?

A

Genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE, most commonly directed against environmental allergens.

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3
Q

Up to ___% of the population has atopy.

A

10

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4
Q

What is the age of onset of atopy?

A

6 months to 3 years

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5
Q

What are the breed dispositions for atopy?

A

Frenchies, terriers, retrievers, bulldogs, GSD

(but any dog at any age can develop it)

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6
Q

What are common clinical signs of atopy?

A

Pruritus, otitis externa, hot spots, acral lick dermatitis, hives (rare), recurring skin infections, alopecia, +/- lichenification

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7
Q

T/F: There is no definitive test for atopy.

A

True

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8
Q

Do allergy tests diagnose or confirm atopy?

A

No

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9
Q

What are Favrot’s Criteria?

(There are 8 of them)

A
  1. Age of onset <3 yo
  2. Dog kept mostly indoors
  3. Pruritus is steroid responsive
  4. Pruritus was first symptom
  5. Affected front paws
  6. Affected ear pinnae
  7. Non-affected ear margins
  8. Non-affected dorsolumbar region
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10
Q

How many of Favrot’s criteria does a dog usually have to assume it is mostl likely atopy?

A

5

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11
Q

What type of diagnosis is atopy?

A

diagnosis of exclusion

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12
Q

What are the 4 major causes of allergy?

A

Fleas, parasite hypersensitivity, cutaneous adverse food reaction, canine atopy

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13
Q

What is the #1 reason for dogs to be itchy?

A

Fleas (C. felis)

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14
Q

What parasites are likely to causes hypersensitivity?

A

Scabies and Cheyletiella

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15
Q

What is the BASIC mechanism for allergy?

A

Allergen enters the system –> allergen binds IgE –> IgE binds mast cells –> allergic response

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16
Q

What are the predominant cell types in atopy?

A

lymphocytes and langerhans cells

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17
Q

What type of lymphocytes are involved in atopy?

A

Th1, Th2, Treg

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18
Q

What are some other cell types involved in atopy?

A

Mast cells, eosinophils, neutrophils, keratinocytes

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19
Q

What composes the barrier function of the skin?

A

Lipid lamellae surrounded by keratinocytes - composed of ceramides, 3 FAs, and cholesterol

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20
Q

What does the barrier function of atopic patients look like?

A

There are holes in the lipid lamellae

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21
Q

What are the components of the swiss cheese atopy comparison?

A
  1. Keratinocytes are active in the immune
  2. Ceramides are deficient
  3. Filaggrin is mutated
  4. Increased water loss
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22
Q

What cytokine stimulates itch?

A

IL-31

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23
Q

What is the most important aspect of management?

A

Client education

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24
Q

What supportive care can we give atopic patients?

A

antihistamines, FFAs, bathing and barrier care

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25
Q

What disease-specific therapies can we give to atopic patients?

A

GCs, cyclosporine, IL-31 inhibitors, allergen-specific immunotherapy

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26
Q

What are the most common antihistamines given to atopic patients?

A

Diphenhydramine and Cetirizine (Zyrtec)

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27
Q

What antihistamine is Rx?

A

Hydroxyzine

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28
Q

What antihistamine is the most expensive?

A

Fexofenadine (Allegra)

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29
Q

Antihistamines do not stop _____.

A

pruritus

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30
Q

Why are antihistamines used?

A
  1. Prevention of subsequent flare-ups and safety
  2. Helpful in mild cases
  3. Drug-sparing effects
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31
Q

What fatty acids can be used?

A

Omega-6 and Omega-3

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32
Q

What is the MOA of FAs?

A

Downregulate inflammatory eicosanoid production, inhibit inflammatory cell activation, and improve epidermal lipid quality

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33
Q

What are some examples of commercial diets that contain FAs?

A

Hill’s Derm Defense, Purina DRM, RC Skin Support

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34
Q

What are the purposes of bathing?

A

Remove allergen, soothe and hydrate, deliver meds, barrier care (ceramides and precursors)

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35
Q

What are things to consider for bathing?

A

Can and will the owners do it?

Contact time, water temperature, drying

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36
Q

What is the downside to GC therapy?

A

Many adverse effects

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37
Q

GCs are made for ____ use in atopy.

A

Short-term

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38
Q

What 2 side effects should owners always be warned about with GCs?

A

PU/PD, polyphagia

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39
Q

What are additional side effects of GCs?

A

Behavior changes, panting, fat redistribution, muscle wasting, recurrent UTIs, hepatopathy

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40
Q

What are clinical syndromes/diseases that can occur as a result of GC therapy?

A

Iatrogenic Cushing’s, DM, thyroid suppression, pancreatitis, calcinosis cutis, weakened ligaments

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41
Q

What are 6 reasons when you should consider GCs?

A
  1. Acute flares and first time episodes
  2. Prior to starting IL-31 inhibitors
  3. Seasonal disease (3 mos or less)
  4. Other forms of therapy have failed
  5. Multimodal therapy
  6. Financial constraints
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42
Q

What are the 2 phases of GC therapy?

A

Reactive and Proactive

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43
Q

What does reactive therapy (phase 1) mean?

A

Induction of remission

44
Q

What drugs would you use at point A?

A

Oral +/- topical GCs

45
Q

What drugs would you use at point B?

A

Oclacitinib

46
Q

What therapies would you use at A?

A

Allergen avoidance +/- immunotherapy

47
Q

What drug would you use at B?

A

lokivetmab

48
Q

What drug would you use at C?

A

cyclosporine

49
Q

What drug would you use at D?

A

Oral +/- topical GCs

50
Q

What drugs would you use at E?

A

Proactive topical GCs, Oclacitinib

51
Q

What formulation of GC should be used in atopy?

A

Oral only

52
Q

T/F: GCs should never be combined with other things

A

False; should be adjunctive with baths, fish oils, diet, etc.

53
Q

What is the anti-inflammatory dose of steroids?

A

0.5-1 mg/kg/day PO (prednisone)

54
Q

What is the minimum age and weight for cyclosporine use?

A

6 months, 4#

55
Q

What is the basic MOA of cyclosporine?

A

It messes with IL-2 production from lymphocytes

56
Q

What type of drug is cyclosporine?

A

Calcineurin inhibitor

57
Q

What happens when IL-2 transcription is blocked?

A

Lymphocyte proliferation is suppressed and further production of relevant cytokines is inhibited

58
Q

What are the 3 functions of a calcineurin inhibitor?

A
  1. Blocks IL-2 transcription
  2. Decreases APC #s and activation
  3. Decreases mast cell and eosinophil activation and production
59
Q

What is the time to effect and overall efficacy of cyclosporine?

A

6 weeks and works in 4/5 dogs

60
Q

What are possible reasons for failure of cyclosporine?

A

Dog doesn’t tolerate it, cost/benefit ratio to woner, dog has food allergy that we missed, dog has secondary infections that haven’t been properly addressed

61
Q

How often should monitoring be done with cyclosporine?

A

every 6 months to 1 year

62
Q

What are common adverse events of cyclosporine?

A

V/D, anorexia, gingival hyperplasia, hypertrichosis

63
Q

What are 6 reasons to consider CsA?

A
  1. Patient >6 mos of age
  2. Smaller dogs (more cost effective)
  3. Condition is more inflammatory
  4. Otitis is major manifestation
  5. IL-31 inhibitors are ineffective or contraindicated
  6. Allergen specific immunotherapy has failed
64
Q

What are the 2 IL-31 inhibitors?

A

Apoquel and Cytopoint

65
Q

How many patients benefit from Apoquel?

A

60-70%

66
Q

What is the FDA labeled use for Apoquel?

A

Control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 mos of age

67
Q

What is the MOA of Apoquel?

A

JAK inhibitor (1 and 3), suppresses IL-31 signaling, and suppresses other CKs involved with the cellular and inflammatory response ot atopy

68
Q

What other CKs does Apoquel suppress?

A

IL-2, 4, 6, 13

69
Q

What is the overall success of Apoquel?

A

Works in 6/10 dogs BID - but long term labeled use is SID and no longer works in 4/10 patients

70
Q

What is the #1 adverse event with Apoquel?

A

V/D and anorexia

71
Q

What are 3 things which Apoquel might increase susceptibility to?

A

Bacterial infections, viral papillomas, demodicosis

72
Q

What are additional side effects of Apoquel?

A

Lethargy and behavior change, increased thirst, weight loss or gain

73
Q

What are 5 reasons when you should consider Apoquel?

A
  1. Patient is >1 yo
  2. Pruritus is main symptom or presentation
  3. Owners do not wish to pursue ASIT
  4. Recurrent pyoderma or Malassezia dermatitis
  5. Owner elects this form of therapy given options
74
Q

Who is cytopoint labeled under? What is the label?

A

USDA - Shown to be effective for the treatment of dogs against allergic dermatitis and atopic dermatitis

75
Q

What does it mean if a drug is USDA-labeled?

A

It is safe but doesn’t have to show efficacy

76
Q

What type of drug is Cytopoint?

A

Lokivetmab (monoclonal Ab)

77
Q

Why can’t cytopoint be used in cats?

A

It is a mAb which is produced for and is identical to the spp that the drug is intended for (dogs)

78
Q

What are the 4 unique aspects of mABs?

A
  1. Administered by injection
  2. Long half-lives
  3. Very targeted therapy with anrrower adverse event profiles
  4. Metabolized and excreted differently
79
Q

How does cytopoint work?

A
  1. Ab binds and prevents binding of a protein to its receptor
  2. Ab has an agonist/antagonist effect on a membrane R
  3. Ab eliminates virus or malignant cell by C’ or cytotoxicity
80
Q

What is nice about Cytopoint vs the other therapies (steroids, CsA, Apoquel)?

A

It has the least adverse effects

81
Q

What is the duration of activity of Cytopoint?

A

4-8 weeks (usually 4)

82
Q

What is the onset of action of Cytopoint?

A

<72 hr

83
Q

What is the efficacy of Cytopoint?

A

7/10 dogs

84
Q

What are the possible adverse effects of Cytopoint?

A

GI upset, lethargy, injection site discomfort

85
Q

What are the major advantages to using Cytopoint?

A

Any age, any concurrent disease, any concurrent meds

86
Q

When should Cytopoint be considered?

A

In any patient with atopy whose major symptom is pruritus, and in multimodal therapy

87
Q

What does ASIT stand for?

A

allergen specific immunotherapy

88
Q

ASIT is the most _____ long term management strategy.

A

economical

89
Q

ASIT lacks long-term _____.

A

complications

90
Q

ASIT is the best chance for a _____.

A

“cure”

91
Q

What are the 5 indications for ASIT?

A
  1. Any atopic patient (early/first choice)
  2. Symptomatic therapy is not effective alone
  3. Patient can’t tolerate medical options
  4. Patient has conflicting concurrent medical conditions (chronic infections, DM)
  5. Owner chooses to address cause vs. symptoms
92
Q

What are the multimodal components of the MOA of ASIT?

A

T cells, Ig class switching, CK expression

93
Q

What is allergen selection for ASIT based on?

A

history and test results

94
Q

The _____ of the reaction in ASIT does not necessarily correlate with the _____ of the allergen.

A

strength, significance

95
Q

What are the 5 ASIT protocols?

A

Classic, Modified, Rush, Sublingual (SLIT), Intralymphatic

96
Q

What is the classic ASIT protocol?

A

2 or 3 vial

Start out with 200-1000 PNU vial and progress to 10,000-20,000 PNU maintenance vial

Frequent injections

97
Q

What is the modified ASIT protocol?

A

Starts with 20,000 PNU vial

98
Q

What is the rush ASIT protocol?

A

Series of injections reaching maintenance in a day

99
Q

What is the sublingual ASIT protocol?

A

3 vial series with increasing []

Given twice a day

100
Q

When might we see improvement with the intralymphatic ASIT protocol?

A

By the 3rd injection

101
Q

What is the main side effect of ASIT no matter what the route is?

A

Increased pruritus at the site of administration

102
Q

What are other side effects of ASIT?

A

Swelling at injection site, urticaria/angiodema, anaphylaxis, V/D

103
Q

What is the efficacy of ASIT?

A

60-70% of dogs demonstrate improvement

104
Q

How long does it take for ASIT benefits to show?

A

6-12 months

105
Q

What is RESPIT?

A

Regionally-specific immunotherapy available as an injectable or oral spray

Dermatology (14 decks)

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