Steoid/nonsteroidal Pharm Flashcards
Anti-inflammatory effects glucocorticoids
Limits visible & microscopic signs of inflammation
Radiant, physical, chemical, infectious, hypersensitivity, immunmedited
What type of inflammation do NSAIDS not work against?
Hypersensitivity and immune mediated inflammation
GC mechanism of action
Transactivation of anti genes
- activate gene at locus by presence of particular gene at another locus
Transrepression of pro inflame genes
- one protein represses that activity of second protein
Action & effects of GC
Anti-inflammation
Immunosuppression
Adverse
Dose dependent effects
Physiologic doses - GC
Use low dose
- form of replacement therapy (dog w hypoadrenocorticism)
Prednisone & prednisolone (mineralocorticoid) + DOCP (desoxycorticosterone pivalate)
Fludrocortisone acetate
Dosing GC - anti inflame dose
Inhibit phospholipase A2
Decrease movement of WBC into inflamed tissue
Inhibit release of inflame mediators /enzymes
Stabilization of micro vascular integrity
Inhibit phospholipase A2
- proximal mediator of arachidonic acid cascade
Decrease movement of WBC into inflamed tissue
- reduce release of cytokines
Inhibit release of inflame mediators /enzymes
- histamine, bradykinin
Stabilization of micro vascular integrity
- for shock or CNS inflame
- penetrate BBB (NSAIDS dont)
- reduce edema
- reduce cellular extravasation
Immunosuppressive doses of GC
Decrease macrophage function
Decrease lymphocyte function
T cell»_space;> B cell
Chronic/cumulative dosing
Anti inflame or immunosuppressed dose
Chronic use can result in inhibition of Bcell antibody production
Dermatology & soft tissue effects
GIT adverse effects
Neuropsychiatric adverse effects
Eye adverse effects
Renal adverse effects
Bone adverse effects
Cardio adverse effects
Muscle adverse effects
Endocrine adverse effects
Minimizing adverse effects
Alternate date therapy
Taper dosing
Alternative routes of admin
Alternative therapeutic options
(Minimize not prevent)
Average blood work on GC - CBC
Neutrophilia
Lymphopenia
(Eosinopenia)
(Monocytosis)
(Basopenia)
“Stress leukogram”
Average chemistry work on GC
Hyperglycemia - glucosuria
Increased ALP/ALT - dogs esp
Hyperalbuminemia - cats esp
Dyslipidemias - cholesterol
Dosing for dogs - prednisolone
Prenisolone
Physiologic replacement - 0.2-0.3 mg/kg
Anti inflame - 0.55-1.1 mg/kg
Immunosuppressive - 2.2-4.4mg/kg
Dosing for cats - prednisolone
2.2-8.8mg/kg
Fewer # of GC receptors
Lower affinity of GC receptors
Action of prednisone
Intermediate action (12-36hr)
3.5x more potent than endogenous cortisol
Mineralocorticoid action (less than endo)
Oral in dogs - cheap
Cats & horses - low bioavailability
Action of prednisolone
Intermediate action (12-36 hr)
4x more potent than endogenous cortisol
Mineralocorticoid activity (< endo)
Active metabolism of prednisone
Oral in cats, dogs, horses & non rum species
IV use - prednisolone sodium succinate - ER drugs, wide species spectrum
Action of dexamethasone
Long action >48 hr
30x more potent than endo
No mineral activity
Dexamethasone injection
2mg/mL
Polyethylene glycol base - caution repeated use in cats
Dexamethasone sodium phosphate
4mg/mL
Equivalent to 3mg/mL dex - adjust dose
Dexamethasone PO tablet & powder
Fine just adjust dose
Triamcinolone base
Intermediate action 24-48 hrs
5x more potent
No mineral activity
Oral
Triamcinolone ester
Long action (weeks)
8x more potent
No mineral activity
IM/SC, intra-articular, intralesional
Methylprednisolone Na suc
Intermediate acting (12-36hr)
5x more potent
No mineral activity
IV/IM
Methylprednisolone acetate
Long acting (days to weeks)
2x more potent than prednisolone
No mineral activity
IM/SC, Intra articular intralesional
When to use GC
Immune mediated diseases
Hypersensitivity
Neurological disease / TBI (crosses BBB)
Shock
When to use NSAIDS
Musculoskeletal disease (DJD)
Infections
Fever
Peri-operative
Wounds
Atypical NSAIDS
Acetaminophen (therapeutic not toxin)
Dipyrone
Grapirant
Acetaminophen - similarities to other NSAIDS
Anti-inflame properties
- pain, fever, loss of function, fever, redness
Same clinical indications as COX-2 inhibitors
Acetaminophen- differences from other NSAIDS
Minimal effects on COXI/COX2 in peripheral inflame
Toxicity profile is different - liver, blood, not GI or kidney
Paracetamol
Same thing as acetaminophen
Mechanism of action for acetaminophen
Analgesics effects are centrally mediated (CNS)
Reaches high concentrations in CNS
Interacts w opioid receptors
Increases serotonin in brain
Inhibits substance P
Inhibit COX 3 ? (Found in CNS of some species including dog)
clinical use for acetaminophen in horses
Pain/lameness - alone or combined w NSAIDS
Fever
Clinical use for acetaminophen in dogs
Combined w codeine
Tablet strength 300/60
Dose 10-15 mg/kg & 1-2 mg/kg
What species should you not use acetaminophen in ?
Cats - absolutely not
They lack the liver enzyme to break down for proper function - hepatotoxic
Dipyrone
“Metamizole”
IV use in horses
Fever, PO ?
Prohibited in food animals
Why is Dipyrone banned in food animals?
- causes blood of dyscrasias in humans
Pulled from human market
Action of Dipyrone
Spasmolytic
- inhibits release of intracell Ca
- blocks muscle contraction (GIT)
Rapidly metabolized
- multiple active metabolites (4-MMA)
- prodrug
Clinical uses for Dipyrone
Fever
Colic (+butylscopolamine), anticholinergic/spasmolytic
Analgesics & anti-pyretic in dogs
Analgesics & anti inflame in cats
Grapiprant
First in class piprant
Non-cox inhibiting prostaglandin receptor antagonist
Specifically blocks EP4 receptor
Labeled use of grapiprant
Control of pain /inflammation associated w OA in dogs
Safe up to 15x label dose for up to 9 months
- dose dependent decreases in albumin
Effective when compared to placebo
Adverse effects of grapiprant
Diarrhea, hemorrhagic
MDR1 mutant
Grapiprant in cats
Orally absorbed - levels similar to therapeutic concentrations in dogs
Safe after 28 days of admin
grapiprant in horses/alpacas
Not absorbed well
- horses 30mg/kg = $6400/week
Baby goats is fine
Efficacy of grapiprant
Some analgesics in dog spays
Not as good as carprofen
Minimal analgesics in cat spays
PSGAGs
Adequan - canine & equine
Disease modifying osteoarthritis drug
- IM 2x /week for 4 weeks
Heparin analog
Cautions with PSGAGs
- avoid use in animals w bleeding disorders
- avoid concurrent use w COX1 or non selective NSAIDS
DMSO
Free radical scavenging properties
Used in horses to treat
Endo tox, GIT, neurological disease, laminitis, rhabdomyolysis, HIE
Admin of DMSO
IV of 5-10% DMSO
Lack efficacy data
Cannot use in dairy operations
