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Immunology > L17 > Flashcards

L17 Flashcards

1
Q

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

A

Arachidonic acid
FROM membrane phospholipids w/ AA
Via phospholipase 2

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2
Q

What are the 2 generic names for Tylenol?

A

Acetaminophen

Paracetamol

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3
Q

What do you use acetaminophen to treat?

A

Pain
Fever
- Only weakly anti-inflam

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4
Q

Does acetaminophen have GI side effects?

A

NOPE

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5
Q

What 4 patient populations are specifically mentioned for acetaminophen use?

A

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

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6
Q

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

A 
1. Osteoarthritis 
Others:
Allergies: asthma
Eye: conjunctivitis
GI: IBD
Neuro: cerebral edema
Transplant: prevent rejection 
Skin: dermatitis & dermatoses
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7
Q

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

A

Codeine

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8
Q

Would you use acetaminophen for RA or a sprained ankle?

A

NO

Weak anti-inflam

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9
Q

What is the mechanism of action for acetaminophen?

A

Unknown

Reversible inhibition of COX

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10
Q

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

A

Liver toxicity

Acetaminophen + p450 –> NAPQI = toxic metabolite

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11
Q

How does acetaminophen affect Stevens-Johnson syndrome?

A

Causes SCAR

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12
Q

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

A
    • 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
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13
Q

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

A

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

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14
Q

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

A

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

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15
Q

What is the effect of cortisol on cytokines produced?

A

↓TNF alpha & IL6 = pro-inflam

↑IL 10 = anti-inflam

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16
Q

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

A
  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
Q

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

A
  1. Interfere with membranes of the cell or mitochondria

2. Binds membrane GCPR

18
Q

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

A

Prednisone

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

19
Q

What is lupus?

A

Autoimmune @ joints, organs, skin
Women
Butterfly rash

20
Q

What do you use to treat lupus?

A

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

21
Q

What are some side-effects of prednisone?

A 
Weight gain - central obesity 
Osteoporosis 
Buffalo hump 
Can't sleep 
Etc, etc
22
Q

Which glucocorticoid is used topically?

A

Betamethasone

Topical for skin rashes

23
Q

When is betamethasone used as an injection?

A

MS flares
Babies - lung maturation
Asthma attack

24
Q

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

A

Fluticasone (flonase)

Allergies!

25
Q

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

A

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

26
Q

Which diseases are DMARDs first line treatment for?

A

RA
Lupus
Crohn’s
Esp. methotrexate

27
Q

What are 2 cytokines elevated in RA?

A

↑TNF & IL1 –> pro-inflammatory

28
Q

What are the 2 small molecule DMARDs?

A

Methotrexate - first choice

Leflunimide

29
Q

Explain the 2 effects of methotrexate.

A 
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
Q

What is leflunomide’s mechanism? Side effects?

A

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

31
Q

What are biologics/TNFs?

A

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
Q

What are the 4 important TNF blocking biologics?

A

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

33
Q 
Infliximab:
Mechanism
Effect
Drug composition 
Diseases used
Fun facts
A 
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
Q 
Adalimumab:
Mechanism
Effect
Drug composition 
Diseases used
Fun facts
A 
ADA-LIM-UMAB
TNF alpha binder (sponge) 
Less T/macrophage fxn
Monoclonal Ab
RA, Crohn's, psoriasis
35
Q 
Etanercept:
Mechanism
Effect
Drug composition 
Diseases used
Fun facts
A

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

36
Q

What are 2 biologics that bind IL6 and IL1 respective?

A

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

37
Q

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

A

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

38
Q

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

A

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

Immunology (25 decks)

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