MSI pharm- biological therapies Flashcards
Methotrexate drug class?
anti-metabolite
Drug class of Adalimumab, Tocilizumab, Rituximab ?
Monoclonal antibodies
When someone is diagnosed with RA, what are the three classes of drugs they are typically started on after their first visit?
NSAIDs and Glucocorticoids (for symptom relief) and also a DMARD (such as methotrexate) to slow the clinical and radiographic progression of RA
(Remember that DMARDs can take 8-12 weeks to start working, so they need sx relief initially!)
What is the first choice DMARD, aka “the gold standard”?
Methotrexate
** MOA for Methotrexate?
Antimetabolite (folate analogue), inhibits cell proliferation
Increases adenosine level (anti-inflammatory- Reduces inflammation quickly and keeps it under tight control)
Reduces the production of damaging polyamines
Induces apoptosis of activated CD4+ and CD8+ T-cells
What is considered the “Anchor drug” in combination therapies for AI disease?
Methotrexate
What type of supplementation is required along with Methotrexate administration?
Folic acid- Orally or subcut 1/week
** Side effects of DMARDs/Methotrexate (30% of patients experience adverse effects)
Nausea Loss of appetite Diarrhoea Rash, allergic reactions Headache Hair loss Risk of infections (pneumonia) Hepatotoxicity (metabolism) Bone marrow suppression & thrombocytopenia \_\_\_\_\_\_\_\_\_ toxicity (route of elimination)
Kidney
Biological therapy is a form of treatment that uses portions of the body’s natural immune system to treat a disease.
Biological DMARDs (bDMARDs) are proteins derived from human genes genetically engineered to inhibit precise components of the immune system- such as targeting a single __________
TNF-blockers (TNF- Tumour Necrosis factor)
Drugs targeting IL-1, IL-6 , B-cells and T-cells
cytokine
Biological therapy nomenclature:
“-cept” refers to fusion of a receptor to the __ part of human immunoglobulin G1 (IgG1)
Fc
Biological therapy nomenclature:
“-mab” indicates a _________ antibody (mAb)
monoclonal
Biological therapy nomenclature:
“-ximab” indicates a ________ mAb
chimeric- partially human, partially animal derived, like mouse derived
Biological therapy nomenclature:
“-zumab” indicates a ________ mAb
humanized
Biological therapy nomenclature:
“-umab” indicates a fully ______ mAb
human
** What is one of the key cytokines in the process of driving inflammation?
TNF- Can be derived from macrophages, T cells
** Enzymes that are very destructive (produced by synovial fibroblasts). Responsible for the cartilage destruction of RA (along with PGE2 and IL-6)
Matrix metalloproteases
Biological therapies are protein drugs that are administered …
parenterally (or subcut)
Biologics are extremely expensive, so NICE has strict guidelines for eligibility:
Patient has failed to respond to treatment with at least two standard (synthetic) DMARDs, one of which must be ___ (unless patient cannot take it for medical reason)
Patient’s RA disease activity score (DAS 28) is measured at 3.2 (moderate RA activity) or over, on two occasions, one month apart
MTX
MOA for Adalimumab?
TNF-blocker
MOA for Rituximab?
Monoclonal antibody against B cells
MOA for Tocilizumab?
Monoclonal antibodies against IL-6R
Method of administration for Adalimumab (fully human anti-TNF monoclonal Ab)
subcut injection
What is the biggest and most common ADE of Adalimumab?
Risk of infection
Considerations for prescribing anti-TNF therapy (Adalimumab):
Patients screened before starting treatment to exclude an increased risk of side effects, in particular for a past history of ____________, multiple sclerosis, recurrent infection, heart failure (III/IV).
Chest X-ray to be taken to exclude signs of previous TB and to exclude signs of heart failure
Screen for HIV, Hepatitis B and C
Live vaccines, against e.g. yellow fever or polio, should be avoided.
tuberculosis (TB)
Adalimumab should not be prescribed with
other biologic therapies, as it increases the risk of infection
Which biologic drug is a partially humanized anti-CD20 monoclonal antibody?
Rituxumab
_________ opsonized B-cells are attacked and killed by three mechanisms:
Complement mediated cytotoxicity
2-3)Antibody-dependent cell mediated cytotoxicity (ADCC) – FcgR or CR (complement receptor) mediated opsonic phagocytosis
4) Apoptosis
Rituximab
Biologic drug that is a humanized anti-IL-6 receptor monoclonal antibody used to treat juvenile idiopathic arthritis, Giant cell arteritis, critical Covid-19
Tocilizumab
Risk of TB (or reactivating latent TB infection) is most associated with which biologic drug?
Adalimumab (anti-TNF)
Which two biologic therapies are Contraindicated in pregnancy and while breast feeding?
Rituximab, Tocilizumab
Adverse effects of biological therapies:
** Increased risk of __________: Upper respiratory tract infections (nasopharyngitis), pneumonia, urinary tract infections and tuberculosis.
It is recommended to receive influenza and pneumococcal vaccines before embarking on biological therapy
Avoid live vaccines
Booster Covid
infections
Which biologic drug is associated with increased Lipid Levels?
Tocilizumab
Combination therapy- this is the concept of taking two immunosuppressants together – with regards to biologics. This is usually __________.
** This increases the response of biologics.
Reduces immuno-genicity of the biologics
methotrexate
