文档介绍：抗中枢退行性疾病药
抗帕金森病药
PARKINSONISM (Paralysis Agitants)
Parkinsonism is characterized by bination of rigidity, bradykinesia, tremor, and postural instability that can occur for a wide variety of reasons but is usually idiopathic. The pathophysiologic basis of the idiopathic disorder may relate to exposure to some unrecognized neurotoxin or to the occurrence of oxidation reactions with the generation of free radicals. Studies in twins suggest that ic factors may also be important, especially when the disease occurs in patients under age 50. Parkinson's disease is generally progressive, leading to increasing disability unless effective treatment is provided.
The normally high concentration of dopamine in the basal ganglia of the brain is reduced in parkinsonism, and pharmacologic attempts to restore dopaminergic activity with levodopa and dopamine agonists have been essful in alleviating many of the clinical features of the disorder. An alternative plementary approach has been to restore the normal balance of cholinergic and dopaminergic influences on the basal ganglia with antimuscarinic drugs. The pathophysiologic basis for these therapies is that in idiopathic parkinsonism, dopaminergic neurons in the substantia nigra that normally inhibit the output of γ-aminobutyric acid (GABA)ergic cells in the corpus striatum are lost.
Schematic representation of the
sequence of neurons involved in
parkinsonism.
Top: Dopaminergic neurons (color)
originating in the substantia nigra
normally inhibit the GABAergic
output from the striatum, whereas
cholinergic neurons (gray) exert an
excitatory effect.
Middle: In parkinsonism,
there is a selective lossof
dopaminergic neurons (dashed, color).
Fate of orally administered levodopa and the effect of carbidopa, estimated from animal data. The width of each pathway indicates the absolute amount of the drug present at each site, while the percentages shown denote the relative proportion of the administered dose. The benefits o