Anti-Rheumatic Pharm

Question 1

Rheumatoid Arthritis 
Therapy Goals (3) Non-Pharm Interventions (6)

Answer 1

Stop inflammation
Relieve symptoms
Prevent joint and organ damage

Rest
Exercise
Physical/Occupational/Nutritional Therapy
Bone Protection
Cardiovascular risk reduction
No live vaccines

Question 2

Analgesics Used For RA

First Line, Adverse Effects (4)

Answer 2

NSAIDs

GI Ulcers
Thromboembolism
Bleeding
Cardiovascular events

Question 3

Prednisone

Classification, MOA (3) Indications (2) Formulations (3) Adverse Effects (4)

Answer 3

Glucocorticoid

Binds Glucocorticoid receptor
GR complexes with NFKB and AP-1 transcription factors
Activates Lipocortin to inhibit PLA2

Short term RA relief (less than 6 months)
Treats RA flares (pain and inflammation)

Oral
IM
Intra-articular

Adrenocortical-Pituitary Insufficiency
Cushing’s Syndrome
Diabetes
Hypokalemic alkalosis

Question 4

Methotrexate

MOA (2) Action Timeline, Indication, Formulations (2) Adverse Effects (5)

Answer 4

Polyglutamination causes buildup that blocks Thimidylate synthase and AICAR transformylase
Causes adenosine buildup that binds Purinergic GPCR to decrease inflammation

Fastest onset, works in 3-6 weeks

First line drug for Rheumatoid Arthritis

Weekly oral or injections

Teratogenic (take folate supplement)
Bone marrow suppression
Hepatic fibrosis
GI Ulcers
Pneumonitis

Question 5

Hydroxychloroquine

MOA (2) Timeline, Indications (2) Use Benefit, Formulation, Adverse Effect

Answer 5

Liphophilic weak base, accumulates in lysosomes
Decreases MHC II binding

3-6 months to work

Rheumatoid arthritis
Anti-malarial

Safe in Pregnancy

Oral, given in loading doses

Retinal damage (visual changes)

Question 6

Sulfasalazine

MOA (3) Timeline, Indications (2) Formulation, Adverse Effects (5)

Answer 6

Metabolized to sulfapyridine
Releases anti-inflammatory adenosine
Inhibits NFKB

~1 month

Rheumatoid Arthritis
Inflammatory Bowel Disease

Oral

Sulfa allergy
GI disturbance
Inhibits folate absorption
Hepatitis
Bone Marrow Suppression

Question 7

Leflunomide

MOA (3) Drug Combo, Indication, Formulation, Adverse Effects (5) Serious Complications (3)

Answer 7

Inhibits mitochondrial dihydroorotate dehydrogenase
Blocks rUMP synthesis
Inhibits T cell proliferation

Used in combo with other Non-Biological DMARDs

Rheumatoid Arthritis (used in combo with other drugs)

Oral, given in loading doses

Diarrhea 
Respiratory Infection
Alopecia
Rash
Nausea
Hepatotoxic

Stevens Johnson syndrome
Pancytopenia
Severe hypertension

Question 8

Non-Biologic DMARDS

Examples (4) RA Triple Therapy Combo (3)

Answer 8

Methotrexate
Hydroxychloroquine
Sulfasalazine
Leflunomide

Sulfasalazine
Hydroxychloroquine
Methotrexate

Question 9

Etanercept

MOA (2) Indications (3) Formulation, Adverse Effects (2)

Answer 9

Inhibits TNF-alpha by binding it with IgG-bound receptors

Rheumatoid Arthritis
Psoriatic Arthritis
Ankylosing Spondylitis

Subcutaneous injection 1-2 times weekly

Risk of Tuberculosis
Risk of Severe allergic reaction

Question 10

Infliximab

MOA, Indications (3) Formulation, Adverse Effects (2)

Answer 10

Chimeric monoclonal Ab against TNF-alpha

Rheumatoid Arthritis
Psoriatic Arthritis
Inflammatory Bowel Disease

IV infusion every 6 weeks

Risk of Tuberculosis
Risk of Severe allergic reaction

Question 11

Adalimumab

MOA, Indications (4) Formulation, Adverse Effects (2)

Answer 11

Recombinant human monoclonal Ab against TNF-alpha

Rheumatoid Arthritis
Psoriatic Arthritis
Ankylosing Spondylitis
Crohn’s Disease

Subcutaneous injection every two weeks

Risk of Tuberculosis
Risk of Severe allergic reaction

Question 12

Rituximab

MOA (2) Drug Combo, Indication, Formulation, Adverse Effects (3)

Answer 12

Monoclonal Ab to CD20
Causes B cell depletion

Used with Methotrexate

Rheumatoid Arthritis
(with + testing for RF and anti-CCP)

IV infusion every 6 months

Infusion related hypersensitivity reactions
Stevens Johnson syndrome
Hep B reactivation

Question 13

Abatacept

MOA (3) Drug Combo, Indications (2) Formulations (2) Adverse Effects (2)

Answer 13

Uses CTLA4 to bind CD80/CD86
Blocks CD28 from binding 80/86
Blocks T cell activation

Non-biological DMARDS

Moderate to severe Rheumatoid Arthritis
Juvenile Idiopathic Arthritis

Subcutaneous injection q 2 weeks
IV infusion q 4 weeks

Well Tolerated
Increased risk of serious infections

Question 14

Tocilizumab

MOA (3) Drug Combo, Indication, Formulation, Adverse Effects (4)

Answer 14

Anti-IL6 receptor Ab
Limits hepatic acute phase response
Decreases T cell, B cell, Macrophage and Osteoclast activation

Methrotrexate (used with or without)

Moderate to severe Rheumatoid Arthritis

IV infusions monthly

Upper Respiratory Infections
Life Threatening Infections (TB, fungal, opportunistic)
Neutropenia
Thrombocytopenia

Question 15

Tofacitinib

MOA (4) Drug Combo, Indication, Formulation, Adverse Effects (2)

Answer 15

JAK3 inhbitor
Supresses IL17, IFN-gamma, and CD4+ T cells

Methotrexate (with or without)

Moderate to severe Rheumatoid Arthritis

Oral

Serious infections with opportunistic pathogens
Increased malignancies

Question 16

Anakinra

MOA (2) Indication, Formulation, Adverse Effects (2)

Answer 16

Recombinant glycosylated IL-1 receptor antagonist
blocks proinflammatory IL-1 activity

Moderate to severe Rheumatoid Arthritis

Subcutaneous daily injections

Increased serious infections
Anaphylactic reactions

Question 17

Biologic DMARDs

Examples (8) and Caution

Answer 17

Abatacept (intercepts CD80/86)
Etanercept (intercepts TNF)
Tofacitinib (JAK3 inhibitor)
Anakinra (anti-IL1)

Adalimumab (human recombinant anti-TNF)
Infliximab (chimeric anti-TNF)
Rituximab (anti-CD20)
Tocilizumab (anti-IL6)

Biologic CANNOT be combined with EACH OTHER, only with non-biologic