If a benzodiazepine increases the frequency of channel opening by 300%, and a barbiturate increases the duration of their opening by 300%, then the combined effects of the drugs increases the channels overall function by 900%, not 600%). The longest-acting barbiturates have half-lives of a day or more, and subsequently result in bioaccumulation of the drug in the system. The therapeutic and recreational effects of long-acting barbiturates wear off significantly faster than the drug can be eliminated, allowing the drug to reach toxic concentrations in the blood following repeated administration (even when taken at the therapeutic or prescribed dose) despite the user feeling little or no effects from the plasma-bound concentrations of the drug. Users who consume alcohol or other sedatives after the drugs effects have worn off, but before it has cleared the system, may experience a greatly exaggerated effect from the other sedatives which can be incapacitating or even fatal. Barbiturates induce a number of hepatic CYP enzymes (most notably CYP2C9, CYP2C19, and CYP3A4), leading to exaggerated effects from many prodrugs and decreased effects from drugs which are metabolized by these enzymes to inactive metabolites. This can result in fatal overdoses from drugs such as codeine, tramadol, and carisoprodol, which become considerably more potent after being metabolized by CYP enzymes.
The pathological process that result in subcortical dementia shows neuronal changes that involve primarily the thalamus, basal ganglia, and rostral brain-stem nuclei and mostly, some projections in the white matter from these regions to the cortex, with relative sparing of the cerebral cortex. It affects arousal, attention, mood, motivation, language, memory, abstraction, social skills (especially empathy), extrapyramidal functions, and visuospatial skills. Additionally, damage to the basal forebrain can cause amnesia and psychotic disorders. Controversy
One of the problems with the concept of subcortical dementia is the fact that name implies that it is due to lesions confined to subcortical structures. Anatomically none of the neurodegenerative dementias are strictly cortical or subcortical. In fact, there is invariably an overlap of both cortical and subcortical neuronal changes in both types. History
Charcot described dementia as a feature in Parkinsons disease. McHugh introduced the concept of subcortical dementia.Mayeux and Stern and their colleagues and Tierney and coworkers have been critical of the concept of subcortical dementia. Examples
Progressive supranuclear palsy (chronic acetogenin poisoning)
Atypical Parkinsonism
Binswanger disease (and other forms of vascular dementia)
Corticobasal degeneration
Huntington disease
Multiple system atrophy
HIV-associated neurocognitive disorder (HAND)
HIV-associated dementia


== References ==