MSKS Pharmacology Lecture 4_DMARD

Question 1

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

Tofacitinib

Answer 1

Class: Tyrosine Kinase Inhibitor
MOA: Inhibits JAK (a tyrosine kinase protein) which prevents the phosphoralation of STAT (aka the activation). STAT is a transcription factor for inflamitory mediators
Half Life: 3 to 6 hours
Indication: RA
Side Effects: Increase in LDL and HDL levels, skin cancer, anemia, infectious disease,
Blackbox Warning: serious infections leading to death
Considerations: Cholesterol should be monitored, do not give live vacinations

Question 2

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

Azothioprine

Answer 2

Class: Antimetabolite
MOA: Suppresses cell-mediated hypersensitivities and causes alterations in antibody production
Half Life: 5 hours
Indication: RA, Lupus, Transplant rejection
Side Effects: Nausea, Vomiting, Leukopenia, Hepatotoxicity, Infectious disease
Blackbox Warning: increased risk of malignancy with long term use
Considerations: use sunscreen to limit increased risk of skin cancer

Question 3

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

of Tocilizumab

Answer 3

Class: Interleukin-6 (IL-6) receptor inhibitor
MOA: Interleukin-6 (IL-6) receptor inhibitor that bind specifically to both soluble and membrane-bound IL-6 receptors and inhibits IL-6 mediate signaling.
Half Life: 11 - 13 days
Indication: RA
Side Effects: Injection site reaction, increased ALT/AST levels, headache, hypertension, hyperlipidemia, Neutropenia, hepatic toxicity, upper respiratory infection
Blackbox Warning: Risk of fatal infection, test for latent TB.
Considerations: Do not give live vaccines, monitor cholesterol, tocilizumab is more affective than adalimumab as a monotherapy in patients that cant tolerate methotrexate

Question 4

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

of Abatacept

Answer 4

Class: CD80/86 Inhibitor
MOA: A biological response modifier that demonstrates anti-inflammatory effects by downregulating T cell activation. Abatacept binds to CD80 and CD86 receptors on the antigenpresenting cell and prevents them from binding to CD28 on the T cell for optimal T cell activation
Half Life: 13 - 14 days
Indication: RA
Side Effects: Nausea, headache, infectious disease, nasopharyngitis, upper respiratory infection
Blackbox Warning:
Considerations: false high glucose readings, may worsen COPD symptoms

Question 5

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

of infliximab, etanercept, adalimumab, golimumab, certolizumab

Answer 5

Class: TNF-𝛼 Inhibitors
MOA: Monoclonal antibody with specific activity for human tumor necrosis factoralpha
Half Life: Infliximab, adalimumab, golimumab, certolizumab -14 days; etanercept - 102 hours
Indication: RA
Side Effects: Injection site reaction, Upper respiratory infection, reactivation of Heb B or TB infections, autoimmune hepatitis, increased risk of cancer
Blackbox Warning: Increased risk of developing fatal infection, test for latent TB
Considerations: Do not give live vacines, etenercept is less sensitive and will also bind TNF-beta

Question 6

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects: 
Blackbox Warning:
Considerations:

of Prednisone, Methylprednisolone and triamcinolone

Answer 6

Class: Corticosteroid
MOA: inhibition of antigen presentation
to T lymphocytes, inhibit prostaglandins and
leukotriene synthesis, inhibit neutrophil and
monocyte superoxide radical generation
Half Life: Prednisone- 2-3 hours;
methylprednisolone and triamcinolone- 18-36
hours
Indication: RA
Side effects:
Blackbox Warning: cardiac arrest, impaired wound healing
Considerations:Can increase blood glucose levels and insulin resistance

Question 7

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

Sulfasalazine

Answer 7

Class:5-Aminosalicylate
MOA: A pro drug that is cleaved in the terminal ilium and colon. Blocks cyclooxygenase and prostaglandin synthesis in the colon. Inhibits production of IL-1 and TFNα. Inhibits natural killer cells, mucosal lymphocytes and macrophages
Half Life: 7 - 14 hours
Indication: Rheumatoid arthritis, ulcerative colitis, Crohn’s Disease
Side Effects: Headache, nausea, diarrhea, interstitial nephritis, Allergic reactions, hemolytic anemia, leukopenia, hepatitis
Blackbox Warning:
Considerations: Cannot be tolerated by 40% of patients, causes yellow orange urin or skin

Question 8

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

Hydroxychloroquine

Answer 8

Class: Aminoquinoline
MOA: interferes with antigen presentation and inhibits the activity of many enzymes including collagenase and the proteases that cause cartilage breakdown
Half Life: 172 hours to 50 days
Indication: RA, Lupus
Side Effects: Nausea, vomiting, dizziness, tinnitus,Retinal disorder, Hypoglycemia, Torsades de pointes
Blackbox Warning:
Considerations: May cause vision changes

Question 9

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

of Anakinra

Answer 9

Class: Interleukin-1(IL-1) Inhibitor
MOA: Competitive inhibitor of IL-1 binding to the IL-1 type receptor.
Half Life: 4 to 6 hours
Indication: RA
Side Effects: Injection site reaction, diarrhea, nausea, vomiting, flu-like symptoms Neutropenia, infections disease
Blackbox Warning:
Considerations: Do not give live vacine

Question 10

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

Methotrexate

Answer 10

What is the
Class: Antimetabolite
MOA: folate analogue that inhibits dihydrofolate
reductase (DHFR). Inhibits cytokine production,
purine biosynthesis, and thus DNA/RNA replication
Half Life: 3-10
Indication: RA, Cancer
Side Effects: Nausea, vomiting, diarrhea, aplastic anemia, leukopenia, bone marrow suppression, hepatotoxicity
Blackbox Warning:embryo fetal toxicity,
Considerations: First line DMARD for RA, effective in suppressing fast dividing cells

Question 11

What is the
Class:
MOA:
Half Life:
Indication:
Side Effects:
Blackbox Warning:
Considerations:

Leflunomide

Answer 11

Class: Dihydroorotate Dehydrogenase Inhibitor
MOA:Pyrimidine synthase inhibitor; lymphocytes depend upon de novo pyrimidine synthesis after immune cell activation.
Half Life: 14-16 days requires use of loading dose
Indication: RA, cancer
Side Effects :Rash, diarrhea, stomatitis, Stevens-Johnson syndrome, elevated liver enzymes, respiratory tract infections, thrombocytopenia
Blackbox Warning:
Considerations: contraindicated in patients with
liver disease, Avoid live vaccines during therapy