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PHARMACOLOGICAL CAUSES
A small proportion of cases
of Parkinson's Disease have a pharmacological cause. To varying extents some
drugs can also be a partial cause or the sole cause of Parkinson's Disease. The
use of the drugs must usually be persistent in order to cause Parkinson's
Disease. The withdrawal or gradual reduction of the dosage of these drugs can
lead, in most cases but not with all drugs, to the reduction in the Parkinson's
Disease symptoms they cause or contribute to.
AMIODARONE
Amiodarone is the most widely used anti-arrhythmic agent. Use of Amiodarone
causes a marked increase in the duration of transmembrane action potential.
Use of Amiodarone is associated with Parkinsonism, which can revert after
withdrawal of Amiodarone. Amiodarone can cause Parkinson's Disease symptoms
because amiodarone is able to inhibit the dopamine D1 and D2 receptors and
can therefore reduce dopaminergic activity.
AMPHETAMINES AND
METHAMPHETAMINES
Amphetamines and methamphetamines are central nervous stimulants. They are
also often used as recreational drugs. In certain parts of the brain
amphetamines and methamphetamines can have some of their effects by
increasing the concentration of dopamine in the synaptic cleft. In
methamphetamine and amphetamine users there was nearly a three fold
increased risk of Parkinson's Disease, indicating them as a cause of
Parkinson's Disease. Prolonged amphetamine exposure made Parkinson's Disease
eight times more likely.
ARIPIPRAZOLE
Aripiprazole is a novel atypical neuroleptic used in the
treatment of psychosis. The use of Aripiprazole is associated with Parkinsonism.
Neuroleptics generally tripled the risk of developing Parkinson's Disease.
Aripiprazole can cause Parkinson's Disease symptoms because it acts as a D2
dopamine receptor antagonist and can therefore reduce dopaminergic activity.
BENZAMIDES
Cisapride is a benzamide derivative that is used as a gastroprokinetic agent
as it increases the motility in the upper gastrointestinal tract.
Levosulpiride is a substituted benzamide that is widely used for the
management of dyspepsia and emesis. Benzamide derivatives including
cisapride, sulpiride, tiapride, and metoclopramide can cause drug-induced parkinsonism. Benzamides can cause
Parkinson's Disease symptoms because benzamides bind to D2 dopamine
receptors, especially D2Sh and can therefore reduce dopaminergic activity.
CALCIUM
CHANNEL BLOCKERS
Calcium channel blockers are used as
antihypertensive drugs. Calcium channel blockers disrupt the movement of
calcium (Ca2+) through calcium channels. Calcium
channel blockers can cause Parkinsonism. Parkinsonism can cease in
most people after withdrawal of Calcium channel blockers but tremor, and
sometimes most symptoms persist. However, some dihydropyridine calcium
channel blockers can instead lessen the likelihood of developing Parkinson's
Disease. Calcium channel blockers are one of the most common
pharmacological causes of Parkinson's Disease.
DOPAMINE
AGONISTS
Dopamine D2 receptor antagonists include haloperidol,
clebopride, metoclopramide and lurasidone. Dopamine
antagonists inhibit the dopamine receptors. Haloperidol is one of the commonest drugs related to Drug Induced
Parkinsonism. Clebopride can cause Parkinsonism but there is no suggestion
that its withdrawal reverses Parkinsonism. Metoclopramide can cause the
symptoms of Parkinson's Disease but they can cease after withdrawal of
Metoclopramide. Increased risk of Parkinsonism is one of the most common
adverse effects of lurasidone. Dopamine antagonists inhibit dopamine receptors, and can
therefore reduce dopaminergic activity.
EPHEDRONE
Ephedrone is intravenous methcathinone that is prepared using potassium
permanganate. Ephedrone can cause the symptoms of Parkinsonism. Ephedrone
abusers also have widespread white matter damage with the greatest severity
of damage underlying executive motor areas. Ephedrone can cause a mixed
hypokinetic-dystonic dysarthria after about eight months. Ephedrone, due to
including manganese, can cause Manganism. Manganese inhibits tyrosine
hydroxylation, which is essential for the formation of dopamine. So
manganese can cause Parkinson's Disease by lowering dopamine levels.
ESTROGEN
Oral contraceptives, which includes estrogen and
progestin, are widely prescribed to women in order to prevent pregnancy. Having used a hormone therapy demonstrated a suggested elevated
risk with esterified estrogen use that was three times the normal. However,
there was no increase in the risk of developing Parkinson's Disease in those
people who had taken conjugated estrogen. Progestin also moderately increased the risk of developing
Parkinson's Disease in those people who had taken conjugated estrogen. Estrogen decreases the levels of the dopamine D2 receptors,
which has an effect on Parkinson's Disease by decreasing dopaminergic
activity.
LITHIUM
Lithium, usually as lithium carbonate,
is used as a mood stabiliser for the treatment of bipolar disorder, which
includes mania, depression and reducing the risk of suicide. Lithium can make Parkinson's Disease more
likely or can cause Parkinsonism. The symptoms can improve after Lithium has
been discontinued but the symptoms do not always improve. Lithium appears to
cause Parkinsonism by diminishing dopaminergic activity. This is probably
due to a direct action on the G proteins, thereby reducing the capacity of
the G proteins, once they are activated, in order to stimulate adenylyl
cyclase.
PHENOTHIAZINES
Phenothiazines used as
antipsychotics can cause Parkinson's Disease symptoms. These include
chlorpromazine, which is a neuroleptic used in the treatment of psychosis. From around 30% to 61% of people can develop mild to
moderate Parkinson's Disease symptoms as a result of taking chlorpromazine. Parkinson's Disease symptoms can cease after discontinuation of
chlorpromazine. Other phenothiazines that can cause Parkinson's
Disease symptoms are fluphenazine, perphenazine,
prochlorperazine, thioridazine, and trifluoperazine. Phenothiazines can cause Parkinson's Disease symptoms by
decreasing the effect of dopamine on the dopamine receptors.
TRIMETAZIDINE
Trimetazidine is an anti-ischaemic
agent, which provides symptom relief and functional improvement in patients
with angina pectoris. Trimetazidine inhibits beta-oxidation of fatty acids,
which enhances glucose oxidation. The use of trimetazidine can cause
Parkinsonism. However, the symptoms of Parkinsonism can revert after the
withdrawal of Trimetazidine. Trimetazidine can cause Parkinson's Disease
symptoms because trimetazidine is able to blockade the dopamine D2 receptors
and can therefore reduce dopaminergic activity.
VALPROIC ACID
Valproic acid is a drug used for the treatment of a variety of psychiatric
and neurological disorders including for the treatment of epilepsy. Valproic Acid can cause the symptoms of Parkinson's Disease. The estimates as to what proportion of people taking valproic acid
develop the symptoms of Parkinson's Disease differ enormously. However, the
symptoms of Parkinson's Disease can reduce after the withdrawal of the use
of valproic acid. Valproic acid increases the levels of GABA, which has an
effect on Parkinson's Disease by decreasing dopaminergic neuron activity.
ZOLPIDEM
Zolpidem is a
non-benzodiazepine hypnotic for the treatment of insomnia that potentiates
GABA. Zolpidem marginally increases the risk of
developing Parkinson's Disease, which increased to some extent according to
the number of cumulative daily doses of zolpidem. Parkinson's Disease is
more prevalent amongst zolpidem users but not after 5 years. The risk of
Parkinson's Disease was even higher in those people that had depression. The
risk of Parkinson's Disease increased according to the dose of zolpidem. Zolpidem increases the activity of GABA,
which has an effect on Parkinson's Disease by decreasing dopaminergic neuron
activity.
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THE
COMPREHENSIVE GUIDE TO PARKINSON'S DISEASE
Keith Bridgeman, Tahira Arsham
The Comprehensive
Guide to Parkinson's Disease, which is fully referenced, and nearly
800 pages long, is the most comprehensive book concerning
Parkinson's Disease ever written. It includes its history, famous
people with Parkinson's Disease, its complete biochemisty, cytology
and cytological effects, anatomy and anatomical effects, physiology
and physiological effects, symptoms (of every system in the body),
diagnosis methods (observational, technological, chemical),
biochemical causes, toxic causes, genetic causes, pharmacological
causes, medical causes, treatments (biochemical, pharmacological,
surgical, natural, exercise methods, technological methods),
organisations, web sites.
CLICK HERE FOR MORE DETAILS |
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