The Emerging Focus on Pharmacogenomics

Drugs are designed to treat medical conditions for the general population. Idiosyncratic reactions to drugs are determined by the individual’s respective genetic variations that direct effectiveness and side effects. Adverse drug reactions rank within the top ten leading causes of death in the developed world. The field of pharmacogenomics has advanced in the last fifty years, picking up significant momentum with recent biotechnological developments that allowscientists to investigate the human genome and provide individualized drug therapy that will increase the efficacy of drugs and decrease the incidence of adverse drug reactions. Pharmacogenomics has reached a milestone in making personalized medicine accessible and effective. The medical community shares this responsibility for the emerging focus on pharmacogenomics with regulatory agencies and bioinformatics specialists as they struggle to streamline vast libraries of information and reconcile public and regulatory approval on this critical path to the next level of health care.

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Pharmaceutical Sales and Frequency of Adverse Drug Reactions / 医薬品情報学

<b>Objective</b>: It is very difficult to identify the frequency of rare adverse drug reactions (ADRs) precisely.  A study was conducted to estimate the frequency of ADRs that were not observed in clinical studies by referring to the sales volume of the pharmaceuticals until the date when the ADR was first observed after a drug was marketed.<br><b>Methods and Subjects</b>: The study was conducted for the 17 pharmaceuticals to estimate the frequency of Hepatopathy.  The date of report of the ADR to the Minister was obtained through information disclosure requests.  The sales volume of the relevant pharmaceuticals was provided by IMS Japan.  On the premise that all the ADRs were detectable, the probability (<i>P</i>) that an ADR was not detected right before drug administration in the first case of the ADR was estimated through Formula 1.<br>Formula 1 : <i>P</i>=1−{(<i>D</i>₀<i>−S</i>)!÷(<i>D</i>₀<i>−S−D_N</i>)!}/{<i>D</i>₀!÷(<i>D</i>₀−<i>D</i><i>_N</i>)!} = 1−{(<i>D</i>₀<i>−D</i>₀×<i>F</i>)!÷(<i>D</i>₀<i>−D</i>₀×<i>F</i><i>−D_N</i>)!}/{<i>D</i>₀!÷(<i>D</i>₀−<i>D</i><i>_N</i>)!}<br>  <i>D</i>₀ referred to the estimated person-days for all the patients subject to the drug therapy, <i>S</i> to the number of patients with ADR, <i>D</i>_<i>N</i> to the person-days until the date when the ADR was observed and <i>F</i> to the frequency of the ADR.  <i>F</i> was estimated where the detection <i>P</i> was 0.95 or was close to 0.95.<br><b>Results and Discussion</b>: Among the pharmaceuticals investigated, the frequency was highest in product A (0.038%) and was lowest in product X (0.0000088%).  In many cases, the package inserts describe the frequencies of rare ADRs as unknown.  However, the frequency can be estimated relatively precisely through the method stated above using data, which may be kept by pharmaceutical manufacturers.

Adverse Drug Reactions Induced by Qingkailing Injection:Literature Analysis of 66 Cases / 中国药房

OBJECTIVE:To discuss the characteristics and regular patterns of adverse drug reactions (ADRs) induced by Qingkailing injection for references of clinical rational drug use. METHODS:ADR cases induced by Qingkailing injection reported in Chinese pharmaceutical journals from 2003 to 2005 were retrieved and analyzed statistically. RESULTS:The ADRs induced by Qingkailing injection were more often seen in men than in women, with children and young adults showing higher percentages. Allergic reactions were the main type of adverse drug reactions. Of the total ADR cases induced by Qingkailing injection, 22 cases(33.33%) were anaphylactic shock,15(22.73%) were allergic reactions,10(15.15%) were allergy of circulation system. CONCLUSION:The ADRs induced by Qingkailing injection may be resulted form many factors, which should be given fully attention in the clinic. ADRs monitoring should be stressed when this drug being used by western medicine physicians to make sure rational use of which and to reduce incidences of ADRs.

Retrospective Analysis of 266 Adverse Drug Reaction Cases / 药物流行病学杂志

Objective:To observe the occurrence of ADRs in a hospital and analyze its correlative factors.Meth- od:131 ADR cases collected in a hospital in 2006 were categorized statistically analyzed.Result:121 of the 131 ADR ca- ses were induced by chemical drugs,and the other 10 cases,induced by the traditional Chinese drugs.In the 121 ADR ca- ses induced by chemical drug,the most were induced by intravenous injection,which occupied 49.62%.Antimicrobial drugs were the first category of drugs to cause ADRs,totaling 77 cases from 42 drugs.ADR most commonly manifested themselves in the injury of skin and appendents,which accounted for 52.89%(64 cases).There were 10 comparatively serious ADR cases.Conclusion:The occurrence of ADRs was related to many factors,such as administration route and drug varieties.ADRs monitoring and publicizing of ADRs knowledge should be strengthened so as to lessen and avoid the occurrence of ADRs.