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Autonomic Nervous System Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Metacholine (methacholine), instilled into the conjunctival sac, does not affect the size of the normal pupil, but it causes pupillary constriction if parasympathetic innervation is impaired. This is because of the denervation supersensitivity of the constrictor muscle of the pupil.
Effects of Neuropeptides on Intestinal Ion Transport
Published in Edwin E. Daniel, Neuropeptide Function in the Gastrointestinal Tract, 2019
Studies have shown mucosal transport defects in streptozotocin-treated rats.101 Frank secretion was noted which could be rectified by the α2-adrenoceptor agonist clonidine. There was a denervation supersensitivity as well. How the lack of change in NPY-containing nerve fibers modifies this problem is not clear. Complex changes occur, and it is not easy to translate these observations into the observed clinical picture. Both intractable diarrhea and chronic constipation are seen in diabetes, and the experimental reports provide some explanation for the latter observations.
Alcohol
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
A number of general theories which have been advanced to explain the development of tolerance to and physical dependence on drugs acting upon the central nervous system may have some application to the special case of ethanol as well. Most proposed hypotheses postulate some kind of homeostatic response to the effect of administered drugs. A self regulatory process is assumed to adapt to the drug effect in such a manner as to restore normal function if the drug is being administered. However, on drug withdrawal, the adaptive process then constitutes an uncompensated disturbance in its own right leading to withdrawal reaction. Various formulations of this hypothesis have been proposed. One of these is the denervation supersensitivity hypothesis of Jaffe and Sharpless.191 This is based on the observation that many withdrawal phenomena represent an exaggeration of behavior which may be suppressed by the agent that induces dependence. It is postulated that during its administration, the agent induces an increase in excitability of nervous pathways that is masked by the depressing action of the drug on the same pathway or, alternatively, the drug induces depression through activation of suppressive pathways. Withdrawal will reveal a rebound excitability. The relevance of this theory to alcohol remains to be assessed.
Managing autonomic dysfunction in Parkinson’s disease: a review of emerging drugs
Published in Expert Opinion on Emerging Drugs, 2020
Dinkar Kulshreshtha, Jacky Ganguly, Mandar Jog
Droxidopa (L-3-O dihydroxyphenylserine or L-DOPS) is the most recent addition to the current list of medications in managing OH in PD patients. It is approved for managing symptoms related to OH in the USA/Europe but not in Canada. A recent post hoc analysis using the earlier phase 2 clinical trials of Droxidopa in OH was conducted by Hauser et al. In all three trials, patients received 100–600 mg Droxidopa in three divided doses and it was given over periods varying from 3 weeks to 8 weeks in different trials. In all the three studies, droxidopa was associated with significant improvement in blood pressure measurements on standing, OH questionnaire (OHQ) and OH daily activity scale (OHDAS) [64]. The clinical benefits of droxidopa were shown to be related to lower baseline supine plasma norepinephrine levels in OH patients by Palma et al. in their study on 20 nOH patients. Three patients with extremely low supine plasma norepinephrine levels responded to doses as low as 200 mg while six patients with high norepinephrine levels did not respond even to a maximum dose of 600 mg droxidopa. This might be related to denervation supersensitivity and has clinical implications in identifying patients who would respond to droxidopa [69]. The most common adverse effects noted with droxidopa were dizziness, headache and hypertension but overall, the drug was well tolerated with no drug discontinuation in any group [64]. Thus, droxidopa is a promising agent in managing nOH in PD, for at least short-term use till the beneficial effect of the drug over long term use can be supported by further studies.
Chemical pharmacotherapy for the treatment of orthostatic hypotension
Published in Expert Opinion on Pharmacotherapy, 2019
About one-half of patients with nOH will also manifest neurogenic supine hypertension, or nSH, defined as a SBP ≥ 140 mmHg or DBP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position [48]. As nSH can be blocked by sympathetic antagonists, its basis is residual sympathetic tone [49,50]. Among the multiple factors contributing to nSH are impairment of the baroreflex arc, disruption of the renin-angiotensin-aldosterone axis, and peripheral vascular α-adrenoreceptor denervation supersensitivity [48]. Some patients with nSH will report a supine headache, but most are asymptomatic. The most concerning consequence of nSH is an exacerbation of nocturnal pressure diuresis, which causes nocturia (with risk of falling if the patient gets out of bed during the night) and intravascular volume depletion, which worsens nOH the following morning [48].
The Hemisection Approach in Large Animal Models of Spinal Cord Injury: Overview of Methods and Applications
Published in Journal of Investigative Surgery, 2020
S. Wilson, S. J. Nagel, L. A. Frizon, D. C. Fredericks, N. A. DeVries-Watson, G. T. Gillies, M. A. Howard
Almost two decades later, Murray and Goldberger [20] explored the role of collateral sprouting as a possible mechanism that could explain the restoration of partial function after hemisection in the chronic feline model. As was well known by that time, complete regeneration of CNS neurons could not account for the apparent recovery. Alternative hypotheses including denervation supersensitivity and neuronal hyper-excitability were proposed by various groups working on this question but the debate remained unsettled.