Pharmacology Flashcards
What are the aims of treatment for IBD?
Induce remission
Maintain remission
Prevent secondary effects
What is the first line of treatment for Ulcerative colitis and what does this drug do?
Aminosalicylates (ASAs)
- induce remission
- maintain remission
- prevent colonic cancer
What is the mechanism of action of Aminosalicylates?
Anti inflammatory (note entirely know how)
Inhibit synthesis of inflammatory mediators:
- prostgaglandins
- thromboxane
- platelet-activating factor
Scavenger of oxygen-radicals
What role do Aminosalicylates have in Crohn’s disease?
No evidence that is is any better to placebo for maintenance of medically induced remission
Give examples of aminosalicylates?
Sulfasalazine
Mesalazine
- Asacol
- Pentasa
- Mezavant
Olsalazine
Balsalazide
What are the side effects of sulfasalazine?
Allergic reactions
- rash
- fever (sign of infection)
- leucopenia
- agranulocytosis
Male infertility
- due to oligospermia and reduced sperm motility
Orange discolouration of body secretions
What should be done if someone has side effects to sulfasalazine?
Withdraw drug
Note does dependent
- reducing dose doess not rid of allergic reactions
Where is Mesalazine absorped in the body?
Completely and rapidly absorbed in the jejunum
- well tolerated
How can mesalazine be administered?
Oral and topical
How do the three main Mesalazine preparations differ?
Asacol
- pH dpeendent release mechanism
- favours ileum and colon release
Pentasa
- time controlled release
- pH-independent coating - acts throughout GI tract
Mezavant
- Multimatrix delivery system
What are the adverse effects of Mesalazine?
Diarrhoea
Headache
Nausea
Rash (1%)
Renal impairment rare but still monitor renal function
What interacts with Mesalazine?
Lactulose
What are the aim of Corticosteroids in IBD?
Induce remission in both IBDs
Do not play a role in maintenance therapy
What is the mechanism of action of corticosteroids?
Potent anti-inflammatory agents
Inhibit inflammatory responses
What are the anti-inflammatory and immunosuppresive effects of corticosteroids?
Inactivates pro-inflammatory transcription factors
- NF-KB
- AP-1
Prevent stimulation of inflammatory mediators
- prostaglandins
- leukotrienes
- cytokines
- platelet activating factor
What are the adverse effects of corticosteroids?
Symptoms of Cushing’s
Why must corticosteroids not be stopped immediately after use?
Risk of addisonian crisis due to feedback mechanisms
What else must be given when administrating steroids?
Give bone protection
- Ca2+
- Biphosphonates
What are the steroids used and in what order for inducing remission of IBD?
IV hydrocortisone, then reduce to:
Oral prednisolone, then:
Stop
What are thiopurines used for in IBD?
Unlicensed medication used in both Crohn’s and UC when ASAs and innefective or untolerated, and steroid use is not having enough effect
Give examples of Thiopurines used in IBD?
Azathiprine
Mecaptopurine
What is Azathiprine metabolised to?
6-Mecaptopurine
What are the adverse effects of Azathioprine?
Allergic reactions
- fever
- arthralgia
- rash
Bone marrow suppression
Leukopenia
Hepatotoxicity
What must be done to ensure safety in use of azathiprine?
Blood monitoring: FBCs and LFTs weekly for first 8 weeks then every 3 months
What enzyme metabolises Thiopurines?
Thiopurine methyltransferase
What is Ciclosporin used for in IBD?
Used to induce remission in active severe Ulcerative colitis in patients who have failed to respond to IV steroids
What are the adverse effects of ciclosporin?
Hypertension
Infection
Renal impairment
Increase seizures with IV if:
- hypocholesterolaemia
- hypomagnesaemia
GUM hypertrophy and hirsutism
Which drugs do ciclosporin interact with?
Enzyme inhibitors
e.g. Macrolides
What is Methotrexate used for in IBD?
Induction and maintenance of remission in Crohn’s disease
2nd line immunosuppressant in patients resistant or intolerant to AZA or 6-mecaptoupurine
What are the side effects of methotrexate?
GI (folic acid may reduce risk of SEs)
- nausea, vomiting, diarrhoea
Hepatotoxicity
Blood dyscrasias
What do monoclonal antibodies do and give two examples?
Target specific immunological and inflamamtory pathways
e.g. Infliximab and Adalimumab inhibit TNF-alpha
What is infliximab?
Describe it’s mechanism of action
A chimeric (human and mouse) anti-TNF antibody
Targets membrane bound TNF
Kill host cell by complement induced lysis
Anti-inflammatory action
What should infliximab be used for?
Severe active Crohn’s or fistulating severe active crohn’s
- surgery innapropriate and unresponsive to AZA and steroids
Ulcerative colitis
- ciclosporin is contraindicated or clearly innapropriate
What are the cautions when using infliximab?
Tuberculosis screening
Delayed hypersensitivity reaction
Contraindicated in severe infection and severe heart failure
What is adalimumab and its indication?
Humanised monoclonal antibody
Inhibits TNF-alpha
Severe active Crohn’s only
