Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
96 Cards in this Set
- Front
- Back
What are eicosanoids?
|
includes all prostaglandins, leukotrienes, thromboxanes, etc. derived from anarchidonic acid
|
|
What is the ANALGESIC mode of action of NSAIDs, and where are their principal sites of analgesic action?
|
* inhibit synthesis of eicosanoids (prostaglandins) from arachidonic acid by blocking action of the cyclo-oxygenase enzymes
* have both peripheral and central actions |
|
Which NSAIDS are highly COX2 selective
|
> With the exception of firecoxib (Previcox) no NSAID licensed for animal use is highly selective for COX-2
|
|
What are the principal side effects of NSAIDs? (5)
|
- GI ulceration
- Nephrotoxicity - Risk of renal decompensation - Depressed platelet aggregation - Plasma protein binding |
|
List 5 key contraindications for NSAID administration
|
- concurrent corticosteroid medication
- hypotension or hypovolaemia (b/c NSAIDs will vasodilate?) - gastric ulceration or vomiting - renal dysfunction - coagulopathy (clotting disorder) |
|
Phospholipase A2 converts cell membrane phospholipids into ?
|
phospholipase A2 converts cell membrane phospholipids into ARACHIDONIC ACID
|
|
CYCLOOXYGENASE converts ARACHIDONIC ACID into ?
|
CYCLOOXYGENASE (COX) converts ARACHIDONIC ACID into PGG2/H2
(fyi: i think PGG2 is called an endoperoxide; it is reduced to form PGH2) |
|
PG-ISOMERASES convert PGG2/H2 into?
|
PGI2, PGE2, PGD2, PGF2
|
|
Thromboxane synthetase converts PGG2/H2 into ?
What does it do? |
Thromboxane synthetase converts PGG2/H2 into TXA2 (not TXB2)
TXA2 (thromboxane) is a platelet activation factor |
|
NSAIDs are divided into ?
|
1. carboxylic acids
2. enolic acids ----- 3. cox-2 inhibitors (Coxibs) - but this group of NSAIDs no longer used due to |
|
different types of carboxylic acids NSAIDs?
SAP |
1. Salicylic acid and esters
2. Acetic acids (hetero-/carbocyclic and Phenylacetic acids) 3. Propionic Acids |
|
Carboxylic acids NSAIDs:
Examples of Salicylic acid and esters? (2) SAAD |
1. Acetyl salicylic acid
2. Diflunisal SAAD |
|
Diclofenac is what kind of drug?
|
Diclofenac = Phenylacetic acid (NSAID -> carboxylic acid -> acetic acid)
PAD |
|
What group do these drugs fall into?
Tolmetin Sulindac Indomethacin Ketorolac |
Carbo/Heterocyclic Acetic acids (NSAID -> carboxylic acid -> acetic acid):
CA Tolmetin Sulindac Indomethacin Ketorolac CAT SIK |
|
Carboxylic acids NSAIDs:
Give examples of the propionic acid drugs? Hint: these usually end with what? Hint #2: KFC Tastes Incredible For N (sorry but it helps :\ ) |
Propionic acid drugs:
* usually end with -profen (except 1 -proxen and 1 -profenic acid) Ketoprofen Flurbiprofen Carprofen Tiaprofenic Acid Ibuprofen* Fenoprofen Naproxen* |
|
What group do these drugs fall into?
Firocoxib Deracoxib Rofecoxib Valdecoxib Celecoxib |
There are all Cox-2 inhibitors
Firocoxib Deracoxib Rofecoxib Valdecoxib Celecoxib |
|
Carboxylic acids NSAIDs:
Example of Acetic acid that is a Phenylacetic acid? PAD |
Diclofenac <- a phenylacetic acid
PAD |
|
Carboxylic acids NSAIDs:
Examples of Acetic acids that are carbo-and hetero cyclic acetic acids? (4) |
Carbo-and hetero cyclic acetic acids:
Tolmetin Sulindac Indomethacin Ketorolac CAT SIK |
|
What pH are NSAIDs soluble in?
Are they soluble in plasma? Are they acids or bases? |
- NSAIDs are weak acids
- insoluble in plasma at neutral pH (more lipid soluble) - more soluble in alkaline solutions (when ionized?, but this decreases absorption) note: acidity due to the presence of acid carboxcylic group or an enol group |
|
Are NSAIDs readily absorbed when admin. orally?
|
NSAIDs are lipid soluble, weak organic acids and generally well absorbed when admin. orally, b/c not ionized at LOW pH of stomach
|
|
Are NSAIDs ionized in plasma/physiological pH?
Are injectables a good route of admin.? |
Yes, being weak acids they are ionized in blood; therefore capacity to penetrate mem. decreases
No, tend to be alkaline, cause pain, necrosis if perivascular leakage occurs |
|
Are NSAIDs highly protein bound?
|
Yes, mainly albumin - for most of NSAIDs % of plasma protein binding is greater than 90%
|
|
Which NSAIDs is not 90% PP bound?
|
Aspirin only 50% PP bound
also salicylate |
|
Ketorolac is a ?
|
carbo/heterocyclic acetic acid
CAT SIK |
|
How does fact that NSAIDs are highly protein bound facilitate function?
|
facilitates passage into inflammatory exudate; therefore more concentrated at site of inflammation
fyi: exudate carries proteins, cells, fluid from local blood vessels to damaged area to mediate local defenses |
|
What can inhibit absorption/ bioavailability of NSAIDs?
|
food, drugs bind to food e.g. hay
|
|
Ketoprofen is ?
|
Propionic acid drugs:
KFC Tastes Incredible For N |
|
T/F NSAIDs are:
Optical activity - optically active - chiral compounds |
True
|
|
Diclofenac is a ?
|
Diclofenac <- it is the only phenylACETIC acid
PAD |
|
What anti-platelet drug is Acetyl salicyclic acid, irreversibly inhibits cyclooxygenase enzyme, and therefore synthesis of prostaglandins and thromboxane A2?
|
Aspirin
|
|
Another name for aspirin?
What group does it fall into? |
Aspirin = Acetyl salicylic acid
Example of Salicylic acid and esters |
|
What are mediators of inflammation released or formed de novo from cells?
|
histamaine, 5-hydroxytryptamine, the eicosanoids, platelet activating factor, free radicals and cytokines (interleukin, interferon, tumor necrosis factor)
|
|
Diflunisal is a ?
|
Examples of Salicylic acid and esters? (2)
1. Acetyl salicylic acid 2. Diflunisal SAAD |
|
What are examples of Enolic Acids?
|
pyraxolones and oxicams
|
|
Tolmetin is a ?
|
Carbo/Heterocyclic Acetic acids (NSAID -> carboxylic acid -> acetic acid):
caT sik |
|
What is an example of a pyrazolones?
|
Phenylbutazone
Enolic Acid -> pyrazolones -> **Phenylbutazone** |
|
What are examples of oxicams?
|
piroxicam and MELOXICAM
|
|
Are NSAIDs chiral?
|
Yes
|
|
What is cyclooxygenase?
|
enzyme that catalyzes the conversion of arachadonic acid to cyclic endoperoxide, prostaglandin, to the eicosanoids PGE2 and PGI2 which have pro-inflammatory properties
|
|
What is a constitutive enzyme expressed in most tissues and blood platelets?
|
COX-1
|
|
COX-1 mediates the formation of constitutive prostaglandins which are involved in what?
|
cellular "housekeeping" functions such as coordinating the action of circulating hormoned and regulating vascular homeostasis.
|
|
What are the most important functions of COX-1?
|
gastic protection, platelet function regulation, endothelial cell regulation, maintenance of renal blood flow during periods of shock and low systemic BP
|
|
What is the inducible cyclooxygenase, that is expressed only following cell activation, is upregulated in CNS and plays an essential role in the mediation of pain and the febrile response?
|
COX-2
|
|
COX-2 can also be found as constitutive in what tissues?
|
brain, kidney, OVARY, UTERUS, ciliary body and bone
|
|
Complete inhibition of COX-2 can potentially lead to what?
|
abortion, fetal deformities, delayed bone healing, delayed wound healing, cardiovascular events, renal toxicity
~ that is why a lot of COX-2 inhibitors (coxibs) have been taken off market |
|
Inhibition of cyclooxygenase can be of two types:
(which is irreversible?) |
1. competive inhibition of (arach.acid) substrate binding site of COX (reversible)
2. Acetylation of key serine w/in active site (irreversible) |
|
As consequence of inhibition of prostaglandin synthesis, NSAIDs produce what three main therapeutic effects?
|
Antipyretic (lower febril state), analgesic, anti-inflammatory
|
|
How are NSAIDs antipyretic (fever suppression)?
|
the role of PGE2 in the pathogenesis of fever, PGE2 is the second messenger of IL-1 at the hypothalamus
|
|
How are NSAIDS analgesic (reduction of inflammatory pain)?
|
role of PGE2 in sensitizing sensory nerve endings to other mediators such as histamine and bradykinin
|
|
How are NSAIDS anti-inflammatory?
|
role of PGE2 in inducing vasodilation
|
|
Is it advisable to give NSAIDs with food?
|
? no, food can impair the oral absorption of some NSAIDS
|
|
Why is it better to give NSAIDs orally, then administering injectable preparations?
|
injectibles are alkaline and can cause necrosis or pain if perivascular leakage occurs
|
|
Being weak acid, NSAIDs are ___ in blood, therefore their capacity to penetrate membrane is _____.
|
ionized in blood; decreased
|
|
NSAIDs are metabolized in the liver and and generally undergoes what two reactions?
|
oxidation (a phase I reaction) followed by conjugation (a phase II reaction)
|
|
Phenylbutazone is metabolized to the active metabilite _______?
What kind of NSAID is it again? |
Phenylbutazone (an enolic acid and pyrazolone) is metabolized to the active metabilite OXYphenbutazone!!!
|
|
Aspirin is metabolized to the active metabolite __________?
|
salicylic acid
|
|
NSAIDS are mainly excreted in the urine, but what compounds are excreted in bile?
|
tolfenamic acid and naproxen
|
|
Why is excretion of NSAIDS faster in herbivores?
|
* NSAIDs are ionized in alkaline urine; therefore reabsorption in renal tubules is decreased (opposite in carnivores)
|
|
The toxicity of NSAIDs on the GIT is a consequence of what?
|
the inhibition of gastric mucosal PG synthesis
|
|
Because of the affects of NSAIDs on the GIT, it is always advised to administer NSAIDS with a what?
|
cytoprotectant/ misoprostol (PGE replacement)
|
|
Inhibition of cyclooxygenase by NSAIDs in renal compromised patients induces what?
|
renal vasoconstriction, thereby decreasing renal blood flow and glomerular filtration rate
|
|
NSAIDs interfere with platelet activity due to what?
|
impaired thromboxane synthesis
|
|
What are factors that increase or predispose NSAID toxicity?
|
* if administered to patients with GIT inflammation or ulceration, inadequate dose regimens, age
* if administered to hypotensive , dehydrated, hyponatremic patients (low sodium - electrolyte inbalance), administration with highly plasma protein bound drugs or corticosteroids |
|
NSAIDs can be indicated for the treatment of what medical conditions?
|
joint disease, bone tumors (e.g. meloxicam COX-2 inhibitor), intervertebral disc lesions, pancreatitis, external otitis, inflammatory eye conditions
|
|
DO NOT use NSAIDs in patients with what problems?
|
GIT inflammation or ulcerative disease, hyperchlorhydria, renal insufficiency, patients with reduced CO, patients receiving corticosteroids
|
|
What is the mechanism of action of Aspirin?
|
irreversible inhibition of cyclooxygenase enzyme activity, inhibits the formation and release of kinins, stabilize lysosomes
|
|
How is aspirin (salicylic acid) eliminated?
|
by glucuronide conjugation
|
|
What are signs of acute toxicity of aspirin?
|
depression, vomiting, hyperthermia, electrolyte imbalance
|
|
What drug is approved by the FDA in horses and dogs, administered IV/oral, metab. in liver to form active oxyphenbutazone, prolonged duration of action with long half-life?
|
phenylbutazone
|
|
What are some adverse affects of phenylbutazone?
|
GI toxicity, bone marrow hypoplasia, hepatotoxicity and renal papillary necrosis
|
|
When should you use phenylbutazone?
|
osteoarthritic and osteoporotic conditions (porous bones), equine colic
|
|
What is a nicotinic acid derivative, is approved for use in horses, is a potent analgesic agent, and also possesses antiendotoxic effects?
|
flunixin meglumine
|
|
When should you use flunixin meglumine?
|
colic and treatment of endotoxic shock
|
|
What can accidental intra-arterial administration in horses of flunixin meglumine cause?
|
CNS stimulation, ataxia, and hyperventilation
|
|
What is flunixin meglumine used to treat in ruminants?
|
acute mastitis and acute bovine pulmonary emphysema
|
|
What can flunixin meglumine used to treat in dogs?
|
septic shock
|
|
What is the mechanism of action for carprofen?
|
Mechanism of action for carprofen (propionic acid)?
~inhibition of COX2 (reversible), inhibition of phospholipase A2, impaired release of arachidonic acid |
|
When should you use carprofen?
|
to treat osteoarthritis, and for post-operative pain
|
|
What is an adverse affect of carprofen?
|
hepatotoxicity
|
|
What drug is approved by FDA for use in horses, and is used to treast myositis and soft tissue inflammation?
|
naproxen
|
|
What animals are more sensitive to naproxen, and extensive enterohepatic recycling leads to prolonged elimination?
|
dogs (cats) sensitive to naproxen
infact not recommended in either of these animals; no safe dose for cats |
|
What is a less effective analgesic compared to aspirin, commonly used in humans, dogs are sensitive to GI toxicity (use is not recommended in dogs)
|
Ibuprofen
|
|
What is a derivative of anthranilic acid, an analogue of salicyclic acid, has a slow onset of action, thus clinical efficacy requires 2-4 days?
|
meclofenamic acid is a derivative of anthranilic acid, an analogue of salicyclic acid, has a slow onset of action
used for joint and muscular pain. It inhibits the synthesis of prostaglandins.[1] No other complications |
|
What is a proprionic acid NSAID approved for use in humans, horses, and small animals, it is a strong inhibitor of COX, so has powerful anti-inflammatory, analgesic and antipyretic properties.
|
Ketoprofen
|
|
How does ketoprofen interfere with the formation of leukotrienes?
|
inhibits lipooxygenase
|
|
What are side effects of ketoprofen?
|
GI upset, CNS reactions, nephritis
|
|
When is piroxicam used?
|
for treating osteoarthritis in dogs, for reducing the size of transitional cell TUMORS in dogs, and a potent anti-inflammatory for treating musculoskeletal conditions
also evidence of antitumor activity in squamous cell carcinoma of oral cavity and skin in dogs (Schmidt et al. 2001) |
|
What is an effective analgesic and antipyretic agent, but has weak anti-inflammatory activity, does not inhibit COX, but interferes with endoperoxidase intermediates formed during the arachidonic acid metabolism?
|
Acetaminophen
|
|
For what animal is acetaminophen toxic?
|
cats
|
|
What are the adverse effects of acetaminophen?
|
hepatotoxicity, methemoglobinemia
|
|
How do you treat acetaminophen toxicity?
|
antioxidants, a precursor of glutathione and ascorbic acid, cimetidine administration
|
|
What enzyme converts cell membrane phospholipids into ARACHIDONIC ACID?
|
phospholipase A2 converts cell membrane phospholipids into arachidonic acid
|
|
What enzyme converts ARACHIDONIC ACID into PGG2/H2?
|
CYCLOOXYGENASE (COX) converts arachidonic acid into eicosanoids PGG2/H2
(fyi: i think PGG2 is called an endoperoxide; it is reduced to form PGH2) |
|
What enzyme converts PGG2/H2 into PGI2, PGE2, PGD2, PGF2?
|
PG-ISOMERASE converts PGG2/H2 into PGI2, PGE2, etc.
|
|
What enzyme converts PGG2/H2 into TXA2?
|
Thromboxane synthetase converts PGG2/H2 into TXA2 (platelet/clotting factor)
|
|
How aspirin affect clotting factor thromboxane synthesis?
|
Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2.
TXA2 is generated from prostaglandin H2 by thromboxane-A synthase. |