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;
44 Cards in this Set
- Front
- Back
what is mediator pharmacology |
subdivision pharmacology whig teaches the functions of molecules released in the body and produces pharmacological effects |
|
give an example of mediators |
hormones, cytokines, nucleosides, neuclotides, basic amines, fatty acids, enzymes, peptides |
|
what is the criteria for establishing a substance as a mediator |
released from local cells in sufficient quantity to mediate biological activity on target cells within a time frame application of an authentic sample of the proposed mediator reproduce it biological effect interference with the synthesis/release/action of the mediator modifies the original biological response |
|
explain eicosanoids |
group of mediators generated from arachidonic acid pre-formed in the cell mediate paracrine autocrine signalling degraded quickly so cannot travel far in the body |
|
where is paracrine signalling and autocrine signalling |
its effect in another cell its effect in the same cell |
|
type of eicosanoid derived from arachidonic acid depends on what |
enzymes involved |
|
what are the three enzymes involved in transferring arachidonic acid to eicasanoid |
epoxygenase, oxygenase( COX1/COX2) lipoxygenase (LOX) |
|
what does each enzyme do in the arachidonic to eicosanoid pathway |
Epoxygenase- makes EETs COX1/COX2:prostanoids- prostaglandins, prostacyclins(PGI2) Thromboxane (TXA2) LOX- HETEs, leukotrienes, lipoxins |
|
what is the rate limiting step in the synthesis of eicosanoid |
phospholipase A2 |
|
explain how arachidonic acid goes through COX1 COX2 pathway |
arachidonic acid- prostaglandin G2- COX1- prostaglandin H2 arachidonic acid- prostaglandin G2-COX2- prostaglandin H2 to tissue specific isomerases/ synthase |
|
what is the next step in “tissue specific isomerases/synthase” |
prostacyclin thromboxane prostaglandin E2 prostaglandin F2a |
|
oxygenation and cyclization of arachidonic acid to give what |
PGG2 and PGH intermediates |
|
the eicosanoid generated depends upon what |
depend upon the cell type and isomerases/synthases enzymes present |
|
what predominates in the endothelium, kidney and brain |
prostacyclin (PGI2) |
|
what prediminates in platelets macrophages kidney and smooth muscle |
thromboxane A2 |
|
what predominates in the brain, kidney and smooth muscle |
prostaglandin E2 and prostaglandin F20 |
|
explain characteristics of COX 1 |
constituituve expression almost all cell types low to moderate PG RELEASE transient release of PG protective roles in kidney and stomach known inhibior-asprin |
|
explain characteristics of COX 2 |
induced by inflammatory cytokines primarily in inflammatory cells sustained PG release known inhibitor- asprin |
|
explain characteristics of asprin |
asprin irreversibly inhibits COX1 and COX2- in addition to its properties as an anti-inflammatory drug, asprin is used clinically as an anti-platelet TXA2 synthesis through inhibition of COX1. rhis reduced the risk of thrombosis |
|
why is COX2 more relevant as a target for anti-inflammatory drugs |
COX2 is induced strongly by inflammatory stimuli therefor tends to be more relevant as a target for anti-inflammatory drugs |
|
what are the 5 different prostanoid receptors |
g protein coupled receptor -prostaglandin D2 -prostaglandin E2 -prostaglandin F - prostaglandin I2 -Thromboxane |
|
explain the pathway for prostanoids and PGI2 |
in endothial cells, COX-2 metabolises arachidonic acid to produce PGI2, this then bids to IP2 receptors this promotes Gs coupling pathway resulting in increased adenylcyclase and cAMP this will reduce platelet aggregation, and vasodilation |
|
explain the pathway for prostanoids and TXA2 and how its inhibited |
in platelets, COX-1 metabolises arachidonic acids to promote synthesis and release of TXA2 this then binds to TXA2 receptor promiting coupling of G Protein pathway (Gq, G12, G13) this results i platelet shape change and release thus resulting in increased platelet aggregation and increased vasoconstriction inhibition of COX-1 by asprin- how it is used as an anti-platelet agent |
|
what are the main cox inhibitors characteristics |
inhibit prostaglandin and thromboxane synthesis reduce inflammation antithrombotic and analgesic effects |
|
what can happen if patients lack cox-1 |
have mild bleeding disorders |
|
why are NSAIDs considered non-selective |
because they inhibit both COX-1 and COX-2 |
|
what happens with inhibition of COX-2 |
anti inflammatory features of NSAIDs |
|
what can happen when you inhibit COX-1 |
side effects(ulcers, prolonged bleeding, kidney problems) |
|
what COX-2 selective NSAID (celebrex) was developed and what followed |
vioxx and bextra-withdrawn from use due to side effects arcoxia and prexige- rejected by FDA FOR LIVER COMPLICATIONS |
|
what protective role to prostaglandins have |
in gastrointestinal tract inhibit gastric acid secretion and prevent gastric ulcers |
|
what are some other side effects of cox inhibition |
NSAIDs are acidic so damage to the gut adverse effect of NSAIDs is irritation of the gastric mucosa |
|
what do cox 2 inhibitors do |
increase the risk of thrombosis, heart attack and strike even in short term use |
|
explain a example of natural cox inhibition |
diet: fish oils provide an alternative fatty acids to arachidonic acid metabolised to anti inflammatory prostacyclins not pro inflammatory prostacyclins |
|
what gives you eicosanoids- lipoxins, leukotriene and HETEs |
peroxidation of arachidonic acid by 5-lo |
|
5-lo gives what |
leukortriene A4 which is converted into LTB4 and cysteine residues LTC4, LTD4, LTE4 |
|
what cells synthesises leukotrienes |
WBC, mast cells and platelets |
|
how do leukotrienes signal |
through GPCRs principally coupled to Gai and Gaq G PROTEINS |
|
leukotrienes are synthesised from arachidonic acid by what and give the pathway |
lipoxygenase enzymes- main one being 5-lo this involved accessory protein FLAP which results in the formaton of ubstable leukotriene LTA4 shich js converted to LTB4 Or cysteine LTC4, LTD4, LTE4 |
|
leukotrienes are synthesised from arachidonic acid by what and give the pathway |
lipoxygenase enzymes- main one being 5-lo this involved accessory protein FLAP which results in the formaton of ubstable leukotriene LTA4 shich js converted to LTB4 Or cysteine LTC4, LTD4, LTE4 |
|
what is LTB4 mainly produced by |
neutrophils and is a potent chemotactic agent fo neutrophils and mafrophages and promotes cytokine production from macrophages and lymphcyte- how they play a role in inflammation |
|
what are cysteine leukotrienes produced by |
eosinophils, mast cells, basophils, muscle and increase mucus secretion. cys-LT receptor agonists are currently in use for treatment of asthma |
|
what are examples of leukotrienes in inflammatory disease |
asthma - Cys-LTs atherosclerosis- LTB4 and Cys-LTs rheumatoid arthritis (LTB4) inflammatory bowl disease- LTB4 and Cys-LTs cancer- LTB4 inflammatory pathways in obesity (LTB4) Other emerging roles- insulin resistance - LTB4 |
|
what are some inhibitors of LOx Pathway and what do they do |
5-lo inhibitor: zileuton for asthma cys- LT1 antagonist- montelukast and zarfirlukast for asthma and seasonal allergy |
|
what are alternative mechanisms to block arachidonic acid inflammation |
inhibit PLA2- mediated arachidonic acid release through steroids ( promote synthesis of lipocortin- inhibits PLA2) synthesis of lipoxins-> block LT RECEPTORS: asprin promotes synthesis of anti inflammatory lipoxins |