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55 Cards in this Set
- Front
- Back
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Mechanism of action of the NSAIDs
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They inhibit the enzyme cyclo-oxygenase (COX)
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Mainly non-selective reversible inhibitors of COX-1 and COX-2
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NSAIDs
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Drugs classified as COX-2 selective agents
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carprofen, meloxicam, firocoxib and mavacoxib
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How do NSAIDs produce analgesia?
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They reduce the production of prostaglandins (associated with the pain of inflammation)
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How do NSAIDs reduce pyrexia?
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They reduce the production of prostaglandins
- during pyrexia, the temperature set point is elevated due to IL-1 mediated release of prostaglandins |
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Lipopolysaccharides generated by gram -ve bacteria that damage white blood cells and vascular endothelium thus releasing vasoactive mediators
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endotoxins
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How do NSAIDs produce anti-endotoxic effects?
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They prevent the generation of vasoactive mediators
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What are the routes of administration for the NSAIDs?
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Given orally and parenterally
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What is the plasma protein binding figure for NSAIDs?
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Approaching 99%
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What is the volume of distribution for the NSAIDs?
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Small apparent Vd (often < 0.2 L/Kg)
- accumulate at sites of inflammation |
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What is the half-life of the NSAIDs?
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Often a short half-life
- duration of effect long (binding to the COX enzyme) |
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What is the metabolism of the NSAIDs?
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Hepatic metabolism
- some excretion of unaltered drug - some metabolites are active (salicylate) - slow metabolism and excretion in young (up to 6 weeks old) |
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What NSAID displays zero order kinetics?
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phenylbutazone (in the dog)
salicylate (in the cat) |
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What are the side effects of the NSAIDs related to?
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The inhibition of COX-1
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What are the beneficial effects of GI prostaglandins (PGE2)
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They inhibit gastric acid secretion and promote mucus secretion
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NSAID banned in food-producing species because of it's relationship with aplastic anemia in man
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phenybutazone
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NSAID displaying zero order kinetics in the dog. Cat.
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phenylbutazone
aspirin |
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NSAID that has been associated with protein-losing enteropathy in ponies
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phenylbutazone
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NSAID restricted to large animals with a good endotoxic shock activity
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flunixin
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NSAIDs that have antagonist action directly at prostaglandin receptors
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fenamates (tolfenamic acid, meclofencamic acid)
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Ubiquitous molecule that is structurally similar to the NSAIDs
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hyaluronan
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NSAID that has cartilage sparing effects in osteoarthritis
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meloxicam
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Most widely used intraarticular medication in the horse
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hyaluronan acid
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What is the structure of biologically active steroids?
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21-carbon, 4-ring molecules with a double bond between C4 and C5, and a ketone group at C3
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Where are steroids produced?
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adrenal cortex
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What groups can corticosteroids be divided into?
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mineralocorticoids and glucocorticoids
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Where are the mineralocorticoids produced?
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The zona glomerulosa of the adrenal cortex
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Where are the glucocorticoids cortisol, hydrocortisol and corticosterone produced?
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The zona fasciculata (cortisol, hydrocortisol) and the zona reticularis (corticosterone)
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What are the corticosteroids produced from?
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cholesterol
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What system regulates the release of glucocorticoids?
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The HPA
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What system regulates the release of mineralocorticoids?
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The RAAS
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What type of receptor do the steroids bind to?
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Steroid-specific cytoplasmic receptors
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What are the four main effects steroids have on the body?
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- metabolic
- systemic - anti-inflammatory - immuno-suppressive |
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How do steroids act in a similar fashion to NSAIDs?
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They can inhibit COX leading to a decrease in prostanoid levels
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What is the plasma protein binding for corticosteroids?
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around 90%
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How long is the half-life for corticosteroids?
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Short (cortisol is only 90 minutes)
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What is the site of metabolism of the corticosteroids?
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liver
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How are corticosteroids eliminated from the body?
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They are excreted in the urine
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What corticosteroids are prodrugs that must undergo liver metabolism to become active?
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cortisone (becomes hydrocortisone) and prednisone (becomes prednisolone)
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How can steroids be administered?
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Topically (eyes, ears, skin), orally, parenterally, inhalation and intra-articularly
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How can you prevent causing atrophy of the pituitary gland as a result of exogenous steroids?
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Alternate day therapy. Otherwise, a gradual dose reduction is of paramount importance to prevent a crisis.
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What condition can you cause by steroid administration?
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Iatrogenic Cushing's disease
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A mineralocorticoid
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aldosterone
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Released by the hypothalamus in the HPA axis
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corticotropin releasing factor (CRF)
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Released by the anterior pituitary in the HPA axis
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adrenocorticotropic hormone (ACTH)
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Proteins induced by glucocorticoids
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- angiotensin converting enzyme (ACE)
- beta-2 adrenoceptor |
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Proteins whose synthesis is inhibited by glucocorticoids
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- cytokines
- cyclo-oxygenase (COX) - collagenase |
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What are the metabolic effects of glucocorticoids?
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Mainly catabolic and primarily affect carbohydrate and protein metabolism (think glucose, protein, calcium)
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What are the systemic effects of glucocorticoids?
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- elevated liver enzymes
- induction of abortion/parturition |
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What are the anti-inflammatory effects of glucocorticoids?
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Affect:
- blood vessels - inflammatory cells - inflammatory mediators |
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What are the immuno-suppressive effects of glucocorticoids?
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Low doses:
- cellular response inhibited (lymphocytes, eosinophils, monocytes and basophils) - neutophils increased High doses: - humoral response inhibited |
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What are the clinical uses for the glucocorticoids?
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- inflammatory disease (allergic disease, osteoarthritis)
- immune-mediated disease (immune-mediated hemolytic anemia, myasthenia gravis, immune-mediated skin disease) - shock - cerebral edema - neoplasia |
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What two glucocorticoids are used intra-articularly?
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- Methylprednisolone (low serum concentration after 24 hours, but levels maintained in the joint for up to 39 days. Adverse cartilage effects)
- Triamcinolone (more prolonged plasma levels, but levels in joint undetectable after 2 weeks. No adverse cartilage effects) |
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What is the glucocorticoid used in the States for treatment of Addison's?
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DOCP (Percorten-V)
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What are the adverse effects of glucocorticoids?
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- gastric ulceration
- muscle atrophy - cutaneous atrophy - hyperglycemia - osteoporotic effect - pu/pd (decreased ADH) - increased susceptibility to infection - corneal ulceration - suppression of the HPA axis - iatrogenic Cushing's disease |
