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Pharmacology > MCPHS PA Pharmacology Gout DMARD Drug Info Exam 3 > Flashcards

MCPHS PA Pharmacology Gout DMARD Drug Info Exam 3 Flashcards

1
Q

WHat must be present for a Diagnosis of Gout?

A

Hyperuricemia

Plus

Deposition of monosodium urate crystals

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2
Q

What are normal uric Acid Levels?

A

Men

2.5-8.0 mg/dL

Women

1.5-6.0 mg/dL

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3
Q

What are the two types of Gout?

A

Acute Gout (Gouty Arthritis)

Severe Pain with erythema

-Usually Big Toe (Podagra)

Chronic Gout

Recurrant attacks

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4
Q

What are the complications of Gout?

A

Nephrolithiasis

AKI

CKD

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5
Q

What are the two primary causes of Gout?

A

Underexcretion of Urate

(90% of Cases)

Overproduction of Urate

(10% of Cases)

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6
Q

What are the principles of Gout Treatment?

A

Reduce swelling / Treat Pain

Accelerate Renal excretion of Uric Acid

Uricosuric Agents

Probenecid & Lesinurad

Reduce conversion of purines to Uric Acid by Xanthine Oxidase

Uricostatic Agents

Allopurinol & Febuxostat

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7
Q

What can be used in an acute Gout Attack?

A

Colchicine

NSAIDs

Corticosteroids

IL-1 Inhinitors (in some cases)

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8
Q

What is the MOA of Colchicine in an Acute Gout attack?

A

Selective inhibitor of Microtubule assembly

Reduces Leukocyte migration and phagocytosis decreasing inflammation

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9
Q

What is the administration window and onset of Colchicine?

A

Give within 48 hrs of an acute attack

Onset within 12-24 hrs pain relief comes not from the drug, but the anti-inflammitory affect.

Give with NSAID for pain

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10
Q

What are the ADEs of Colchicine?

A

Diarrhea (indicates toxicity - stop med)

GI discomfort - N/V and Abdominal pain

Bone Marrow Suppression

Neutropenia

Renal Failure - Monitor renal function / Avoid in Advanced Kidney disease

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11
Q

What DDIs does Colchicine have?

A

Strong 3A4 inhibitors (increase the toxicity of Colchicine (Grapefruit Juice!))

Protease Inhibitors (Lower Efficacy)

Azole Antifungals

Macrolides

Verapamil

Diltiazem

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12
Q

What are some facts we need to know about Colchicine?

A

Start treatment as soon as possible

NSAID pain therapy is faster

NSAID therapy preferred if no C/I

Avoid ASA (competes with Uric Acid for excretion)

If PTs have C/Is or Renal Insufficiency Corticosteroids can be used, but have more ADRs

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13
Q

What is the MOA of Anthine Oxidase Inhibitors like Allopurinol and Febuxostat?

A

Inhibit the Action of Xanthine Oxidase to inhibit production of Uric Acid

Used for both Underexcreters and Overproducers

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14
Q

What are Allopurinol’s ADEs?

A

GI Upset

Exfoliative Rash (serious, can happen acutely or years after exposure)

Bone Marrow Suppression

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15
Q

What are Febuxostat’s ADEs?

A

Rash (not as serious as Allopurinol)

LFT elevations (<2%)

Diarrhea

Reports of CV disease (Do not use in Cardiac PTs)

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16
Q

What DDIs do Xanthine Oxidase Inhibitors have?

A

Mercaptopurine

Azathioprine

(Increase in toxicity because these both need Xanthine Oxidase)

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17
Q

Does Allipurinol or Febuxostat have better Selectivity?

A

Febuxostat has better selectivity and may have better efficacy.

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18
Q

Is Allipurinol or Febuxostat better for Renal PTs?

A

Febuxostat

More expensive though

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19
Q

What is the metabolite of Allopurinol?

A

Oxypurinol

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20
Q

What is the MOA of Probenecid?

A

Antagonize URAT1 to block Uric Acid Reabsorption (increases Excretion)

(May also interfere with tubular secretion of multiple substrates via OAT1 and OAT3)

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21
Q

When is the use of Probenecid indicated?

A

Useful in underexcretors (most gout cases) when Allopurinol and Febuxostat are C/I or when Tophi present.

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22
Q

What are the ADEs of Probenecid?

A

Uric Acid Kidney Stones (Less reabsorption means more in kedney)

GI intolerance (Dyspepsia / Acid Reflux)

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23
Q

What extra considerations are there when evaluating use of Probenecid?

A

Requires Good Kidney function

Adequate Hydration

Urine pH monitoring

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24
Q

What DDIs does Probenecid have?

A

Penicillins

Cephalosporins

Methotrexate

ASA (Low doses <2g/day)

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25
Q

What is the MOA of Lesinurad?

A

Antagonist of URAT1 and OAT4 transporters to block Uric Acid reabsorption (increases excretion)

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26
Q

What Black box warning does Lesinurad have?

A

It cannot be used as monotherapy, it is only cleared fro use with Allopurinol to reduce renal related events.

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27
Q

What are the ADEs of Lesinurad?

A

Headache

Elevations in SCr

Influenza

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28
Q

What DDIs does Lesinurad have?

A

Hormonal contreceptives (Reduced Efficacy)

(Estrogen +/- Progestin)

ASA

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29
Q

What is the MOA of Pegloticase?

A

It Catalyzes Oxidation of Uric Acid to readily eliminated metabolite (allantoin)

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30
Q

When is Pegloticase Use appropriate?

A

For Refractory Gout

PTs unresponsive to conventional therapy

31
Q

How is Pegloticase administered?

A

IV every other week (Extremely expensive)

32
Q

What ADEs does Pegloticase have?

A

GI intolerence

Anaphylaxis

Development of antipegloticase antibodies

Arthralgia

Nephrolithiasis

33
Q

How are IL-1 inhibitors used with gout?

A

Off label - Inhibits the inflammatory cytokines that are at work in a Gout attack.

For PT’s refractory to coventional therapies or that have C/I.

34
Q

How do DMARDs treat RA?

A

Slow disease progression and preserve structure / function of joint by either

Inhibiting Cytokines

Suppressing activity of lymphocytes (T&B cells)

35
Q

What is the Critical concern when using DMARDs?

A

Safety considerations are critical as these drugs are immunosuppressive.

36
Q

What Cytokines are active in RA?

A

TNF-Alpha

(Important mediator of acute inflammation; recruits neutrophils& macrophages to site of injury/infection)

Interleukin-1 (IL-1)

(Similar to TNF Alpha, also helps activate T-Cells)

IL-6

(Activates T-Cells; STimulates Fibroblasts)

37
Q

What Effects do Cytokines have in RA?

A

Increased Endothelial permiability to Leukocytes

Stimulate Osteoclasts / Stimulates release of Collagenase

(Breakdown collagen and bone)

Progressive irreversible deformities in joints and functional impairment

(RA has to many pro-inflammitory and not enough anti-inflammitory effects)

38
Q

What is JAK-STAT signaling?

A

Janus Kinase Signal Transducer and Activation of Transcription

Ligand activation of JAK forms STAT dimer which travels to nucleus and changes Gene expression

39
Q

How are they administered and what is the Onset of the Non-Biologic DMARDs?

A

Orally

Methotrexate - 4-8 weeks

Leflunomide - 4-12 weeks

Sulfasalazine - 8-12 weeks

40
Q

What is the MOA of Methotrexate?

A

Multifactorial

Reduce purine biosynthesis -> reduces DNA synthesis

At low doses (RA), selectively inhibits the replication of Tand B cells

(high doses treat cancer)

41
Q

What is the preferred DMARD treatment for RA unless contraindicated?

A

Methotrexate

42
Q

What are the C/Is for Methotrexate?

A

Pregnancy / breastfeeding

(discontinue 3 months before conception)

43
Q

What are Methotrexate’s ADEs?

A

Decreased Immune response (Myelosupression)

GI Toxicity (Nausea and Mucosal ulcers (mucositis))

Pulmonary Toxicity (Pneumonitis)

Hepatic Fibrosis (Monitor LFT’s every 3 mos (avoid if LFTs >2x ULN))

THrombocytopenia

Mild Apnea

44
Q

Can anything decrease ADEs when on Methotrexate?

A

Folic Acid (1-5 mg daily)

(Reduces liver toxicity 5mg best)

45
Q

What is Leflunomide’s MOA?

A

Inhibits autoimmune T-Cell proliferation and production of autoantibodies by B cell

46
Q

Does Leflunomide have comparable efficacy to Methotrexate?

A

Yes, and it has a longer half-life.

47
Q

What are Leflunomide’s C/Is?

A

C/I in pregnancy and Breast feeding

(will need to stop sooner than methotrexate due to Half-life)

48
Q

What are Leflunomide’s ADEs?

A

Alopecia

Hematologic Toxicity

Diarrhea -> significant (25%)

Rash ->Steven’s Johnson Syndrome (Very bad)

Severe Hepatotoxicity (avoid if LFTs >2x ULN)

49
Q

What is the MOA and Efficacy of Sulfasalazine?

A

The MOA is not known, and the efficacy is less than the other drugs we have covered.

50
Q

Is Sulfasalazine safe to use in pregnancy?

A

Rated B, Probably safe to use while pregnant, but not for breastfeeding.

(May cause neonatal Jaundice)

51
Q

What are Sulfasalazine’s ADEs?

A

GI effects (less with EC coated tabs)

Lupus-like Syndrome

HA / Fever / Rash

Hepatotoxicity

Avoid if documented Sulfa Allergy

52
Q

What is monitored on non-biologic DMARDS?

A

CBC / LFT / SCr

for

Methotrexate / Leflunomide / Sulfasalazine

Every 2-4 weeks for first 3 months

then every 8-12 weeks after

53
Q

What are the advantages of Biologic DMARDS?

A

These Monoclonal Anti-bodies are

Rapid onset 1-4 weeks for most!

54
Q

What are the disadvantages of Biologic DMARDs?

A

They are Expensive

More immunosuppressive increasing infection risk.

55
Q

Which type of DMARDs are the First Line biologics?

A

Tumor Necrosis Factor (TNF) inhibitors

(Anti-TNFs)

56
Q

How are Anti-TNFs administered?

A

MABs are always injected.

All are SQ except Infliximab which is IV

57
Q

What is the MOA of Etanercept?

A

Soluble TNF receptor blockade

58
Q

What is the MOA of Adalimumab and Golimumab?

A

Human Anti-TNF antibody

59
Q

What is the MOA of Infliximab?

A

Chimeric anti-TNF antibody

60
Q

What is the MOA of Certolizumab Pegol?

A

Pegylated humanized Fab fragment of TNF-alpha antibody

61
Q

What are the ADEs of anti-TNF antibodies?

A

Increased susceptibility to infection

  • Bacterial and fungal infection
  • Potential for reactive TB -> check PPD before use
  • No live vaccines while on drug

New or worsening cases of HF

-Changes in LV remodeling, negative inotropic effect

Increased risk of Lymphoma (low incidence to date)

Injection site reactions, arthralgia, rash, cough

62
Q

Are there any C/Is for anti-TNF DMARDs?

A

DO not use with HF

63
Q

What are the Routes of administration for the Non Anti-TNF Biologic DMARDs?

A

SQ

Anakinra

Sarilumab

IV

Toclizumab

Abatacept

Rituximab

64
Q

What is the Specific Action of Anakinra?

A

IL-1 receptor inhibitor

65
Q

What is the Specific Action of Rituximab?

A

B-Cell inhibitor

66
Q

What is the Specific Action of Abatacept?

A

T-Cell co-stimulation inhibitor

67
Q

What are the Specific Actions of Toclizumab and Sarilumab?

A

IL-6 receptor inhibition / antagonist

68
Q

What are the ADEs of Abatacept?

A

Avoid combining with anti-TNF biologics -> increased infection

Malignancy

-Respiratory events in COPD PTs

69
Q

What are the ADEs of Rituximab?

A

Fatal infusion related reactions

Severe mucocutaneous reactions

Hep B reactivation

Infections

70
Q

What are the ADEs of Toclizumab?

A

Severe infections

GI perforations

Netropenia

Thrombocytopenia

LFT elevations

Dyslipidemia

(Most Lab complications / Most headache to monitor)

71
Q

What are the ADEs of Anakinra?

A

Avoid with anti-TNF biologics

72
Q

What are the Oral biologics?

A

Small non-protein molecules

Tofacitinib

Baricitinib

-Citinibs

Nibs are small

73
Q

What is the MOA of Oral Biologics?

A

Inhibits activity of JAK enzyme at the Cytokine receptor -> Reduces Cytokine transmission signaling -> Decrease inflammation

74
Q

What are the ADEs of JAK inhibitors (oral biologics)?

A

Similar to other biologics

Infection

Reactivation of TB

Risk of malignancy

Avoid live Vaccines

GI perforation

Dyslipidemia

Anemia / Neutropenia

Hepatoxixity

Thrombosis (screen for risk)

Pharmacology (14 decks)

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