ABSTRACT
Systemic toxicity by local anesthetics (LAs) is a severe and feared complication in anesthetic practice that generally results from the administration of an inappropriately high dose of LAs or an injection at an inappropriate place, either intravascular or a site with high absorption[1]. However, it is known that the susceptibility to these drugs may vary within the population, which may occur due to genetic changes in the LA binding site, located in the potential-dependent Na+ channels (Nav), thus increasing or decreasing its affinity and, therefore, its clinical consequences. We present a case of a 61 years-old female patient with a medical history of increased sensitivity to LAs. In this scenario, a genetic study was performed to exclude a Nav channel dysfunction.
La toxicidad sistémica por anestésicos locales (ALs) es una grave y temida complicación en la práctica anestésica que generalmente resulta de la administración de una dosis inapropiadamente alta de ALs o a una inyección en un lugar inadecuado, llámese intravascular o un sitio al alta absorción[1]. A pesar de lo anterior, es conocido que la susceptibilidad al efecto de estos fármacos puede variar dentro de la población, lo cual puede ocurrir debido a cambios genéticos en el sitio de unión de los AL, localizado en los canales de Na+ dependientes de potencial (Nav), incrementando o disminuyendo así su afinidad y, por ende, sus consecuencias clínicas. Presentamos el caso de una paciente de 61 años con historia de sensibilidad aumentada a Als. En este escenario, se le ofreció un estudio genético para excluir una disfunción específica a nivel de canal Nav
Subject(s)
Humans , Female , Middle Aged , Sodium Channels/drug effects , Drug Hypersensitivity/etiology , Drug Hypersensitivity/genetics , Anesthetics, Local/adverse effects , Lidocaine/adverse effects , Sodium Channels/genetics , Anesthetics, Local/pharmacology , Lidocaine/pharmacologySubject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Anti-HIV Agents/adverse effects , Dideoxynucleosides/adverse effects , Drug Hypersensitivity/genetics , Gene Frequency/genetics , HIV Infections/genetics , HLA-B Antigens/genetics , Anti-HIV Agents/therapeutic use , Brazil/ethnology , Case-Control Studies , Dideoxynucleosides/therapeutic use , Drug Hypersensitivity/ethnology , Genotype , HIV Infections/drug therapy , HIV Infections/ethnology , Real-Time Polymerase Chain ReactionABSTRACT
It has been demonstrated that HLA-B*5701 screening reduces the risk for hypersensitivity reaction to abacavir in HIV-infected patients. Since B*5701 prevalence varies among different populations, it is important to determine the carrier frequency prior to its use for the screening of HIV-infected patients.The aim of this study was to determine HLA-B*5701 carrier frequency in Chilean general population and HIV-infected patients referred for B*5701 typing. For that purpose 300 blood bank donors and 492 abacavir-naïve HIV-infected patients from Chile were screened for B*5701 by a sequence specific primer PCR.We detected 14/300 (4.7 percent) B*57-positive individuals in the Chilean general population, 11 (3.7 percent) were B*5701 positive, and 3 (1 percent) had another subtype.All were heterozygous,thus a B*5701 allele frequency of 2 percent was determined.Eleven of 492 (2.2 percent) HIV-patients carried a B*5701 allele. The difference between these frequencies is probably due to slow progression of HIV infection in HLA-B*5701 carriers, thus less patients would require antiretroviral therapy and B*5701 typing. Considering the usefulness of B*5701 screening, its prevalence in the Chilean general population,and the availability of a validated method,we conclude that HLA-B*5701 typing in Chilean HIV-infected patients about to initiate abacavir treatment is strongly recommended.
Subject(s)
Humans , Anti-HIV Agents/adverse effects , Dideoxynucleosides/adverse effects , Drug Hypersensitivity/genetics , HIV Infections/drug therapy , HLA-B Antigens/analysis , Anti-HIV Agents/therapeutic use , Chile , Dideoxynucleosides/therapeutic use , Gene Frequency , Genotype , HLA-B Antigens/genetics , Polymerase Chain Reaction , Prevalence , Prospective StudiesABSTRACT
Individual response to drugs, toxicants, environmental chemicals and allergens varies with genotype. Some respond well to these substances without significant consequences, while others may respond strongly with severe consequences and even death. Toxicogenetics and toxicogenomics as well as pharmacogenetics explain the genetic basis for the variations of individual response to toxicants by sequencing the human genome and large-scale identification of genome polymorphism. The new disciplines will provide a new route for forensic specialists to determine the cause of death.
Subject(s)
Humans , Cytochrome P-450 Enzyme System/genetics , Drug Hypersensitivity/genetics , Forensic Medicine , Genetic Predisposition to Disease/genetics , Genome, Human , Pharmacogenetics/trends , Pharmacokinetics , Polymorphism, Single Nucleotide , Toxicogenetics/trendsABSTRACT
A farmacodermia é a reação adversa mais comum aos medicamentos. As reações variam desde desconfortos leves até situações graves. Essa variedade de reações sugere uma multiplicidade de mecanismos envolvidos em sua patogenia