Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim of this review is to investigate whether sex differences exist for efficacy and adverse effects of these drugs.Sex-related differences have been shown in the pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between females and males, significantly higher plasma concentrations in women have been demonstrated only for olanzapine and clozapine. To date, sex differences in adverse effects have not been well studied, but some adverse effects such as weight gain, hyperprolactinaemia and cardiac effects are reported to be particularly problematic for women. Most of the studies reviewed indicate that clozapine and olanzapine are associated with greater bodyweight gain than the other atypical antipsychotics, and that serious adverse effects such as metabolic syndrome, which includes increased visceral adiposity, hyperglycaemia, hypertension and dyslipidaemia induced by SGAs, are more frequent in females. According to most studies, the risk for cardiac adverse effects induced by SGAs is the same in male and female patients. Although women are at a lower risk of sudden cardiac death, they have a higher risk of induced long QT syndrome from antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual dysfunctions is higher with conventional antipsychotics than with SGAs. Additionally, there is some evidence that female sexual dysfunction is associated with high prolactin levels; however, whether the degree of prolactin level elevation is different between female and male patients remains controversial. There is no evidence for sex differences for any of the SGAs to cause a higher rate of extrapyramidal symptoms, acute dystonia or any other movement disturbance. Knowledge of the risks and benefits associated with the use of SGAs during pregnancy and lactation is limited, although the direction of dose adjustments during pregnancy depends on the drug and the enzyme that is responsible for its metabolism. In general, data on sex differences were mostly obtained by posthoc analysis and, therefore, the conclusions that can be drawn are limited. For a better understanding of the basic mechanisms of sex differences, future studies with a primary focus on this topic are required. Data that are more specific will help determine the extent to which these differences will have implications for clinical management.
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PMID:Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles? 1680 51

Including of balneological therapy with the use of the baths Bi-olong in the programs of medical rehabilitation makes possible to improve considerable the state of peripheral haemodynamics, the indices of adaptation and regulation in patients with vegetative vascular dystonia. This fact can be explained with the positive corrective effect of bath Biolong reactant mitophen on cell respiration by the system cytochrome P450 activation. Also it is possible to assume that mitophen leads to decrease imbalance between sympathetic and parasympathetic nervous systems participating in regulation and adaptation of vascular wall. Use of bath Biolong in the therapy of patient with hypertonic vegetative vascular dystonia ought to consider as an effective, harmless and pathogenetically reasonable method which can be recommended to include in combined rehabilitation.
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PMID:[State-of-the-art corrective and diagnostic technologies in medical rehabilitation of patients with vegetative vascular dystonia]. 1837 77

A case of an acute dystonic reaction in a child presumptively treated for malaria with amodiaquine, and a case of persistent asymptomatic bradycardia in another child with mild pulmonary stenosis treated with a standard dose of amodiaquine for parasitologically confirmed uncomplicated malaria, is reported. Both subjects were homozygous for the wild type allele of cytochrome P450 2C8, the main enzyme responsible for amodiaquine metabolism. In both subjects, plasma concentrations of N-desethylamodiaquine and N-bis-desethylamodiaquine, the main metabolites of amodiaquine, were normal. No other drugs were detectable in the plasma of these two subjects after further toxicological screening. These observations, which suggest altered metabolism in the subject with an acute dystonic reaction, support the assertion that amodiaquine-associated dystonia is an idiosyncratic reaction. However, the occurrence of bradycardia after a standard dose of amodiaquine, which coincided with the time of expected peak concentrations of the active metabolite of amodiaquine, suggests a direct drug effect. These less reported adverse effects are likely to increase in parallel with the increased use of amodiaquine as a partner drug for combination therapy of malaria in Ghana. Further studies aimed at elucidating the mechanisms underlying these effects are, therefore, required.
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PMID:Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose. 2012 27

Hereditary spastic paraplegia (HSP) is a neurological disorder characterized by a progressive spasticity and muscle weakness of the lower limbs. It is divided into two subtypes, uncomplicated and complicated forms. Biallelic mutations in the cytochrome P450 2U1 gene (CYP2U1) are associated with spastic paraplegia type 56 (SPG56), manifesting both uncomplicated and complicated HSP. Accompanying clinical features include intellectual disability, dystonia, cerebellar ataxia, subclinical peripheral neuropathy, visual impairment, as well as abnormalities in brain magnetic resonance imaging. As a rare clinical feature, delayed myelination has previously been reported in only two patients with CYP2U1 mutations. Here, we report a patient with SPG56 with novel compound heterozygous mutations in CYP2U1 which were identified by whole exome sequencing. Our patient exhibited complex features together with delayed myelination, broadening the phenotypic spectrum of SPG56, and implying that CYP2U1 should be screened in HSP with delayed myelination.
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PMID:An atypical case of SPG56/CYP2U1-related spastic paraplegia presenting with delayed myelination. 2872 25

Cannabis has been used as a medicinal plant for thousands of years. As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes. Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors. Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System. The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol. The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive. Cannabis and cannabinoids have been indicated for several medical conditions. There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette's syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington's Disease, Parkinson's Disease, and dystonia, but there is not good evidence to support its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe. Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.
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PMID:A Brief Background on Cannabis: From Plant to Medical Indications. 3013 15