Home' Australian Pharmacist : Australian Pharmacist June 2012 Contents Australian Pharmacist June 2012 I ©Pharmaceutical Society of Australia Ltd. 461
Studies including high risk patients with
various co-morbidities and those who are
undergoing other cardiac procedures are
lacking and need to be addressed.
The evidence included in the above
mentioned systematic review
demonstrates that a pre-operative statin
therapy is useful for patients undergoing
cardiac surgical procedures in terms of
a reduction of post-operative AF and a
potential bene t in terms of a shorter
stay both in ICU and in hospital. Although
a pre-operative statin therapy was
linked with lower incidence for MI and
renal failure, these results did not reach
statistical signi cance.
1. Liakopoulos OJ, Kuhn EW, Slottosch I, et al. Preoperative statin
therapy for patients undergoing cardiac surgery. Cochrane
Database of Systematic Reviews 2012, Issue 4. Art. No.:
CD008493. DOI: 10.1002/14651858.CD008493.pub2
2. Alexander JH, Emery RW Jr, Carrier M, et al. Efficacy and
safety of pyridoxal 5'-phosphate (MC-1) in high-risk patients
undergoing coronary artery bypass graft surgery: the MEND-
CABG II randomized clinical trial. JAMA. 2008; 299(15):1777--87.
3. Gummert JF, Funkat A, Beckmann A, et al. Cardiac surgery
in Germany during 2008. A report on behalf of the German
Society for Thoracic and Cardiovascular Surgery. Thorac
Cardiovas Surg. 2009; 57(6):315--23.
4. Ludman A, Venugopal V, Yellon DM, et al. Statins and
cardioprotection -- more than just lipid lowering? Pharmacol
Ther. 2009; 122(1):30--43.
OLD DRUG NEW INDICATION
block certain types of enzyme activity
at the blood brain barrier, which helps
restore the integrity of the barrier, making
migration of T cells into the central
nervous system more di cult.
Newer monoclonal antibody therapies
such as natalizumab, daclizumab,
alemtizumab and rituximab are also
under investigation for MS because they
work by blocking the attachment of
immune cells to brain blood vessels, thus
reducing the immune cell in ammatory
action in the brain nerve cells. Other
agents, including mitoxantrone,
a well-established chemotherapy
drug with broad immunosuppressive
and cytotoxic activity and other
immunosuppressant agents including
methotrexate, sulphasalazine and
azathioprine have also been used.
Azathioprine has been used since
the 1970s and is one of the oldest
treatments for MS, pre-dating the use of
interferon therapy. It is a pro-drug which
is metabolised to 6-mercaptopurine,
this impedes DNA synthesis and thus
inhibits the proliferation of cells,
especially the fast-growing lymphocytes.
T-cells and B-cells are particularly a ected
by the inhibition of purine synthesis.
Azathioprine is an e ective drug used
alone in certain autoimmune diseases,
or is sometimes used in combination with
other immunosuppressant's in organ
transplantation. Although its side-e ect
pro le, particularly the potential
long-term risk of malignancy has reduced
its favour as a rst line treatment in MS
over the years, it has shown good results
more recently in reducing lesions in
refractory interferon-treated MS patients
and continues to be a cost-e ective
alternative to the more accepted current
standard interferon therapies.
The results of a large Cochrane Review
have shown that azathioprine is an
appropriate maintenance treatment for
patients with MS who frequently relapse
and require steroids. While considering
the risk of possible malignancy it
has been noted from the review that
cumulative doses of 600 grams should
not be exceeded. Gastrointestinal
complaints and leukopenia are the most
frequent adverse events of azathioprine
therapy in MS, occurring in more than
10% of the patients, while infections,
allergy, anaemia, thrombocytopenia and
pancytopenia are common (>1%-<10%).
Pancreatitis is not common (>0.1%-
<1%). Most of them are easily managed
by dosage adjustment or therapy
interruption and it is known that the
cancer risk increases with the treatment
duration and cumulative dose. With
appropriate management of these factors
azathioprine therapy can be e ectively
utilised in MS patients.
Azathioprine and the newer disease
modifying therapies have dramatically
changed how we treat MS. Prior to their
introduction there were no proven
treatments that a ected the course of
MS. Unfortunately, all of these agents
carry risks and bene ts, and symptoms
still occur in MS patients. Many of the
common symptoms can be controlled
well with a variety of therapies and the
emphasis of MS care still is directed
toward symptom management and
the prevention of complications from
disability and an improvement in quality
• Casetta I, Iuliano G, Filippini G.
Azathioprine for multiple sclerosis.
Cochrane Database Syst Rev. 2007 Oct
• La Mantia L, Mascoli N, Milanese C.
Azathioprine. Safety pro le in multiple
sclerosis patients. Neurol Sci. 2007
• Confavreux C, Moreau T. Emerging
treatments in multiple sclerosis:
azathioprine and mofetil. Mult Scler.
[Continued from page 444]
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