Drug Therapy of Inflammation

Question 1

3 phases of inflammatory response

Answer 1

1. acute transient phase (local vasodilation and increased capillary permeability)
2. a delayed, subacute phase, most prominently characterized by infiltration of leukocytes and phagocytic cells
3. a chronic proliferative phase, in which tissue degeneration and necrosis occur

Question 2

histamine

Answer 2

made from histidine, stored in mast cells and basophils throughout body. released from storage site in response to injury and antigens, and is a mediator of immediate allergic reactions. increases blood flow by dilation, causes edema by increasing venule permeability, and causes itching by sensitizing primary sensory neurons

Question 3

kinins

Answer 3

bradykinin and kallidin. formed in blood or in tissues at sites of injury, allergic reaction, viral infection, etc. kallikreins are the enzymes that make them. have acute effects (pain) due to excitation of primary sensory neurons, and chronic effects due to capillary dilation, increase in permeability, and activation of arachidonic acid release

Question 4

cytokines

Answer 4

orchestrate inflam response and defense mechanisms in general. IL-1 = fever, IL-8 = chemotaxis. TNF regulates production of other cytokines and induces fibrosis and tissue catabolism

Question 5

eicosanoids

Answer 5

metabolites of arachidonic acid

Question 6

COX-1

Answer 6

constituitively produced, involved in gastric cytoprotection, platelet aggregation, renal blood flow autoregulation, initiation of parturition

Question 7

COX-2

Answer 7

induced during inflammation, produces prostaglandins at the site of inflammation/damage.

Question 8

how do NSAIDs produce therapeutic effects?

Answer 8

inhibit COX enzymes, and thus the synthesis of prostaglandins, prostacyclins, and thromboxanes but not leukotrienes.

Question 9

what does aspirin do

Answer 9

irreversibly blocks COX 1 and 2 through acetylation

Question 10

anti-inflammatory effect of salicylates

Answer 10

treats rheumatic and connective tissue disorders. inhibits eicosanoid formation and thus vasodilation, permeability, chemotaxis etc. reduces inflammation. need a lot to get this effect

Question 11

analgesic effects of salicylates

Answer 11

alleviates headache, myalgia, arthralgia, dysmenorrhea. inhibits eicosanoid induced sensitization of pain receptors. not effective in alleviating visceral pain

Question 12

antipyretic effects of salicylates

Answer 12

reduces elevated temperature by blocking pyrogen induced eicosanoid synth in vicinity of hypothalamus

Question 13

platelet effects of salicylates

Answer 13

increases bleeding time by inhibiting TXA synth and thus platelet aggregation.

Question 14

side effects of salicylates

Answer 14

GI irritation, nephrotoxicity, bleeding and enemia, hepatotoxicity, hypersensitivity reactions, salicylate toxicity

Question 15

why is acetaminophen have weak anti-inflammatory properties?

Answer 15

poor ability to inhibit COX in presence of high concentrations of peroxides, as are found at sites of inflammation. might be better in brain, which explains why it is so good at stopping fevers

Question 16

what are propionic acid derivatives used for

Answer 16

mainly rheumatic disorders, osteoarthtiris, ankylosing spondylitis, etc.

Question 17

how do coxibs selectively inhibit COX-2?

Answer 17

they are large so they only fit the large channel of COX 2.