NSAIDs & Corticosteroids

sihirlifil's version from 2016-05-04 11:51


Question Answer
What is inflammation?Vascular and cellular response of living tissue to injury; main defense mechanism of the body against injury
Cardinal signs of inflammationRedness, swelling, heat, pain, loss of function
2 phases of inflammationVascular (dilation of bv, increase permeability), cellular (chemotaxis, leukotrien B4, C5A, chemokines, soluble bacterial product)
4 actions of NSAIDsAntipyretic, anti-inflammatory, analgesic, anticoagulant
2 vascular responses leading to inflammationDilation of blood vessels, increased permeability of venules, capillaries, arterioles
Chemical mediators turn on which enzyme, which leads to arachidonic acid formation?Phospholipase A2
What does the enzyme Phospholipase A2 catalyzeMembrane phospholipids release arachidonic acid, which enters cascade
Which cyclo-oxygenase enzyme is ideally inhibited by NSAIDs?COX-2
Why would inhibition of lipo-oxygenase lessen the GIT effects of NSAID use?Function of LOX = convert arachidonic acid into leukotrienes. Arachidonic acid is converted to LeuB4 --> gastric ulceration; LOX inhibition protects GI from ulcers
Which prostaglandin's inhibition by NSAIDs is responsible for analgesia?PGE2 (causes hyperalgesia and allodynia)
Why is the prostaglandin E1 analog administered?Treat and prevent gastric ulcerations (regulate gastric acid secretion, cytoprotective effects on gastric mucosa)
Why is there increased risk of GI ulceration when NSAIDs and corticosteroids are administered concurrently?NSAIDs decrease prostaglandins, mucus, and bicarbonate
Which NSAID is associated with treating visceral pain?Flunixin Meglumine (horses with colic)
Which NSAID can be used against endotoxemia?Flunixin Meglumine
Flunixin meglumine is administered to which species?USA: horses, cattle, swine. Outside: dogs
Is Acetaminophen an anti-inflammatory drug?No, antipyretic and analgesic only
What is the toxic metabolite in Tylenol metabolism?NAPQI
What conjugates NAPQI so that it can be eliminated?Glutathione
Ketoprofen is administered to which species?USA: horse. Canada & UK: horse, cattle, swine, dog, cat
How is ketoprofen metabolized and eliminated?Eliminated by kidneys unchanged or conjugated metabolites
Carprofen is administered to which species?USA: dogs; UK: dog, cat, horse, pony, cattle
Carprofen is most COX-2 specific in which species?Dogs
Carprofen isn't as popular as it was in the past, why is this the case?Reports of acute hepatic necrosis in dogs
Diclofenac is administered to which species?Horses (pain and inflammation associated with osteoarthritis in limbs)
In the first-pass effect, Aspirin (acetosalicyclic acid) is metabolized into what?Salicylic acid
For how many days after aspirin is administered is platelet aggregation compromised?10 days (life of the platelet)
Why do cats have prolonged NSAID half lives?Salicylate is metabolized in the liver by conjugation with glucuronic acid and glycine via glucoronyl transferase (cats are deficient)
Phenylbutazone is administered to which species?USA: horses (acute laminitis, muscsk inflammation)
Meloxicam is administered to which species?USA: dogs and cats
What is the unique way Meloxicam can be administered to dogs? are there other routes?Oral is unique, can also give IV and SQ
Meloxicam is unique among NSAIDs because it is approved to be administered in what species?Cat - single injection
How many times and in what administration route can a cat be given Meloxicam?Approved for a single one-time SQ injection
Why was Rofecoxib/Vioxx removed from the market?Cardiovascular side effects related to reduced PGI2 formation
Deracoxib/Deramax is approved in the US for what species?Dogs
How is Deracoxib administered? Chewable tablets (postprandial)
Firocoxib is administered to which species?USA: dogs, horses
What are the directions for administering Rubenacoxib?Oral tablets for cats only (5.5 lbs & >4 m old), use no more than 2 days
Which NSAID has the longest half life?Mavacoxib (17 days!)
Tepoxaline/Zubrin has a unique administration quality:Tablets rapidly disintegrate ('melt-a-ways')
Etodolac is administered to which species?USA: dogs
DMSO is a scavenger of what?Inhibits prostaglandins, free radical scavenger
Why should you use gloves when you administer DMSO?Used topically & IV, causes garlic taste
What is Boswellia?Tree resin, anti-inflammatory in horses
Most NSAIDs are weak acids or weak bases?Weak acids
Most NSAIDs are metabolized by?Liver


Question Answer
What are the 3 layers of the adrenal cortex and what do they synthesize?Zona glomerulosa (mineralocorticoid), fasciculata (glucocorticoid), reticularis (androgen)
What is synthesized in the adrenal medulla?Catecholamines (via oxidation of tyrosine)
3 examples of catecholaminesNorephinephrine, epinephrine, dopamine
Precursor for the 5 classes of steroid hormonesCholesterol
In the hypothalamic-pituitary-adrenal axis, what is released from each?Stress stim. hypothalamus --> CRH --> corticotropin (ACTH) from anterior pituitary --> cortisol from adrenal cortex
What is the negative feedback mechanism in the hypothalamic-pituitary-adrenal axis?Cortisol inhibits CRH and ACTH release
Glucocorticoids have what effect on plamsa glucose levels and why?Glucose dependent organs (brain, heart), during times of starvation are protected by glucocorticoids. Inc glucocorticoids --> gluconeogenesis --> inc plasma glucose
Glucocorticoids have what effect on protein metabolism and why?Inc protein breakdown --> inc AA, enzyme synthesis, liver protein; inc redistribution of fat, inc action of lipolytic hormones (growth hormones, beta adrenergic agonists)
Glucocorticoids cause PU/PD, why?Inc glucocorticoids --> dec ADH secretion --> dec water reabsorbtion
ineralocorticoids cause increased sodium reabsorption in the kidneys and absorption in the large intestine. What effect does this have on water balance?Water conservation (prevents excretion)
How is parathyroid hormone influenced by glucocorticoids?Inc glucocorticoids --> dec GIT and renal Ca2+ absorption --> inc PTH --> inc plasma Ca2+
What are the effects of glucocorticoids on feeling of well-being?Inc = euphoria, inc appetite; dec = depression
Mineralocorticoid effects on the CVS have what influence on Ca levels in the myocardium?Dec K in ECF --> inc Ca in mycardium
Glucocorticoid effects on the CVS include blood vessel constriction and increases HR, contractability, and CO- why?Increase in epinephrine --> inc alpha and beta1 adrenergic receptors
Why do glucocorticoids lead to broncodilation?Increase in Beta1 adrenergic receptor expression
Why are glucocorticoids anti-inflammatory in the respiratory system?Decrease in mast cell retention (decreased histamine release)
What are the effects of mineralocorticoids in skeletal muscles?Inc mineralocorticoids --> hypokalemia, muscle weakness
What are the effects of glucocorticoids in skeletal muscles?Inc over a long time --> wasting of muscles, weakness
What are the 3 blood cells that increase in number in the circulation as a result of glucocortocoid use?RBCs, neutrophils, platelets
What are 4 blood cells that decrease in number in the circulation as a result of glucocorticoid use?Lymphocytes, eosinophils, monocytes, basophils
What are 4 ways glucocorticoids have anti-inflammatory actions?Suppress cell immunity by: 1) dc IL-8, chemoattractive/adhesion factor (--> dec migration of WBC to inflamed area); 2) dec PLA2 or dec arachidonic formation from cell mb breakdown; 3) dec autocoid-like histamine release from mast cells; 4) dec proteolytic ezymes
How is skin and hair growth affected by glucocorticoids?Dec skin and hair growth (alopecia)
The structure of corticosteroids imparts what 2 characteristics?glucocorticoid activity and duration of action
Which bonds impart corticosteroid activity?3-keto; 4,5-delta
Which bonds impart glucocorticoid activity?11beta, 17alpha-OH
Long acting corticosteroids have what structural characteristics (which bonds strengthen and protect other bonds)?4,5 dleta = 1,2 delta; 11-OH = 6,9-fluoro & 6-methyl; 17-OH = 16-methyl-OH
What are 4 variables that influence the duration of action of glucocorticoids?% bound to plasma proteins, affinity of drug for enzyme involved in their metabolism, lipophilicity, affinity of the drug for the glucocorticoid receptor
Short acting corticosteroid?Hydrocortisone
4 intermediate corticosteroids?Prednisolone, prednisone, methyl-prednisolone, triamcinolone acetonide
3 long acting corticosteroids?Flumethasone, betamethasone, dexamethasone
Why is prednisolone preferentially given to horses and cats?Not efficient at absorbing or converting prednisone to prednisolone
2 glucocorticoids that can be used to treat Addison's disease in small animals?Fludrocortisone acetate, desoxycorticosterone pivalate (DOCP)
If you look at a bottle of injectable drugs, what are 3 moieties that would indicate that it should be used IV?Succinate, phosphate, polyethylene glycol
If you look at a bottle of injectable drugs, what are 2 moieties that would indicate that it should be used IM or SQ?Acetate, pivalate
If ongoing glucocorticoid administration is abruptly stopped and the negative feedback mechanism of ACTH release from the anterior pituitary is still in effect, what may occur?Iatrogenic Addison's disease (ACTH initiates natural glucocorticoid secretion by the adrenal glands)
What are some side effects of corticosteroid administration? (9)Inc susceptibility to infection, dec wound healing, GIT ulcers, myopathy, edema from fluid and electrolyte imbalance, diabetes mellitus, abortion, laminitis (horses), hepatotoxicity
In what conditions should glucocorticoids not be used? (7)Corneal ulcers, burns, diabetes mellitus, uncontrolled infection, cardiac disorders, late pregnancy, concurrent NSAID
Another name for hyperadrenocorticism?Cushings disease
2 types of hyperadrenocorticism?Pituitary dependent (PDH), 85% of dogs; adrenal dependent (adrenal tumors), 15%
4 adrenal steroid inhibitors? how do they work?Mitotane (destroys cells of fasciculata and reticularis); ketoconazole (anti-fungal, inhibits steroid synthesis reversibly by blocking CYP450); selegiline (MAO I-B, inhibits ACTH secretion); trilostane (suppresses adrenal gland, reduces corticol, aldosterone, androgen synthesis)
Ketoconazole is an anti-___ drugAnti-fungal
Why does ketoconazole have drug interactions?Causes enzyme inhibition in CYP450 system
Which drug used as an adrenal steroid inhibitor is also used to tread old age dementia?Selegiline (canine cognitive dysfunction)
Why does Trilostane reduce the synthesis of cortisol, aldosterone, and androgens?Inhibits 3-beta-hydroxysteroid dehydrogenase. Cholesterol will not be converted to cortisol, aldosterone, androgens
What is another name of hypoadrenocroticism?Addison's disease
In veterinary medicine, in what species is hypoadrenocorticism most often seen?Dogs (young to middle age; young adult female). Occasionally horses
Which layers of the adrenal cortex are affected in Addison's disease?All three zones of cortex (NOT MEDULLA)
What electrolyte imbalances are seen in patients with Addison's disease?Reduction in mineralocorticoid lvls --> hyponatremia & hyperkalemia (low Na/K ratio)
Will a drug with primarily glucocorticoid activity be a good drug to use as a maintenance treatment in a dog with Addison's disease?Maintenance therapy requires mineralocorticoid replacement

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