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International Journal of Molecular... Mar 2017Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging... (Review)
Review
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson's disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin-proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol--methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the "wearing-off phenomenon", with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics.
Topics: Adult; Aged; Aged, 80 and over; Animals; Antiparkinson Agents; Disease Susceptibility; Dopaminergic Neurons; Humans; Middle Aged; Oxidative Stress; Parkinson Disease; Pharmacogenetics; Pharmacogenomic Variants; Risk Factors
PubMed: 28273839
DOI: 10.3390/ijms18030551 -
Movement Disorders : Official Journal... Oct 2011The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was... (Review)
Review
The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Ω-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not useful for the above-mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short-term management of the different non-motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication-related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non-motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research. © 2011 Movement Disorder Society.
Topics: Antiparkinson Agents; Autonomic Nervous System Diseases; Cognition Disorders; Evidence-Based Medicine; Humans; Mental Disorders; Mood Disorders; Parkinson Disease; Psychotropic Drugs; Randomized Controlled Trials as Topic; Sleep Disorders, Intrinsic; Treatment Outcome
PubMed: 22021174
DOI: 10.1002/mds.23884 -
Veterinary Sciences Oct 2022Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs,... (Review)
Review
Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing hormone (TRH) used to assess ACTH response to TRH stimulation is not commercially available as a sterile registered product in many countries. The relationship between PPID and insulin dysregulation and its association with laminitis, as well as additional management practices and long-term responses to treatment with pergolide also require further investigation.
PubMed: 36288169
DOI: 10.3390/vetsci9100556 -
Archives of Cardiovascular Diseases May 2013Numerous reports have shown an unquestionable association between fibrotic valve disease and the following drugs: ergot alkaloids (such as methysergide and ergotamine),... (Review)
Review
Numerous reports have shown an unquestionable association between fibrotic valve disease and the following drugs: ergot alkaloids (such as methysergide and ergotamine), ergot-derived dopaminergic agonists (such as pergolide and cabergoline) and drugs metabolized into norfenfluramine (such as fenfluramine, dexfenfluramine and benfluorex). This review focuses on different aspects of drug-induced valvular heart disease: historical background; echocardiographic features; different drugs recognized as being responsible for valvular heart disease; and pathophysiology.
Topics: Animals; Evidence-Based Medicine; Fibrosis; Heart Valve Diseases; Heart Valves; Humans; Risk Assessment; Risk Factors; Ultrasonography
PubMed: 23769407
DOI: 10.1016/j.acvd.2013.02.003 -
Journal of Psychopharmacology (Oxford,... Mar 2024Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting... (Review)
Review
Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2-4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies.
Topics: Humans; Hallucinogens; Psilocybin; Cardiotoxins; Lysergic Acid Diethylamide; Fibrosis
PubMed: 38214279
DOI: 10.1177/02698811231225609 -
The Cochrane Database of Systematic... Mar 2011According to clinical guidelines, dopamine agonists are the first-line treatment of restless legs syndrome (RLS). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
According to clinical guidelines, dopamine agonists are the first-line treatment of restless legs syndrome (RLS).
OBJECTIVES
To evaluate efficacy and safety of dopamine agonists for RLS.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE, EMBASE, PsycINFO and CINAHL, from January 1985 to December 2008, plus reference lists of articles. We contacted pharmaceutical companies.
SELECTION CRITERIA
We included double-blind randomised controlled trials (RCTs) of dopamine agonist treatment versus placebo or other treatment for a period of at least seven days in patients with RLS (≥ 18 years). Outcomes included the International RLS Severity Rating Scale (IRLS), Clinical Global Impressions (CGI-I), polysomnography and self rated sleep quality, quality of life, daytime functioning, and safety parameters.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data separately; assessed risk of bias; and contacted pharmaceutical companies and authors for additional information. We collected dropout rates due to adverse events and experience of adverse events.
MAIN RESULTS
We included 35 placebo controlled and three active controlled RCTs (N = 7365). The mean reduction on the IRLS was -5.7 points lower in dopamine agonist treatment compared to placebo (95% confidence interval (CI) -6.7 to -4.7). Periodic limb movements in sleep per hour of sleep (PLMS-Index; PLMSI) were -22.4/h lower than in placebo (95% CI -27.8 to -16.9). Self rated quality of sleep and disease specific quality of life were improved by a standardised mean difference (SMD) of 0.40 (95% CI 0.33 to 0.47) and 0.34 (95% CI 0.23 to 0.44), respectively. Patients were more likely to drop out (odds ratio (OR) 1.82, 95% CI 1.35 to 2.45) and experienced more adverse events under dopamine agonist treatment than with placebo (OR 1.82, 95% CI 1.59 to 2.08). Visual inspection of forest plots showed the highest efficacy in three studies investigating cabergoline and pergolide (N = 3). Active controlled trials investigated effects of cabergoline, pergolide, and pramipexole in a number of outcomes. The IRLS score was lower with cabergoline and pramipexole compared to levodopa (MD -5.3, 95% CI -8.4 to -2.1). Only four studies investigated treatment efficacy up to seven months. The most severe side effect, augmentation, was not assessed reliably.
AUTHORS' CONCLUSIONS
The meta-analyses show the superiority of dopamine agonists over placebo in RCTs up to seven months. Cabergoline and pramipexole showed larger efficacy compared to levodopa in some but not all outcomes.
Topics: Benzothiazoles; Cabergoline; Dopamine Agonists; Ergolines; Humans; Levodopa; Pergolide; Pramipexole; Randomized Controlled Trials as Topic; Restless Legs Syndrome; Severity of Illness Index
PubMed: 21412893
DOI: 10.1002/14651858.CD006009.pub2