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Flashcards in L17 Deck (38)
1

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

Arachidonic acid
FROM membrane phospholipids w/ AA
Via phospholipase 2

2

What are the 2 generic names for Tylenol?

Acetaminophen
Paracetamol

3

What do you use acetaminophen to treat?

Pain
Fever
- Only weakly anti-inflam

4

Does acetaminophen have GI side effects?

NOPE

5

What 4 patient populations are specifically mentioned for acetaminophen use?

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

6

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

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

7

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

Codeine

8

Would you use acetaminophen for RA or a sprained ankle?

NO
Weak anti-inflam

9

What is the mechanism of action for acetaminophen?

Unknown
Reversible inhibition of COX

10

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

Liver toxicity
Acetaminophen + p450 --> NAPQI = toxic metabolite

11

How does acetaminophen affect Stevens-Johnson syndrome?

Causes SCAR

12

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

13

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

14

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

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

15

What is the effect of cortisol on cytokines produced?

↓TNF alpha & IL6 = pro-inflam
↑IL 10 = anti-inflam

16

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

17

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

18

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

Prednisone
Many things - Crohn's when aspirin doesn't work

19

What is lupus?

Autoimmune @ joints, organs, skin
Women
Butterfly rash

20

What do you use to treat lupus?

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

21

What are some side-effects of prednisone?

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

22

Which glucocorticoid is used topically?

Betamethasone
Topical for skin rashes

23

When is betamethasone used as an injection?

MS flares
Babies - lung maturation
Asthma attack

24

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

Fluticasone (flonase)
Allergies!

25

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
2. Biologics

26

Which diseases are DMARDs first line treatment for?

RA
Lupus
Crohn's
Esp. methotrexate

27

What are 2 cytokines elevated in RA?

↑TNF & IL1 --> pro-inflammatory

28

What are the 2 small molecule DMARDs?

Methotrexate - first choice
Leflunimide

29

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

30

What is leflunomide's mechanism? Side effects?

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

31

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)

32

What are the 4 important TNF blocking biologics?

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

33

Infliximab:
Mechanism
Effect
Drug composition
Diseases used
Fun facts

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

34

Adalimumab:
Mechanism
Effect
Drug composition
Diseases used
Fun facts

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

35

Etanercept:
Mechanism
Effect
Drug composition
Diseases used
Fun facts

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

36

What are 2 biologics that bind IL6 and IL1 respective?

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

37

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

38

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

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