Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PDAT4 > 24 - DMARDS > Flashcards

24 - DMARDS Flashcards

1
Q

TNFR1 Function
(TNF-Receptor 1)

A

ALL CELLS HAVE THIS

TNF-a Binds
VVV
APOPTOSIS

TRADD -> death domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

MethoTrexate MoA

2nd Target

A

MTX-PG
VV–down regulates–VV
Thymidylate Synthase = TS
VVV
disrupts PYRIMIDINE SYNTHESIS
VVV
disrupts Proliferation of Anti-inflammatory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Abatacept = Orencia

MoA / Target

A

IgG domain - Fused to CTLA4
V targets V
CD80/86
which blocks the interaction with
CD28

Action:

  • *Dampents T-Cell CO-STIMULATION**
  • inhibits the production of:*
  • *TNFa / INF-y / IL-2**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

TNF-a

Functions

A

Multifuncitional Pro-inflammatory Mediator

A) Induction of further Cytokine Production

B) Activation / Expression of ADHESION molecules

C) Growth Stimulation

Key roles in:
Acute+Chronic Inflammation
Anti-Tumor Response
Infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

TNFR2 Function

TNF-a Receptor 2

A
  • *found ONLY in IMMUNE CELLS**
  • no death domain –> does NOT induce apoptosis*

Recruitment of TRAF2
VVV
Activation of NFkB Pathway
VVV
cytokines / inhibitors of apoptosis

  • *more TNF-A // IL-1**
  • *Adhesion molecules**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which DMARD?

  • weakly inhibits pro-inflammatory effects of:*
  • *Arachidonic Acid Cascade**

inhibits: ATIC & DHFR
resulting in ↑ADENOSINE release

downregulates Neutrophil:
activation / chemotaxis / migration / degranulation

  • *Immunomodulatory:
  • inhibits* T-Lymphocyte proliferation//NK-Cell Activity**
  • *B-cell activation**
A

SULFASALAZINE

Uses GUT/COLONIC BACTERIA
to breakdown SSZ
VV
5-ASA & Sulfapyridine
Antiinflammatory & Antibiotic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

HydroxyChloroQuine

Indication

A

Relatively Safe & Well Tolerated
Anti-Malarial

limited ability to prevent joint damage on THEIR OWN
SLOWEST onset of action, equal or less efficacy
Suited for:
Early / Mild RA

Usually a part of:
TRIPLE THERAPY
w/ MTX + SSZ

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Most Important

ANTI-RHEUMATIC DRUG

A

MTX

Methotrexate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

MethoTrexate

PK

A
  • *Wide Range of Bioavailability** for PO
  • worsens with INCREASED dose*

MTX half life = 6 hours
Most is excreted via URINE –> Consider Creatinine Clearance
we DONT measure SERUM MTX

MTX-PG half life = 60 DAYS
POLYGLUTAMATED MTX –> stays inside cell
we measure MTX-PG in RBC to monitor for MTX

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which DMARD?

Blocks DiHydroOrotate DeHydrogenase = DHODH
VVV
↓ PYRIMIDINE SYNTHESIS
Primarily in:
Mitogen-Stimulated T-cells
in the MITOCHONDIRA

A

LEFLUNOMIDE
Arava

Prodrug
rapidly & completely converted to
Active Metabolite @ MITOCHONDRIA

CATEGORY X

HT & HYPERcholesteremia & Weight Loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

3 Drug Strategies for
Inhibition of Cytokine Action

in RA

A

Neutrolization of Cytokines
mABs = Remicade / Humira
soluble Receptor = Enbrel

Receptor Blockade
Recept Antagonist = Kineret

Activation of Anti-Inflammatory Pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do these drugs target?

REMICADE

HUMIRA

ENBREL

CIMZIA

A

TNF-A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which DMARD?

Weak base that can INCREASE pH
within cytoplasmic vesicles –> immunoregulatory effects

  • *Attenuates AntiGen Processing & Presentation**
  • macrophages / monocytes require PRECISE pH –> digestion*
  • Inhibits proinflammatory cytokines:*
  • *IL-1 / IL-6 / INF-y**
A

HydroxyChloroQuine
HCQ

Retinal/Ocular Toxicity

Large VD / 40-50 day half life
Most excreted in:
Unchanged in Urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which Drug may be the best choice for WOMEN
Of CHILD BEARING age?

A

SSZ
sulfasalazine

Category B / C for pregnancy

REDUCED FERTILITY
In MALES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which DMARD requires COLONIC BACTERIA

A

SSZ
sulfasalazine

Colonic bacteria –> 5-asa + Sulfapyridine

Antinflammatory:
Inhibits ATIC / DHFR / AA cacade / neutrophils

Immunomodulatory:
inhibits T-lymphocytes / NK cells / B-cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Two Forms of TNF-a

A

Membrane Bound TNF-a

Soluble TNF-a
converted by TACE (TNFa Converting Enzyme)

17
Q

MethoTrexate MoA

1st Target

A

MTX-PG
VV–*INHIBITS–VV
**ATIC**
–> **↑*ADENOSINE↑**
source of anti-inflammatory effects, modulates cytokines

SUPPRESSES PRO-inflammatory mediators
IL-2 / INF-y / IL-12 / TNF-a / IL-6 / IL-8 / NO

  • *ENHANCES** production of ANTI-Inflammatory mediators
  • *IL-4** / IL-10 / IL-1 receptor antagonist
18
Q

Glucocorticoids for RA

A

One of the MOST effective:
Anti-Inflammatory**&**IMS therapies

Cornerstone for:
SLE / Vasculitis / Polymyalgia Rheumatica / Myostis

Joint Sparing Effect is based on:

  • *INHIBITION of Pro-Inflammatory Cytokines**
  • *IL-1 & TNF-a**
19
Q

Sulfasalazine

PK

A

BioAvailability of SZA = 10%
Most undergoes EnteroHepatic Circulation
& is secreted unchanged in BILE

Sulfapyridine (biproduct)
extensively metabolized in LIVER
excreted in URINE

CATEGORY B / C for Pregnancy
may be best choice for women of child bearing age
but Reduced fertility in men

20
Q

Treatment of Rheumatoid Diseases ​target WHAT?

A

Cycle of:

Proinflammatory Cytokines

Autoantibody Production

Tissue Damage

Autoaggresive T-cells

21
Q

MethoTrexate MoA

3 Targets & 3 Results

A

MTX enters cells via:
RFC (reduced folate carrier) or FR (Folate Receptor)
tries to leave via ABC but…
FPGSynthase makes …, to also prevent it from leaving
VVV
–> POLYGLUTAMATED METHOTREXATE ( MTX - PG )
which inhibits 3 targets:
ATIC –> MORE ADENOSINE
TS –> reduce PYRIMIDINE synthesis
DHFR –> inhibits TRANSMETHYLATION reactions

22
Q

Anti-Inflammatory Cytokines
in RA

A

In RA, we have a lack of these things:
want to INCREASE to balance out the Pro-Inflammatory Cytokines

IL-10

TGF-B

IL-1 receptor antagonist

sTNF-R = soluble TNF-receptor

23
Q

Infliximab = Remicade

MoA / Targets

A

CHIMERIC monoclonal AB

Binds & Neutralizes:
BOTH TNF-A’s
soluble & membrane bound

24
Q

Tocilizumab

MoA / Target

A

IL-6 RECEPTOR
approved for Arthritis

25
Q

EULAR Recommendations

for DMARD progression

3 Phases

A

wait 3-6 months BETWEEN each

Phase 1
MTX + short term Glucocorticoid
VV if 50% improvement not seen VV
Phase 2
Add SECOND DMARD or Biologic / JAK-Inhibitor
VV if 50% improvement not seen VV
Phase 3
Change or ADD - Biologic / JAK-inihbitor

26
Q

MethoTrexate MoA

1st Target

A

MTX-PG
VV–I**NHIBITS–VV
DiHydroFolate Reductase = DHFR
VVV
Methylation of RNA & DNA
VVV
disrupts
DNA Synthesis & Proliferation of Anti-Inflammatory Cells

PDAT4 (34 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions