L17

Question 1

What is the membrane derived molecule of important in anti-inflammatory drugs? What enzyme makes this?

Answer 1

Arachidonic acid
FROM membrane phospholipids w/ AA
Via phospholipase 2

Question 2

What are the 2 generic names for Tylenol?

Answer 2

Acetaminophen

Paracetamol

Question 3

What do you use acetaminophen to treat?

Answer 3

Pain
Fever
- Only weakly anti-inflam

Question 4

Does acetaminophen have GI side effects?

Answer 4

NOPE

Question 5

What 4 patient populations are specifically mentioned for acetaminophen use?

Answer 5

Kids
Pregnant women
Aspirin sensitivity
Patients on blood thinners (might be new genetic implications against this)

Question 6

Which diseases are treated via acetaminophen for first line anti-inflam?

Answer 6

1. Osteoarthritis 
Others:
Allergies: asthma
Eye: conjunctivitis
GI: IBD
Neuro: cerebral edema
Transplant: prevent rejection 
Skin: dermatitis & dermatoses

Question 7

What can you combine acetaminophen with to enhance its pain killing effects (and in turn use less opiates)?

Answer 7

Codeine

Question 8

Would you use acetaminophen for RA or a sprained ankle?

Answer 8

NO

Weak anti-inflam

Question 9

What is the mechanism of action for acetaminophen?

Answer 9

Unknown

Reversible inhibition of COX

Question 10

What is the most concerning side effect with acetaminophen? Explain the mechanism of action.

Answer 10

Liver toxicity

Acetaminophen + p450 –> NAPQI = toxic metabolite

Question 11

How does acetaminophen affect Stevens-Johnson syndrome?

Answer 11

Causes SCAR

Question 12

How can the liver deal with NAPQI? Explain both hepatocyte survival and death.

Answer 12

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

Question 13

What is the body’s natural steroid? Where is it made? Under the influence of what hormone? When is it produced?

Answer 13

Cortisol = glucocorticoid
@ Adrenal cortex (zona fasiculata)
ACTH (adrenocorticotropic hormone) from pituitary gland
For ACUTE protection in emergency

Question 14

What is the most potent analog of cortisol? Name its uses. Name the diseases it treats.

Answer 14

Dexamethasone
Anti-inflam & IMMUNOSUPRESS
1. RA/arthritis
2. Bacterial meningitis for immune suppression before general antibiotics

Question 15

What is the effect of cortisol on cytokines produced?

Answer 15

↓TNF alpha & IL6 = pro-inflam

↑IL 10 = anti-inflam

Question 16

What are the 4 possible mechanisms of cortisol at the DNA?

Answer 16

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

Question 17

What are the 2 possible mechanisms of cortisol outside the DNA (non-genomic)?

Answer 17

1. Interfere with membranes of the cell or mitochondria

2. Binds membrane GCPR

Question 18

What glucocorticoid drug in the liver is converted by 3B-HSD? Name its uses.

Answer 18

Prednisone

Many things - Crohn’s when aspirin doesn’t work

Question 19

What is lupus?

Answer 19

Autoimmune @ joints, organs, skin
Women
Butterfly rash

Question 20

What do you use to treat lupus?

Answer 20

Flare ups - steroids
- Prednisone = immediate relief
Remission - NSAIDs

Question 21

What are some side-effects of prednisone?

Answer 21

Weight gain - central obesity 
Osteoporosis 
Buffalo hump 
Can't sleep 
Etc, etc

Question 22

Which glucocorticoid is used topically?

Answer 22

Betamethasone

Topical for skin rashes

Question 23

When is betamethasone used as an injection?

Answer 23

MS flares
Babies - lung maturation
Asthma attack

Question 24

What is the aerosol spray glucocorticoid? What is it used for?

Answer 24

Fluticasone (flonase)

Allergies!

Question 25

What are DMARDs? What is unique about these vs NSAIDs? What are the 2 categories?

Answer 25

Disease modifying anti-rheumatic drugs ALTERS the course of disease - slows/blocks progression (not a cure) 1. Small molecules 2. Biologics

Question 26

Which diseases are DMARDs first line treatment for?

Answer 26

RA Lupus Crohn's Esp. methotrexate

Question 27

What are 2 cytokines elevated in RA?

Answer 27

↑TNF & IL1 --> pro-inflammatory

Question 28

What are the 2 small molecule DMARDs?

Answer 28

Methotrexate - first choice | Leflunimide

Question 29

Explain the 2 effects of methotrexate.

Answer 29

``` 1. High doses = chemotherapy No folic acid - X purine synthesis 2. Low doses - immune suppression No folic acid - adenosine accumulation Suppress T & B cells ```

Question 30

What is leflunomide's mechanism? Side effects?

Answer 30

X pyrimidine synthesis --> no DNA synthesis --> no T/B cell proliferation Side effects - liver & blood toxicity

Question 31

What are biologics/TNFs?

Answer 31

Biologic response modifiers Stop inflammation by blocking TNF, one of the cytokines it upregulates, or other molecules of the inflammatory cascade (JAK, CD80/86)

Question 32

What are the 4 important TNF blocking biologics?

Answer 32

Adali-mu-mab & inflix-imab Etaner-cept Goli-mu-mab

Question 33

``` Infliximab: Mechanism Effect Drug composition Diseases used Fun facts ```

Answer 33

``` IN-FLIXI-MAB TNF alpha binder T cell death Chimeric Ab - 1/2 mouse RA, AS, Crohn's Use w/ methotrexate to decrease infusion reactions ```

Question 34

``` Adalimumab: Mechanism Effect Drug composition Diseases used Fun facts ```

Answer 34

``` ADA-LIM-UMAB TNF alpha binder (sponge) Less T/macrophage fxn Monoclonal Ab RA, Crohn's, psoriasis ```

Question 35

``` Etanercept: Mechanism Effect Drug composition Diseases used Fun facts ```

Answer 35

ETAN-ER-CEPT Decoy TNF alpha recptor - binds what's soluble Less T/macrophage fxn RA, Crohn's, AS, etc

Question 36

What are 2 biologics that bind IL6 and IL1 respective?

Answer 36

IL 6 = tocil-izumab IL 1 = anak-inra Monoclonal Ab

Question 37

What are 2 biologics that inhibit T cells and B cells respectively?

Answer 37

Abatacept - inhibit T cells - CD20 receptor = target - Also used as cancer therapy Rituximab - inhibit B cells

Question 38

What is the biologic that blocks that JAK/STAT pathway?

Answer 38

TOFA-CITI-NIB RA when methotrexate fails Oral pill!!!