E2: DMARDs Flashcards
What are the toxicites of Gold salts?
Bone marrow damage, dermatitis, enterocolitis, jaundice, and peripheral neuropathy
What are the mediators of chronic inflammation?
- Interleukins 1, 2, and 3
- GM-CSF
- TNF-a
- interferons
- PDGF
What are the effects of Gold salts?
- Inhibitions of phagocytosis, uncouple oxidative phosphorylation and inhibit cellular respiration
- prevent PG synthesis
- suppress cellular immunity
What kind of drug is Aurothioglucose?
A Gold salt
What kind of drug is Penicillamine?
A cheating agent effective in RA and Wilson’s disease
-unknown mechanisms but similar to gold compounds
What are the adverse effects of Penicillamine?
- Pruritis, rash, and alternation in taste
- Thrombocytopenia, leukopenia, agranulocytosis
- proteinuria, nephrotic syndrome
- Lupus like Disease, pemphigus
What are the effects of Hydroxychloroquine?
- Possess antihistamine, anticholinesterase, and antiprotease properties
- inhibits PG synthesis
- Inhibits biosynthesis of mucopolysaccharide
- Inhibits response to chemotactic stimuli and phagocytosis
When does hydroxychloroquine concentrate in the body and why?
It has a high affinity for melanin so it is concentrated in the epidermis and retina
What are the toxicites associated with hydroxychloroquine?
Pruritis, hemolysis, ototoxicity, retinopathy, and peripheral neuropathy
What are the uses of sulfasalazine?
- Used to treat RA
- just as effective as gold compounds and Penicillamine but with less side effects
Why does mesalamine have anti-inflammatory action?
- inhibition of arachidonic acid metabolism by inhibition of Cyclooxygenase
- inhibits leukotriene synthesis, possibly through inhibition of lipoxygenase
What are the toxicites of sulfasalazine?
- GI disturbance, rash
- Hepatitis and blood dyscrasias are rare
- Monitoring for hepatitis and marrow suppression is recommended for 2-3 weeks during the first 3 months of treatment
What are the 5 anti TNFa drugs?
- Infliximab
- adalimumab
- certolizumab
- golimumab
- etanercept
What are the two inhibitors of B cell differentiation and T cell activation?
- Rituximab
- Abatacept
What are the 2 interleukin receptor antagonists?
- Anakinra
- Tocilizumab
What is the MOA of Infliximab?
- Chimeric IgG1k monoclonal antibody targeted against TNFa
- composed of human constant and murine variable regions
What is Infliximab used to treat and what drug is it often combined with?
-Combined with methotrexate to treat Crohns and RA
What are the contraindications of Infliximab?
Pregnancy, breast feeding, children, and infections
What is the MOA of Adalimumab?
- Recombinant human IgG1 monoclonal antibody
- Has human derived heavy and light chain variable regions and human IgG1k constant reactions (100% human peptide sequences)
- Specific for TNFa
What are the uses of Adalimumab?
Approved as Monotherapy for treatment of RA
What are the most common adverse effects of adalimumab?
-Influenza like symptoms, fatigue, headache, pruritis, and nausea/vomiting
What is the MOA of Certrolizumab?
- Humanized antibody that is a potent neutralizer of the TNFa
- adverse effects similar to other TNFa binders
What is the MOA of Golimumab?
- Human derived monoclonal antibody with human derived variable and constant regions TNFa
- Adverse effects similar to other TNFa binders
What is the MOA of Etanercept?
-Dimeric fusion protein produced by recombinant produced by recombinant DNA technology, this protein consistent of extracellular ligand binding portion of the human 75 kilo dalton TNF receptor linked to the FC portion of the human IgG1
What are the contraindications to Etanercept?
Bone marrow suppresion, breast feeding, children, DM, infection, sepsis, vaccination, varicella
What is the MOA of Ritubximab?
- A genetically engineered chimeric murine/human monoclonal antibody
- Binds specifically to CD20, a B-lymphocyte differentiation antigen on. Pre-B and mature B lymphocytes
What is the MOA of Abatacept?
- Fully recombinant fusion protein categorized as a costimulatory or second signal blockers for T cell activation
- Disturbs a key mechanism of inflammation and progressive ointment destruction in RA
How is etanercept administered?
SubQ
How are rituximab and abacept administed?
IV
What are the two inhibitors
Leflunomide and Mycophenolate mofetil
What is the MOA of Leflunomide?
Inhibits dihydroorotate dehydrogenase (DHODH), an enzyme located in cell mitochondria that catalyzes a key step in de novo pyrimidine
- Secondary mechanism of action is inhibitionof cytokines and growth factor receptor associated with TK activity
- Inhibits the induction of COX2
What are the contraindications of Leflunomide?
Pregnancy, breast feeding, hepatic and renal failure
What is the MOA of Mycophenolate Mofetil?
-a prodrug that inhibits lymphocyte purine synthesis by reversible and non competitively inhibiting the enzyme inosine monophosphate dehydrogenase
What are the contraindications to Mycophenolate mofetil?
Active GI disease, diarrhea, pregnant, breast feeding, infections
What is the MOA of anakinra?
-Recombinant non glycosylated form of the human interleukin-1 receptor antagonist
What is the use of Anakinra?
RA patients experienced improvements of swollen and painful joints
-Given SubQ
What are the contraindications to Anakinra?
Breast feeding, children, hypersensitivity reactions, renal disease
What is the MOA of tocilizumab?
- Humanized interleukin-6 receptor inhibiting monoclonal antibody
- competes for IL-6 for binding to the IL-6 receptor
What are the two Janus Kinase inhibitors?
Tofacitinib and Baricitinib
What is the MOA of Tofacitinib?
-Primarily inhibits JAK1 and JAK3 and to a lesser extent, JAK2
What is the use of Tafcitinib?
-For adults with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate
What is the MOA of Baricitinib?
-Oral JAK inhibitor, has greater affinity for JAK1 and JAK2 relative to JAK3
What is the used of Baricitinib?
- Indicated for the treatment of adult patients with moderately to severely active RA
- may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs
