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Pharm 1 - NSAIDs

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isabellepjk's version from 2017-05-06 15:31

NSAIDs 1

Question Answer
*What are the two phases of inflammation?Vascular response
Cellular Response
*5 main pillars of inflammation?(1) Calor (Heat)
(2) Rubor (Redness)
(3) Tumor (Swelling)
(4) Dolor (Pain)
(5) Loss of fxn
What can cause inflammation?Pathogenic organisms; Bacteria, Viruses, Rickettsia, Fungi and Parasites
Poisons and toxins
Mechanical and thermal energy
Immune rxns
What happens during the vascular phase of inflammation?Dilation of BV leading to redness and heat at injury site
Increased permeability of venules, caps, and arterioles leads to fluid leakage from vascular to interstitial fluid
Vascular leakage caused by endothelial cell contraction and opening on endothelial gaps
What can initiate the vascular phase?Bradykinin, Histamine
Direct injury to endothelial cells
Injury to endothelial cells resulting for leukocyte release of O2 free radicals and proteolytic Enzymes
What occurs in the cellular phase of inflammation?Increased permeability leads to leukocytes chemotaxis
What are some things that are involved in chemotaxis?Leukotriene, a product of lipoxygenase pathway
C5a, a component of the complement system
Chemokines
soluble bacterial product
Where do the chemical mediators of inflammation arise from?Tissue cells and some are components of plasma
What are the 2 types of inflammatory mediators released by tissue cells?preformed and Newly formed
What are some of the pre-formed chemical mediators of inflammation and what do they do/where are they from?Histamine-from basos, mast cells, and blood platelets, they cause transient dilation of BV and increase vascular permeability
serotonin causes transient dilation of BV and increases vascular permeability
lysosomal enzymes
What are some of the chemical mediators of inflammation released from the plasma?Complement activation (C3a, C5a, C5b-9, C3b)
Bradykinins (cause increase in vascular permeability
coagulation/fibrinolysis system
What are some of the newly synthesized chemical mediators of inflammation?cytokines
Defensins
IL-1, 6, 8, TNF
Leukotrienes
Nitric oxide
Platelet activating factor
Prostaglandins
Which enzyme do chemical mediators of inflammation regulate?Phospholipase A2
* What is the action of phosphlipase 2?membrane phospholipids interaction with the enzyme phospholipase A2 result in the release of arachidonic acid
What are some characteristics of Cox 1? Cox 1 - Present all the time
Has houskeeping functions
Protects gastric mucosa
Regulates blood flow to kidneys
What are some characteristics of Cox 2?Cox 2 is present in normal tissues in small amounts
increases during inflammation
NSAIDs goal is COX-2 inhibition
The #1 chemical of the inflammatory response? (What mediates the inflammatory response)?Prostaglandins
* What are the goal of NSAIDS?INHIBITION of an increase in cyclooxygenase enzyme levels involved in the inflammatory process cox 2
What is the action of LOX?Converts arachidonic acid into leukotrienes
Is there a benefit if NSAIDS inhibit lipooxygenase activity?Leukotriene B4 causes gastric ulcerations (chemotaxis attracts inflammatory cells)
LOX inhibition by certains NSAIDs (protect GI from inflammation/ulceration
What is the function of prostaglandin?Stimulate inflammation
regulate BF to organs
Control ion transport to organs
control ion transport
aid synaptic transmission and induce sleep
What drug can be used to induce aborptions in cattle after 150 days?Dexmethasone
What can PGf2a cause?Hyperalgesia - increased duration and increased sensitivity of the impulse of afferent fibers that are stimulated by inflammatory chemical mediators (histamine, bradykinin)
Allodynia
The analgesic effect is a result from NSAID inhibition of Pgf2a
*What is Misoprostol? When is it given? What is its function?Prostaglandin E1 analog
Given to NSAID using patients to treat and prevent gastric ulcerations
regulates gastric acid secretions and has cyto protective effects on the gastric mucosa
DONT USE WHICH TWO DRUG TYPES TOGETHER AND WHYNSAIDs and CORTICOSTEROIDS = GASTRIC ULCERS
What are the individual NSAIDs we talked about?Acetaminophen
Aspirin
Coxibs
Flunixin
Oxicams
Phenylbutazone
Proprionic Acid derivatives
and others
What are the coxib NSAIDsDeracoxib, Firocoxib, Robencoxib, Rofecoxib, Mavacoxib
(DERek, ROB, and, ROF were FIRed because they were being COX to MAVA)
What are the oxicam NSAIDs?Meloxicam and Piroxicam
What are the Propionic Acid derivatives?Carproifen, Ibuprofen, Ketoprofen, Naproxen (CINK)
For which species if Flunixin Meglumine approved?Horses, cattle, and swine
outside of the US, it's also approved for dogs
What can Flunixin Meglumine be used as?Analgesic, anti-inflamm, anti-pyretic
* What are examples of uses of Flunixin Meglumine in horses? When can it not be used?Inflammation and pain associated with msk disorders and Visceral pain associated with colic.
should not be used in a horse intended for food
What is the Flunixin injectable DoA, peak response, and half life in a horse?24-36 hours DoA
peak at 12-16 hours
Half life is 1.6 hours
How can flunixin meglume be administered?IV or IM, or PO as a paste
once daily for up to 5 days
* For what can flunixin meglumine be used in cattle and swine?Control pyrexia associated with bovine resp disease and endotoxemia and acute bovine mastitis
Swine: Pyrexia with swine resp dz
What are some specifics about flunixin meglumine regarding cattle?Cattle can't be slaughtered for human food within 4 days of the last treatment
dump the milk
not for use in dairy
not for calves meant to be veal
How is flunixin meglumine excreted primarily?by the liver as bile
* What types of effects foes flunixin meglumine have?indirect anti-endotoxin effects
blocks prostanoid (inflammation mediators) synthesis related to endotoxemia
What are liposaccharides? How does the immune system respond to LPS glycolipids incorporated into the cell wall of G- bacteria
immune system responds by fever and other signs on inflammation
memorize

NSAIDs 2

Question Answer
Tylenol/paracetamol, though rare in vet med is used asantipyretic and analgesic
How does the antipyretic effect of acetaminophen work?Blocks prostaglandin formation and release in the CNS
(Prostas into the CNS prevent head loss, therefore, increasing heat)
What is important regarding acetamin toxicity in humans?Acetamin has been linked to 50% of cases of human acute liver failure in the US
* What is NAPQI?A toxic metabolite from acetaminophen (Tylenol) resulting from enzyme metabolism by cytochrome p450 in
*What can NAPQI cause and how?Can cause heinz bodies in cats through oxidation of hemoglobin to methmoglobin
* What are three important things about NAPQI?Can be conjugated by glutathione and then excreted
NAPQI in high concentrations leads to glutathione depletion
NAPQI leads to hepatotoxicity
*What are the 7 clinical signs related to acetaminophen toxicity in cats?Brown or muddy MM
Heinz bodies
Hyperpnea
Lethargy
Methemoglobinemia
tachycardia
Weakness
* How do cats metobolize acetaminophen and what happens if that reaches capacity?Cats have more acetaminophen left for the sulfation pathway because they don't glucuronidate. If sufation pathway capacity is reached, the drug is converted to NAPQI by Cp450
prolonged NSAID half life
*What drug can be used in emergency Acetamin toxicity? What are some important things about itN-Acetyl-cysteine mucomyst, which is a precursor of gluthathione. Glutathione conjugates NAPQI so it can be eliminated. It has to be given before liver damage has occured, and it is NOT a tx for hepatotoxicity post NAPQI damage
Ketoprofen, Carprofen, Phenbutazone, Meloxicam act as what three thingsAnalgesic, Anti-inflam, antipyretic
* Ketoprofen in the USA, can be used in horses for what? When can it not be used?alleviating pain in msk disorders
Can't be used in horses meant for food
Ketoprofen, in the UK and Canada, can be used in horses for what: What can it be used for in cattle?SAME in canada and UK as states (allviated inflammation associated with MSK disorders)
Cattle in UK and Canada: Tx of fever, pain, and inflammtion (wait 24h after last tx for slaughter for food)
Ketoprofen, in the UK and Canada, can be used in swine for what? What is important to note about using it in swine?alleviate fever and inflammation associated with resp infection
wait 7 days after the last tx before slaughtering for food
Ketoprofen, in the UK and Canada, can be used in cats and dogs for whatRelief of pain and inflammation in msk disorders and other pain dz
*What are some main characteristics of ketoprofen?Non selective COX inhibitor; may also inhibit LOX
Is metabolised in the liver and eliminated by kidneys (unchanged) as conjugated metabolites
Toxic to carrion birds (vultures)
For what is Carprofen approved for the USA?pain and inflam of osetoarthritis, post-op control with soft tissue and orthopedic injuries in dogs
For which species is Carprofen approved for the UK?Dogs, Cat, horse, pony and cattle
*What two things are important regarding carprofen and dogs?it is COX2 specific in dogs, but less so in the cat and horse
Reports of acute hepatic necrosis in dogs being adminstered carpro
For what is Vedaprofen approved for in Europe? In what forms can it be found?MSK pain in dogs and horses, also colic pain in horses
gel or injectable forms
* For what is Diclofenac (Surpass) used? What form is it? What is important about itTopical Anti Inflam cream
used in horses to control pain and inflamm assocaited with osteoarthritis in the limbs

not for horses for human consumption
slightly cox2 selective
* Which drug changes to salicylic acid d/t the first pass effect?aspirin (acetylsalicylate) to salicyclic acid
What is aspirins and salicylic acid's functions?Aspirin is COX 1 inhibitor
S acid is 50:50 Cox 1/cox 2
*Acetylsalicylate has a fourth thing it can be used foranti-coag
but it is used extra label for everything as it is not approved for veterinary use
What is the half life of salicylic acid in dogs and catsD-7.5h ; C-40h
* How does acetylsalicylate affect platelets?destroys COX1 in platelets and then they can't make anything to replace the cox1 enzyme and their clotting ability is fucked for their life, which is like 10 days
What are some considerations to take regarding aspirin?Consider when then last dose was given before doing a surgery
don't use aspirin in pt with possible spinal cord trauma
it is a GIT irritant
How is salicylate matabolized? What enzyme is used in its conjugation?conjugation with glucuronic acid and glycine
enz=glucoronyl transferase (cats are def therefore, have prolonged aspirin half lives)
* What is phenylbutazone approved for in horses?MSK dz tx, and acute laminitis
*What is significant about dosing of phenylbutazone?Has a narrow dosing window, so should use the lowest effective dose
*What are the side effects of Phenylbutazone?Ulcers of the mouth, stomach, cecum, and right dorsal colon
*Even though it is approved for use in dogs, why is phenylbutazone a bad choice?CNS, GIT, and Resp side effects
*For what is phenylbutazone prohibited by the FDA?use in dairy cattle old than 20 months because it can cross the placenta and be detected in milk
How is phenylbutazone metabolized and excreted?Metab by liver; excreted in feces after biliary excretion
What are some characteristics of meloxicam? How is it metab/elim?COX 2 prefferential
approved for in cats and dogs
available in oral or liquid
Liver and eliminated in feces
*How is meloxicam used in cats?Single one time injection to control post op pain and inflamm associated with Ortho surgery, OVH, and castration
admin before sx SQ
How is meloxicam used in dogs?Pain control and inflamm of osteoarthritis
IV, IM, PO adminstration
Even though Piroxicam is not labeled for vet usage, how is it still used?Neoplasia tx; transitional cell carcinoma, and other neoplasts that express COX2
What is the fx of Deracoxib (deramax) and Firocoxib (Previcox) ? How are they eliminated and excreted?COX2 inhibitors at therpeutic doses
metabolized by liver, eliminated in feces
* What form can deracoxib and firocoxib be found and what is important to note about it? To which species ?Chewable (better bioavailability), be careful with labels!
DOGS
*For what can deracoxib be use in dogs?Osteoarthritis, post ortho op pain, dental pain and inflamm
For what is Firocoxib (previcox) approved in dogs in the USA?Soft tissue and ortho post op pain/inflammation, ostheoarth pain
*Specifically, what age range/weight of dogs can use firocoxib?over 12.5 pounds and over 7 months of age
* For what is Firocoxib used in horses? What is important about using it in horses?pain and inflamm with osteoartritis
don't use for more than 14 days
Elimination by feces and metab by liver
*What are important features of Rubenacoxib (Onsior)?SELECTIVE cox2 inhibitor for oral use in cats only
post op for OVH and castrations and ortho sx
for cats weighing more than 5.5 lbs and over 4 months
no more than 3 days of use
OUTSIDE the usa dogs can use it too
*What are important feature of Mavacoxib (trocoxil)?COX 2 inhibitor
approved for dogs in europe and australia
pain and inflamm for Degenerative joint dz
Biliary excretion
LONGEST HALF LIFE
*What are important features of Tepooxaline?Inhibits COX1, 2, AND LOX
metabolite is tepoxaline pryazol acid which inhibits ONLY cox 1 and 2
LOX inhbition minimized the GI effects
for dogs osteoarthritis
Rapid dissolving tablets
liver/feces
*What are important features of Etodolac?FOR DOGS
Inibits cox 2 selectively and inhibit macrophage chemotaxis
dogs in us: osteoarth
liver/feces
* What are important features of DMSO?Inhibits prostaglandins and is a free radical scavenger
use gloves because it tastes like garlic
* Why was Rofecoxib (Vioxx) removed from the market?CV sides effects related to reduction in PGI2 function
* What can be administered to prevent ulcers?Prostaglandin E1 anaglog
Where are most NSAIDs metabolized?Liver
* What type of acid are most NSAIDs?Weak
What is boswellia?Tree resin
memorize