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pharmacology > Treating Rheumatological Disorders > Flashcards

Treating Rheumatological Disorders Flashcards

1
Q

What is rheumatoid arthritis?

A

An autoimmune multisystem disease which presents with morning stiffness, symmetrical arthritis and rheumatoid nodules.

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2
Q

What is the pathophysiology of rheumatoid arthritis?

A

There is an altered balance between pro and anti inflammatory signals. This causes inflammatory change and proliferation of synovium which leads to dissolution of cartilage and bone.

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3
Q

What is lupus?

What systems does it affect?

A

A multisystem disease affecting the nervous system (seizures, psychosis, headaches, low grade fever), heart and lungs (pericarditis, myocarditis, endocarditis, pleuritis), kidneys (oedema, hypertension, proteinuria), blood (anaemia, thrombocytopenia).

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4
Q

What are the major groups of rheumatological drugs?

A

Corticosteroids- best avoided in this case
Azothioprine
Mycophenolate mofetil
Calcineurin inhibitors
Disease Modifying Anti Rheumatic Drugs (DMARDs)

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5
Q

What is the mechanism of action of azothioprine?

A

It is cleaved to 6MP by TPMT. 6MP decreases DNA and RNA synthesis.

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6
Q

What is azothioprine used for?

A

SLE and vasculitis as a maintenance therapy

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7
Q

What enzyme is it important to check for before starting someone on azothioprine?

A

TPMT activity- low levels of TPMT risk myelosuppression on azothioprine.

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8
Q

What monitoring does azothioprine require ?

A

FBC- risk of myelosuppression
Infection markers- risk of infection
LFTs- risk of hepatitis.

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9
Q

What is the mechanism of action of mycophenolate mofetil?

A

Inhibits guanosine synthesis- impairs B and T cell proliferation. Spares other rapidly dividing cells as they have guanosine salvage pathways.

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10
Q

In what situations is mycophenolate mofetil used?

A

Used mainly in transplantation but also in induction and maintenance therapy for lupus.

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11
Q

What are the common side effects of mycophenolate mofetil?

A

Nausea
Vomiting
Diarrhoea
Myelosuppression.

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12
Q

What is the mechanism of action of calcineurin inhibitors?

A

Active against T helper cells. Prevents production of IL2 via calcineurin inhibition.

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13
Q

What are some examples of calciuneurin inhibitors?

A

Ciclosporin and tacrolimus.

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14
Q

What is the main use of calciuneurin inhibitors?

A

Mainly in transplantation, but also atopic dermatitis and psoriasis.

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15
Q

What are the major side effects of calciuneurin inhibitors?

A

Renal toxicity- not often used. GFR and BP are measured when it is being used.

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16
Q

What are the different types of DMARDs?

A

Sulphalazine
Cyclophosphamide
Methotrexate
Anti TNF agents

17
Q

What is the mechanism of action of methotrexate in non malignant disease?

A

Inhibition of T cell activation,

Suppression of intercellular adhesion molecule expression.

18
Q

In what situations is methotrexate indicated?

A

Crohns disease
RA
Malignancy
Psoriasis

19
Q

What are the adverse effects of methotrexate?

A 
Mucositis
Marrow suppression
Hepatitis, cirrhosis
Pneumonitis
Immunosuppression
Teratogenic
20
Q

What is the mechanism of action of cyclophosphamide?

A

A cytotoxic alkylating agent that cross links DNA so that it cannot replicate. So suppresses T cell and B cell activity.

21
Q

What is cyclophosphamide indicated for?

A

Lymphoma, leukemia, solid cancers, lupus nephritis, wegeners granulomatosis (ANCA vasculitis),

lupus (mycophenolate mofetil is safe and as effective)

22
Q

What are the side effects of cyclophosphamide?

A

It is excreted by the kidney. One of its metabolites- acrolein- is toxic to bladder epithelium so can lead to haemorrhagic cystitis. Can be prevented with aggressive hydration.

Can also cause increased risk of bladder cancer, lymphoma and leukemia.

23
Q

What monitoring is required with cyclophosphamide?

A

FBC, adjustment of dose is required in renal impairment

24
Q

What is the mechanism of action of sulphalazine?

A

Inhibits proliferation of T cells and may induce apoptosis. Inhibits IL2 production. Causes reduced neutrophil chemotaxis and reduced degranulation.

25
Q

What are the side effects of sulphalazine?

A

Myelosuppression, hepatitis, rash.

Nausea, abdo pain, vomiting.

26
Q

What is the benefit of using sulphalazine?

A

Very few drug interactions, safe in pregnancy, no long term monitoring needed.

27
Q

What are the newer biologicals being introduced?

A

Monoclonal antibodies designed to block any given substance in body or to target any specific cell type. Eg rituximab.

28
Q

What is the effect of anti TNF alpha drugs?

A

Decreased inflammation
Decreased angiogenesis
Decreased joint destruction

pharmacology (22 decks)

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