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Rheumatology > MKSAP 2: Principles of Therapeutics > Flashcards

MKSAP 2: Principles of Therapeutics Flashcards

1
Q

What is the general MOA of NSAIDs?

A

Cyclooxygenase inhibition to block generation of lipid prostaglandin E2 (PGE2)

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2
Q

What does PGE2 do normally?

A

Stimulates inflammation, vasodilation, smooth muscle contraction, pain and fever

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3
Q

What are the benefits of PGE2?

A

Maintains gastric mucosa and promotes kidney sodium excretion and glomerular filtration.

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4
Q

What are other beneficial COX products?

A

Thromboxane A2 - prothrombotic regulator of platelets

Prostacyclin - antithrombotic and vasodilatory lipid

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5
Q

What are the side effects of NSAID use?

A 
HTN, MI, exacerbation of HF
Bleeding
Dyspepsia, reflux, PUD, GI bleeds
Delayed labor, bleeding in labor
Asthma exacerbation
HTN, decreased GFR, salt and water retention, AIN or ATN
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6
Q

What is the benefit of selective COX-2 inhibitors?

A

less gastrotoxicity and bleeding

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7
Q

What is the official recommendation by the ACR regarding NSAID use in adults > 75 yrs old?

A

Topical NSAID use

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8
Q

What is the general rule for glucocorticoid use?

A

Lowest effective dose for shortest period possible

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9
Q

What are the side effects of long term glucocorticoid use?

A

DM, osteoporosis, weight gain, fluid retention, HTN, CVD, straie, bruising, glaucoma and cataracts

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10
Q

What other medication should you consider giving patients on long term glucocorticoids?

A

All patients should be on calcium and VitD supp
Glucocorticoids for more than 4 weeks at doses greater than 5mg of prednisone QD should be considered for bisphosphonate therapy

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11
Q

What is the MOA of colchicine?

A

Disrupts microtubules to interfere with leukocyte adhesion and migration. Also inhibition of IL-1 generation.

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12
Q

What are the conditions that colchicine is used to treat?

A

Gout, familial Mediterranean fever and hypersensitivity vasculitis

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13
Q

What is a common side effect of colchicine?

A

Diarrhea

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14
Q

What drug do you have to watch interactions with colchicine and why?

A

Clarithromycin & antiretroviral drugs (CYP3A4 inhibitors)
Cyclosporins (P-glycoprotein inhibitors)
Statins - drug induced myopathy

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15
Q

Methotrexate - description

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A

Inhibits folic acid metabolism and increases extracellular adenosine levels

  • MOA: inhibits DHFR; increases adenosine extracellularly
  • Indications: initial drug in RA, psoriatic arthritis, vasculitis and sarcoidosis, dermatomyositis, polymyositis
  • Monitoring
    - Baseline: CXR, hepatitis screening, CBC, LFTs, Scr
    - Thereafter: CBC, LFTs, Scr q3 months
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16
Q

Hydroxychloroquine - description

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A

Antimalarial med that appears to inhibit antigen processessing

  • MOA: stabilization of lysosomal vacuoles
  • Indications: SLE (skin and joint disease, prevent systemic and organ specific flare ups and reduce mortality; used alone or in combo with methotrexate or sulfasalazine to treat undifferentiated CTD, RA and inflammatory arthritis
  • Monitoring
    - Baseline: CBC, LFTs, Scr
    - Thereafter: yearly eye exam to watch for hydroxychloroquine eye deposition
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17
Q

Sulfasalazine - description

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A

Exerts systemic effects through its metabolite sulfapyridine an dintracolonic effects via the salicylate moiety

  • MOA: a pro-drug broken down into 5-amino salicylic acid (active in GI tract) and sulfapyridine (systemic effects)
  • Indications: RA with or without methotrexate, SpA and IBD
  • Monitoring - GI upset, HA, agranulocytosis, hepatitis, reversible oligospermia
    - Baseline: CBC, LFTs, Scr
    - Thereafter: CBC, LFTs, Scr q3 months
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18
Q

Leflunomide - description

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A
  • MOA: blocks lymphocyte activation by blocking the pyrimidine synthesis pathways
  • Indications: RA (comparible to methotrexate)
  • Monitoring - GI upset, diarrhea, aminotransferase elevations, cytopenias, infection and teratogenesis
    - Baseline: CXR, hepatitis screening, CBC, LFTs, Scr
    - Thereafter: CBC, SCr q3 months, LFTs q 8-12 weeks and temporarily or permanently stop if LFTs > 2x normal and treat with cholestyramine for elevations > 3x normal
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19
Q

Azathiaprine - description

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A
  • MOA: purine analogue that inhibits nucloetide synthesis
  • Indications: maintain control of SLE, vasculitis, inflammatory myopathies, and other autoimmune diseases
  • Monitoring - GI upset, diarrhea, aminotransferase elevations, cytopenias, infection and teratogenesis** Avoid coadministration with allopurinol/febuxostat bc they compete for same metabolic pathway
    - Baseline: CBC, LFTs, Scr
    - Thereafter: CBC, LFTs, Scr q3 months
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20
Q

Cyclophosphamide

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A
  • MOA: DNA alkylating agent with potent immunosuppressive properties
  • Indications: severe & life threatening manifestations of SLE (nephritis), systemic sclerosis, inflammatory myopathies, ILD and vasculitis
  • Monitoring - bone marrow suppression, leukopenia, anemia, infections, infertility, hemorrhagic cystitis and bladder cancer, lymphoma and other malignancies. Patients with painless hematuria and hx of cyclophosphamide use should have cystoscopy
    - CBC, chem, LFTs, UA q 3 months
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21
Q

Mycophenolate mofetil

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A
  • MOA: inhibits purine pathway of nuclotide synthesis
  • Indications: may be as effective as cyclophosphamide for SLE (including nephritis) but with milder side effects; autoimmune myositis and glucocorticoid sparing agent in systemic vasculitis
  • Monitoring - diarrhea, cytopenias, infection
    - Baseline: CBC, LFTs, SCr
    - Thereafter: CBC. LFTs, Scr q2-3 months
22
Q

Cyclosporine - description

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A
  • MOA: calcineurin and T lymphocyte inhibitor
  • Indications: RA, SLE, autoimmune myositis, psoriasis and IBD; third line agent due to toxicities
  • Monitoring: nephrotoxic, HTN, tremors, hirsutisim
    - Baseline: CBC, LFTs, SCr
    - Thereafter: CBC. LFTs, Scr q2-3 months
23
Q

Apremilast

  • MOA
  • Indications
  • Monitoring
    - Baseline
    - Thereafter
A
  • MOA: inhibits phosphodiesterase 4 which increases cAMP which inhibit inflammatory responses
  • Indications: psoriasis and psoriatic arthritis
  • Monitoring
    - Baseline: weight
    - Thereafter: weight, neuropsychiatric effects
24
Q

What do the suffixes of the biologic DMARDs mean?

  • “mab”
  • “cept”
A
  • “mab” = monoclonal ab

- “cept” = receptor derived

25
Q

What are the general recommendations for using biologic DMARDs?

A

They should be interrupted during any infection and/or procedures.
Concurrent use of 2 or more biologic agents is contraindicated

26
Q

What are the 5 TNF-alpha inhibitors FDA approved to treat RA, psoriatic arthritis and AS

A

Infliximab - Remicade
Etanercept - Enbrel
Adalimumab - Humira
Golimumab - Simponi
Certilizumab = Cimzia
Decrease disease activity and inhibit progression of structural damage in RA most effectively in combo with methotrexate
Psoriasis/PA: suppress cutaneous and articular disease
AS: improve axial and peripheral joint symptoms
Off label in uveitis, Behcet syndrome, sarcoidosis, IBD and pyoderma syndromes

27
Q

What are common and rare toxicities for the TNF alpha inhibitors?

A

Risk of TB, hepatitis B reactivation, fungal (aspergillosis, histoplasmosis, coccidiomycosis) and bacterial infections. Injection site and infusion reactions, leukopenia, DILE and heart failure. Rare: psoriasiform skin erruptino and demyelinating syndromes. Skin cancer increased risk.

28
Q

Abatacept (Actemra)

A

Interferes with antigen presentation to T cells. Indicated for moderate to severe RA in patients with inadequate response to methotrexate and/or TNF alpha inhibition .
Increased risk of infection and COPD exacerbation. Increased risk of lymphoma and lung cancer

29
Q

Rituximab (Rituxan)

A

Depletes B cell populations and used in combo with methotrexate to treat RA in patients who have not responded to methotrexate and/or TNF alpha
Also used for ANCA associated vasculitis, SLE and sarcoidosis.
Can cause severe infusion reactions; rare: progressive multifocal leukoencephalopathy. Not associated with increased infections.

30
Q

Tocilizumab (Actemra)

A

Block IL-6 receptors. Used to treat RA in patients not responsive to TNF alpha inhibition. Associated with elevated LFTs, leukopenia, thrombocytopenia and elevated lipid levels. Reactivation of TB and invasive fungal infections. Rare: colon or small bowel perf in hx diverticulitis

31
Q

Tofacitinib (Xeljanz)

A

Orally available small molecule agent to treat moderate to severe RA in patients with inadequate response to methotrexate. Works to inhibit JAK pathway signaling (which inhibits T-cell/T-cell interaction.
Bone marrow suppression and elevated LFTs
TB, fungal infections, lipid abnormalities and intestinal perforation risk.

32
Q

Ustekinumab (Stelara)

A

An anti-IL-12/IL-23 ab FDA approved for active psoriatic arthritis and moderate to severe plaque psoriasis. Administered subQ q12 weeks.
Serious infections uncommon but have been reported.

33
Q

Anakinra (Kineret)

A

IL -1 beta inhibitor. FDA approved for RA but infrequently used due to limited efficacy.
Approved for cryopyrin associated periodic fever syndrome (neonatal onset multisystem inflammatory disease). Off label for Muckle Wells syndrome, familial cold autoinflammatory syndrome and adult onset Still disease. Also off label for severe cases of gout refractory to other therapies.

34
Q

Rilonacept

A

IL-1 beta inhibitor. also beneficial in treatment of cryopyrin associated periodic fever syndrome

35
Q

Canakinumab (Ilaris)

A

IL-1 beta inhibitor. also beneficial in treatment of cryopyrin associated periodic fever syndrome

36
Q

Belimumab (Benlysta)

A

Anti-BLyS (B lymphocyte stimulator) antibody FDA approved to treat active SLE in patients on standard therapy. Cytopenias and infection may occur. In one trial, Benlysta failed to demonstrate efficacy among black patients with SLE.

37
Q

What are the principles for immunization of patients on nonbiologic vs biologic DMARDs?

A
  • Patients should be brought up to date on vaccines prior to starting immunosuppressive therapy
  • Patients on nonbiologic DMARDs can receive vaccines of all types
  • The use of live attenuated vaccines (HZV, yellow fever) is contraindicated in patients on biologic DMARDs; they can get these vaccines 4 weeks prior to starting the med
38
Q

What screening needs to be done for patients prior to starting immunosuppressive meds?

A
  • Tb screening with skin test or interferon gamma release assay
  • Hep B & C serologies
  • HIV
  • Strongyloides screening in patients from endemic areas (tropical and subtropical regions)
39
Q

What are the indications for starting urate lowering therapy according to ACR guidelines?

A

Patients with gout with:

  • 2 or more attacks within a 1 year period
  • 1 attack in the setting of CKD 2 or worse
  • 1 attack with the presence of tophi visible on exam or imaging
  • 1 attack with history of urolithiasis
40
Q

What is the urate level to target?

A

6.0 mg/dL

41
Q

Allopurinol

  • MOA
  • contraindication
  • other meds to avoid
A
  • MOA: first line therapy for serum urate reduction; purine analogue that inhibits xanthine oxidase (final enzyme in the pathway of urate synthesis from purine precursors)
  • severe hypersensitivity reaction with fever, lymphadenopathy, widespread erythema, purpura and skin necrosis (discontinue with any sign of rash)
  • other purine analogues such as azathiaprine or 6-MP
42
Q

What is the ACR recommended dosing and titration regimen for allopurinol?

A

Starting dose of 100mg/d (50 mg/d in CKD 4-5) with a urate check and titration upward q2-5 weeks until a target level of 6.0 mg/dL or less is achieved.

43
Q

Febuxostat

  • MOA
  • cautions
  • other meds to avoid
A

Alternative first line therapy for urate lowering. Non-purine, non-competitive xanthine oxidase inhibitor
Less likely to cause hypersensitivity reactions.
Used for patients with adverse reactions to allopurinol.
Avoid with azathiaprine or 6-MP

44
Q

Probenecid

A

2nd line agent that promotes kidney uric acid excretion (uricosuric effect). May be used with xanthine oxidase inhibitor for synergistic effect. Limited efficacy in patients with creatinine clearance < 50ml/min and contraindicated in patients with kidney stones or hyperuricosuria.

45
Q

Pegloticase

A

recombinant pegylated uricase that dramatically lowers serum urate
Indicated for patients with persistently moderate to severe gout who have failed standard ULT.
If serum urate levels increase to > 6.0, suggests failure of the drug due to immunogenicity and patient at risk for immune reactions and requires discontinuation

46
Q

Anti-inflammatory agents in pregnancy:

  • NSAIDS
  • glucocorticoids
  • Colchicine
A

NSAIDs small risk of miscarriage before 20 weeks, after 30 weeks can cause premature closure of ductus arteriosus
Glucocorticoids - risk of cleft palate & gestational DM but can be used
Colchicine: C, only use if benefit outweighs risk

47
Q

Analgesics in pregnancy

  • acetaminophen
  • opiates
  • tramadol
  • topical agents
A
  • acetaminophen: B; generally safe
  • opiates: various; fetal opioid withdrawal
  • tramadol: C; only use if benefit outweighs risk
  • topical agents: various; depends on dosage
48
Q

Nonbiologic DMARDs in pregnancy

  • Methotrexate
  • Hydroxychloroquine
  • sulfasalazine
  • leflunomide
  • azathioprine
  • cyclophosphamide
  • mycophenolate mofetil
  • cyclosporine
A
  • Methotrexate: X; stop 3 months before pregnancy
  • Hydroxychloroquine: C; relatively safe and should not be discontinued
  • sulfasalazine: B; relatively safe in pregnanacy
  • leflunomide: X; not to be used before/during pregnancy; cholestyramine is required to remove drug from body of women of childbearing age, and check levels
  • azathioprine; D; routine use not recommended but if only option, if imperatively needed
  • cyclophosphamide: D; not used unless necessary
  • mycophenolate mofetil: D; stop 3 months before pregnancy
  • cyclosporine: C; may be used if benefit outweigh risk
49
Q

Biologic DMARDs in pregnancy

  • TNF- alphas
  • Ustekinumab, anakira
  • abatacept, rituximab, tocilizumab, belimumab, tofacitinib, rilonacept, canakinumab
A
  • TNF- alphas: B; can be continued if absolutely needed
  • Ustekinumab, anakira: B; should be used if benefit outweighs risk
  • abatacept, rituximab, tocilizumab, belimumab, tofacitinib, rilonacept, canakinumab; C; should be used only if benefit outweighs risk
50
Q

ULT in pregnancy

  • allopurinol
  • febuxostat
  • probenecid
  • pegloticase
A
  • allopurinol: C; should be used only if benefit outweighs risk
  • febuxostat: C; should be used only if benefit outweighs risk
  • probenecid: B; no adverse effect known
  • pegloticase: C; should be used only if benefit outweighs risk
51
Q

Which agents are category X in pregnancy? If leflunomide is inadverently used, what med is given?

A

Methotrexate, leflunomide

cholestyramine

Rheumatology (15 decks)

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