Pharmaceutical care - drugs used in IBD Flashcards
(60 cards)
Before drug modifications where the absorption of Mesalazine occur?
Primarily all within the small intestine, therefore would be inappropriate for the indication of UC which would require drug targeting of the large intestine.
Describe the modifications made to Mesalazine for colonic drug delivery?
In sulfasalazine, Mesalazine is bound to a sulfapyridine via an azo-bond.
The drug is delivered to the colon and the active drug Mesalazine is absorbed there as it is the colonic bacterium present within the colon that releases azo-reductase which cleaves the azo-bond releasing the active drug.
What is the outcome of Sulfapyridine when it is released from the drug molecule?
Absorbed by the colon
Metabolised in the liver
Excreted in the urine
What is the outcome of Mesalazine when it is released from the drug molecule?
Mesalazine exerts a topical effect on the mucosa.
30% of the free drug is absorbed
Metabolised locally and in the liver to an inactive form and free/conjugated drug is
excreted in the urine or faeces
What are the contra-indications of Sulfasalazines?
Hypersensitivity to sulfapyridine/sulfonamides or 5-
aminosalicylate/salicylates
What are the cautions of Sulfasalazine use?
History of asthma (due to causing dyspnoea and cough and therefore cautioned with those with a reduced pulmonary reserve)
Risk of haematological toxicity (ability to cause blood disorders)
Renal and hepatic impairment (metabolism and excretion routes are dependent)
Glucose-6-dehydrogenase (G6PD) deficiency
Slow acetylator status (sulfapyridine undergoes acetylation before excretion)
What are the common side effects of sulfasalazines?
Headaches
Nausea
Fever
Rash
Reversible infertility in men
Reduced white cell count
What are some of the common patient reported symptoms?
Loss of appetite
Nausea
Sensitivity to sunlight
Nervousness
How common are headaches with sulfasalazine use?
Occur in up to 1/3 of patients
But is more commonly associated with higher doses
Reduced rate when the dose is increased gradually
What are some of the uncommon and rare side effects associated with sulfasalazine use?
Uncommon:
Pancreatitis
Rare:
Hepatitis
Pneumonitis
Skin reactions
Kidney inflammation / renal impairment
Haemolysis
What are the monitoring parameters for sulfasalazine?
FBC and LFTs: Before initiation and every second week for first 3 months, then monthly for three months then every 3 months
Creatinine/eGFR – Monthly for 3 months then as indicated
All are as indicated, if there are deteriorations in results you would expect an increase in monitoring frequency
What symptoms would you advise patients to look out for whilst taking sulfasalazine?
Sore throat, fever, malaise, jaundice and unexpected non-specific illness - may indicate myelospuppression, haemolysis or hepatotoxicity
What can sulfasalazine stain?
Urine
Contact lenses
State the four delivery mechanisms for Mesalazine and give brand examples.
Attachment to other carrier molecules (olsalazine – mesalazine dimer, could either be drug-carrier or drug-drug)
* pH dependent formulations (Salafalk/granules)
* Time dependent formulations (Pentasa/granules)
* Multi-matrix system (Mezavant)
Are there specific patient groups that would benefit for one Mesalazine formulation over another?
No, there doesn’t appear to be any evidence to suggest that certain formulations of Mesalazine are more beneficial for certain patients.
Instead a formulation choice is made upon disease distribution, efficacy, side effects, release profile and patient preference
What is the purpose of using enteric coated Mesalazine?
Prevents early disintegration of the drug in the upper gastrointestinal system by binding the drug to a pH sensitive carrier molecule.
What is the difference between Eudragit S and Eudragit L- which would be more appropriate for UC?
Eudragit S is sensitive and will dissolve at a pH greater than or equal to 7.
Eudragit L is sensitive and will dissolve at a pH greater than or equal to 6.
As the duodenum has a pH of 6-7 and the ileum has a pH of above 7- choice is dependent of which part of the large bowel is affected by UC.
It is also important to consider that the pH of the large bowel is reduced by IBD
What is Eudragit S and L made from?
Methyl acrylate copolymer coating
How does time dependent drug delivery of Mesalazine work?
Consists of microspheres of mesalazine encapsulated in ethylcellulose semi-permeable membrane.
The release of the drug is dependent upon time and moisture and independent of the pH.
How does the multi-matrix system work?
Mesalazine incorporated into lipophilic matrix and enterically coated (so will dissolve at a pH greater than 7).
The matrix will swell up to form a gel allowing slow diffusion and enabling delivery of the drug to the terminal ileum and entire colon.
What is the formulation, optimal pH for drug release and site of release for Asacol MR / Mesren?
Formulation: enteric coat with Eudragit S
Optimal drug release pH: greater than seven
Site of release: Terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Salofalk?
Formulation: enteric coat with Eudragit L
Optimal drug release pH: greater than six
Site of release: mid to terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Salofalk granules?
Formulation: Matrix core with Eudragit L coating
Optimal drug release pH: greater than six
Site of release: mid to terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Octasa?
Formulation: Enteric coat with Eudragit S
Optimal drug release pH: greater than seven
Site of release: Terminal ileum and large bowel
