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Disorders of Consciousness
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Serotonin syndrome9: Can be seen in patients taking serotonergic agents in the past 5 weeks. Implicated agents include selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, opiate analgesics, over-the-counter cough medications, antibiotics, weight-reduction agents, herbal products, antiemetics, antimigraine agents, and illicit drugs.Clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities such as tremor, myoclonus, and hyperreflexia.The rapid onset of symptoms and hyperkinesia (in contrast to bradykinesia) can help distinguish this from neuroleptic malignant syndrome.Management includes removal of the offending agents; supportive measures including management of hyperthermia, agitation, and autonomic instability; and the use of 5-hydroxytryptamine (5-HT) 2A antagonists such as cyproheptadine.
Poison Absorption
Published in David J. George, Poisons, 2017
Nasal sprays administered by squeeze bottles or metered dose devices are used to deliver medications for both local and systemic effects. Decongestants and anti-inflammatory agents are examples of locally acting medication. Drugs that are administered intranasally for systemic absorption from the nasal mucosa include nicotine, fentanyl, antimigraine agents, and some hormones. Absorption from the nasal mucosa can be relatively rapid and provide a quick onset of action.
Research Planning and Development Perspectives
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
At the second critical stage of the R&D cycle, the movement of compounds into man, we need skilled and observant clinical pharmacologists. At this stage and also as compounds move into broader Phase III trials the phenomenon of "clinical serendipity," which is the accidental or unexpected discovery of various clinical effects, can be an important factor in the generation of new therapies. Many historical examples of such drug usage may be noted. Recently, however, we have seen propranolol broaden its approved use from an antiarrhythmic in 1967 to an antianginal in 1973, to an antihypertensive agent in 1976, and to an antimigraine agent in 1979. It is now also being used to prevent second heart attacks. Since such utility, sometimes discovered through unexpected clinical observations, has been the method by which an impressive array of new drugs and drug uses have been generated in the past, one can conclude that drug "discovery" is not restricted to the early phases of the R&D process but extends to all stages including postmarketing. Figure 2 illustrates the role of clinical observation and investigation in the evolution of new drugs [2]. Observations in the clinic may generate impetus for specific clinical programs aimed at providing new therpeutic applications. Clinical observations and studies may also stimulate fundamental knowledge about the behavior of drug substances and related pharmacological phenomena which results in new or revised hypotheses that trigger preclinical research or entirely new clinical investigations. In these ways the astute and observing clinical pharmacologist can be a prime factor in the discovery of utility in novel drug moieties and in designing new drug substances.
A critical review of the neurovascular nature of migraine and the main mechanisms of action of prophylactic antimigraine medications
Published in Expert Review of Neurotherapeutics, 2021
Bruno A. Marichal-Cancino, Abimael González-Hernández, Raquel Guerrero-Alba, Roberto Medina-Santillán, Carlos M. Villalón
Interestingly, the efficacy of non-contractile antimigraine agents [49] has been used as an argument to propose migraine as an entirely neurogenic pathology [50]. Nevertheless, those agents lacking contractile actions in mammal arteries (e.g. lasmiditan) still prevent trigeminal CGRP release [51] and, hence, both its direct vascular (i.e. vasodilatation) and neural (i.e. pain transmission) actions. On the other hand, not every section of the intracranial blood vessels seems to be phenomenologically associated with migraine, and some studies have omitted this peculiarity, as examined recently by Prof. Shevel [52]. In support of the above notion, cautery ablation of selected terminal branches of the external carotid artery was reported to suppress sporadic hemiplegic migraine in three patients [53], suggesting a critical vascular role of these terminal branches in these specific cases. In fact, an interesting method for detecting when migraines have a cranial vascular origin of pain has been recently proposed by Prof. Shevel [54], suggesting that cranial blood vessels are also essential elements in the pathophysiology of migraine.
Pharmacogenomics of drugs used to treat brain disorders
Published in Expert Review of Precision Medicine and Drug Development, 2020
At least 13 categories of CNS drugs can be differentiated: (i) general anesthetics; (ii) analgesics and antipyretics (nonsteroidal anti–inflammatory agents, opiate agonists, opiate partial agonists); (iii) opiate antagonists; (iv) anticonvulsants (barbiturates, benzodiazepines, hydantoins, succinimides); (v) psychotherapeutic agents (antidepressants: monoamine oxidase inhibitors, selective serotonin and norepinephrine-reuptake inhibitors, selective serotonin-reuptake inhibitors, serotonin modulators, tricyclics and other norepinephrine-reuptake inhibitors; antipsychotics: atypical antipsychotics, butyrophenones, phenothiazines, thioxanthenes); (vi) anorexigenic agents and respiratory and cerebral stimulants (amphetamines); (vii) anxiolytics, sedatives, and hypnotics (barbiturates, benzodiazepines, and miscellaneous anxiolytic, hypnotic and sedative agents); (viii) antimanic agents; (ix) antimigraine agents (selective serotonin agonists); (x) antiparkinsonian agents (adamantanes, anticholinergic agents, catechol-O-methyltransferase (COMT) inhibitors, dopamine precursors, dopamine receptor agonists, monoamine oxidase B inhibitors); (xi) anti-dementia agents (cholinesterase inhibitors, nootropics, neuroprotective agents, vasoactive agents, immunotrophins, anti-atherogenic compounds, other anti-dementia drugs); (xii) fibromyalgia agents; and (xiii) miscellaneous CNS agents [8, 9].
A systematic review with expert opinion on the role of gepants for the preventive and abortive treatment of migraine
Published in Expert Review of Neurotherapeutics, 2022
Andreas A. Argyriou, Elisa Mantovani, Dimos-Dimitrios Mitsikostas, Michail Vikelis, Stefano Tamburin
Nonetheless, the development of triptans in the early 90s heralded a new class of acute antimigraine agents, which thereafter have been increasingly used and still represent the standard of care in the treatment of moderate/severe acute migraine attacks and associated symptoms of nausea, photophobia, and phonophobia. Triptans have selective affinity for 5-hydroxytryptamine (5-HT)1B, 5-HT1D serotonin receptors and variable activity on 5-HT1F receptors, resulting in much higher efficacy and more favorable safety profile, compared to ergotamine [9], and no risk of dependence or addiction compared to barbiturate or opioid medications.