HLA antigens in drug‐induced parkinsonism

Metzer, W. Steven; Newton, Joseph E. O.; Steele, Russell W.; Claybrook, Marsha; Paige, Stephen R.; McMillan, D. E.; Hays, Sarah

doi:10.1002/mds.870040203

Cited by 22 publications

(9 citation statements)

References 35 publications

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“…HLA B44 is reported to be common (relative risk of 7.16) in neuroleptic-induced parkinsonism in white schizophrenic individuals (Metzer et al, 1989). Several hypotheses can be discussed.…”

Section: Primary Parkinson's Diseasesmentioning

confidence: 98%

“…The first one is a close proximity between HLA-B44 antigen and genes that code for neuroleptic induced-parkinsonism. The second could be the fact that the HLA system mediates an autoimmune genesis of neuroleptic-induced parkinsonism (Metzer et al, 1989). Finally, these authors have also suggested that HLA antigens on postsynaptic neurons might influence dopaminergic transmission by acting as cell surface receptors.…”

Section: Primary Parkinson's Diseasesmentioning

confidence: 99%

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Drug‐induced parkinsonism: a review

Llau

Rascol

et al. 1994

Fundamemntal Clinical Pharma

100

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The main clinical features, pathophysiology and underlying mechanisms of drug-induced parkinsonism are reviewed. The clinical manifestations of drug-induced parkinsonism are often indistinguishable from idiopathic Parkinson's disease. However, some subtle differences may exist: for example drug-induced parkinsonism is often associated with tardive dyskinesias, bilateral symptoms and the absence of resting tremor, etc. Besides toxins (eg manganese, carbon monoxide or MPTP), many drugs are known to produce parkinsonism: dopamine blocking drugs (true neuroleptics used as antipsychotics: phenothiazines, butyrophenones, thioxanthenes but also sulpiride, "hidden" neuroleptics prescribed as anti-nausea or anti-vomiting drugs (such as metoclopramide and other benzamide derivatives), dopamine depleting drugs (reserpine, tetrabenazine), alpha-methyldopa, calcium channel blockers (flunarizine, cinnarizine, etc). The putative role of other drugs (eg fluoxetine, lithium, amiodarone) as well as the therapeutic management of this side effect are reviewed.

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“…HLA B44 is reported to be common (relative risk of 7.16) in neuroleptic-induced parkinsonism in white schizophrenic individuals (Metzer et al, 1989). Several hypotheses can be discussed.…”

Section: Primary Parkinson's Diseasesmentioning

confidence: 98%

Section: Primary Parkinson's Diseasesmentioning

confidence: 99%

Drug‐induced parkinsonism: a review

Llau

Rascol

et al. 1994

Fundamemntal Clinical Pharma

100

View full text Add to dashboard Cite

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“…Another risk factor is female gender,8,15-17 suggesting that estrogen suppresses the expression of dopamine receptors;18 however, the exact mechanism underlying the gender difference in DIP remains to be clarified. Genetic factors are also thought to be involved in the development of DIP because not all patients taking dopamine receptor blocking agents (DRBAs) develop parkinsonism 19-21. Genome-wide screening showed that the genes associated with the gamma-aminobutyric acid (GABA) receptor signaling pathway are involved in neuroleptic-induced TD in schizophrenic patients,21 suggesting that genetic factors predispose to both DIP and TD.…”

Section: Epidemiology Of Drug-induced Parkinsonismmentioning

confidence: 99%

Drug-Induced Parkinsonism

2012

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Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders.

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“…This suggests that genetic predisposition might play a role in the development of DIP. Shiroma et al showed genetic polymorphisms in genes involved in dopamine transmission [29] whereas Metzer et al found a higher prevalence of HLA antigen B44 in DIP patients [30] and there have been described families with a hereditary predisposition to DIP [31]. Many drugs have been described to cause parkinsonism but there are several factor that modulate this risk.…”

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confidence: 99%

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

Estévez-Fraga¹,

Zeun²,

Moreno

2018

Drugs Aging

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Drug induced parkinsonism and tardive dyskinesia are iatrogenic consequences of the use of antidopaminergic drugs. Both entities share risk factors, physiopathological mechanisms and to some degree, therapeutic approaches. Here we review both entities and discuss emerging therapies including the recently approved drug deutetrabenazine and relevant aspects for clinical practice such as new diagnostic techniques. Key points:-Drug induced parkinsonism and tardive dyskinesia are iatrogenic consequences of the use of antidopaminergic drugs.-DIP is considered a direct consequence of the blockage of D2 receptors while TD has a more complex physiopathology, including enhanced sensitivity of dopamine receptors.-Both entities are more frequent in older people due to a progressive loss of dopaminergic neurons with age.-New therapies are available for TD, including deutetrabenazine. Compliance with ethical Standards:Disclosure of potential conflicts of interest: no funding was received for this study.The risks of drug-induced parkinsonism/tardive dyskinesia in the elderly and current methods to overcome it. 1.-IntroductionTardive dyskinesia (TD) and drug-induced parkinsonism (DIP) are iatrogenic disorders caused by dopamine receptor blockers (DRB) [1]. They were recognized early after the introduction of antipsychotics[2] to the clinical practice, leading to the finding that DIP caused by reserpine, a dopamine depleter, was related to dopamine deficiency [3].Elderly patients are more susceptible to these side effects, probably due to an age-related decrease in nigral neurons and dopamine [4]. Since the introduction of newer second generation antipsychotics (SGA) the frequency and intensity of these side effects has improved [5] , [6] , [7] , [8] but there is still room for concern [9], [10].TD and DIP share risk factors, pathological mechanisms and management, and might coexist in one given subject. Latest available evidence has clarified some intriguing features of TD and DIP. Meanwhile, new medications to treat TD are now available, highlighting the importance of a thorough, updated, knowledge of this pathologies.This article offers a comprehensive review of the incidence, clinical features and mechanisms behind DIP and TD. The benefits and risks of previous available drugs and those that have been recently approved by regulatory agencies are discussed. Drug induced Parkinsonism DefinitionDIP occurs when symptoms emerge after exposure to drugs, usually those that either deplete dopamine storages [11] or block dopamine receptors [12]. By definition, symptoms should be reversible, six months after the offending agent has been withdrawn[13] but actually up to 20% of patients develop persistent deficits despite drug discontinuation [14] leading to the hypothesis that these patients might have subclinical Parkinson's Disease (PD) unmasked by neuroleptic exposure (umPD), complicating the differential diagnosis [15], especially between aged patients, who are more prone to both PD and DIP. Epidemiology and risk factorsAfter PD, DI...

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HLA antigens in drug‐induced parkinsonism

Cited by 22 publications

References 35 publications

Drug‐induced parkinsonism: a review

Drug‐induced parkinsonism: a review

Drug-Induced Parkinsonism

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

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