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DMARDs Flashcards

1
Q

Methotrexate (MTX) description

DMARD

A

DOC -> first DMARD prescribed for mild, moderate or severe RA

Decreases purine synthesis

Decrease toxicity with leucovorin or folic acid

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2
Q

Methotrexate Mechanism

DMARD

A

Inhibits AICAR transformylase -> final step in de novo purine synthesis forming IMP

Also leads to the accumulation of adenosine which is a potent anti inflammatory mediator -> decrease NF-kB

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3
Q

Methotrexate PK/PD

DMARD

A

Requires much lower dose than what is needed to CA chemotherapy -> inhibits DHF reductase

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4
Q

Methotrexate AE/contraindications

A

Nausea, ulcers
Hepatotoxicity (dose related)
Pseudolymphomatous rxn

Contraindicated in pregnancy

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5
Q

Leflunomide description

DMARDS

A

Prodrug converted to an active metabolite

Cells are arrested in G1

Decreases pyrimidine synthesis

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6
Q

Leflunomide mechanism

DMARDS

A

Inhibits dihydroorotate dehydrogenase -> decrease UMP

Inhibits autoimmune T&B cell proliferation which have increased need for DNA precursors (other cell are able to maintain basal pyrimidine requirements through salvage pathways)

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7
Q

Leflunomide PK/PD

DMARDS

A

Can cause severe hepatotoxicity when combine with MTX

Monitor CBC and LFT’s

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8
Q

Leflunomide AE/contraindications

DMARDS

A 
Frequent diarrhea
Alopecia, rash
Myelosuppression
Increase aminotransferase activity
*Contraindicated in pregnancy*
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9
Q

Hydroxychloroquine description

DMARDS

A

Often used with MTX and sulfasalazine

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10
Q

Hydroxychloroquine PK/PD

DMARDS

A

Ophthalmology exam before treatment and annually thereafter for high risk pts

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11
Q

Hydroxychloroquine AE/contraindications

DMARDS

A
  • *Hemolysis in patients with decreased G6PD**

* *Retinal damage** is rare

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12
Q

Sulfasalazine description

DMARDS

A

In contrast to use for the treatment of ulcerative colitis, Sulfapyridine is the active DMARD

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13
Q

Sulfasalazine PK/PD

DMARDS

A

Diazo bond metabolized by bacteria in colon to sulfapyridine and 5-ASA

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14
Q

Sulfasalazine AE/contraindications

DMARDS

A 
Nausea, anorexia, rash
Hepatitis, leukopenia
*Lupus like syndrome*
*Hemolysis in decrease G6PD*
****Safe in pregnancy*****
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15
Q

Cyclosporine description

DMARDS

A

Inhibits Ag triggered signal transduction in T cells

Only used in severe cases

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16
Q

Cyclosporine mechanism

DMARDS

A

Forms a comlpex with cyclophilin -> prevents calcineurin from desphosphorylating NFAT -> decrease IL-2

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17
Q

Cyclosporine PK/PD

DMARDS

A

Many drug interactions and widespread nephrotoxicity -> limited use

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18
Q

Cyclosporine AE/contraindications

DMARDS

A

Nephrotoxicity
Hirsutism & gum hyperplasia
Tremor, HTN, hyperglycemia, hyperlipidemia, osteoporosis

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19
Q

Azathioprine description

DMARDS

A

Purine antimetabolite

Only used in cases of refractory RA

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20
Q

Azathioprine mechanism

DMARDS

A

Converted to 6-MP -> inhibition of de novo purine synthesis -> suppression of T & B cells

21
Q

Azathioprine PK/PD

DMARDS

A

Reduce dose in pts taking allopurinol due to inhibition of xanthine oxidase

22
Q

Azathioprine AE/contraindications

DMARDS

A

BM suppression
GI disturbance
Infection and malignancy risk

23
Q

Cyclophosphamide description

DMARDS

A

Generally limited to the most severe cases of RA

24
Q

Cyclophosphamide mechanism

DMARDS

A

Alkylating agents -> cross links DNA -> prevents cell replication

25
Cyclophosphamide PK/PD | DMARDS
*Mesna* is used to treat hemorrhagic cystitis caused by cyclophosphamide
26
Cyclophosphamide AE/contraindications | DMARDS
BM suppression, infertility **Hemorrhagic cystitis** Infection and malignancy risk **Fanconi's anemia**
27
Gold sodium thiomalate & Auranofin description | DMARDS
**Macrophage poisons** with high toxicity rendering them basically obsolete
28
Gold sodium thiomalate & Auranofin mechanism | DMARDS
Suppress phagocytosis and lysosomal enzyme activity
29
Gold sodium thiomalate & Auranofin PK/PD | DMARDS
GST is given IM | Auranofin is oral
30
Adalimumab description | DMARDS
Fully human **IgG1 anti-TNF Ab**
31
Adalimumab mechanism | DMARDS
Binds to soluble TNF alpha preventing is interaction with receptors -> *downregulation of T-cell and macrophage function*
32
Infliximab mechanism | DMARDS
Binds to soluble TNF alpha preventing is interaction with receptors -> *downregulation of T-cell and macrophage function*
33
Etanercept mechanism | DMARDS
Binds to soluble TNF alpha preventing is interaction with receptors -> *downregulation of T-cell and macrophage function*
34
Anakinra mechanism | DMARDS
IL-1 receptor antagonist
35
Adalimumab PK/PD | DMARDS
Pts need to be *screened for latent TB* prior to and during treatment with any TNF alpha inhibitor (also used in IBD)
36
Infliximab PK/PD | DMARDS
Pts need to be *screened for latent TB* prior to and during treatment with any TNF alpha inhibitor (also used in IBD)
37
Etanercept PK/PD | DMARDS
Pts need to be *screened for latent TB* prior to and during treatment with any TNF alpha inhibitor (also used in IBD)
38
Infliximab description | DMARDS
Chimeric anti TNF alpha | mouse and human
39
Etanercept description | DMARDS
Recombinant fusion protein -> 2 TNF receptors linked to IgG1
40
Adalimumab AE/contraindications | DMARDS
Cytopenia -> monitor CBC *Serious infection* Do not give to patients with active infection
41
Etanercept AE/contraindications | DMARDS
Cytopenia -> monitor CBC *Serious infection* Do not give to patients with active infection
42
Infliximab AE/contraindications | DMARDS
Cytopenia -> monitor CBC *Serious infection* Do not give to patients with active infection
43
Glucocoritcoids description | DMARDS
Prompt and dramatic effect, but use is controversial | Not real DMARDS
44
Glucocorticoids mechanism | DMARDS
Used for *short term symptomatic relief* until beneficial effects of DMARDs become apparent Inhibit PLA2 and COX-2
45
Glucocorticoids PK/PD | DMARDS
AE associated with long term use Do not affect CV risk
46
Glucocorticoids ae/contraindications | DMARDS
Osteoporosis, weight gain, ulcers, HTN, hyperglycemia, etc.
47
DMARD therapy
More effect if combination than monotherapy without significanly increasing toxicity Combo typically includes MTX and another agent MTX + leflunomide can increase risk for hepatoxicity **Never use multiple biological agents in combination therapy**
48
DMARD biological agents
Adalimumab Infliximab Etanercept Anakinra
49
Relief of RA | DMARDs
NSAIDs off symptomatic relief of RA, but have little effect on progression of disease DMARDs have no immediate analgesic effect, but can *control symptoms and delay progression* of disease Typically takes 6 weeks to 6 months for DMARD clinical effects to be seen, but some of the biologic DMARDs can have effects within 2 weeks

Pharmacology (24 decks)

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