Drug Therapy in Ulcerative Colitis

Ulcerative colitits (UC) is a type of inflammatory bowel disease that involves the inflammation of the colon and rectum. It causes continuous lesions and affects primarily the mucosa and submucosa.

The extent of bowel involvemnt in UC

Proctitis: involvement limited to the rectum
Distal/left-sided colitis: inflammatory process extends from the rectum 40cm
Pancolitis: inflammation that affets the entire colon

Treatment of UC centres on agents used to relieved the inflammatory process and the pharmacologic agents are:
1) Aminosalicylates- Sulphasalazine, 5-aminosalicyclic acid (Europe: mesalazine, USA: mesalamine)

2) Corticosteroids 3) Immunosuppresive agents
-Thiopurines: azathioprine, mercaptopurine
(primary benefit: steroid sparing effect; limitation: slow onset of action, up to 3-6 months treatment may be necessary to appreciate an optimal effect)
-Cyclosporine
-Infliximab


Sulphasalazine is cleaved by gut bacteria in the colon to sulfapyridine & mesalazine (active component). Sulfapyridine is responsible for many of the side effects of sulphasalazine-
Dose-related: GI disturbances, headache, arthralgia
Idiosyncratic reactions: toxic epidermal necrolysis, exfoliative dermatitis, hepatotoxicity

Sulfapyridine is a sulfonamide, hence it is NOT to be used in patient with allergy to sulfa drug or G6PD deficiency.

Despite the side effects of sulphasalazine, it is still used due to its much cheaper price.



Free mesalazine is a zwitter ion; when administered orally, it undergoes rapid and nearly complete systemic absorption from the proximal small intestine.

There are 2 brands of mesalazine available in Malaysia: Pentasa and Salofalk. The different delivery characteristics of Pentasa and Salofalk (as shown in the table below) mean that they are not interchangeable. Hence, prescription should be by the trade-name rather than the generic drug name. The choice of mesalazine depends on the extent/site of bowel involvement in UC.



Mesalazine suppository is most appropriate for proctitis, while mesalazine enema is suitable for more extended disease affecting the sigmoid or greater parts of the left colon.



The following algorithms are derived from Ulcerative colitis practice guidelines in adults: American college of Gastroenterology, Practice Paramameters Committee.



Antibiotics Use in UC
There have been cases whereby UC patient was given t. ciprofloxacin 500mg bd and t. metronidazole 400mg tds in the ward.

In fact, there is no evidence to support the use of antibiotics in UC.

BMJ 2006; 333 :

-Antibiotics indicated if doubt exists about the diagnosis (e.g.in the case of a first attack) or if the patient has recently travelled to an area where amoebic dysentery is endemic.

-Patients can be started on metronidazole and a quinolone empirically in this situation. Stool should be taken for culture (including assessmentof C difficile toxin) in all patients.

Gastroenterology 1998; 115(5):

-Ciprofloxacin reduced treatment failure in ulcerative colitis at 6 months but not at 12 months

-prednisone (0.75 mg/kg/day for 4 weeks then 0.5 mg/kg/day for 4 weeks then 0.25 mg/kg/day for up to 12 weeks then tapered if possible) and mesalamine (800 mg twice daily for 12 months) and ciprofloxacin (500-750 mg twice daily for 6 months)

-prednisone and mesalamine and placebo

Am J Gastroenterol 2010; 105:

In the absence of any proven infection, controlled trials of antibiotics have showed no therapeutic benefit from the use of IV metronidazole or ciprofloxacin when added to intravenous steroids.

However, protocols outlining treatment regimens for severe colitis generally include broad-spectrum antibiotics for patients with signs of toxicity, or with worsening symptoms despite maximal medical therapy.

Antidiarrhoeals Use
Antidiarrhoeals such as loperamide and diphenoxylate do not reduce stool frequency in colitis; instead, they increase the risk of toxic megacolon and are best avoided in patients with severe disease.



References

1. DiPiro JT and Schade. Inflammtory bowel disease. In Wells BG, Dipiro JT, Schwinghammer TL and Hamilton CW (editors) Pharmacotherapy. USA: The McGraw-Hills Company; 2006. p.649-662.

2. Baumgart DC and Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. The Lancet 2007; 369: 1641-1657.

3. John Hopkins Medicine. Ulcerative colitis (Accessed 2010 April 28^th). Available from: URL:http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Disease_ID=2A4995B2-DFA5-4954-B770-F1F5BAFED033&GDL_DC_ID=D03119D7-57A3-4890-A717-CF1E7426C8BA

4. Collins P and Rhodes J. Ulcerative colitis: diagnosis and management. BMJ 2006; 333: 340-343.

5. Dukes GE and Duncan BS. Inflammatory bowel disease. In Yong LL, Koda-Kimble MA (editors). Applied therapyeutics-the clinical use of drugs. Pennsylvania: Lippincott Williams & Wilkins;1995. p. 24-2—24-11.

6. Sandborn WJ and Hanauer SB. Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis. Aliment Pharmacol Ther 2003; 17: 29–42.

7. Forbes A and Chadwick C. Mesalazine Preparations. The Lancet 1997; 250 (9087): 1329.

8. Turunen UM, Färkkilä MA, Hakala K et al. Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study [Abstract]. Gastroenterology 1998; 115(5): 1072-1078.

9. Kornbluth A and Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 105:501–523. Available from: URL: http://www.gi.org/physicians/guidelines/UlcerativeColitis.pdf

Is aspirin taken at night time better than morning?

Recently a friend of mine asked about whether is it rationale to change aspirin recommendation to be taken at night than morning? What do you think :

"Aspirin taken at bedtime compared with on awakening significantly diminished 24-hour plasma renin activity and excretion of cortisol, dopamine, and norepinephrine in 24-hour urine. Decreased activity of these pressor systems forms a biologically plausible explanation for the finding that aspirin at night may reduce blood pressure, whereas aspirin at morning does not. "

Snoep JD, Hovens MMC, Pasha SM, et al. Time Depedent Effects of Low-Dose Aspirin on plasma renin activity, aldosterone, cortisol and catecholamine.Hypertension 2009; 54: 1136.

"This prospective trial documents a significant administration time-dependent effect of low-dose ASA on BP in untreated hypertensive patients. The timed administration of low-dose ASA could provide a valuable approach, beyond the secondary prevention of cardiovascular disease, in the added BP control of patients with mild essential hypertension. "

Hermida RC, Ayala DE, Calvo C, et al. Aspirin Administered at Bedtime, But Not on Awakening, Has an Effect on Ambulatory Blood Pressure in Hypertensive Patients. Journal of the American College of Cardiology. 2005; 46: 975-83

& you may check out these 2 sites more for information :

Commentary from Yip HL et al, based on a reply from Kriszbacher I et al on the possible of aspirin for stroke prevention taken in the evening? http://stroke.ahajournals.org/cgi/content/full/35/12/2760

Snoep JD et al. Time Depedent Effects of Low-Dose Aspirin on plasma renin activity, aldosterone, cortisol and catecholamine.Hypertension 2009; 54: 1136. & Commentary from Black HR on this article,published in Medscape Cardiology: Available online http://www.medscape.com/viewarticle/716196

PRP Posting

Congratulations to all B106!! Now that it is over and done, the next big thing after convocation (the attire/shoes hunting, booking of hotels/plane tics for family etc.) and perhaps, graduation trip, at this juncture in your life is none other than the provisionally registered pharmacist (PRP) placement location.


By now, the uni would have gotten you all to fill up the necessary forms and what awaits you all is the SPA interview. My seniors had told me that whatever state you fill (for your posting) in the previous forms are not that important, it is THE FORM which you will be filling in during the day of SPA interview that counts...so you do have some time to think about it before your interview.


Now the interview is just a formality but a grand senior had told me that a few friends of hers failed the interview. They were asked 'if we send you to sabah/sarawak, would you go?' and they answered 'no'. My senior's reasoning is that the gov is trying to see if we 'menurut perintah'so probably the political-correct-cum-neutral answer is 'I will go but I will be sad that I am leaving my parents in my home state'. (Disclaimer: I am no HR manager in the gov sector)

For fledgling pharmacists in overseas who would like to practise their PRP year (known as 'pre-reg' in UK) back home, do visit HERE as my friend ka keat has put up a comprehensive guide on PRP application.


But I digressed. Back to the posting location; after the spa interview, we will be placed by KKM to a particular STATE, the exact hospital which we will be posted to lies on the Jabatan Kesihatan Negeri (JKN) of the particular state. If you are placed in a certain state, (based on past examples), you will most likely be in the state for some time as cross-state transfer is very difficult indeed and you need really valid reason or strong cable.


I am sure as resourceful as all bpharmers are (thanks to all the portfolios and PBLs)*cough*, you all would have done or must be doing your 'research' and are pondering over factors like:
-the love for clinical (hospital) or bureau?

-higher allowance for those who from west malaysia who get placed in east malaysia (but higher chances of getting smaller districts in east malaysia in 2nd year)


You should MAXIMISE your chances of getting what you what by being willing to 'compromise'; you probably would like to consider putting other state in the THREE choices that you have instead of filling them up with hospitals/institutions in kl/selangor (if you are from kl/selangor)


When I filled up my choice, I did it based on probability. If you look at the Second Schedule of your Registration of Pharmacists Act 1951, there is a list of premises that you can be posted to. There are 13 premises (10 hosps, bureau, bhg farmasi, cawangan penguat kuasa farmasi) in Selangor, 3 in WP Kuala Lumpur (I didn't know then that HKL is a 'separate entity', so in actual fact only Hosp Putrajaya and cawangan penguat kuasa farmasi fall under WP Kuala Lumpur).


Although there are hospitals like Hosp Tg. Karang, Kuala Kubu Baru, Banting and Sabak Bernam in Selangor, based on probability, Selangor is still the sensible choice (to me). At that time, I was thinking, how 'ngam' can it be, right? So I bit the bullet and never did take the middle ground.


I was posted to Hosp. Sabak Bernam (the furthest hosp in Selangor!!). Now, here are the probably-not-so-known-facts to you all: a prp who is posted to district hospitals like Hosp Sabak Bernam, Hosp Banting will get to do their clinicals in Hosp Klang or Hosp Selayang! So if you get the place, don't think you will be missing out and quickly appeal for placement at another state. And as most seniors who get postings out of their home states will tell you, after some time, you will see past all the initial frustrations/disappointments.......


To me, getting over the posting (for those who do not get what they want) is indeed like the Kubler-Ross Model: 5 Stages of Grief

1. Denial
'This can't be happening to me..... (name of state), I am not 'related' to it in any way (not even my parents' hometown)'


2. Anger
'Why me? It is not fair!!' 'He/she who................(fill in the blanks yourself) get that but I get this?'


3. Bargaining
'I'd rather be in that hospital in (name of state) although it is very hot!!'
'I don't mind working in (name of state) as I love the food there!'


4. Depression
[Thankfully, so far there is nobody that I know of who was in this stage]


5. Acceptance
'It is going to be alright. It is just one year'
'At least I get to come back on weekends'


So to bite the bullet or not to? to have a soft landing or not to? Please analyse the market yourself....the rumoured rough numbers of frps leaving gov service, the number of fresh graduates like you all going into the job market, any shortage in a certain state, the number of ppl with cables..... At the end of the day, there is just so much we can do, but we should still maximise our chance nonetheless. Wherever you may be, do keep an open mind and embrace your profession with passion=)

Immunosuppressant for Renal Transplant : Update & Summary

As a special offer to whoever viewing this blog, again, "Immunosuppressant for Renal Transplant : Update & Summary", is available upon your request to :

1. bpharmer05@gmail.com

OR

2. dmcancw@yahoo.com, direct to me, Mai. I will then send to you after receiving your email.

I guess we will be happy to share the knowledge from any institution. If you want to post up anything or any information, u can email to us the content.

also, if u do come across any issue that you would like us to look into, u may also email to us. we will try our best to dig n to response to u, as soon as possible.

=) Mai

How Should I Respond to an Angry Client?

All of us once-awhile, will have to deal with some angry client, whether the public, nurses or doctors. Here is an article extracted from Medscape, from Bonnie L. Senst, MS, RPh Clinical Assistant Professor, University of Minnesota College of Pharmacy, Minneapolis, Minnesota; Director, Allina Pharmacy Practice, Allina Hospitals and Clinics, Minneapolis, Minnesota. (published 08/04/2010)

Some basic principles of communication can help ease an otherwise tense interaction. As the angry person explains his or her problem or need, it is very important to listen attentively. Do not interrupt, or you may escalate his or her anger. The book Crucial Confrontations discusses the need to dissipate the emotion before you can address the content of the argument. The author lists several things that you should not do:

• Don't get hooked. Don't allow yourself to become angry in response.
• Don't try to "one up" the other person. Stay focused on the central problem, and don't introduce your own problems.
• Don't patronize. Telling people to calm down only throws gas on the flames.

Once the client's anger is de-escalating and you get an opportunity to respond, acknowledge the complaint and say that you are sorry. Ask for additional details or suggestions for an acceptable resolution of the problem. Be sure to keep a positive attitude. Show the client that you are intent on solving his or her problem. Describe what steps you will take and follow through on your commitments. Thank the individual, and encourage him or her to let you know if any other issues arise in the future.

Some people believe that saying "I'm sorry" is admitting guilt and therefore have suggested the alternative term "I regret..." Quint Studer, founder of the Studer Group, an outcomes-based healthcare consulting firm, maintains that saying you are sorry does not mean you are admitting a mistake. He suggests using such phrasing as "I am sorry you are disappointed" or "I am sorry that we are not meeting your expectations."

Suggested Reading (along with the article)

• Clark PA, Malone MP. Making it Right: Healthcare Service Recovery Tools, Techniques, and Best Practices.Marblehead, MA:HCPro, Inc.; 2005.
• Baker SK, Bank L. I'm Sorry to Hear That: Real Life Responses to Patients' 101 Most Common Complaints About Health Care. Gulf Breeze, FL:Fire Starter Publishing; 2008.
• Diering SL. Love Your Patients! Improving Patient Satisfaction with Essential Behaviors that Enrich the Lives of Patients and Professionals. Nevada City, CA: Blue Dolphin Publishing; 2004.

Also available from http://www.medscape.com/viewarticle/719548?src=mp&spon=30&uac=102525PG (Accessed 15/4/2010)

Refeeding Syndrome

In my 2-week attachment at the surgical ward, I came across quite a few Total Parenteral Nutrittion (TPN) cases. The calories required by patient is calculated based on 20 kcal/kg then titrate up by 5 kcal/kg. The reason for this is to prevent refeeding syndrome.


Refeeding syndrome is the potentially fatal shift in fluids and electrolytes that may occur in malnourished patients receiving artificial feeding (enterally or parenterally). It was first described inFar East prisoners of ward in WWII. Eating again after prolonged period of starvation seemed to precipitate cardiac failure.

Prolonged Fasting
Muscles & other tissues: decrease use of ketone bodies, use fatty acids as main energy source

Increase in blood levels of ketone bodies stimulate the brain to use ketone bodies (instead of glucose) as its main energy source

Liver decreases rate of gluconeogenesis, thus preserving muscle protein

Several intracellular minerals become severely depleted during the period of prolonged starvation. However, serum concentrations of these minerals (including phosphate) may remain normal because they are mainly in the intracellular compartment.

Refeeding
Sudden shift from fat to carbohydrate metabolism occurs and secretion of insulin increases

Insulin stimulates glycogen, fat & protein synthesis, which require minerals such as phosphate (Po4) & Magnesium (Mg) and cofactors such as thiamine.

Insulin stimulates the absorption of K into the cells through Na-K-ATPase symporter, which also transports glucose into the cells.

Mg and PO4 are also taken up into the cells, water follows by osmosis.

These result in a decrease in the serum levels of PO4, Mg, K, all of which are already depleted.

This phenomenon usually occurs within 4 days of starting to feed again.


How can refeeding syndrome be prevented?
Identify patients with high risk of developing refeeding syndrome, and the management that follows suit is illustrated in the figure below.

Patients with high risk of developing refeeding syndrome-
1. Patients with 1 or more of the following:

• BMI <16>
• Unintentional weight loss > 15% in the past 3-6 months
• Little or no nutritional intake for > 10 days
• Low levels of K, Mg, or PO4 before feeding

2. Patients with 2 or more of the following:

• BMI > 18 kg/m2
• Unintentional weight loss > 10% in the past 3-6 months
• Little or no nutritional intake for > 5 days
  
• History of alcohol misuse or drugs, including insulin, antacids, chemotherapy or diuretics

The NICE guidelines recommend that refeeding should start at a maximum of 0.021 MJ/kg/day (10 kcal/kg/day), with cardiac monitoring due to the risk of cardiac arrhythmias.



References
1. Hearing SD. Refeeding syndrome is underdiagnosed and undertreated, but treatable. BMJ 2004; 328 (7445): 908-909. Available from: URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC390152/

2. Mehanna HS, Moledina J and Travis J. Refeeding syndrome: what it is, and how to prevent adn treat it. BMJ 2008; 336: 1495-1498. Available from: URL: http://www.bmj.com/cgi/content/full/336/7659/1495

Antibiotics Use in MRSA

An ICU patient was undergoing continuous veno-venous haemodiafiltration and had line-related bacteraemia. She has MRSA currently and was put on IV linezolid. IV Vancomycin was deemed not suitable as patient was on it for 2 months (previous admission) and showed no clinical response. Interestingly, blood culture showed sensitivity to vancomycin, rifampicin, fusidic acid, and clindamycin.


The issue raised by one pharmacist was, is linezolid a substitute for vancomycin (when patient does not response to it) in bacteraemia? She pointed out that while linezolid is efficacious when vancomycin fails in pneumonia, linezolid is not indicated for bacteraemia.


The most appropriate (antibiotic) treatment [can include removal of source, i.e. the line] is beyond the scope of this post as we did not follow up the case personally and thus do not have a full picture of her condition. However, the ICU case presentation prompted me to read up on antibiotics use in MRSA and I would like to share the findings here.


Community-acquired MRSA (CA-MRSA)- acquired by persons who have not been recently (within the past year) hospitalised or had a medical procedure (e.g. dialysis, surgery, catheters)

Hospital-acquired MRSA (HA-MRSA)-acquired by persons who have had frequent or recent contact with hospitals or healthcare facilities (e.g. nursing homes, dialysis centres) withint the previous year, have recently undergone an invasive medical precodure, or are immunocompromised.

A very good comparison between CA-MRSA and HA-MRSA (in the aspects of areas affected, modes of transmission, treatment & management, prevention) is available at a glance HERE.

Some other points of interest:
The treatment of choice for cutaneous abscesses caused by S aureus, irrespective of antibiotic susceptibility, is incision and drainage.


Vancomycin: still considered the first-line treatment for hospitalised patients with invasive S. aureus infection.

Microbiologic treatment failure may occur with vancomycin even if there is no increase in the minimal inhibitory concentration (MIC) on susceptibility testing. S. aureus isolates with low-level (so-called intermediate) resistance to vancomycin (MIC, >2 µg per milliliter) as well as those with high-level resistance (MIC, >16 µg per milliliter) have been described. <--Perhaps an explanation to patient's lack of response to vancomycin?

Also, nephrotoxicity is associated with high doses needed to attain the recommended vancomycin trough concentrations of 15—20 μg/mL.


Linezolid is FDA-approved for the treatment of complicated skin infections and hospital-acquired pneumonia due to MRSA in adults.

However, linezolid is expensive and has the potential for substantial toxicity, including myelosuppression, peripheral neuropathy, optic neuritis, and lactic acidosis.

Parenteral linezolid lacks bactericidal activity, which some experts believe is important in treating intravascular infection, a common feature of invasive disease. One of the selling points by the drug company is that linezolid is also available in oral form [Tab linezolid 600 mg is available in the blue book] so patient can be converted to the oral form upon discharge. However, this situation is more applicable in overseas (discharged while disease is almost resolved as they have healthcare system which includes home visits); in the government hospitals here, patients will be managed in the hospital until they are fully recovered.


Rifampicin or fusidic acid could be used as adjunctively with another active drug or together; neither agent should be used alone because resistance is likely to emerge during single-drug therapy.

Watch out for potential drug-drug interactions in patient on this regimen as rifampicin is a potent inducer of drug-metabolizing enzymes.


Tigecycline, a parenteral glycylcycline–minocycline derivative, was also recently approved by the Food and Drug Administration (FDA) for the treatment of skin and soft-tissue infections caused by MRSA.

A fixed combination of the streptogramins quinupristin and dalfopristin was licensed by the FDA for the treatment of skin and soft-tissue infections caused by MRSA. Its use has been limited by the potential for drug–drug interactions and by side effects (including arthralgias, myalgias, and gastrointestinal toxic effects).


References:

1. Deleo FR et al. Community associated methicillin-resistant Staphylococcus aureus. The Lancet, 2010 March 5. Available from: URL: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961999-1/fulltext?_eventId=login
2. Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. New Engl J med 2007; 357: 380-390. Available on: URL: http://content.nejm.org/cgi/content/full/357/4/380
3. Strategies for Clinical Management of MRSA in the Community: Summary of an Experts’ Meeting Convened by the Centers for Disease Control and Prevention.2006 March. Available from: URL: http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf