Drug Therapy of Inflammation

Question 1

COX-1 is produced constitutively and is involved in what?

Answer 1

Gastric cytoprotection, platelet aggregation, renal blood flow autoregulation, initiation of parturition, and renal electrolyte homeostasis.

Question 2

COX-2 is induced during inflammation, and so produces what at the site of inflammation and/or tissue dmg?

Answer 2

Prostaglandins

Question 3

Histamine, kinins, and PGE2 all do what?

Answer 3

Sensitize peripheral pain receptors = pain

Question 4

NSAIDs produce their therapeutic effects by inhibiting the COX enzymes and thus the synthesis of what?

Answer 4

prostaglandins, prostacyclins, and thromboxanes

Question 5

Acetylsalicylic acid (aspirin) mechanism of action. How does salicylic acid slightly behave differently?

Answer 5

Irreversibly (noncompetitively) blocks the synthesis of eicosanoids by acetylating COX-1 and COX-2. SA is a competitive inhibitor, thus reversibly inhibits.

Question 6

List the broad pharmacological effects of ASA

Answer 6

Anti-inflammatory, analgesic, antipyretic, antiplatelet

Question 7

List the broad major adverse effects of ASA

Answer 7

GI irritation (loss of cytoprotective effect of PGE2 and PGI2), nephrotoxicity (inhibits renal vasodilator eicosanoids and decreases blood flow), bleeding and anemia, hepatotoxicity, hypersensitivity rxns (i.e. bronchoconstriction), salicylate toxicity.

Question 8

Mechanism for the anti-inflammatory effects of ASA and the tx of symptoms of what general conditions?

Answer 8

Inhibits eicosanoid formation and thus vasodilation, pcv permeability, leukocyte chemotaxis, etc. Tx of symptoms of rheumatic and conn tissue disorders.

Question 9

Mechanism for the analgesic effects of ASA and the tx of symptoms of what general conditions?

Answer 9

Inhibits eicosanoid-induced sensitization of pain receptors, i.e. indirectly antagonizes the effects of histamine, kinins, etc. Alleviates HA, myalgia, arthralgia, dysmenorrhea, but not visceral pain.

Question 10

Mechanism for the antipyretic effects of ASA and the tx of symptoms of what general conditions?

Answer 10

Reduces high temp by blocking pyrogen induced eicosanoid synthesis in vicinity of hypothalamus (PGE2).

Question 11

Mechanism for the platelet effects of ASA and the tx of symptoms of what general conditions?

Answer 11

Inhibits TXA2 synthesis and thus platelet aggregation. Prophy for thrombosis (coronary and cerebral).

Question 12

Diflunisal: class, mechanism, comparison to ASA, uses.

Answer 12

Salicylate. COMPETITIVE inhibitor of COX-1 and 2. Analgesic and weak antipyretic activity; longer half-life. Better tolerated cuz of fewer GI S.E.s and has less effect on platelets. OA, cancer bone met pain, dental extraction and postepisiotomy pain.

Question 13

Acetaminophen: class, uses and comparison to ASA

Answer 13

Para-amino phenol. Analgesic and antipyretic effects similar to ASA, weak anti-inflammatory properties and doesn’t produce GI irritation or bleeding like ASA.

Question 14

What is a rare complication associated with chronic abuse of acetaminophen?

Answer 14

RTN

Question 15

Potentially fatal what may occur from acetaminophen overdose? What is given to treat acetaminophen overdose?

Answer 15

Hepatic necrosis. Mucomyst.

Question 16

Acetaminophen is primarily metabolized by what means? A minor pathway involves what to form a potentially toxic intmd, N-acetylbenzoquinoneimine?

Answer 16

Conjugation with sulfate and glucuronide for renal excretion (phase II). Oxidation by P450 enzymes to form that quinone intmd, which at thx doses is renally excreted via conj with glutathione.

Question 17

Indomethacin: class, use, potency compared to ASA, what population is it generally not used in?

Answer 17

Indole. 10x more potent. RA, AS, OA, acute gout, control of pain. Children.

Question 18

Serious adverse effects of Indomethacin

Answer 18

Thrombocytopenia, aplastic anemia, and severe frontal HAs in 25-50%.

Question 19

Sulindac: class, potency compared to Indomethacin, S.E.s compared to Indomethacin, what toxicity does it not have?

Answer 19

Indole, prodrug. Half as potent as indomethacin. Less freq S.E.s with long term use. No renal tox.

Question 20

Propionic Acid Derivatives and Analogs: List them

Answer 20

Ibuprofen, Flurbiprofen, Naproxen, Oxaprozin

Question 21

Propionic Acid Derivatives general characteristics

Answer 21

RA, OA, AS. Effective analgesics to relieve postpartum pain, dysmenorrheal pain, and oral, ophthalmic or other types of surgery. Usual range of adverse effects. Better tolerated than ASA or Indomethacin.

Question 22

Piroxicam: Class, unique feature, use

Answer 22

Enolic acid. Long half-life, longterm tx of RA, OA, AS, acute gout, acute musculoskeletal disorders.

Question 23

Ketorolac: class, unique feature, uses

Answer 23

Heteroaryl acetic acid. Injectable, relatively non-irritating to tissues, used topically for eye. For postop pain.

Question 24

Since it is associated with inflammation, which class of drugs should be better anti-inflammatory drugs than the older NSAIDs?

Answer 24

Selective COX-2 inhibitors.

Question 25

The COX-2 'coxibs' have the same anti-inflamm, antipyretic, and analgesic benefits as the tNSAIDs, but they produce less what?

Answer 25

GI toxicity.

Question 26

COX-2 inhibitors are contra'd in patients with what problems or when what?

Answer 26

Heart problems, pregnancy.

Question 27

Coxibs have no impact on what, thus do not offer the cardioprotective effects of traditional NSAIDs?

Answer 27

platetet aggregation

Question 28

A few coxibs with even greater selectivity for COX-2 were withdrawn from the market due to increased risk for what?

Answer 28

MI, stroke, and thrombosis