Flashcards in L17 Deck (38)
What is the membrane derived molecule of important in anti-inflammatory drugs? What enzyme makes this?
FROM membrane phospholipids w/ AA
Via phospholipase 2
What are the 2 generic names for Tylenol?
What do you use acetaminophen to treat?
- Only weakly anti-inflam
Does acetaminophen have GI side effects?
What 4 patient populations are specifically mentioned for acetaminophen use?
Patients on blood thinners (might be new genetic implications against this)
Which diseases are treated via acetaminophen for first line anti-inflam?
Neuro: cerebral edema
Transplant: prevent rejection
Skin: dermatitis & dermatoses
What can you combine acetaminophen with to enhance its pain killing effects (and in turn use less opiates)?
Would you use acetaminophen for RA or a sprained ankle?
What is the mechanism of action for acetaminophen?
Reversible inhibition of COX
What is the most concerning side effect with acetaminophen? Explain the mechanism of action.
Acetaminophen + p450 --> NAPQI = toxic metabolite
How does acetaminophen affect Stevens-Johnson syndrome?
How can the liver deal with NAPQI? Explain both hepatocyte survival and death.
1. + Glutathione
- Might be gone/low if alcoholic
W/o you'll get hetpaocyte damage. You can either:
- Fix the damage by inhibiting T cells: IL10 present
- TNF & IL1 beta present so you can't change T cells and they induce hepatocyte apoptosis
What is the body's natural steroid? Where is it made? Under the influence of what hormone? When is it produced?
Cortisol = glucocorticoid
@ Adrenal cortex (zona fasiculata)
ACTH (adrenocorticotropic hormone) from pituitary gland
For ACUTE protection in emergency
What is the most potent analog of cortisol? Name its uses. Name the diseases it treats.
Anti-inflam & IMMUNOSUPRESS
2. Bacterial meningitis for immune suppression before general antibiotics
What is the effect of cortisol on cytokines produced?
↓TNF alpha & IL6 = pro-inflam
↑IL 10 = anti-inflam
What are the 4 possible mechanisms of cortisol at the DNA?
1. DIRECT: binds gluco-corticoid receptor --> TF & binds DNA @ GRE (glucocorticoid response element) to promote synthesis of IL10/anti-inflam molecules
2. DIRECT: binds GCR --> TF @ DNA non-GRE elements (other areas)
3. INDIRECT: sequesters other TFs
4. INDIRECT: with SRC1 (steriod receptor co-activator) changes histones via acetylating & deact enzymes
What are the 2 possible mechanisms of cortisol outside the DNA (non-genomic)?
1. Interfere with membranes of the cell or mitochondria
2. Binds membrane GCPR
What glucocorticoid drug in the liver is converted by 3B-HSD? Name its uses.
Many things - Crohn's when aspirin doesn't work
What is lupus?
Autoimmune @ joints, organs, skin
What do you use to treat lupus?
Flare ups - steroids
- Prednisone = immediate relief
Remission - NSAIDs
What are some side-effects of prednisone?
Weight gain - central obesity
Which glucocorticoid is used topically?
Topical for skin rashes
When is betamethasone used as an injection?
Babies - lung maturation
What is the aerosol spray glucocorticoid? What is it used for?
What are DMARDs? What is unique about these vs NSAIDs? What are the 2 categories?
Disease modifying anti-rheumatic drugs
ALTERS the course of disease - slows/blocks progression (not a cure)
1. Small molecules
Which diseases are DMARDs first line treatment for?
What are 2 cytokines elevated in RA?
↑TNF & IL1 --> pro-inflammatory
What are the 2 small molecule DMARDs?
Methotrexate - first choice
Explain the 2 effects of methotrexate.
1. High doses = chemotherapy
No folic acid - X purine synthesis
2. Low doses - immune suppression
No folic acid - adenosine accumulation
Suppress T & B cells
What is leflunomide's mechanism? Side effects?
X pyrimidine synthesis --> no DNA synthesis --> no T/B cell proliferation
Side effects - liver & blood toxicity
What are biologics/TNFs?
Biologic response modifiers
Stop inflammation by blocking TNF, one of the cytokines it upregulates, or other molecules of the inflammatory cascade (JAK, CD80/86)
What are the 4 important TNF blocking biologics?
Adali-mu-mab & inflix-imab
TNF alpha binder
T cell death
Chimeric Ab - 1/2 mouse
RA, AS, Crohn's
Use w/ methotrexate to decrease infusion reactions
TNF alpha binder (sponge)
Less T/macrophage fxn
RA, Crohn's, psoriasis
Decoy TNF alpha recptor - binds what's soluble
Less T/macrophage fxn
RA, Crohn's, AS, etc
What are 2 biologics that bind IL6 and IL1 respective?
IL 6 = tocil-izumab
IL 1 = anak-inra
What are 2 biologics that inhibit T cells and B cells respectively?
Abatacept - inhibit T cells
- CD20 receptor = target
- Also used as cancer therapy
Rituximab - inhibit B cells