Saturday, May 22, 2010

The Other Indication of N-acetylcysteine

Apart from being the antidote to paracetamol poisoning, N-acetylcysteine is also used for the prevention of nephropathy associated with radiographic contrast media. (For instance, before and after primary angioplasty for acute myocardial infarction to reduce the risk of contrast-induced nephropathy.)

When it is used for such indication, the dose is 600mg bd orally before and the day of contrast media administration (total of 4 doses) [cf antidote to paracetamol poisoning: 150mg/kg over 15 min, then 50mg/kg over 4h, then 100mg/kg over 16h intravenously]. This indication is not in the MOH Formulary hence Ketua Pengarah Kesihatan (KPK) application is required.

Contrast agents reduce renal function by altering renal haemodynamics and by exerting direct toxic effects on tubular epithelial cells. It is on the assumption that reactive oxygen species in the pathogenesis of acute contrast-agent–induced reductions in renal function that the effects of the prophylactic oral administration of the antioxidant acetylcysteine have been studied in various trials.

According to EBSCO, to date, the outcomes for the use of acetylcysteine in the prevention of contrast nephropathy is of level 2 (mid level) and level 3 (lacking direct evidence). For those who are interested in the summary of various trials from EBSCO, you may email me at bpharmer05[at]gmail[dot]com.

  1. Tepel M, van der Giet M, Schwarzfeld C et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180-184.
  2. Acetylcysteine. Dynamed-powered by EBSCOhost. 2010 May 8 [Accessed 2010 May 22]; Available from: URL:

Antibiotic Prophylaxis in Thalassaemia

The other day, I received a call from a house officer regarding penicillin V dose in thalassaemic children. She was unsure of the indication.

Splenomegaly (enlarged spleen) is common in thalassaemia major and intermedia due to the high rate of haemolysis (red blood cell destruction). This takes place because the spleen sees the defective red cells of the thalassaemic as deficient and the transfused red cells as invaders (much the same as with host vs graft disease) and removes them from circulation.

In some patients, splenectomy is performed as it may help decrease transfusion requirements for patients with splenomegaly.

The drug of choice for prophylaxis in patients with thalassaemia who have undergone a splenectomy is penicillin. This is because it is active against most microorganisms considered to be major pathogens in splenectomised patients (ie, streptococcal, pneumococcal, and some staphylococcal microorganisms) but not penicillinase-producing species.

Sanford Guide to Antimicrobial Therapy
Asplenic children to have antimicrobial prophylaxis until age 5:
Amoxicillin 20mg/kg/day OR
Penicillin V 125mg bd

Children over age 5:
Penicillin V 250mg bd for at least 1 year in children post-splenectomy

If allergic to penicillin:
-trimethoprim-sulfamethoxazole [National Antibiotic Guidelines states dose as 960mg od] OR
[NAG also recommends erythromycin 400mg bd OR azithromycin 250mg od]

The National Antibiotic Guidelines, based on article from BMJ 307, 1372-1373, recommends the duration of treatment to be minimum 2 years post splenectomy in adults and up to 16 years of age in children. Life long is not recommended.

  1. Sanford Guide to Antimicrobial Thearpy 2006
  2. National Antibiotic Guidelines
  3. Yaish HM. Thalassaemia Intermedia. Emedicine. 2009 September 29 [Accessed 2010 May 22] Available from: URL:

Thursday, May 6, 2010

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)

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 ( 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.


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 28th). Available from: URL:

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: