Pharm: DMARDs Flashcards
What are the drugs of first choice for RA due to efficacy and rapid onset of action?
NSAIDs
What is important to remember about using NSAIDs for RA?
Do NOT alter disease progression
What is the important role of using glucocorticoids in managment of RA; which have longer half-lifes and potency?
- Relieves pain and inflammation while waiting for DMARD effects
- Fluorinated prednisolones: Betamethasone, Dexamethasone, Triamcinolone
How can exogenous glucocorticoids be fatal?
If abruptly stopped, rather than discontinuing slowly
Which DMARD is the drug of first-choice for RA?
Methotrexate
RA pt’s taking low doses of methotrexate should also take what?
Weekly folate supplements
What are the life-threatening major toxicities associated with higher doses of Methotrexate?
- Bone marrow suppression
- Hepatic fibrosis
- GI ulceration
- Pneumonitis
What is the MOA of low-dose Methotrexate used for RA?
- Polyglutamation –> MTX-(glu)n which accumulates in cells
- Blocks thymidylate synthase and AICAR
- AICAR causes Adenosine efflux which binds purinergic GPCRs –> anti-inflammatory effect
What is the MOA of Hydroxycloroquine used in RA; how quick is onset?
- Lipophilic weak base –> accumulates in lysosomes –> ↑ pH
- ↑ pH of lysosome in APC’s limits the assoc. of peptides w/ class II MHC
- Can slow disease progression, but delayed onset (3-6 mo.)
Which DMARD can a pregnant mother with RA use safely?
Hydroxychloroquine
What is a rare dose-related, but serious, AE of Hydroxychloroquine?
Retinal damage
What is the active metabolie of the DMARD Sulfasalazine when used for RA?
Sulfapyridine
What is the MOA of the DMARD, Leflunomide?
- Inhibition of mitochondrial enzyme dihydroorotate dehydrogenase to block synthesis of rUMP and pyrimidine synthesis
- Inhibits T cell proliferation (especially memory T cells)
Which traditional DMARD disrupts pyrimidine synthesis and is a 2nd choice due to more common serious AE’s?
Leflunomide
5 most common AE’s assoc. w/ the DMARD, Leflunomide?
- Diarrhea
- Respiratory infection
- Reversible alopecia
- Rash
- Nausea
The DMARD, leflunomide is toxic to which organ?
Hepatotoxic –> ↑ risk of serious infections
What is the rule for using biologic and non-biologic DMARDs together?
- CAN combine biologics and non-biologics
- Biologics should NEVER be combined w/ other biologics
What are the 3 TNF-α blockers used for RA?
- Etanercept
- Infliximab
- Adalimumab
What is the clinical indication for using the TNF-α blockers (etanercept, infliximab, and adalimumab) for RA?
Moderate to severe RA, gen. after traditional DMARDs have been ineffective
What are some of the serious AE’s associated with the TNF-α blockers used for RA?
- Serious infections: including tuberculosis
- Pt’s may also experience severe allergic reactions
Which drug targets CD20 antigen of B cells to cause a B cell ‘do-over,’ and is used to treat HL and CLL + in combo with MTX for RA in those who have no responded to TNF-blockers?
Rituximab
What testing in a pt with RA would indicate a greater likelihood of response to Rituximab?
(+) testing for rheumatoid factor or anti-cyclic citrullinate peptide (CCP)
Rituximab is associated with what serious AE?
Severe infusion related hypersensitivity rxns
What is the MOA of Abatacept used for RA?
Prevents CD28 from binding to its counter-receptor, CD80/CD86
What is the MOA and effects of Tocilizumab used for RA?
- Humanized anti-human IL-6 receptor antibody
- Limits hepatic acute phase response and activation of T cell, B cells, macrophages, and osteoclasts
What is the most common AE and a serious AE of Tocilizumab?
- Most common = upper respiratory tract infections
- Serious = life-threatening infections (TB, invasive fungal infections, opportunistic, etc.)
Which biologic DMARD used for RA stands out due to it being available as an oral formulation?
Tofacitinib - JAK3 antagonist
What is the MOA of Tofacitinib used for RA?
Inhibitor of JAK3 –> directly suppresses the prod. of IL-17 and IFN-y and the proliferation of CD4+ T cells
What are AE’s associated with Tofacitinib and which warning comes with this drug?
- Serious and sometimes fatal infections due to bacteria, mycobacterial, invasive fungal and other opportunistic pathogens
- Warning = ↑ risk of malignancies (i.e., lymphoma)
What is the MOA of Anakinra used for RA; clinical indication?
- A recombinant non-glycosylated version of human IL-1 receptor antagonist–> blocks the pro-inflammatory activity of naturally occurring IL-1
- Less efficacious than others, so used as late choice
Which TNF-antagonist consists of two TNF receptors bound to Fc portion of IgG and is administered 1-2x/weekly by SQ injection?
Etanercept
The TNF-antagonist, Etanercept is effective in treating what conditions?
RA + psoriatic arthritis + ankylosing spondylitis
