L18 and L19 NSAIDS Flashcards

Question

prostacyclin

Answer 1

-eicosanoid drug -PGI 2 -Powerful vasodilator -Inhibitor of platelet aggregation -Used to treat pulmonary arterial hypertension by IV injection or inhalation. -Should not be used with anticoagulants.

Answer 2

-Anti-inflammatory -Analgesic -Antipyretic

Answer 3

-Treatment of moderate pain, fever, and inflammation from acute inflammation -Treatment of early-stage rheumatoid arthritis and osteoarthritis -Cancer preventio

Answer 4

-Inhibition of prostaglandin endoperoxide H synthase (PGHS or COX), which catalyzes the formation of prostaglandins. -Many NSAIDs inhibit both COX-1 and COX-2

Answer 5

-salicylates -arylacetic acids -arylpropionic acids -non carboxylase NSAIDs -COX 2 selective NSAIDs

Answer 6

-Mild (common): dyspepsia, nausea, vomiting -severe (rare: blood loss, ulcer, GI hemorrhage -administration with food may decreases GI side effects. -Aspirin ~ indomethacin > naproxen > sulindac

Answer 7

-Acidity of many NSAID --> primary insult -Inhibition of synthesis of cytoprotective prostaglandins (PGEs) in gastric mucosa->secondary insult -Inhibition of platelet aggregation (increased tendency of bleeding)

Answer 8

-Aspirin prolongs bleeding time by irreversible inhibition of platelet COX-1 and the consequent reduced formation of thromboxane. -Aspirin use before surgery or tooth extraction is contraindicated. -can be used to some patients with cardiovascular disease to prevent blood coagulation.

Answer 9

-Little effect in normal patients. -Renal failure in patients with cardiovascular, hepatic, and renal diseases

Answer 10

-Characterized by skin rashes, hives, angioedema, and an asthma-like syndrome (blocked by 5-lipoxygenase inhibitors). -Occurs in 0.3% of the population (10% in asthmatics).

Answer 11

-specific to salicylates -A rare, acute, life-threatening condition characterized by vomiting, delirium, an coma (20-30% mortality) -Brain damage is common in survivors. -Occurs in children who have had the flu or chicken pox. -Aspirin should not be given to anyone under the age of 12 who has a fever

Answer 12

-Tinnitus -Dizziness -Headache

Answer 13

-Synthetic PGE1 analog -Used prophylactically to prevent NSAID-induced gastric ulcers in patients at high risk

Answer 14

-Greatly reduce acid secretion in stomach and protect against ulceration in the absence of COX-1 activity.

Answer 15

-Many NSAIDs are highly bound to serum albumin (typically 90-99%). -NSAIDs may compete for serum albumin binding sites with other drugs that are highly bound to these sites

Answer 16

-Naproxen/esomeprazole -Naproxen/misoprostol -Diclofenac/misoprosto

Answer 17

– combination with oral anticoagulants -Increases the plasma concentration of free anticoagulant. -The ability of salicylate to produce GI bleeding and inhibit the clotting mechanism aggravates the problem. -Necessitates a possible decrease in the dosage of anticoagulant

Answer 18

-Commonly contains an acidic group (e.g. carboxylic acid) -the acidic group is located one carbon atom adjacent to an aromatic or heteroaromatic ring. -Substitution of a methyl group on the carbon atom separating the acidic group from the aromatic ring (acetyl  propionic) tends to increase activity (“profens”). -A second area of lipophilicity (aromatic or alkyl) that is noncoplanar with the aromatic or heteroaromatic ring generally enhances activity

Answer 19

-salicylic acid -aspirin -salsalate -disunisal

Answer 20

-salicylate -First obtained in 1838 from salicin, a glycoside present in willow and poplar bark (from Latin salix, willow tree). -Hippocrates prescribed chewing willow bark for pain relief in the 5th century BC (no formal record). -Sodium salicylate was used as an antipyretic /antirheumatic agent in 1875. -Slightly acidic (pKa = 3.0) -absorbed as an ionic form from the small intestine and, to lesser extent, from the stomach as an acid form. -Inhibits COX-1 and COX-2 reversibly. -May suppress COX-2 induction.

Answer 21

-salicylate -prepared in 1853 but was used as a drug in 1899. -The only NSAID that irreversibly inhibits COX by acetylating a serine residue in the active site. -Absorbed largely as the intact form but hydrolyzed rapidly to salicylate by plasma esterase. -2-fold more potent than salicylic acid as analgesic/antipyretic. -Blocks platelet-aggregating factor TXA 2 effectively; increases the risk of bleeding but also reduces the risk of myocardial infarction. -Not stable in solutions

Answer 22

-salicylate -Dimer of salicylic acid -Hydrolyzed to two salicylates in the small intestine and absorbed. -Does not cause GI bleedin

Answer 23

-salicylates -More potent analgesic than aspirin, but produces fewer side effects. -Less antipyretic activity than aspirin. -3-4 fold longer t 1/2 than aspiri

Answer 24

-indomethacin -sulindac -etodolac -diclofenac

Answer 25

-One of the most potent NSAIDS in use -High incidence of side effects -Not suitable for a long-term use. -Not stable in solution due to the hydrolysis of the amide bond.

Answer 26

-Prodrug; the sulfoxide group is reduced to the active sulfide intermediate in the circulatory system. -Less GI side effects. -Suitable for a long-term use to treat chronic inflammation

Answer 27

-Pyranocarboxylic acid -As potent as indomethacin. -Somewhat selective for COX-2. -Less GI bleeding -suitable for long-term use to manage osteoarthritis

Answer 28

-The most widely used NSAID in the world. -As potent as indomethacin -Somewhat selective for COX-2. -inhibits both COX and lipoxygenase pathways

Answer 29

-ibuprofen -naproxen -ketorolac

Answer 30

-Popular OTC analgesic -More potent than aspirin, but less potent than indomethacin. -Moderate degrees of gastric irritation -α-Methyl group enhances it activity and reduces many side effects. -Bioequivalent racemic mixture -S-(+)-enantiomer possesses greater activity in vitro. -R-(-)-enantiomer is converted to S-(+)-enantiomer enzymatically in vivo.

Answer 31

-Cyclized heteroarylpropionic acid derivative -Short-term management of moderate to severe pain. -Analgesic activity similar to centrally acting analgesics. -Widely accepted alternative to narcotic analgesics.

Answer 32

-S-(+)-enantiomer -More potent than ibuprofen. -Moderate degrees of gastric irritation. -Used to treat rheumatoid arthritis and osteoarthritis

Answer 33

-nabumetone -meloxicam

Answer 34

-Nonacidic prodrug -Metabolized rapidly to 6-methoxynaphthalene-acetic acid (6-MNA), which is an effective inhibitor of COX. -Minimum gastric side effects. -Potent anti-inflammatory, but weak analgesic activity

Answer 35

-Belongs to the oxicam class, which resembles the peroxy radical intermediate in COX. -Enolic acid -Long acting; single daily dose. -As potent as indomethacin. -Somewhat selective for COX-2

Answer 36

-Stomach irritation and ulceration *Decreased production of cytoprotective prostaglandins *Bleeding from inhibition of thromboxane formation -Blockade of platelet aggregation -inhibition of uterine motility -Inhibition of prostaglandin-mediated renal function -Hypersensitivity reactions -Preferential inhibition of COX-2 gives anti-inflammatory effects with lower incidence of gastric ulceration

Answer 37

-Valine in the NSAID binding site of COX-2 is substituted for isoluecine in that of COX-1. -Selective COX-2 inhibitors exploit the larger NSAID binding site in COX-2 with larger and relatively rigid substituents. -FDA classifies only celecoxib, rofecoxib, and valdecoxib as selective COX-2 inhibitors (“coxib”)

Answer 38

-Selective inhibition of COX-2 results in elevated blood pressure and accelerated atherogenesis. -Constitutive expression of COX-2 in endothelium is critical for production of PGI2 (prostacyclin) -selective COX-2 inhibitors do not affect the production of TXA2 by COX-1; heightened thrombotic response on the rupture of atherosclerotic plaque. -Selective COX-2 inhibitors increase cardiovascular hazard (heart attack and stroke). -Merck withdrew rofecoxib from the US market in 2004. -Pfizer withdrew valdecoxib from the US market in 2005.

Answer 39

-First NSAID to be marketed as selective COX-2 inhibitor. -Used for osteoarthritis and rheumatoid arthritis. -Good efficacy against pain, inflammation, and fever. -As potent as naproxen. -Less risk of GI side effects. -No antiplatelet activity

Answer 40

-Analgesic and antipyretic effects similar to aspirin. -Much weaker as an anti-inflammatory agent

Answer 41

-Does not inhibit arachidonic acid binding to PGHS. -Scavenges peroxynitrite required for PGH synthase activity. -Peroxynitrite is the major oxidant for PGH synthase activity in the CNS. -In inflammation, high concentrations of peroxides are present, and acetaminophen scavenging is overwhelmed

Answer 42

-Lower incidence of gastrointestinal disturbance. -Tolerated in patients with blood coagulation disorders. -Not associated with Reye’s syndrome. -May cause a rash but a low incidence of hypersensitivity. -Does not cross-react with aspirin

Answer 43

-Cytochrome P450-mediated N-hydroxylation to form N-acetylimidoquinone, which reacts with glutathione. -toxic doses overload the glutathione, and cell damage occurs in the liver.

Answer 44

-Alprostadil (Edex®) -Misoprostol (Cytotec®) -Latanoprost (Xalatan® , Monopost ®) -Prostacyclin (Epoprostenol ®

Answer 45

-Salicylic acid -Aspirin -Salsalate (Disalcid®) -Diflunisal (Dolobid ®

Answer 46

-Indomethacin (Indocin®, Tivorbex®) -Sulindac (Clinoril ®) -Etodolac (Lodine®) -Diclofenac (Cataflam® ,Voltaren®

Answer 47

-Ibuprofen (Advil ®, Motrin®) -Naproxen (Aleve ®) -Ketorolac (Toradol ®, Biorolac®

Answer 48

Celecoxib (Celebrex ®)

Answer 49

-Nabumetone (Relafen®) -Meloxicam (Mobic®, Vivlodex®)

L18 and L19 NSAIDS Flashcards

(73 cards)