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PHARMACOLOGICAL CAUSES OF PARKINSON'S DISEASE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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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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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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