Term
| Which enzyme, COX-1 or COX-2, is expressed constitutively? |
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Definition
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Term
| Which enzyme, COX-1 or COX-2, is found at sites of inflammation? |
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Definition
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Term
| Which enzyme, COX-1 or COX-2, promotes platelet aggregation? |
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Definition
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Term
| Which enzyme, COX-1 or COX-2, is responsible for reducing polyp growth in the colon |
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Definition
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Term
| Which enzyme, COX-1 or COX-2, is involved in the synthesis of PG-E and thromboxane A2? |
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Definition
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Term
| What does prostacyclin do and which enzyme, COX-1 or COX-2, synthesizes it? |
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Definition
| inhibits platelet aggregation, promotes vasodilation; COX-2 |
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Term
| What are some effects of NSAIDs that are not due to inhibition of COX enzymes? |
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Definition
- inhibition of neutrophils
- stabilizing lysosomes
- reducing vascular permeability
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Term
| What are the two major types of NSAIDs and which category does aspirin fall under? |
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Definition
non-selective COX-inhibitors and selective inhibitors
aspirin is a non-selective inhibitor |
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Term
| What are the two major types of NSAIDs and which ones binds COX covalently? |
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Definition
| non-selective (1st generation) inhibitors |
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Term
| What are the two major types of NSAIDs and which has greater affinity for inhibiting COX-2? |
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Definition
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Term
| What makes aspirin different from all other NSAIDs in the non-selective category? |
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Definition
| It binds and irreversibly inactivates COX, while all others are reversible inhibitors |
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Term
| What is the prototype drug in the selective inhibitor category? |
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Definition
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Term
| What is some advantages of NSAIDs that opioid drugs do not have? |
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Definition
anti-inflammatory properties;
+ do not cause constipation, dependence, or impairment of motor/cognitive function |
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Term
| What are some advantages of NSAIDs over corticosteroids? |
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Definition
| more specific effects and fewer, less severe side effects |
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Term
| What are the three organic acid components that NSAIDs are derived from? |
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Definition
| salicylic acid, propionic acid, acetic acid |
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Term
| What is salicyclic acid used for? |
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Definition
| keratolytic agent (acne, calluses, warts)- not an NSAID |
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Term
| What is methyl salicylate used for? |
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Definition
| topically for muscle aches (i.e. Bengay) |
|
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Term
| What is the active metabolite of aspirin? |
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Definition
| Salicylate, a reversible inhibitor of COX-1 and COX-2 |
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Term
| What are non-acetylated salicylates used for? |
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Definition
| anti-inflammatory effects in osteoarthritis and rheumatoid arthritis |
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Term
| Why do the effects of platelet-inhibition by aspirin last 8-12 days? |
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Definition
| the lifetime of the platelet is 8-12 days |
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Term
| How does aspirin work as an analgesic in the periphery? |
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Definition
| inhibits synthesis of PGE2 and PGI2 so they cannot synergize with bradykinin and histamine and activate nociceptors |
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Term
| How does aspirin work as an analgesic in the spinal cord (CNS)? |
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Definition
| inhibiting PGE2 reduces Ca influx and thus reduces the release of pain neurotransmitters |
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Term
| How is the set point for body temperature elevated? |
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Definition
| formation of cytokines leads to increases in synthesis of PGE2 in the preoptic hypothalamic area, which increases cAMP and leads to increased body temperature |
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Term
| Where does most of the absorption of aspirin take palce? |
|
Definition
| In the lower intestinal tract, via passive diffusion |
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Term
| How can you help avoid the first-pass-metabolism effect for oral administration of aspirin? |
|
Definition
| sustained release (enteric coating) |
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Term
| What does duodenal-gastric reflux have to do with NSAIDs? |
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Definition
| cause mucosal damage to the stomach after enterohepatic recirculation from the bile into the duodenum |
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Term
| What are the effects of salicylate overdose? |
|
Definition
| hyperventilation, metabolic acidosis, hyperpyrexia, coma, renal, vasomotor, and respiratory failure |
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Term
| What are some contraindications for use of salicylates/aspirin? |
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Definition
| pregnancy, hemophilia, children with viral illnesses |
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Term
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Definition
propionic acid derivative
adverse GI reactions |
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Term
| Which propionic acid derivative is 20x more potent than aspirin as a COX-inhibitor? |
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Definition
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Term
| What NSAID drugs are acetic acid derivatives? |
|
Definition
- Ketorolac
- Indomethacin
- Sulindac
- Nabumetone
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|
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Term
| Which acetic acid derivative is used for short-term management of post-operative pain? |
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Definition
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Term
| What are some adverse reactions associated with Indomethacin use? |
|
Definition
- GI tract
- CNS
- renal toxicity
- ocular toxicity
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|
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Term
| What are some therapeutic uses of Indomethacin? |
|
Definition
- arthritis (ankylosing spondylitis)
- acute gout
- patent ductus arteriosus (prevents vasodilation by blocking release of PGE2 and PGI2)
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|
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Term
| Why might Sulindac be renal sparing? |
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Definition
| It is a prodrug that is metabolized by the liver into an active form and by the kidney into an inactive form |
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Term
| Which NSAIDs are used to suppress familial intestinal polyposis? |
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Definition
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|
Term
| What are three advantages to Nabumetone? |
|
Definition
- it's a ketone (non-acidic and minimal reflux and gastrotoxicity)
- half life >24 hrs (once-daily dosing)
- few anti-platelet effects
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|
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Term
| What are three NSAIDs that are organic sulfur compounds? |
|
Definition
- celecoxib
- rofecoxib *
- valdecoxib *
Both withdrawn from market due to increased risk of cardiovascular events and skin reactions (Steven Johnson syndrome) |
|
|
Term
| What are some adverse reactions associated with celecoxib? |
|
Definition
- nephrotoxicity
- edema and hypertension
- headache, abdominal pain, indigestion
- Stevens Johnson syndrome
- thrombosis
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|
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Term
| Which NSAID is used to treat primary dysmenorrhea? |
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Definition
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Term
| What is the mechanism of action of acetaminophen? |
|
Definition
- inhibits COX-1 and COX-2 in the CNS but not in the periphery
- does not have anti-inflammatory effects *possibly because of selective inhibition of COX-3 |
|
|
Term
| How is acetaminophen metabolized? |
|
Definition
major pathway (95%): glucuronidation and sulfation
minor pathway (5%) is via P450/CYP, needs glutathione (GSH) to detox the hepatotoxic metabolite formed (NAPQI) |
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Term
| What is the current drug therapy for acetaminophen overdose? |
|
Definition
| N-acetylcysteine (orally within 8 hrs), does not reverse damage to liver cells |
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|
Term
| What does the nuclear receptor CAR do? |
|
Definition
| Induces expression of CYP enzymes that convert acetaminophen into NAPQI (toxic) |
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|
Term
| What interactions are there with acetaminophen? |
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Definition
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