Pharm For Skin 2 Flashcards
Uses for inflammatory /auto immune conditions
Atopy
Flea allergy
Food allergy
Culicoides hypersensitivity
Pemphigus
Glucocorticoids doses
Immunosuppressive does higher than anti inflammatory/anti allergic dose
- prednisolone: 2.5-6.6mg/kg
- dexamethasone: 0.2-0.5mg/kg vs 0.1-0.2mg/kg
GC’s
Standard treatment for inflammatory /auto immune
Highly effective
Work at multiple sites of cascade
Can cause transactivation of anti inflammatory genes and treansrepression of pro inflame genes
Major ADR of corticosteroids
Derm:
Cushingoid appearence
Skin thinning
Alopecia
Hirsutism
Hypertrichosis
Alternatives for GC’s - allergic
Allergic/inflammatory
- cyclosporine
- oclacitinib
- lokivetmab
- antihistamines
Alternatives for GC’s - auto immune
Auto immune:
- azathioprine
- chlorambucil
- cyclophosphamide
- mycophenolate mofetil
Cyclosporine
Used locally on the eye in all species
- KCS, anterior uveitis, immune mediated keratitis
- FDA approved for dogs
Use in cyclosporine
Systemic use is mainly for Tx of atopic dermatitis
- dogs & cats
- FDA approved for dogs & cats
Use in immune-mediated disease require higher doses
- response varies
- used in perianal fistulas
Bioavailability of cyclosporine
Greatly affected by formulation & feeding
FDA approved formulations are microemulsions
- capsules for dogs, solution for cats
- smaller particle sizes increase absorption
Metabolism of cyclosporine
EXTENSIVELY metabolized by CYP450 enzymes
- drugs that INHIBIT cyp450 INCREASE CsA conc.
- drugs that INDUCE cyp450 DECREASE CsA conc.
Cyclosporine p-glycoprotein efflux pumps
Substrate for p-glycoprotein efflux pumps
- drugs that INHIBIT p-Gp INCREASE CsA conc.
- drugs that INDUCE p-gp DECREASE CsA conc.
Ketoconazole inhibits
CYP450
P-glycoproteins
Decreases metabolism of CsA
Cyclosporine & ketoconazole
Almost doubles plasma & skin CsA concentrations
Cuts cost of CsA almost in half - cheaper
Contradictions for cyclosporine
Use with history of NEOPLASIA
Systemic immunosuppressant
- increase the susceptibility to development of neoplasia
- exacerbate sub clin neoplasic conditions
precautions of cyclosporine
Should be used with caution in animals w RENAL insufficiency
Precautions of cyclosporines
GI problems
Gingival hyperplasia @inital dose
May cause hirsuitsm in dogs
Killed vaccines are recommended
Diabetes and cyclosporines
Affects glucose metabolism
- decreased insulin secretion
- increased insulin resistance
PK are altered in diabetic dogs = decreased concentrations
Length of effect
Several weeks
After Initial dosing period, every other day may be effective
Oclacitinib
NIB = inhibit kinases
JAK 1,3 kinase inhibitor
Blocks signal for cytokine transduction
Inhibits IL-31 mediated pruritis
IL and oclacitinib
Inhibits
IL-31 med pruritis
IL involve in allergies, 2,4
Apoquel in dogs
Tx for atopic dermatitis & itch in allergic dermatitis
Safe in other species
Apoquel in cats
Used for NON flea, NON food induced hypersensitivity dermatitis
Apoquel in horses
Culicoides hypersensitivity, asthma
Anecedontal evidence only
PK of oclacitinib
Well absorbed EVEN in horses
Moderately /widely distributed
HIGHLY metabolized - eliminated by metabolism
No effects on CYP450 enzymes
Eating does not affect absoption
PD of oclacitinib
Controls itch within 4 hours
Lasts for 24 hours after dosing
No effects on CYP450 enzymes
Feeding does not affect absorption
ADR of oclacitinib
Generally safe
- V/D most common
Transient leukopenia
Pododermatitis
Papillomas
Aggression
Lokivetmab
FDA approved for Atopy in dogs - Cytopoint
1st vet monoclonal antibody
cIL-31 inhibitor - stops itch cycle to brain
Monoclonal antibodies PK
NOT orally absorbed - admin IV, IM, SC
Absorbed via lymphatics
Binds to target receptor cells
Metabolism and admin of monoclonal antibodies
Met by peptides & amino acids - circulated by phagocytic target cells
Admin xxx can trigger an immune response
- form anti drug antibodies
- rapid destruction
- decreased efficiency
ADR of lokivetmab
Lasts <3 days
Can cause urinary incontinence, pain at inj site hyper-excitability, somewhat expensive
Dosing oclacitinib
Range 0.4-0.6mg/kg
Tablets: 3.6mg, 5.4mg, 16mg
Dosing lokivetmab
2mg/kg
1mL vials at 10mg, 20mg, 30mg, 40mg concentrations
Antihistamines
Not as effective
Lower role in skin disease in vet species
First and second gen
First gen antihistamines
Diphenhydramine - Benadryl
Hydroxzyine
Chlorpheniramine
Second generation antihistamines
Loratadine - Claritin
Cetirizine - Zyrtec
Fexofenadine - Allegra
ADR of antihistamines
Relatively safe
Sedation+/-
Mild GI
Anti muscarinic effects (dry mouth, urine retention, constipation)
Topical cal cause local allergic reactions
Sever overdose = CNS & convulsions
Claritin vs Claritin D
Need formulation without decongestion
- can cause behavior changes, panting, tachy, hypertension
H1 receptor blocker
Oddball drugs
Azathioprine
Chlorambucil
Mycophenolate mofetil
azathioprine
Purine antagonist - affects RNA/DNA
Decreases antibody production - pemphigus**
NOT safe in cats - Myelosuppression
Hepatotoxicity common in dogs
Safe in horses
ADR of azathioprine
GI - v/d
Pancreatitis
Skin eruptions
Poor hair growth
^ susceptibility to infection
Teratogenic in rats, mice, humans
Drug/drug interactions - azathioprine
Allopurinol - weird drug, used for leishmania
- risk of Myelosuppression
CsA
GC’s
Chlorambucil
Alkylating agent - cross linking DNA
Targets B cells
Onset is slow - 2 weeks for activity
ADR of chlorambucil
Myelosuppression - mild, reversible, 7-14d of initial therapy
GI toxicity
Reversible neurotoxicity (myoclonus) w overdose
Safer than azathioprine for cats
Mycophenolate mofetil
MPA inhibits inosine monophosphate dehydrogenate
- suppresses lymphocyte proliferation
- decreases antibody production
Mycophenolate mofetil absorption
Variable absorption & elimination dogs
Commonly combined w GC’s
Reduced Hepatotoxicity & cytotoxicity vs azathioprine
GI ADR are common in dogs
