Flashcards in Session 6 Deck (41):
What is rheumatoid arthritis?
A chronic, autoimmune, multi-system condition resulting in inflammation of the synovium.
What causes inflammation in rheumatoid arthritis?
T-cell activation and production of rheumatic factor, stimulating macrophages via IgG Fc receptors.
What is rheumatic factor?
A circulating autoantibody that once bound to the Fc region of the IgG, results in immune complex formation and an inflammatory reaction. Results in persisting synovitis.
What is inflamed synovium known as and what can it cause?
A pannus. Can damage underlying cartilage by blocking its route of diffusion, meaning the cartilage becomes thin and the bone exposed.
How does rheumatoid arthritis present?
Slowly progressing and symmetrical, with peripheral polyarthritis developing over weeks to months. Pain and stiffness in the hands that is worse in the morning, and improves with gentle activity.
What deformities of the hand can be present with RA?
Ulnar deviation, fixed flexion of fixed hyperextension in the PIP.
Swelling and dorsal subluxation of the ulnar styloid process.
What are the main drugs used to treat RA?
Disease-modifying anti-rheumatic drugs.
What is methotrexate and how does it work?
It is a DMARD and an immunosuppressant. It works as a folic acid antagonist.
How does methotrexate differ in malignant and non-malignant disease?
Malignant: allosterically inhibits DHFR, hence inhibits DNA synthesis and subsequent RNA and proteins. Has a greater effect on rapidly dividing cells.
Non-malignant: inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine within the cell. Adenosine reduces activity of T-cells.
What is the oral bioavailability of methotrexate and how is it eliminated?
13-76% and it is renally eliminated mainly.
Give two examples of ADRs of methotrexate.
Mucositis, bone marrow suppression, hepatitis, cirrhosis and it's teratogenic.
Give two examples of methotrexate DDIs.
Immunosuppressants, anti-cancer drugs and autoimmune drugs.
What is sulfasalazine and what is it used for?
A combination of 5-aminosalicylate and sulfapyridine.
Acts in RA to inhibit T-cell proliferation and IL-2 production. Reduces neutrophil chemotaxis and degranulation.
What category of drug are anti-TNF agents and B-cell depletors?
Give two examples of Anti-TNF agents.
Infliximab and Adalimumab.
Name 3 types of immunosuppressants.
4) Mycophenolate Mofetil
5) Calcineurin inhibitors
How do corticosteroids work as immunosuppressants?
Inhibit gene expression. Prevent IL-1 & IL-6 production and inhibit T-cell activation.
How does azathioprine work as an immunosuppressant?
Inhibition of purine metabolism, reducing RNA and DNA synthesis.
What causes undertreatment when using azathioprine?
High levels of TPMT as this eliminates 6-MP, which is the activated form of azathioprine.
How does cyclophosphamide work as an immunosuppressant?
It is a cytotoxic alkylating agent. Forms crosslinks between and within DNA strands, preventing replication.
Give 2 ADRs of cyclophosphamide.
Bladder cancer, lymphoma, leukaemia, infertility and teratogenesis.
How does Mycophenolate Mofetil work as an immunosuppressant?
Increases oral bioavailability of MPA, which inhibits inosine monophosphate dehydrogenase which is needed for guanine synthesis. Impairs B-cell and T-cell proliferation.
How do calcineurin inhibitors work as immunosuppressants?
E.g. ciclosporin and tacrolimus. Prevent the production of IL-2 via calcineurin inhibition.
Give two ADRs of calcineurin inhibitors.
Nephotoxicity, hypertension, hyperlipidaemia, nausea, vomiting, diarrhoea and hyperuricaemia.
What is asthma?
Inflammatory disease, resulting in airway obstruction and inflammation, caused by bronchoconstriction, mucosal oedema and mucus plugging.
What are the two phases of asthma?
Immediate phase: initial response to allergen, causes interaction of mast cells with IgE. Release of histamine and bronchospasm.
Late phase: Leukocytes enter the area, resulting in bronchospasm, thickening of BM, oedema and mucus production.
What is bronchial hyperresponsiveness?
Exaggerated bronchoconstrictor response to direct and pharmacological stimuli such as histamine.
How do bronchodilators work?
Bind to B2-adrenoceptors in bronchial smooth muscle, resulting in increased cAMP, decrease in intracellular calcium and preventing muscle constriction.
What is the ideal size of particles of B2-agonists?
Give two examples of fast onset bronchodilators.
Short duration = salbutamol and terbutaline.
Long duration = formoterol.
Give an example of a slow onset bronchodilator.
Give two ADRs of bronchodilators.
Tachycardia, tremors, palpitations.
How to muscarinic receptor antagonists work to treat asthma?
E.g. Ipatropium. Bind to M3 receptor of bronchial smooth muscle, blocking the constricting effect of ACh and inhibits mucus secretion.
What is the role of corticosteroids in the management of asthma?
Anti-inflammatory as supress gene transcription in inflammatory cells. Also increase expression of b2-receptors and anti-inflammatory IL proteins. Reduce number of mast cells in respiratory mucosa.
Give an advantage of using combined inhalers.
Easy to use, good compliance, safer and cheaper. E.g. Symbicord (budesonide and Formoterol).
Give three signs of good asthmatic control.
-Minimal symptoms during day and night
-Minimal need for reliever inhaler
-No limitation of physical activity
-Normal lung function
Describe step one and two of the 5-step asthma control.
1) Inhaled short-acting B2-agonist when required.
2) Addition of inhaled steroids.
Describe the criteria for initiation of steroids in asthma.
-Using B2-agonists more than 3 times a week
-Symptoms more than 3 times a week
-Waking more than once a week
-Exacerbation requiring oral steroids in the last two years.
Describe steps 3, 4 and 5 of the 5-step astha control.
3) Re-check compliance and inhaler technique. Add a long acting B2-agonist.
4) Increase inhaled steroid levels or add a fourth drug.
5) Add an oral steroid tablet or Anti-IgE therapy.
What are the four criteria for acute severe asthma in adults?
1) Unable to complete sentences
2) Pulse more than 110 BPM
3) RR over 25.
4) Peak flow 33-50% of best/predicted.