The relationship between an individual and their hallucinations is personal, and everyone interacts with their troubles in different ways. There are those who hear solely malevolent voices, solely benevolent voices, those that hear a mix of the two, and those that see them as either malevolent or benevolent and not believing the voice. Mood disorders and dementias
Mood disorders such as bipolar disorder and major depression have also been known to correlate with auditory hallucinations, but tend to be milder than their psychosis-induced counterpart. Auditory hallucinations are a relatively common sequelae of major neurocognitive disorders (formerly dementia) such as Alzheimers disease. Transient causes
Auditory hallucinations have been known to manifest as a result of intense stress, sleep deprivation, and drug use. Auditory hallucinations can also occur in mentally healthy individuals during the altered state of consciousness while falling asleep (hypnagogic hallucinations) and waking up (hypnopompic hallucinations).High caffeine consumption has been linked to an increase in the likelihood of experiencing auditory hallucinations. A study conducted by the La Trobe University School of Psychological Sciences revealed that as few as five cups of coffee a day could trigger the phenomenon. Intoxication of psychoactive drugs such as PCP, amphetamines, cocaine, marijuana and other substances can produce hallucinations in general, especially in high doses. Withdrawal from certain drugs such as alcohol, sedatives, hypnotics, anxiolytics, and opioids can also produce hallucinations, including auditory. Pathophysiology
The following areas of the brain have been found to be active during auditory hallucinations, through the use of fMRIs.
These kinases are present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells compared to uninfected human cells, allowing ganciclovir triphosphate to concentrate in infected cells.Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate (dGTP). It is incorporated into viral DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. Ganciclovir triphosphate serves as a poor substrate for chain elongation. Once incorporated into viral DNA due to its structure similarity to dGTP, chain termination occurs once a single nucleotide is added to the distal hydroxyl group of the incomplete deoxyribose ring of ganciclovir. Pharmacokinetics
Oral bioavailability is approximately 60%. Fatty foods significantly increase the bioavailability and the peak level in the serum. It takes about 2 hours to reach maximum concentrations in the serum. Valganciclovir is eliminated as ganciclovir in the urine, with a half-life of about 4 hours in people with normal kidney function. The mechanism of this drug is activation via a viral protein kinase HCMV UL97 and subsequent phosphorylation by cellular kinases. The phosphotransferase enzyme can likewise activate valganciclovir. Chemistry
The synthesis of valganciclovir has been reviewed. Many routes use ganciclovir as a starting material. Society and culture
Price and patent status
Roches Valcyte is protected by patent. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy was found by the District Court of New Jersey, USA not to infringe Roches patent. In November 2014, FDA approved generics by two manufacturers.The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India.