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104 Cards in this Set
- Front
- Back
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corticosteroids
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split into mineralocorticoids-->affect electrolyte and fluid imbalance
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glucocorticoids
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affect carbohydrate metabolism
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Physiological actions of corticosteroids
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-fluid homeostasis (mineralocorticoids)
-inc. gluconeogenesis -dec. protein synthesis -inc. lipolyisis ( w/ release of glycerol and free fa) -maintain microcirculation and normal vascular permeability -development of pulmonary surfactant in near-term fetus |
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indications for administration of glucocorticoids
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endocrine: replacement therapy (addisons)
non-endocrine: shock therapy(controversial), anti-inflammatory & anti allergic, immunosuprresive therapy, chronic palliative therapy |
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indictions not acceptable for glucocorticoids
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laminitis, snake bite, lack of appetite
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glucocorticoids mechanism of action
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Genomic mechanisms: cytosolic glucocorticoid receptor (cGCR) translocates to nucleus
non-genoic effects associated with cGCR, membrane bound GCR non-genomic/non-specific effects caused by interactions with cell membranes |
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glucocorticoids genomic MOA
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cytosolic glucocorticoid receptor (cGCR) translocates to nucleus:
-inhibits pro-inflammatory transcription factors (NF-Kappa B, STAT) -suppresses transcription of inflammatory genes (IL-1,2) -induces transcription of immunosuppressive genes (lipocortin 1) |
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adverse effects of glucocorticoids
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Hypothal. Pitu. Adrenal axis supression--> why dose must be tapered off
thin skin, potbelly, cushingoid appearance, fluid retention, weight gain, muscle wasting, Na retention/K loss can induce parturition in last trimester potential for congenital abnormalities |
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contraindications for glucocorticoids
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joint injection: fracture, infection
all admin routes: corneal ulcers, GI ulcers, Hyperadrenocrticism,infections (esp. at immunosuppressive doses), |
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all Glucocorticoids act the same way but...
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have different mineralocorticoid effects, different duration of action and different hypothal. pituit. adrenal axis suppression
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Glucocorticoids: low dose response
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used for replacement/low maintenence/ anti-inflammatory
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Glucocorticoids:high dose response
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immunosuppressive
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Glucocorticodis: pulse/shock therapy
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immunosuppressive or initial lymphocytolytic (cancer treatment)
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Glucocorticoids: parental preparations
3 types |
Rapid onset <1 min, short duration 1- hr--> ER uses for shock, anaphylaxis
Rapid onset 5-45 min, middle duration 3-4 hr--> ER use Slow onset and long duration-->skin disease, arthritis, topical, intralesional |
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Glucocorticoids: parental preparations
rapid onset, short duration |
Rapid onset <1 min, short duration 1- hr--> ER uses for shock, anaphylaxis
any GCC sodium succinate, sodium phosphate |
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Glucocorticoids: parental preparations
rapid onset, intermediate duration |
Rapid onset 5-45 min, middle duration 3-4 hr--> ER use
dexamethasone SP or in propylene glycol |
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Glucocorticoids: parental preparations
Slow onset and long duration |
Slow onset and long duration-->skin disease, arthritis, topical, intralesional
triamcinolone, methylprednisolone acetate, flumethasone |
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Glucocorticoids: oral preparations
3 types |
rapid onset/short duration: acute and chronic conditions (alternate day therapy), replacement therapy
rapid onset/short to intermediate duration slow onset/long duration |
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Glucocorticoids: oral preparations
rapid onset/short duration |
rapid onset/short duration: acute and chronic conditions (alternate day therapy), replacement therapy
hydrocortisone, cortisone, prednisolone, prednisone, methylprednisone |
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Glucocorticoids: oral preparations
rapid onset/short to intermediate duration |
rapid onset/short to intermediate duration
triamcinolone base |
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Glucocorticoids: oral preparations
slow onset/long duration |
slow onset/long duration
dexamethasone, betamethasone, flumethasone |
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most common glucocorticoids for cattle
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dexamethasone (injection)
anti-inflammatory, induce abortion/parturition |
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most common glucocorticoids for cats
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methylpredisolone, prednisolone
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most common glucocorticoids for dogs
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prednisone
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most common glucocorticoids for horses
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dexamethasone, methylprednisolone*, triamcinolone*
*=jt injection |
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new glucocorticoids
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budenoside- oral for IBD
Ciclesonide- not common fluticasone- nasal spray |
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budenoside
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new glucocorticoid used for IBD
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Ciclesonide
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new glucocorticoid - not commonly used
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fluticasone
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new glucocorticoid- nasal spray
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Hydrocortisone
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short acting <24 hours GCC
good mineralocorticoid, mild HPAA suppression, alternate day therapy not possible oral, used for acute/chronic conditions or for replacement therapy |
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Cortisone
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short acting <24 hours GCC
good mineralocorticoid, mild HPAA suppression, alternate-day therapy possible but not ideal oral: rapid onset/ short duration--> acute/chronic conditions & replacement therapy |
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Prednisone
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short acting <24 hour GCC
okay mineralocorticoid, mild HPAA suppression, alternate-day therapy possible used for acute/chronic conditions, replacement therapy most common GCC for dogs |
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Prednisolone
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short acting <24 hour GCC
okay mineralocorticoid, mild HPAA suppression, alternate-day therapy possible used for acute/chronic conditions, replacement therapy commonly used in cats |
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methylprednisolone
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short acting <24 hour GCC
okay mineralocorticoid, mild HPAA suppression, alternate-day therapy possible parental has slow onset and long duration oral has rapid onset and short duration-->replacement therapy, and acute/chronic conditions commonly used in horse joints and cats |
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Triamcinolone
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intermediate duration GCC 24-48 hr
no mineralocorticoid activity, inc. HPAA suppression, no alternate-day therapy potential parenteral: slow onset used for skin disease/arthritis, topical oral: rapid onset w/ short to intermediate duration commonly used in horses for jt injections |
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Flumethasone
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long acting GCC >48 hr
no mineralocorticoid activity, SUPER HPAA suppression, no alternate-day therapy potential parental: slow onset w/long duration--> used for skin/arthritis oral:slow onset/long duration |
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Dexamethasone
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ong acting GCC >48 hr
no mineralocorticoid activity, SUPER HPAA suppression, no alternate-day therapy potential parental: rapid onset/intermediate duration oral: slow onset/long duration commonly used in cattle(anti-inflam & induce parturition/abortion) & horses |
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Betamethasone
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long acting GCC >48 hr
no mineralocorticoid activity, SUPER HPAA suppression, no alternate-day therapy potential oral: slow onset/long duration |
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immunosuppressants used for what alterations
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immune mediated diseases, inappropriate/overzealous immune response
example: immune mediated hemolytic anemia, lupus, pemphigus, IMT |
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types of immunosuppressants
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glucocorticoids, calcineurin inhibitors, antiproliferative, antimetabolites,
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major adverse effects of immunosuppressants
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bone marryow suppression-cyclo
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glucocorticoids
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immunosuppressant
MOA: dec. gene expression of genes that affect neutrophil trafficking, suppress macrophage function, lowered lymphocyte activity, esp T-cells |
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Calcineurin inhibitors
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Cyclosporin, Tacrolimus
Immunosuppressant MOA: inhibit normal T-cell transduction -blocks calcineurin phosphatase activity -normally, dephosphorylates NFAT- allowing it to move to nucleus -NFAT induces cytokine genes s/a IL-2 (T-cell growth and differentiation factor) Adverse effects: cyclosporine- GI effects, gingival hyperplasia |
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Antiproliferative (cytotoxic)
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Cyclophosphamide, Chlorambucil
MOA:alkylating agents- prevents cell from reproducing adverse: bone marrow suppression |
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Antimetabolites
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Azathioprine:
MOA: purine analog, inhibits purine synthesis leading to dec. lymphocyte proliferation adverse: bone marrow suppression Mycophenolate MOA: inhibits enzyme involved in purine synthesis leading to dec. lymphocyte proliferation adverse: GI effects |
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immunosupressants w/ unknown mechanism
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Danazol, Gold, Dapsone
dapsone adverse effects: bone marrow suppression Gold adverse effects: nephrotoxicity |
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Cyclosporine
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Calcineurin inhibitors
immunosuppressant adverse effects: GI effects, gingival hyperplasia |
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Tacrolimus
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Calcineurin inhibitors
immunosuppressant |
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Cyclophosphamide
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antiproliferative (cytotoxic)
immunosuppressants |
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Chlorambucil
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antiproliferative (cytotoxic)
immunosuppressants |
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Azathioprine
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Antimetabolite
immunosuppressant antimetabolites immunosuppressant MOA: purine analog, inhibits purine synthesis leading to dec. lymphocyte proliferation adverse: bone marrow suppression |
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Mycophenolate
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antimetabolites immunosuppressant
MOA: inhibits enzyme involved in purine synthesis leading to dec. lymphocyte proliferation adverse: GI effects |
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Danazol
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immunosuppressant
mechanism not well known |
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Gold
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immunosuppressant
mechanism not well known adverse: nephrotoxicity |
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Dapsone
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immunosuppressant
mechanism not well known adverse: bone marrow suppression |
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Immunostimulants used for what alteration
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inadequate immune response
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temporary and correctable need for immunostimulants
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neonates w/o colostrum
correct by supplementing w/ colostrum supplement |
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examples of immunostimulants
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hyperimmune serum, tetanus antitoxin
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NSAID mechanism
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blocks COX (cyclooxygenase)-->prevents formation of prostaglandins (inflammatory mediators that inc. intensity of pain perception); PGs come from metabolism of arachidonic acid
classical NSAID: non-selective inhibits COX 1 &2 COX 2 is the one expressed by infective processes-->inhibition leads to less inflammation |
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NSAID uses
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acute pain/inflammation
chronic pain fever antihemostatic actions endotoxemia atherosclerosis, cancer, neurodegenrative disease, mastitis/metritis/endotoxemia, resp. diseases, calf and piglet scours |
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NSAID: acute pain/inflammation
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causes inc. expression of COX (usually COX2) which inc. production of PGs
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NSAID: chronic pain
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block production of PGs (which cause inc. bradykinin) reduce inflammation
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NSAID: fever
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PGE2 acts in hypothalamus to inc. the thermoregulatory set point
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NSAID: antihemostatic actions
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thromboxane is product of AA metabolism by COX; dec. thromboxane--> dec. hypercogulability
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NSAID: endotoxemia
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LPS/endotoxin stimulates the production of cytokines by monocytes and macrophages, which stimulates production of prostaglandins and leukotrienes
*does not treat endotoxemia directly--> not an antiendotoxin Flunixin in horses |
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NSAID adverse effects general
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erosions, ulcers, GI upset, melena- block good PGs
nephrotoxicity: by blocking good PGs Cats- repeated doses can lead to acute renal failure and death |
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NSAIDS specific adverse effects
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phenylbutazone- hematopoietic; right dorsal colitis in horses
Etodoloc- KCS (dry eye) Carprofen + others: hepatotoxicity carprofen: bone marrow necrosis |
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NSAID toxicity
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species specific
-due to differing degrees of protein binding (horses) -sensitivity to GI effects (dogs w/chronic aspirin, flunixin, naproxen, ibuprofen) -COX-2 vs COX-1 activity in dogs |
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COX 2 dogs and NSAIDS
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Dogs have higher levels of COX-2 in the kidneys
non-selective inhibition by naproxen results in reduced renal blood flow and urinary Na retention-->renal papillary necrosis |
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NSAID contraindications
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acetaminophen and cats
ibuprofen and phenylbutazone in dogs |
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acetaminophen vs. cats
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lack of glucuronyl transferase--> toxic phase 1 metabolites which overwhelm the detoxifying glutathione scavenging system--> methemoglobinemia;
treatment w/ n-acetylcysteine--> allows oxidized glutathione to be reduced and reused |
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ibuprofen and phenylbutazone vs. dogs
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GI effects
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How to avoid NSAID toxicity
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select drug w/ fewest adverse effects in species of interest
use w/gastroprotective drugs s/a misoprostol, omeprazole smallest duration/ dose possible don't use in dehydrated/ vascular compromised animls avoid use in liver/kidney disease patients avoid concomitant use of other drugs w/similiar actions/similiar toxicities example: GCC + NSAIDs potentiate GI effect |
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NSAID elimination
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half-life vary btn species b/c of clearance differences btn species
consider this when dosing animals |
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Selective COX-1 Inhibitors:
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NSAIDs
Aspirin – not approved in animals, but still marketed Ketoprofen Peroxicam Phenylbutazone |
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Selective COX-2 Inhibitors
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NSAIDs
Deracoxib Firocoxib – highly selective! |
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less specific cox inhibitors
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Acetominophen
Carprofen Diclofenac Etodolac Flunixin Flurbiprofen Ibuprofen Meloxicam Naproxen Piroxicam Tepoxalin |
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Tepoxalin
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NSAID: less specific cox inhibitors
works to decrease PGs and leukotrienes – COX & LOX blocker |
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Piroxicam
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NSAID: less specific cox inhibitors
used to treat transitional cell carcinoma – not antineoplastic; not used as anti-inflammatory drug |
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Naproxen
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NSAID: less specific cox inhibitors
not approved in animals Dog ADE: GI sensitivity, reduced renal blood flow and urinary sodium retention-->renal papillary necrosis |
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Meloxicam
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NSAID: less specific cox inhibitors
approved for use in cats Black box warning: assoc w/ kidney disease |
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Ibuprofen
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NSAID: less specific cox inhibitors
not approved in animals GI ADE in dogs, ferrets very sensitive-->neuro and GI signs |
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Flurbiprofen
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NSAID: less specific cox inhibitors
not approved in animals; human ophthalmic preparation – pH balanced; non-irritating |
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Acetominophen
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NSAID: less specific cox inhibitors
not approved in animals by FDA toxic in cats |
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Carprofen
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NSAID: less specific cox inhibitors
1st NSAID approved for dogs; anti-inflammatory, analgesic adverse: hepatotoxicity, bone marrow necrosis |
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Diclofenac
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NSAID: less specific cox inhibitors
– “ac” – anti-inflammatory, acetic acid derivative |
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Etodolac
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NSAID: less specific cox inhibitors
– “ac” – anti-inflammatory, acetic acid derivative Keratoconjuctvitis Sicca = KCS (dry eye) |
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Flunixin
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NSAID: less specific cox inhibitors
approved in cattle; no chronic use in dogs due to GI sensitivities, used for endotoxemia in horses |
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NSAID stems:
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‘-ac’, ‘-butazone’, ‘-coxib’, ‘-fenamic’, ‘-icam’, ‘-metacin’, ‘-nixin’, ‘-profen’, ‘sal-, -sal, o-sal’
-ac- =anti-inflammatory, acetic acid derivative |
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Aspirin
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NSAIDs Selective COX-1 Inhibitors:
not approved in animals, but still marketed |
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Phenylbutazone
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NSAIDs Selective COX-1 Inhibitors:
ADE: hematopoietic, right dorsal colitis in horses Illegal to use in dairy cattle lower protein binding in horses (compared to humans) so much lower theurapeutic serum concentrations; efficacy of lower [ ] may be due to inc. in inflammatory exudates GI effects in dogs |
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Peroxicam
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NSAIDs Selective COX-1 Inhibitors:
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Ketoprofen
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NSAIDs Selective COX-1 Inhibitors:
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Deracoxib
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NSAID: Selective COX-2 Inhibitors
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Firocoxib
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NSAID; Selective COX-2 Inhibitors
– highly selective! |
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Drug COX-1 COX-2
Aspirin ++++ - Carprofen + +++ Diclofenac ++ ++ Flunixin +++ + Ketoprofen +++ + Meloxicam + +++ |
...meh
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NSAIDs most used in ruminants
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Flunixin
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NSAIDs most used in porcine
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Flunixin
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NSAIDs most used in horses
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Phenylbutazone (#1)
Flunixin (#2) |
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NSAIDs most used in dogs
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Carprofen (#1)
Meloxicam (#2) |
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NSAIDs most used in cats
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Meloxicam
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NSAIDs most used in avian and exotics
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Meloxicam
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NSAID elimination
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Half life varies btn species mostly due to differences in clearance--> don't extrapolate doses based on other species
High bioavailability, does penetrate BBB, usually highly protein bound (exception phenylbutazone and horses) Metabolized and then eliminated via kidney |
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Legal constraints
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Amduca regulations: have label for everything including human OTC meds given to animals
Label should include: if lose appetite stop NSAID and call vet Phenylbutazone illegal to use in dairy cows |
