Anti-inflammatory drugs and NSAIDS Flashcards
___ is the main precursor molecule on which COX enzymes act to produce prostaglandins and leukotrienes
Arachidonic acid (from cell membranes) is the main precursor molecule on which COX enzymes act to produce prostaglandins and leukotrienes
The products of the cyclooxygenase pathway include ___, ___ and ___
What are the functions of the products of the COX pathway?
The products of the cyclooxygenase pathway: prostacyclin (PGI2), thromboxane (TXA2) and prostaglandins (D2 and E2)
Prostacyclin inhibits platelet aggregation/promotes vasodilation (recall that this is produced by the endothelial cells)
Thromboxane promotes platelet aggregation (produced by platelets)
Prostaglandins (PGD2 and PGE2): promote increased vascular permability and fever
___ are the body’s natural downregulators of inflammation
The action of glucocorticoids include ___, downregulation of cytokines and ___ activity
Glucocorticoids
Inhibition of Phospholipase A2, downregulate cytokines directly by acting on immune cells, and transcriptionally downregulate synthesis of COX
Generally, how do glucocorticoids downregulate inflammation?
In general, glucocorticoids will upregulate inhibitory processes (like apoptosis or Treg cells which produce anti-inflammatory cytokines), and downregulate either the production of pro-inflammatory cytokines or the number of effector cells – as in the case with mast cells and basophils)
The anti-inflammatory cytokines that are upregulated are ___, while IL-2, ___, 12, ___ and TNFa are all downregulated
The anti-inflammatory cytokines that are upregulated are IL-10, while IL-2, 6, 12, IFNy and TNFa are all downregulated
The direct mechanisms of action of glucocorticoids include binding to transcription factors, ___ or ___
Indirectly, glucocorticoids can also ___ or sequester other transcription factors
Steroids can bind to transcription factors to repress transcription, or sit directly on DNA on glucocorticoid response elements, or bind to membrane receptors
Indirectly, glucocorticoids can also modify of histone acetylating and deacetylating enzymes or sequester other transcription factors
___ is the most potent of all steroids and is generally immunosuppressive and anti-inflammatory
Dexamethasone
(Dexter, boy genius! figured out how to suppress inflammation+ the immune system!) the best there is i.e. most potent
___ is given as a pro-drug, prednisolone (cleaved and activated by ___) and is generally anti-inflammatory and used in autoimmune diseases such as Crohn’s disease
Prednisone is given as a pro-drug, prednisolone (cleaved and activated by 3b-hydroxysteroid-dehydrogenase (3b-HSD) in the liver) and is generally anti-inflammatory and used in autoimmune diseases such as Crohn’s disease
In general, Crohn’s disease is a type of inflammatory bowel disease that affects which parts of the GI tract?
Almost everywhere. **Note also that this is an autoimmune disorder**
Prednisone is also used for ___, an autoimmune disorder characterized by DOPAMIN RASH characteristics
Prednisone is also used for systemic lupus erythematosus (SLE), an autoimmune disorder characterized by DOPAMIN RASH characteristics
___ is primarily used for skin irritation but can be chemically modified and given IV for MS flares, or in premature babies to promote lung maturation
Betamethasone is primarily used for skin irritation but can be chemically modified and given IV for MS flares, or in premature babies to promote lung maturation
(beta-get that skin fixed; beta lungs in premie babies and beta for MS flares)
___ is primarily used for allergic rhinitis (you’ve used this before) and is a pretty potent anti-histamine
Fluticasone/flonase is primarily used for allergic rhinitis (you’ve used this before) and is a pretty potent anti-histamine
(something about somebody tryna play the FLUT -as in fluticasone- with their NOSE - as is rhinitis, also as in sone spelled different)
What are DMARDS and what conditions are they used to treat generally?
Disease-modifying anti-rheumatic drugs
Generally used for rheumatoid arthritis, and other inflammatory conditions that affect the joints
Describe the priming and effector phases that result in RA
Which 2 cytokines are produced that are the main targets of biologics?
Naïve T cells get primed and become helper T cells. Th2 cells interact with B cells which will release autoantibodies, and Th17 will release IL-17 which is very pro-inflammatory
*IL6 and TNFa are also produced priming/effector phase, and are the main targets of biologics*
Which DMARD was originally used for chemotherapy but works to reduce inflammation and joint damage in RA when used in low doses?
Methotrexate
**if you’re doing to do drugs, it has to be METH and apparently you can combine it with other drugs! It used to be used for cancer, turns out just a little bit (at low doses) can treat rheumatoid arthritis (reduce inflammation + joint damage)**
What is the mechanism of action of methotrexate?
Likely the accumulation of adenosine (folic acid metabolism) which prevents the activation and proliferation of B and T cells
(recall that it messes up purine biosynthesis in bugs and is given for that reason)
**METHotrexate don’t like that FOLATE so ade-no where you gon get more B and T cells from now**
___ can be used alone or with methotrexate, and works by inhibiting pyrimidine synthesis (and thus dna), thereby blocking lymphocyte proliferation
Leflunomide (ARAVA) can be used alone or with methotrexate, and works by inhibiting pyrimidine synthesis (and thus dna), thereby blocking lymphocyte proliferation
**LEF(t)enant = 2nd to the captain (can be used a 2nd line of defense, also used with methotrexate) block pyriMIDine synthesis**
Which sulfa drug is used in the treatment of rheumatoid arthritis and of arthritis associated with ankylosing spondylitis and inflammatory bowel disease (ulcerative colitis and Crohn disease)?
Sulfasalazine (Azulfidine)
**the blue drug that likes to sul(f)a but it can’t because its got ankylosing spondylitis and IBD so it always has to go to the bathroom**
____ was originally developed as an antimalarial and can treat RA (early in the course)? *note that chronic use of this is toxic to the retina*
Hydroxychloroquine (Plaquenil) was originally developed as an antimalarial and can treat RA (early in the course)? *note that chronic use of this is toxic to the retina*
**if you chronically go to the pool (hydro + chlorine) your eyes start to burn b/c the hydroxychloroquine is toxic to the retina**
What are the 3 cytokines primarily targeted by most biologics?
Primarily inhibiting IL1, IL6 and TNFa
Etanercept, Golimumab, Adalimumab, Certolizumab, Infliximab all inhibit which pro-inflammatory cytokine?
All inhibit TNFa
IL1 is inhibited by ___ and ___ and IL6/IL6 receptor are inhibited by ___
IL1 is inhibited by Anakinra and Canakinumab, and IL6/IL6 receptor are inhibited by Tocilizumab
**Anakinra - sounds like ankara but is often mispronounced; number 1 cloth there is
Canakinumab - a tribe where the ankara came from? Idk. Probably also the number 1 tribe**
**Tocilizumab - “To Kill Ze Mob”, errbody in there is a devil worshiper (remember the #triple6sign)**
What is the mechanism of action of etenarcept (enbrel)?
Blocks TNF signaling by binding it (basically it’s a fake TNF receptor – fusion protein made from rDNA coding for the TNF receptor + human IgG1)
**etenercept is fake TNF**
Name the enzymes through which the following prostaglandins are synthesized:
PGI2
TXA2
PGE2
PGFa
PGD2
PGI synthase
TX synthase
mPGES1
PGF synthase
L/H/PGD synthase
(she said not to focus on PGD2 but you need to know it for step)
How is NAPQI harmful to the liver?
NAPQI causes reduced expression of CD44 on T cells >> apoptosis of hepatocytes
(see image below)
What are the effects of aspirin intoxication? (from pro-longed use)
(see image below)
What are the mechanisms of signaling for the receptors for the the following prostanoids?
PGI2
PGE2
PGFa
TXA2
PGE2 acts thru 4 different receptors; mainly thru EP4 and EP2 which are synergistic and increase cyclic AMP;
PGI2 also works through increasing cAMP signaling
PGE2 can also work thru EP3 which has varied effects (increasing Ca2+ signaling and modulating cAMP signaling)
TXA2 works through TPa/b (which works the same way as EP3)
(see image below)
**note that the receptors are all GPCRs**
