Pharm aspects of immunology 2

Question 1

What are some therapies for rheumatoid arthritis

Answer 1

anti-inflam drugs for symptom relief

• non-steroidal, NSAIDs
• Steroidal, glucocorticoids

DMARDS
slow the clinical progression of RA
- synthetic DMARDS, hydroxychloroquine
- targeted synthetic DMARDs, JAK inhibitors e.g. tofacitinib & baricitinib

biological agents
- TNF-blockers

Question 2

outline Methotrexate (synthetic DMARD)

Answer 2

increases adenosine level- anti inflam
induces apoptosis of activated CD4+ & CD8+ T-Cells

antimetabolite (folate analogue), Inhibit cell proliferation
must be taken with folic acid supplements to reduce side effects caused by folic acid depletion

Question 3

What are the side effects of synthetic DMARDS

Answer 3

30% exp side effects

- nausea, LOA, diarrhoea, headache, hair loss, hepato/nephrotoxicity

Question 4

Outline the use of targeted synthetic DMARDs and name 2

Answer 4

patients with mod-sev RA who have had a minor response to DMARD may use tsDMARDs

tofacitinib- selectively inhibits JAK1 & JAK3
baricitinib- selectively inhibits JAK1 & JAK2

Question 5

Outline the role of TNF in RA

Answer 5

TNF- secreted by macrophages, has a direct effect on endothelial cells, synovial fibroblasts and monocytes to release cytokines such as IL1 and IL8 which work to induce cartilage degradation

Question 6

Name 4 licensed biologics for the treatment of RA

Answer 6

tnf-blockers- infliximab
monoclonal antibody against b-cells- rituximab
T-cell co stim inhibitor- abatacept
monoclonal antibody against IL-6R- sarilumab

Question 7

Name the TNF-blockers

Answer 7

infliximab- partially humanized mouse monoclonal anti-hTNF alpha antibody

etanercept -soluble TNF receptor dimer

adalimumab- human IgG1 anti-TNF-alpha antibody
golimumab-human IgG1 anti-TNF-alpha antibody

certolizumab pegol- PEGylated anti-TNF-alpha monoclonal antibody fragment

Question 8

Describe the structure of Infliximab and how it works

Answer 8

constant region of the antibody is human but the variable region is mouse derived

neutralizes free, membrane and receptor bound TNF-a

also used in treatment for crohns, uc, psoriasis

Question 9

Describe how etanercept works

Answer 9

binds free and membrane bound TNF, reducing the accessible TNF in RA

Question 10

outline the use of adalimumab and golimumab

Answer 10

both are fully human anti-TNF-alpha mABs

golimumab is used with MTX and has a longer half-life than adalimumab

Question 11

outline the structure and use of certolizumab pegol

Answer 11

PEGylated anti-TNF-alpha monoclonal antibody fragment

PEG- when covalently attached to drugs, it reduces antigenicity/ immunogenicity, prolongs the circulatory time of the drugs

Question 12

What are some consideration and side effects of anti-TNF therapy

Answer 12

patients must be screened for past history of TB, MS, recurrent inf, leg ulcers and past history of cancer.

may reactivate latent TB

Question 13

How does rituximab work

Answer 13

rituximab opsonizes B-cells and are killed by 3 mechs:

• complement mediated cytotoxicity
• ADCC or CR mediated opsonic phagocytosis
• apoptosis

also used in treatment for SLE

Question 14

How does abatacept work

Answer 14

• competitive inhibitor for CD28
• increases the threshold for T-cell activation and suppresses the proliferation of synovial recirculating T cells
• reduces the level of inflam mediators

Question 15

What are the side effects of biological therapies

Answer 15

Increased risk of INF: upper resp tract, pneumonia, UTI’s

nausea, headache, HTN, allergic reactions