CPT S6 Rheumatology Flashcards by Jess Sidney

What is rheumatoid arthritis?

An autoimmune multi-system disease
Initially localized to the synovium
Cytokine involvement in inflammatory changes
Hyperplasia and proliferation of synovium

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Give some diagnostic features of RA

Morning stiffness of more than one hour
Arthritis of three or more joints
Involvement of hand joints
Symmetry
Rheumatoid nodules
Serum rheumatoid factor
X-ray changes

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What are some important factors to remember when considering a diagnosis of RA?

Need to eliminate cancer first
It’s a clinical diagnosis rather than one dictated by test results
Not all symptoms must be present to diagnose as many are late-stage

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What is the basic pathogenesis of RA?

overexpression of pro-inflammatory genes in comparison to anti-inflammatory genes

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What are the treatment goals for RA?

Symptomatic relief

PREVENTION OF JOINT DESTRUCTION

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What are the treatment strategies for RA?

Early use of disease-modifying drugs
Use of combinations of drugs
Use of adequate doses
Aim to achieve good disease control quickly
Avoid use of long-term corticosteroids

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What are the treatment goals in SLE and vasculitis?

Symptomatic relief
Mortality reduction by induction of disease remission the maintenance
Prevention of organ damage
Reduction in long term morbidity caused by disease and drugs

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Give some examples of immunosuppressants

Corticosteroids
Azathioprine
Ciclosporin
Tacrolimus
Mycophenolate mofetil

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Give some examples of other disease-modifying anti-rheumatic drugs (DMARDs)

Methotrexate (best)
Sulphasalazine
Anti-TNF agents (expensive)
Rituximab
Cyclophosphamide (cytotoxic though)

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When is Azathioprine used in practice?

Maintenence therapy in SLE &amp; vasculitis
Rarely in RA
IBD
Bullous skin disease
Atopic dermatitis
As a 'steroid sparing' drug

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What are the problems with Azathioprine?

Metabolized by TPMT, an extremely polymorphic gene, so need to test levels before prescribe because patients can develop myelosuppression

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Give some azathioprine ADRs

Bone marrow suppression (so monitor FBC)
Increased risk of malignancy (as with all immunosuppressants)
Increased risk of infection
Hepatitis (so monitor LFTs)

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How do ciclosporin & tacrolimus have their effect?

Both calcineurin inhibitors

So prevent IL-2 production by T-helper cells

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What is the mechanism of action of mycophenolate mofetil?

Inhibits monophosphate dehydrogenase, an enzyme required for guanosine synthesis
This impairs B and T-cell proliferation but spares other rapidly dividing cells due to guanosine salvage pathways presence in other cell types.

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Give some ADRs for mycophenolate

Nausea
Vomiting
Diarrhoea
Myelosuppression (not as bad as azathioprine
Metallic taste
May require monitoring
Toxicity more likely in renal and hepatic disease

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When is mycophenylate used in practice?

Primarily for transplantation

Lupus Nephritis

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What is the mechanism of action of cyclophosphamide?

Alkylating agent - crosslinks DNA to prevent replications

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What are some indications for cyclophosphamide?

Lymphoma
Leukaemia
Lupus nephritis*
Wegener's granulomatosis
Polyarteritis nodosum
*May not be as good as mycophenolate

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What are the actions of cyclophosphamide?

Extremely strong anti-inflammatory

suppresses B and T cell activity

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What are some ADRs for cyclophosphamide

May cause haemorrhagic cystitis
Renal excretion so adjust dose in renal impairment
Increased cancer risk
Infertility
Requires FBC monitoring
May not be the best drug for lupus nephritis and vasculitis.

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What is the mechanism of action of methotrexate?

For malignancy, it works as an anti-folate, but the mechanism of action is unknown in non-malignant disease

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What is methotrexate used for?

Gold standard for RA
Psoriasis
Crohn’s
Unlicensed for: inflammatory myopathies, vasculitis maintenance, steroid-sparing agent in asthma

Give some ADRs for methotrexate

Mucositis
Myelosuppression
Hepatitis
Cirrhosis
Pneumonitis
Increased infection risk
Highly teratogenic
Abortifacient
WEEKLY NOT DAILY DOSING

What toxicity monitoring is required for methotrexate?

Baseline CXR
Baseline FBC, LFT, U+Es, creatinine
Followed by regular (eg monthly) FBC, LFT, U+E

Give some actions of sulphasalazine

``` T cell inhibition of proliferation T cell apoptosis Inhibition of IL-2 production Reduced neutrophil chemotaxis Reduced neutrophil degranulation ```

Give some ADRs for sulfasalazine

``` Myelosuppression Hepatitis Rash Nausea Abdominal pain Vomiting ```

Give some positives for sulfasalazine

``` Safe in pregnancy Effective Favourable toxicity Long-term blood monitoring may be unnecessary Very few drug interactions Not a carcinogen ```

What are the effects of blocking TNF-alpha?

Inhibition of the cytokine cascade Inhibition of leukocyte recruitent Inhibition of elaboration of adhesion molecules Reduced production of chemokines Reduced angiogenesis due to reduced VEG-F and IL-8 levels Reduced joint destruction due to reduced destructive enzyme release

What is the stepwise management of asthma in adults?

``` Step 1: mild intermittent asthma Step 2: regular preventer therapy Step 3: add-on therapy Step 4: persistent poor control Step 5: continuous or frequent use of oral corticosteroids ```

What is prescribed for each step in the stepwise management of asthmatic adults?

1: Inhaled SABA as required 2: Inhaled corticosteroid 3: Inhaled LABA 4: Increased inhaled corticosteroid dose or addition of a fourth drug (leukotriene antagonist, SR theophylline) 5: Oral corticosteroids

Describe good asthma control

``` Minimal symptoms Minimal need for reliever medication No exacerbations No limitation of physical activity Normal lung function (FEV1 &/or PEFR>%predicted ```

What should be done before initiating a stepping up of asthma control?

Check compliance with current therapies Check inhaler technique Eliminate trigger factors

Briefly describe the pathophysiology of asthma

Th2-driven inflammation leads to: - Mucosal oedema - Bronchoconstriction - Mucus plugging - Bronchial hyperresponsiveness - (Potentially) Airway remodelling

Give examples of SABAs

Salbutamol | Terbutaline

What are the actions and mechanisms of SABAs?

Reversal of bronchoconstriction Prevention of bronchoconstriction Acts on bronchial smooth muscle to cause relaxation

Why should SABAs not be used regularly?

Results in poor asthma control | Due to reduced inhibition of mast cell degranulation in response to allergens

Give some side effects of beta 2 agonists

Tachycardia Palpitations Tremor

What are the actions of inhaled corticosteroids?

``` Improved symptoms Improved lung function Reduced frequency of exacerbations Prevention of death Due to reduced inflammation ```

Give examples of corticosteroids used in asthma

Beclomethasone Fluticasone Budesonide

Give examples of LABAs used in asthma

Formoterol | Salmeterol

Can LABAs be prescribed alone?

No. They are not anti-inflammatory alone, and MUST be prescribbed with steroids. Failure causes increased incidence of exacerbations and deaths.

How do Leukotriene receptor antagonists work?

Reduced LTC4 release by mast cells and eosinophils. | LTC4 can induce bronchoconstriction, mucus secretion and mucosal oedema, and promote inflammatory cell recruitment.

Give some ADRs of LRAs

``` Angioedema Dry mouth Anaphylaxis Arthralgia Fever Gastric disturbance ```

Give the mechanism of action of methylxanthines

We don't really know | Could be phosphodiesterase of adenosine receptors

Give some examples of methylxanthines

Theophylline (PO) | Aminophylline (IV)

Give some methylxanthine ADRs

``` Narrow therapeutic window Nausea Headache Reflux Toxic compilcations; arrhythmias, seizures Many interactions ```

Give some ADRs for LAMAs

Dry mouth Urinary retention Glaucoma

Give some examples of LAMAs

Tiotropium | Ipratropium

What are the clinical uses of LAMAs?

Mainly COPD Can be used in step 4 or 5 of asthma control too Reduces exacerbations in both

Give some signs of severe acute asthma in adults

Any one of: - Unable to complete sentences - Pulse >110b/m - Respiration rate >25/m - Peak flow 33-50% predicted

Give some features of life-threatening asthma

``` PEF 4.5kPa Silent chest Cyanosis Feeble respiratory effort Hypotension Bradycardia Arrhythmia Exhaustion Confusion Coma ```

Give some features of near-fatal asthma

PaCO2 >6kPa | Mechanical ventilation

What is the treatment of severe acute asthma?

``` High flow O2 - aim for >94% sats Nebulized salbutamol Oral prednisolone 40mg for 10-14 days Can add nebulized ipratropium if poor improvement Consider aminophylline if no improvement ```