Hope of keeping drug risk in check

AUSTRALIAN researchers say they have cracked part of the mystery of why some drugs cause higher rates of potentially fatal abnormal heart rhythms.

AUSTRALIAN researchers say they have cracked part of the mystery of why some drugs cause higher rates of potentially fatal abnormal heart rhythms - a step they claim will make it easier to design safer drugs.

At least nine drugs have been taken off the market or severely restricted since 1996 because of dangerous effects on patients' heartbeats.

Experts from Sydney's Victor Chang Cardiac Research Institute say many drugs in development are likely to be plagued by similar side-effects.

But new research by the institute's experts may help drug companies avoid the problem, by shedding light on how drugs interfere with normal heart rhythm.

Research from 2009 found sudden cardiac death affected about 0.1 per cent of adults per year -- equivalent to about 20,000 Australians annually, the institute says.

Among patients with schizophrenia taking anti-psychotic drugs, the incidence is three times higher, at between 0.2 and 0.3 per cent per year.

Jamie Vandenberg, head of the institute's cardiac electrophysiology laboratory, said heartbeats were regulated by the passage of electrically charged ions, or particles, through pores or "channels" in cell membranes.

One channel, called the hERG potassium channel, determined how long each heartbeat lasted, and was the most prone to being blocked by drugs.

"The particular ion channel we have been interested in is also the channel that has been implicated in the vast majority of sudden cardiac death," Professor Vandenberg said.

"There are gates at each end of the channel and people had thought that it was a relatively simple process (when they closed and opened).

"What we have shown is that the gating process involves pretty much every part of the channel. It's not simply opening and closing the door; it's much more like the opening and closing of a Japanese puzzle box."

Because the entire channel changed shape during this process, it meant there were likely to be many more sites where drug molecules could bind to the channels and block them.

Professor Vandenberg said the hope now was that this knowledge could lead to the development of a test, which might happen within five years, that would allow drug companies to discover whether a new drug was likely to block the channels and potentially cause arrhythmias in patients.