Antipruritic Drugs - Dermatology Flashcards
Why should you Avoid long-acting injectable systemic glucocorticoids?
At this time, because of the high risk for adverse effects, the use of long-acting injectable glucocorticosteroids
(ie. methylprednisolone acetate, Depo-Medrol, Zoetis,
4 mg/kg SQ) is not recommended in dogs and cats unless there is an absolute inability to treat the patient orally
Adverse effects: diabetes mellitus, steroid hepatopathy, icterus, pancreatitis, congestive hart failure, skin fragility syndrome (cats), weight gain, demodicosis, dermatophytosis, bacterial pyoderma, iatrogenic hyperadrenocortism (Cushings), calcinosis cutis (dogs), rupture of cruciate ligaments, muscle atrophy, urinary tract infections, pyometra, adrenal suppression/atrophy etc.
How should steroids be used?
Oral glucocorticoids should be commenced at anti-pruritic doses twice daily, and then decreased, as clinical signs abate, to the lowest possible dose and frequency (e.g. once daily to every other day to every 3 days) needed to maintain good quality of life/control of clinical signs and minimal adverse effects
Side effects of oral steroids
Common adverse effects of oral glucocorticosteroids are proportional to dosage and duration of administration:
Polyuria, polydipsia
Polyphagia
Panting
Behavioral changes, depression, lethargy Predisposition to urinary tract infections
Difference between dogs and cats w.r.t. oral prednisolone? Which is superior?
Dexamethasone 8X more potent on lipid/glucose metabolism
Decreased hepatic conversion of prednisone (prodrug) into prednisolone
Only 21% of orally administered prednisone appears in blood in prednisolone
Decreased gastrointestinal absorption of prednisone vs. prednisolone
Historical use of prednisone in cats may have contributed to the perceived ‘glucocorticosteroid resistance’ in cats (ie. the perception that cats seem less sensitive to the adverse effects of glucocorticosteroids than the dog)
What is the monitoring before starting oral GC therapy?
Complete blood count Serum biochemistry profile Urinalysis +/- urine culture Physical and dermatological examinations Body weight FeLV/FIV test (cats)
What is the monitoring 3 to 6 months after starting therapy, then every 6 to 12 months during long-term treatment?
Complete blood count
Serum biochemistry profile
Urinalysis +/- urine culture
Physical and dermatological examinations Body weight and appetite
ME CsA blood levels Not needed for monitoring
Low inter-individual variation in absorption
Atopica accumulates in skin (blood levels irrelevant)
No correlation has been found between blood levels and clinical efficacy or safety in dog and cats
Measurement of blood levels critical for transplanted patient (risk of transplant rejection), not in allergic dogs and cats
Measurement of blood levels were historically recommended for Sandimmune (because of its inconsistent absorption)
Optimum therapeutic range (immune-mediated diseases) = 200-400 ng/mL (> 600 ng/mL is sufficient immunosuppression to prevent organ rejection in canine transplant recipients)
ME CsA adminstration protocol
Prescribe 4 weeks at 5 or 7 mg/kg q24h (Induction phase)
Evaluate situation at the 4 week-mark:
Response treatments for ME CsA adminstration protocol
High responders (> 50% reduction in the level of pruritus) 50% reduction in dose first = 5 or 7 mg/kg q48h from week 4 to week 6, then try to go down to twice a week (q72h) Low responders (< 50% improvement in the level of pruritus) Has to be kept at dose of 5 or 7 mg/kg q24h beyond 4 weeks
What % chance to be giving ME CsA at the 8 week-mark (maintenance phase)?
Overall, at the 8 week-mark (maintenance phase): 25% chance to be giving ME CsA q24h 50% chance to be giving ME CsA q48h 25% chance to be giving ME CsA q72h
Differences with Atopica between dogs & cats Labelled for: How supplied Dosage Minimum age:
Labelled for
Canine atopic dermatitis
Feline allergic dermatitis
How supplied
Dogs: Boxes of 15 soft gelatin capsules 10, 25, 50 and 100 mg capsules
Cats: 100 mg/ml nonflavored oral solution 5 and 17 ml bottles
Once opened:
5 ml bottle is good for 7 weeks*
17 ml bottle is good for 11 weeks*
Dosage
Dogs: 5 mg/kg q24h PO for 4 weeks, then tapered frequency of administration based on clinical response
Cats:7 mg/kg q24h PO for 4 weeks, then tapered frequency of administration Based on clinical response
Minimum age
Dogs: 6 months (and > 2 kg)
Cats: 6 months (and > 1.4 kg)
What about use for atopic a for other indications other than canine atopic dermatitis & feline allergic dermatitis?
Use for any other indication, species = off-label !
Long-term ME CsA combination therapy
Be careful !
The concurrent long-term administration of oral ME CsA and glucocorticosteroids – especially at higher dosages of either or both drugs – should be monitored carefully, as potent combined immune suppression is likely to result in a higher risk for development of potentially severe opportunistic infections of the skin or other organs
The concurrent long-term administration of oral ME CsA and ketoconazole should be monitored carefully, as the drug interaction is likely to result in a higher risk for development of potentially severe adverse effects (ie. hepatotoxcity)
+ ME CsA and adverse reactions ** important
Dogs & cats et vomiting retching & regurg
Cats get weight loss
Less commonly Dogs & cats get Diarrhea soft stools
Cats can also get anorexia, decreased appetite & malaise/lethargy
Drug interaction ME CsA-Ketoconazole
↑ ME CsA absorption < ME CsA and KCZ inhibiting PGP ↓ ME CsA elimination < KCZ inhibiting CYP3A4 ↑ ME CsA blood level ↑ Risk of ME CsA toxicity ↓ administered dose of ME CsA
