Autoimmune diserase Flashcards
1
Q
Aminosalicylates
Common indications
A
- Mesalazine is used first-line in the treatment of mild-to-moderate ulcerative colitis; sulfasalazine is an alternative but has largely been replaced by mesalazine for this indication
- sulfasalazine is one of several options for the management of RA, in which it is used as a disease-modifying antirheumatic drug (DMARD), usually as part of combination therapy
2
Q
Aminosalicylates
MOA
A
- In UC, mesalazine and sulfasalazine both exert their therapeutic effects by releasing 5-aminosalicylic acid (5-ASA)
- The precise mechanism of action 5-ASA in unknown, but it has both anti-inflammatory and immunosuppressive effects, and appears to act topically on the gut rather than systemically
- For this reason, 5-ASA preparations are designed to delay delivery of the active ingredient to the colon
- The oral form of mesalazine comprises a tablet with a coating that resists gastric breakdown, instead of releasing 5-ASA further down the gut
- Sulfasalazine consists of a molecule of 5-ASA linked to sulfapyridine
- In the colon, bacterial enzymes break this link and release the two molecules. Sulfapyridine does not contribute to its therapeutic effect in UC, but it does cause side effects, and for this reason it has largely been replaced by mesalazine for this indication
- By contrast, sulfapyridine is probably active in RA, though its mechanism is unclear. Mesalazine has no role in RA
3
Q
Aminosalicylates
Important adverse effects
A
- Mesalazine generally cause fewer side effects than sulfasalazine
- Most commonly, these are GI upset (N&V, dyspepsia) and headache
- Both drugs can cause rare but serious blood abnormalities (e.g. leucopenia, thrombocytopenia) and renal impairment
- In men, sulfasalazine may induce a reversible decrease in the number of sperm (oligospermia)
- It can also cause a serious hypersensitivity reaction comprising fever, rash and liver abnormalities
4
Q
Aminosalicylates
Warnings
A
- Mesalazine and sulfasalazine are salicylates, like aspirin
- Patients who have aspirin hypersensitivity should not take these drugs
5
Q
Aminosalicylates
Important interactions
A
- Mesalazine tablets with a pH-sensitive coating (Asacol MR) may interact with drugs that alter gut pH (e.g. omeprazole PPI), increase gastric pH so may cause the coating to be broken down prematurely
- Lactulose lowers stool pH and may prevent 5-ASA release in the colon
6
Q
Aminosalicylates (Mesalazine, sulfasalazine)
Prescription
A
- In patients with rectal or rectosigmoid UC, a mesalazine enema or suppository is generally recommended in the first instance
- In an acute attack, this is taken OD/BD for 4-6 weeks in an attempt to induce remission
- If the disease is more proximal, or the patient would prefer not to take the drug rectally, an oral formulation may be used
- Drug choice (and therefore dosage regimen) is likely to be dictated by local policies
- Decisions regarding choice of therapy in RA should be taken by a specialist
7
Q
Aminosalicylates (Mesalazine, sulfasalazine)
Administration
A
- The commonly used Asacol foam enema requires thorough mixing before administration, by shaking the can vigorously for 2 15-second periods
- An applicator is then attached, and this is inserted as far as possible into the rectum
- The can must be upside-down when the dome is pressed and released to deliver a dose
- The applicator should then be removed and disposed of cleanly, and the patient should wash their hands
- For suppositories, patients should empty their bowels first if necessary, insert the suppository, then avoid opening their bowels for at least an hour if possible
- Tablet forms of mesalazine should be swallowed whole; not chewed or crushed
8
Q
Aminosalicylates (Mesalazine, sulfasalazine)
Communication
A
- Explain the aim of treatment as appropriate for the indication
- Ensure the patient understands how to take the medicine, particularly if it is a rectal preparation
- Ask them to report any unexplained bleeding, bruising or ineffective. symptoms to a doctor as soon as possible, since this could be a sign of blood count abnormality that may require urgent assessment
9
Q
Aminosalicylates (Mesalazine, sulfasalazine)
Monitoring
A
- The best guide to efficacy in UC is the patient’s symptoms
- In RA, this may be supplemented by the CRP concentration and calculation of disease activity scores
- For safety, renal function should be checked in patients receiving oral mesalazine, and full blood count and liver profile monitored in patients receiving sulfasalazine
10
Q
Glucocorticoids systemic
Common indication
A
- To treat allergic or inflammatory disorders, e.g. anaphylaxis, asthma
- Suppression of autoimmune disease e.g. inflammatory bowel disease, inflammatory arthritis
- In the treatment of some cancers as part of chemotherapy or to reduce tumour-associated swelling
- Hormone replacement in adrenal insufficiency or hypopituitarism
11
Q
Glucocorticoids systemic
MOA
A
- These corticosteroids exert mainly glucocorticoid effects
- They bind to the cytosolic glucocorticoid receptors, which then translocate to the nucleus and bind to glucocorticoid-response elements, which regulate gene expression
- Corticosteroids are most commonly prescribed to modify the immune response
- They upregulate anti-inflammatory genes and downregulate pro-inflammatory genes (e.g. cytokines, TNF-a)
- Direct actions on inflammatory cells include suppression of circulating monocytes and eosinophils
- Their metabolic effects include increased gluconeogenesis from increased circulating amino and fatty acids, released by catabolism (breakdown) of muscle and fat
- These drugs also have mineralocorticoid effects, stimulating Na+ and water retention and K+ excretion in the renal tubule
12
Q
Glucocorticoids systemic
Important adverse effects
A
- Immunosuppression increases the risk and severity of the infection and alters the host response
- Metabolic effects include diabetes mellitus and osteoporosis
- Increased catabolism causes proximal muscle weakness, skin thinning with easy bruising and gastritis
- Mood and behavioural changes include insomnia, confusion, psychosis and suicidal ideas
- Hypertension, hypokalaemia and oedema can result from mineralocorticoid actions
- Cortico suppresses pituitary ACTH secretion, switching off the stimulus for normal adrenal cortisol production
- In prolonged treatment, this causes adrenal atrophy, preventing endogenous cortisol secretion with CV collapse may occur
- Slow withdrawal is required to allow recovery of adrenal function
- Symptoms of chronic glucocorticoid deficiency that occur during treatment withdrawal include fatigue, weight loss and arthralgia
13
Q
Glucocorticoids systemic
Warnings
A
- Corticosteroids should be prescribed with caution in people with infection and in children (suppresses growth)
14
Q
Glucocorticoids systemic
Important interactions
A
- Corticosteroids increase the risk of peptic ulceration and GI bleeding when used with NSAIDs and enhance hypokalaemia in patients taking b2-agonists (salbutamol), theophylline, loop or thiazide diuretics
- Their efficacy may be reduced by CYP P450 inducers (e.g. phenytoin, CBZ, rifampicin)
- Corticosteroids reduce the immune response to vaccines
15
Q
Glucocorticoids systemic
Prescription
A
- Different corticosteroids have different anti-inflammatory potencies
- Dexa-750mcg=pred-5mg= Hydro-20mg
- Systematic corticosteroid treatment can be given orally or by IV/IM injection
- In emergencies (e.g. treatment of cerebral oedema caused by cancer), dexamethasone is prescribed at a high dose (e.g. 8mg BD orally or IV), then weaned slowly as symptoms improve
- In acute asthma, prednisolone is usually prescribed at a dose of 40mg OD
- Where PO administration is inappropriate (e.g. IBD flares, anaphylaxis), IV hydrocortisone may be used
- In long-term treatment, e.g. for inflammatory arthritis, use the lowest dose of oral prednisolone that controls disease while limiting adverse effects
- This may require co-prescription of steroid-sparring agents (e.g. azathioprine, MTX)
- Also consider the use of bisphosphonates and PPI to reduce some of the steroid side effects
