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MSK II: Test 2 > Pharm: Drugs for Rheumatic Diseases > Flashcards

Pharm: Drugs for Rheumatic Diseases Flashcards

1
Q

Hydroxychloroquine - HCQ

A

Nonbiologic DMARDs-
**ok for pregnancy, but less effective than MTZ and LEF

MOA: unsure, but may suppress T cells responses, decreased leukocyte chemotaxis, inhibition of DNA/RNA synthesis and trapping of radicals

  • takes 3-6 mos

AE’s:

  • ocular toxicity, need opthalmalogic monitoring
  • dyspepsia, nausea, vomiting, ab pain, rashes, nightmares
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2
Q

Leflunomide - LEF

A

Nonbiologic DMARDs

** as effective as MTX **

MOA: prodrug converted to active matbolite, A77-1726, in the intestine and plasma –> inhibits dihydroorotate dehydrogenase, leading to reduced ribonucleotide synthesis and cell arrest at G1
__ ultimately T cell and B cell production of autoAbs are inhibited ___

reponds in 6-12 weeks

response rates are better with MTX + LEF (but hepatotoxicity is increased)

AEs: diarrhea is very common! **liver enzymes elevated, mild alopecia, weight gain, increased BP, leukopenia, thrombocytopenia

CI in pregnancy!!!

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3
Q

** Methotrexate - MTX

A

Nonbiologic DMARDs

** first line DMARD for RA**

MOA: inhibits dihydrofolate reductase that results in impaired DNA synthesis causing cell death

  • at low levels works as anti-inflammatory w/ increased extracellular levels of adenosine
  • also inhibits proliferation and stimulates apoptosis in immune-inflamm. cells
  • works within 4-6 weeks

AE’s: common: nausea, upset stomach, loose stools, stomatitis or soreness of mouth, alopecia, fever, macular punctate rash (usually on extremities); headache, fatigue

  • hepatic enzymes elevated, should discourage drinking alcohol: hepatotoxicity
  • pulmonary damage rare
  • myelosupression is less frequent with low-dose therapy (red blood cell macrocytosis, leukopenia, anemia, thrombocytopenia)
  • nephrotoxicity rare

** Folic acid used to reduce SE **

CI in pregnancy !!

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4
Q

Sulfasalazine - SSZ

A

Nonbiologic DMARDs -

**ok for pregnancy, but less effective than MTZ and LEF

MOA: ?? decreased IgA and IgM RF production, supression of T and B cell proliferation
- takes 1-3 mos.

AE: causes MORE toxicity than HCQ

  • nausea, vomiting, h/a, anorexia, rash
    • reversible infertility in men
    • safe in pregnancy
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5
Q

Rarely used DMARds

A
  1. Azathioprine: immunosuppressive purine, reserved for pts. w/ refractory RA, risk of lymphoma, CI in pregnancy
  2. Cyclosporine: peptide antibiotic that inhibits T cell activation - has nephrotoxicity and DDI’s
  3. Gold salts: can induce remission, but has lots of SE’s: enterocolitis, anaplastic anemia, interstitial pneumonitis
    - only used in severe disease if can’t tolerate other things
  4. minocycline: unlabeled use
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6
Q

Adalimumab

A

TNF-alpha blocking Biologic DMARDs

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7
Q

Certolizumab

A

TNF alph blocking Biologic DMARDs

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8
Q

Etanercept

A

TNF alph blocking Biologic DMARDs

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9
Q

Golimumab

A

TNF alph blocking Biologic DMARDs

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10
Q

Infliximab

A

TNF alph blocking Biologic DMARDs

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11
Q

Abatacept

A

Biologic DMARDs: T-cell Fc fusion

MOA: prevents T cell activation
- genetically engineered fusion protein composed of the extracellular domain of the CTLA-4 receptor and the Fc region of human IgG1; CTLA-4 is normally expressed by Helper T cells and binds to CD80 and CD86 on antigen-presenting cells resulting in inhibition of T cells; CD28 is similar to CTLA-4 and also binds CD80 and CD86, but transmits a stimulatory signal; abatacept binds to CD80 and CD86, inhibiting binding to CD28 and preventing T-cell activation

response time: nearly immediately, but can take 6 mos. for full effect

Uses: if refractory to nonbiologic DMARDs or anti-TNF agents

AE’s: HTN, H/a, dizziness, anaphylactoid rxns
- increased risk of pneumonia, pyelonephritis, cellulitis, diverticulitis

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12
Q

Rituximab

A

Biologic DMARDs: anti-CD20 mAb

MOA: chimeric monoclonal antibody that depletes CD20-expressing B lymphocytes through cell-mediated and complement-dependent cytotoxicity and stimulation of apoptosis; B cell depletion reduces inflammation by decreasing the presentation of antigens to T cells and inhibiting the secretion of proinflammatory cytokines

response time is 6 weeks

USE: pts refractory to nonbio DMARDs or TNF-alpha agents

AE’s: infusion rashes, increased risk of infections

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13
Q

Tocilizumab

A

Biologic DMARDs: anti-IL-6 mAb

MOA: humanized monoclonal Ab that inhibits signaling of IL-6 receptor

takes 6-12 weeks

Use: refractory pts.

AEs: infusion rxns, HTN, neutropenia, dysplipidemia, GI perforation, serious infections

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14
Q

Celecoxib

A

NSAID - COX2 specific inhibitor, decreased GI problems

used as adjunct for anti-inflammatory, and decreased pain

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15
Q

Ibuprofen

A

NSAID - management of pain and inflammatory process in RA

** has higher GI toxicity **

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16
Q

Naproxen

A

NSAID - - management of pain and inflammatory process in RA

17
Q

Prednisone

A

Corticosteroid (oral)

Systemic AE’s: osteoporosis, weight gain, fluid retention, cataracts, glaucoma,poor wound healing, hyperglycemia, hypertension, adrenal suppression and increased risk of infection

Use: syptomatic relief of RA, slows progression

18
Q

Methylprednisolone

A

Corticosteroid (oral and also IV)

Systemic AE’s: osteoporosis, weight gain, fluid retention, cataracts, glaucoma,poor wound healing, hyperglycemia, hypertension, adrenal suppression and increased risk of infection

Use: syptomatic relief of RA, slows progression

19
Q

Triamcinolone

A

Corticosteroid (intra-articular)

Use: syptomatic relief of RA, slows progression

20
Q

Drugs used in acute gout?

A

NSAIDs (naproxen, indomethacin, NOT aspirin)
Colchicine
Corticosteroids - provide rapid pain relief

21
Q

Colchicine

A

used for acute gout

toxic! but used in pts. with NSAID CI’s (GI adverse effects)

** relieves pain and inflamm. of gouty arthritis in 12-24 hours

MOA: binds to tubulin and prevents polymerization into MT’s, leading to inhibition of leukocyte migration and phagocytosis

Use: second-line therapy for acute gout (behind NSAIDs), should be initiated w/in 12-24 hours or onset of sx

AE’s: more toxic!!!
- diarrhea, nausea, vomiting, ab. pain
hepatic necrosis, ARF, DIC, seizures
OD = burning throat pain, bloody diarrhea, shock, hematuria, CNS depression

22
Q

Allopurinol

A

prevention of recurrent gout (don’t use for acute attack, can cause precipitation of urate in the beginning)

MOA: purine analog that competitively and irreversibly inhibits xanthine oxidase (prevents formation, thus effective in ALL cases)

**standard of care therapy for gout during the period b/w acute episodes

AE’s: acute gouty arthritis, GI intolerance, nausea, vomiting, diarrhea, allergic rash

23
Q

Febuxostat

A

prevention of recurrent gout

MOA: non-purine xanthine oxidase inhibitor (prevents formation)

AE’s: precipitate acute gouty arthritis, well tolerated - some diarrhea, h/a, nausea

24
Q

Pegloticase

A

prevention of recurrent gout - recombinant uricase for tx of severe chronic gout refractory to conventional antihyperuricemic therapy

MOA: recombinant mammalian uricase - uricase converts uric acid to allantoin (normally absent in humans) - IV dosing every 2 weeks reduces urate levels

AE’s: acute gouty arthritis, infusion reactions, Ab formation

** don’t use if have G6PD deficiency for concern of hemolytic anemia

25
Q

Probenecid

A

prevention of recurrent gout

  • only potent uricosic agent
  • indicated in pts. w/ impaired renal excretion of uric acid (85-90% of cases)

MOA: an organic acid that acts at the anionic transport sites of the renal tubules to reduce reabsorption of uric acid; tophaceous deposits of urate are reabsorbed

AE’s:
** likelihood of renal stone formation d/t increased uric acid secretion
GI irritation and rash

26
Q

38 y/o woman presents w/ 2 mos hx of pain and swelling in both hands, generalized fatigue, body weight loss, body aches, tenderness in MCP and PIP joints in hands. imaging shows erosions in MCP joints/PIPs, labs are RF+, Anti-CCP +

tx includes MTX, what is the main goal for use of MTX?

A

Slow, stop and possibly reverse joint pathology in RA

27
Q

DMARDs

A

slow, stop and possibly reverse damage of joint pathology in RA - most common is MTX

  • suppress the immune system possibly at low levels
  • in general pretty slow acting (1-6 mos) after initiating therapy

common AE: low dose causes stomatitis

4 main DMARDs: MTX, LEF, HCQ, SSZ!!! – lots of combinations of these 4

MTX and LEF are MOST effective: but worry about elevation of liver enzymes (or pregnant pt.) when used together
- these are both CI’s in pregnancy!!! category X

HCQ and SSZ are safe in pregnancy: category B
- but overall less effective than MTX and LEF

28
Q

what reduces the SE of MTX?

A

Folic Acid supplementation

or

Folinic Acid (Leukovorin)

29
Q

role of NSAIDs in tx of RA?

A

have immediate analgesic and anti-inflamm effects, but don’t effect disease progression

typically used during DMARD induction, during transition to a different DMARD, or during disease flares

  • ibuprofen, naproxen, diclofenac

** worry about GI irritation **
(Celecoxib has less GI problems)

  • no oral NSAID is consistently more effective than others; choice based on toxicity
30
Q

which TNFalpha blocking agent is best?

A

there is no single one! adalimumab, certolizumab, enanercept, golimumab and infliximab all used equally

31
Q

AE of etanercept most likely?

A

opportunistic infection — must screen for latent TB before starting therapy!!!

32
Q

first line therapy for tx of acute gout?

A

NSAIDs!!

naproxen and indomethacin are most commonly used

** don’t use aspirin b/c can inhibit urate excretion!!

33
Q

what if can’t use NSAIDs for tx of acute gout d/t active peptic ulcer disease?

A

use Colchicine

MOA: inhibits microtubule polymerization
- used to be first line, but is pretty toxic - can cause hepatic necrosis, ARF, DISC, diarrhea, nausea, vomiting, abdominal pain

34
Q

which agent most likely to be effective in lowering urate levels, regardless of the pathophysiology of hyperuciemia?

A

allopurinol
(MOA: Xanthine oxidase inhibitor, works through decreased uric acid production) - effective in ALL cases

not as often used: probenecid- (whereas uricosuric agents inhibit the reabsorption of uric acid - they act at transporters in renal tubules, thus don’t prevent the production of uric acid) - these are indicated in 90%, but wouldn’t be indicated in cases where there is increased production of uric acid
- also they are CI in those with renal stones

NEVER GIVE THEM DURING AN ACUTE ATTACK!!! can result in increased precipitaiton of uric acid in the beginning

35
Q

std tx for RA?

A 
MTX and/or LEF (HCQ and SSZ are safer, less efficacious)
\+
corticosteroid to relive joint sx
\+ 
NSAID for pain relief and anti-inflamm.

add biologic DMARD (etanercept, infliximab, adalimumab, golimumab, certolizumab) after inadquate response to non-biologic DMARD
- etancercept is common first choice b/c rapid onset of action and shorter half-life

36
Q

TNF alpha inhibitors

A

= Biologic DMARD’s
- mab (monoclonal Abs) and etanercept

TNF is a pro-inflamm. cytokine predominent in RA - regulates immune cells by binding to TNFR - can induce cell death and inflammation

MOA: prevent binding of TNF-alpha to TNF receptors, resulting in down-regulation of macrophages and T-cells

** much faster response than nonbiologic DMARDs** 1-2 week response time

  • often used in combo w/ MTX (do NOT use in combination w/ each other)

Common AE’s:

  • cytopenias: CBC should be monitored regularly
  • SERIOUS INFECTION! bacterial sepsis and TB (must be screened for TB first)
  • increased dissemination of infection

Rare AE’s:

  • malignancies, lymphomas
  • lupus
  • heart failure
  • demylinating syndromes
37
Q

xanthine oxidase inhibitors vs. uricosuric agents

A

xanthine oxidase inhibitor: allopurinol
- MOA: decreased uric acid production - first line for tx of gout, used in ALL gout

ucircosuric agents: probenecid

  • inhibits reabosorption of uric acid in kidney
  • increased likelihood of renal stone formation
38
Q

response time in DMARDs?

A

Nonbiologic DMARDs are slowest (1-6 months)

Biologic DMARDs are faster (1-2 weeks); some patients report improvement after the first dose

MSK II: Test 2 (4 decks)

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