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Pharmacology > DMARDs > Flashcards

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
Q

Cyclophosphamide PK/PD

DMARDS

A

Mesna is used to treat hemorrhagic cystitis caused by cyclophosphamide

26
Q

Cyclophosphamide AE/contraindications

DMARDS

A

BM suppression, infertility
Hemorrhagic cystitis
Infection and malignancy risk
Fanconi’s anemia

27
Q

Gold sodium thiomalate & Auranofin description

DMARDS

A

Macrophage poisons with high toxicity rendering them basically obsolete

28
Q

Gold sodium thiomalate & Auranofin mechanism

DMARDS

A

Suppress phagocytosis and lysosomal enzyme activity

29
Q

Gold sodium thiomalate & Auranofin PK/PD

DMARDS

A

GST is given IM

Auranofin is oral

30
Q

Adalimumab description

DMARDS

A

Fully human IgG1 anti-TNF Ab

31
Q

Adalimumab mechanism

DMARDS

A

Binds to soluble TNF alpha preventing is interaction with receptors -> downregulation of T-cell and macrophage function

32
Q

Infliximab mechanism

DMARDS

A

Binds to soluble TNF alpha preventing is interaction with receptors -> downregulation of T-cell and macrophage function

33
Q

Etanercept mechanism

DMARDS

A

Binds to soluble TNF alpha preventing is interaction with receptors -> downregulation of T-cell and macrophage function

34
Q

Anakinra mechanism

DMARDS

A

IL-1 receptor antagonist

35
Q

Adalimumab PK/PD

DMARDS

A

Pts need to be screened for latent TB prior to and during treatment with any TNF alpha inhibitor (also used in IBD)

36
Q

Infliximab PK/PD

DMARDS

A

Pts need to be screened for latent TB prior to and during treatment with any TNF alpha inhibitor (also used in IBD)

37
Q

Etanercept PK/PD

DMARDS

A

Pts need to be screened for latent TB prior to and during treatment with any TNF alpha inhibitor (also used in IBD)

38
Q

Infliximab description

DMARDS

A

Chimeric anti TNF alpha

mouse and human

39
Q

Etanercept description

DMARDS

A

Recombinant fusion protein -> 2 TNF receptors linked to IgG1

40
Q

Adalimumab AE/contraindications

DMARDS

A

Cytopenia -> monitor CBC
Serious infection
Do not give to patients with active infection

41
Q

Etanercept AE/contraindications

DMARDS

A

Cytopenia -> monitor CBC
Serious infection
Do not give to patients with active infection

42
Q

Infliximab AE/contraindications

DMARDS

A

Cytopenia -> monitor CBC
Serious infection
Do not give to patients with active infection

43
Q

Glucocoritcoids description

DMARDS

A

Prompt and dramatic effect, but use is controversial

Not real DMARDS

44
Q

Glucocorticoids mechanism

DMARDS

A

Used for short term symptomatic relief until beneficial effects of DMARDs become apparent

Inhibit PLA2 and COX-2

45
Q

Glucocorticoids PK/PD

DMARDS

A

AE associated with long term use

Do not affect CV risk

46
Q

Glucocorticoids ae/contraindications

DMARDS

A

Osteoporosis, weight gain, ulcers, HTN, hyperglycemia, etc.

47
Q

DMARD therapy

A

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
Q

DMARD biological agents

A

Adalimumab
Infliximab
Etanercept
Anakinra

49
Q

Relief of RA

DMARDs

A

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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