Parkinsonian Disorders

Gibb WRG. (1998). The neuropathology of parkinsonian disorders. In Parkinson s Disease and Movement Disorders, 3rd ed. Jankovic J, Tolosa E, ed. Baltimore Williams and Wilkins. 

Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder. Neurology 1996 46 388-393. 

Morris HR, Baker M, Yasojima K, Houlden H, Khan MN, Wood NW, et al. (2002) Analysis of tau haplotypes in Pick s disease. Neurology 59 443-445 Morris HR, Lees Al, Wood NW (1999) Neurofibrillary tangle parkinsonian disorders-tau pathology and tau genetics. Mov Disord 14 731-736... 

L-dopa is effective in the treatment of Parkinson s disease, a disorder characterised by low levels of dopamine, since L-dopa is metabolised into dopamine. However, this biosynthesis normally occurs in both the peripheral nervous system (PNS) and the central nervous system CNS. The related drug carbidopa inhibits aromatic L-amino acid decarboxylase only in the periphery, since it does not cross the blood-brain barrier. So, when carbidopa is given with L-dopa, it reduces the biosynthesis of L-dopa to dopamine in the periphery and, thus, increases the bioavailability of L-dopa for the dopaminergic neurons in the brain. Hence, carbidopa increases the clinical efficacy of L-dopa for Parkinsonian patients. 

Side effects include fatigue, insomnia, and altered motor coordination. Parkinsonian side effects and acute dys-tonic reactions also have been reported. Metoclopramide stimulates prolactin secretion, which can cause galactorrhea and menstrual disorders. Extrapyramidal side effects seen following administration of the phenothiazines, thioxanthenes, and butyrophenones may be accentuated by metoclopramide. 

Roy-Byrne PP, Uhde TW, Post RM, et al The corticotropin-releasing hormone stimulation test in patients with panic disorder. Am J Psychiatry 143 896-899, 1986 Ruberg M, Ploska F, Javoy-Agid F, et al Muscarinic binding and choline acetyltransferase activity in Parkinsonian subjects with reference to dementia. Brain Res 232 129-139, 1982... 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

The first generation antipsychotics, now known as typical drugs, were all D2 receptor blockers and, as such, very likely to produce Parkinsonian side effects. Because antipsychotic potency was associated with D2 receptor affinity, it was assumed that dopamine overactivity was the essential defect in schizophrenia and that a direct dopamine blockade was the definitive route to treatment. But these drugs affected both the target dopamine pathways of the mesolimbic projection and the uninvolved nigrostriatal projection. Unfortunately, that meant that movement disorders were the price that had to be paid for antipsychosis. 

Schizophrenia is certainly not the only disorder with such impairments in cognition. Autism, poststroke dementia, Alzheimer s disease, and many other organic dementias (parkinsonian/Lewy body dementia, frontotemporal/Pick s dementia, etc.) are also associated with some cognitive dysfunctions similar to those seen in schizophrenia (Fig. 10—4). 

Stem M, Roffwarg H, Duvoisin R. The parkinsonian tremor in sleep. J Nerv Ment Disord 1968 147 202-210. 

Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are also associated with parkinsonian-like movement disorders (dystonic reactions) and in rare cases with the neuroleptic malignant syndrome, characterized by "lead-pipe" rigidity, hyperthermia, and autonomic instability (see Chapter 29 Antipsychotic Agents Lithium). 

It is now widely accepted that the term Parkinson s syndrome refers to a collection of neurodegenerative diseases, all of which are characterized by movement disorders. It also applies to drug-induced disorders of the parkinsonian type. A schematic representation of this syndrome is shown in Figure 13.1. 

Correct choice = A. Parkinsonian patients show a deficiency of dopaminergic neurons, without a decrease in cholinergic actions. Elevated levels of dopamine can lead to behavorial disorders. Levodopa and large, neutral amino acids share a transport system that is needed to enter the brain thus high protein diets may lead to elevated levels of circulating amino acids, resulting in a decrease in levodopa uptake. Dyskinesia is usually seen with longer-term therapy and is dose-related and reversible. The mechanism of action of deprenyl is not understood. 

Chlorpromazine, the first modern drug to be used in the treatment of schizophrenia and other psychotic disorders, was introduced into psychiatry in 1952 [61]. It was followed by a number of other drugs for the treatment of these conditions (e.g., haloperidol, thioridazine). These were also called neuroleptics because of their neurological side effects, such as parkinsonian syndrome and tardive dyskinesia. Tardive dyskinesia is a movement disorder characterized by involuntary movements of the face and limbs. The antipsychotic properties of these drugs were inseparable from the extrapyramidal effects. 

Schneider JS, Pope-Coleman A, Van Velson M, Menzaghi F, Lloyd GK (1998) Effects of SIB-1508Y, a novel neuronal nicotinic acetylcholine receptor agonist, on motor behavior in parkinsonian monkeys. Mov Disord 73 637-642. 

Perenyi A, Norman T, Hopwood M, Burrows G. Negative symptoms, depression, and parkinsonian symptoms in chronic, hospitalised schizophrenic patients. J Affect Disord 1998 48(2-3) 163-9. 

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