Two Anti Parkinson's Drugs Linked To Leaky Heart Valves/ergot

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Two Anti Parkinson's Drugs Linked To Leaky Heart Valves

Main Category: Parkinson's Disease News

Article Date: 04 Jan 2007 - 4:00 PST

http://www.medicalnewstoday.com/healthnews.php?newsid=60187

Two studies, one on UK patients and another on Italian patients

suggest that two types of drug for treating Parkinson's disease may

be causing leaky heart valves (cardiac-valve regurgitation).

The drugs in question are the ergot-derived dopamine receptor

agonists " pergolide " and " cabergoline " . Pergolide is sold under the

brand name Permax (Eli Lilly) and cabergoline under the brand names

Dostinex and Cabaser (Pfizer).

The two studies are published in today's issue of the New England

Journal of Medicine.

The UK study looked at records of 11,417 patients in the United

Kingdom General Practice Research Database who were aged between 40

and 80 and had received antiparkinsonian medication between 1988 and

2005 and found 31 cases of cardiac-valve regurgitation.

Of the 31 patients with newly diagnosed cardiac-valve regurgitation

6 were taking pergolide and another 6 were taking cabergoline up to

12 months previously. The ones on pergolide were 7 times more likely

to have leaky heart valves, and the ones on cabergoline, 5 times.

The ones on other types of dopamine agonists did not show this

increase.

The Italian study examined 245 patients of which 155 had been taking

dopamine agonists and 90 were on other medication.

Their results showed that moderate to severe heart valve leaks (i.e.

clinically important regurgitation, graded 3 or 4 according to the

American Society of Echocardiography system) were found with

significantly greater frequency in patients taking pergolide (23.4

per cent increase) and cabergoline (28.6 per cent increase) compared

to patients taking non ergot-derived dopamine agonists.

The two studies conclude that the risk of developing clinically

important valve regurgitation is significantly greater in patients

on pergolide or cabergoline. They suggest this information should

form part of the risk versus potential benefit decision when

prescribing such drugs in the future.

A dopamine receptor agonist is a drug that behaves like dopamine -

it's a " key " that fits in the same receptor " keyhole " as naturally

produced dopamine. (This is different to an antagonist drug which

has a blocking effect on the receptors).

Dopamine-receptors play an important role in the brain's ability to

learn and control movement. They are special proteins that lie

between the inner and outer layer of the membrane around brain and

other nerve cells. There are five types of dopamine receptors, each

type playing a different role in controlling the response of the

cell to the arrival of a dopamine neurotransmitter molecule (also

known as a dopamine ligand since it binds to the receptor in order

to act on the cell).

Dopamine is both a hormone and a neurotransmitter. When the delicate

balance between production and destruction of dopamine, its

inhibition and excitation, and the various connections between the

different types of receptors is upset, different conditions emerge.

One of these is Parkinson's disease, associated with low levels of

dopamine. Too little dopamine reduces the ability of the brain and

nervous system to smoothly perform motor functions, leading to the

jerky movements in people who have the disease.

Dopamine is a natural chemical produced in the brain. It does not

cross the blood brain barrier, so taking a dose of dopamine would

have no effect on the brain. That is why drugs such as dopamine

receptor agonists and antagonists are used to control the action of

dopamine. However, because dopamine has a number of roles, for

instance it is also a hormone, drugs that behave like it will

also " interfere " in these other processes.

In the case of these two studies it is thought that the drugs

interfered with the function of a receptor known as 5-HT2B, which

can seriously impair the function of a heart valve, sometimes

fatally.

Ergot-derived means that the drugs are produced using a fungus

commonly known as ergot, which is parasitic on grains and grasses

such as rye. Many pharmaceuticals are made from it. For instance the

hallucinatory drug LSD was first made from ergot.

Ergot is the French for sprocket, describing the toothed shape of

the fungal sclerotic growth that gradually replaces the ripening

grains of the infected plant. People consuming ergot at the wrong

stage of the fungus life cycle deveop ergotism the symptoms of which

vary (convulsions, gangrene) depending on the species of fungus.

Outbreaks of ergotism were common in Europe in medieval times and

even before that, especially among poor rural communities where the

staple diet was rye and the climate mainly wet and cool, ideal

conditions for the fungus.

" Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation. "

René Schade, M.D., Andersohn, M.D., Samy Suissa, Ph.D.,

Wilhelm Haverkamp, M.D., Ph.D., and Edeltraut Garbe, M.D., Ph.D.

NEJM Volume 356:29-38, January 4, 2007, Number 1.

" Valvular Heart Disease and the Use of Dopamine Agonists for

Parkinson's Disease "

Renzo Zanettini, M.D., Angelo Antonini, M.D., Gemma Gatto, M.D.,

Gentile, M.D., Silvana Tesei, M.D., and Gianni Pezzoli, M.D.

NEJM Volume 356:39-46, January 4, 2007, Number 1.

New England Journal of Medicine

Written by: Catharine Paddock

Writer: Medical News Today