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It was believed for a long time that stimulants did not induce a state of drug dependence allergy symptoms icd 9 code fml forte 5 ml buy otc. This does not negate the significance of the physiologic and neurochemical alterations that underlie stimulant abstinence, causing disturbance of affect and disruption of sleep cycles during the first hours to days of abstinence (Gawin, 1991; Gawin & Ellinwood, 1988). The subsequent weeks to months of abstinence 140 Juan Sanchez-Ramos are associated with anhedonia, anxiety, and high levels of stimulant drug craving that usually result in relapse to former patterns of stimulant use. Even experienced drug users cannot distinguish the immediate subjective effects of 16 mg of cocaine from 10 mg of dextroamphetamine, when both are administered intravenously (Fischman et al. Moreover, the toxic psychosis that may develop with chronic cocaine use is clinically indistinguishable from that induced by chronic amphetamine use. Although the actions and toxicity of amphetamine are emphasized as a prototype, this should not imply that all stimulant drugs have identical mechanisms of action. Even further from the truth would be the assertion that experienced drug abusers cannot distinguish differences between stimulants. Chronic methamphetamine use has been associated with deficits in cognition, anxiety, depression, and psychosis. Approximately 40% of regular methamphetamine users have cognitive deficits that can be documented by neuropsychiatric tests (Rippeth et al. The most frequently reported deficits involved episodic memory, executive function, and motor function (Scott et al. Some experts have speculated that this memory deficit causes them to forget past errors and hence condemns them to relapse into the same self-destructive pattern of stimulant self-administration. Chronic methamphetamine abuse also impacts executive function, leading to impulsiveness, perseveration, and inability to delay gratification and to carry out long-term goals (Gilbert & Burgess, 2008). Some studies report motor deficits in chronic methamphetamine abusers, especially noted when testing fine motor dexterity (Caligiuri & Buitenhuys, 2005). Chronic methamphetamine abusers can exhibit a range of mental disturbances including anxiety, depression, and psychosis (Sanchez-Ramos, Neurologic Complications 141 1993). The fully developed toxic psychosis from chronic methamphetamine or cocaine use is characterized by vivid visual, auditory, and occasionally tactile hallucinations (Rusyniak, 2013). Delusions of parasitosis and compulsive picking at imaginary bugs under the skin (formication) may develop (Rusyniak, 2013). Interestingly, chronic users with toxic psychosis often display little or no sympathomimetic effects and blood pressure is not elevated unduly (Jaffe, 1985). The amphetamine-induced paranoid ideation and thought disorder are similar to paranoid schizophrenia. The most frequently reported symptoms are delusions of persecution and auditory hallucinations (Iwanami et al. Both schizophrenia and amphetamine-evoked psychosis can be effectively treated with dopamine antagonists (Angrist, Lee, & Gershon, 1974). The development of psychosis is more readily seen in people using higher methamphetamine concentrations for prolonged periods of time (Chen et al. The reported doses required, duration of abuse, and onset of symptoms are highly variable, as is the duration of psychotic symptoms (1 week- indefinitely) (Cruickshank & Dyer, 2009). Even if symptoms abate with abstinence, they can reemerge with repeat usage or under stressful situations (Sato, 1992). One of the debates associated with psychosis and methamphetamine is whether it is the result of methamphetamine-induced neurotoxicity. The latter seems to be supported by data showing that persons with predisposition to mental illness, such as strong family histories, are significantly more likely to develop methamphetamine-associated psychosis (Chen et al. Furthermore, schizophrenics given low doses of methamphetamine will have exacerbations of their symptoms (Lieberman, Kinon, & Loebel, 1990). Therefore, it has been suggested that in susceptible individuals, methamphetamine abuse may be a trigger which unmasks schizophrenia/psychosis (Bell, 1965). Some experts have suggested that persons with schizophrenia/ psychosis seek out illicit drugs as a form of self-treatment (Buckley, 1998) and others claim that neuronal deficits underlying the development of schizophrenia make individuals more prone to develop drug addiction 142 Juan Sanchez-Ramos (Chambers, Krystal, & Self, 2001). Regardless of the perspective, it is clear that methamphetamine abuse can result in the development of acute, and in some cases chronic, psychosis. Stereotypic movements involve repetitive, nonfunctional motor behaviors that may be self-injurious (head banging, hand shaking, rocking movements, self-biting, skin picking). Although stereotypic movement disorders are associated with autism, LeschNyhan syndrome, and other neurodevelopmental disorders, methamphetamine can trigger stereotypic movements such as frequent blinking, facial grimacing, lip licking, and grunting in normal individuals. Many examples seem to have a compulsive component with rearrangement of furniture, fastidious bathing, and distinctive and repetitive walking patterns (SanchezRamos, 1993). For example, an artist may doodle, draw, or paint excessively to the point that all walls of the house are covered with the art. A housekeeper may repetitively polish silverware or rearrange the furniture for hours. Punding was first reported in amphetamine users where in one study 26% (40 of 150) of heavy users experienced it (Rylander, 1972). While few controlled studies have been done on punding in substance abusers, there are some data available on its incidence. In a study of 50 patients addicted to cocaine, 38% had some form of punding (Fasano & Petrovic, 2010). It is interesting that the majority of interviewed patients in this study noted their behavior began shortly after their first medication usage.
The tenet uniting all variants of irritability theory was that they reduced all illnesses into just a very small number allergy medicine jittery discount fml forte 5 ml mastercard. For Haller as for Brown, there were basically only two, diseases of irritability and diseases of sensibility. Diseases of irritability were caused by too little stimulation and diseases of sensibility by too much. Diseases of irritability could be treated with stimulants, those of sensibility with narcotics. We think of stimulants in terms of their impacts on substances such as noradrenalin, dopamine, and serotonin, all of which were unknown in the eighteenth century. Eighteenth-century physicians and their patients understood it more simply as an affair of contractions in muscle tissue. It was because of irritability theory and its rivals that opium and alcohol began to be more widely used in medical treatments. A typical list of stimulants in a medical textbook would also have included meat, oxygen or "dephlogisticated air," exercise, and "the exciting passions of the mind. The psychotropic effects of stimulants were always seen as a drawback in this period. Beddoes and Davy abandoned pneumatic medicine in the early 1800s and for a time Beddoes experimented with Galvanism as an alternative stimulant force. It all began with a bout of rheumatic fever, a condition he had contracted at the age of eight. The latest bout coincided with his arrival in Keswick in the Lake District where he had recently moved to be near his friend William Wordsworth. There is always a danger with accepting a diagnosis such as this one retrospectively. Shortly before coming down with the symptoms he recognized as rheumatic fever, Coleridge reported a severe infection of the eyes which prevented him from reading or writing alongside an attack of orchitis that caused his left testicle to swell to three times its natural size (Griggs, ii, 647; 667). Soon afterward the symptoms of rheumatic fever appeared: "six large Boils in the back of the neck," pains in the back of the head, exhaustion, and of course the fever itself (Griggs, ii, 672). After several months, he decided he must have a different condition: "irregular gout. Opium as a Literary Stimulant 333 In doing so, he was in fact appealing to a new theory of gout first put forward by William Cullen (17781784). From ancient times, gout had been thought to arise when morbid humors "dropped" from the trunk of the body and collected in the joints giving rise to gout pains (the name gout, derived from gutta, the Latin for "drop," reflects this etiology). Cullen, arguing against this theory, suggested that gout occurs when pains originating in the stomach are conveyed to the extremities (especially the joints of the fingers, toes, and knees) through the medium of the nervous system by the sentient principle postulated by Whytt. The basis of the distinction was that regular gout chiefly attacked the joints, whereas irregular gout assailed the stomach. Attacks of regular gout usually subsided after a few days, whereas the pains of irregular gout continued indefinitely. Cullen conjectured that the remissions characteristic of regular gout were due to the intervention of nervous "excitement" in the brain. The pains of irregular gout continued indefinitely because this mechanism of self-correction failed. Although Coleridge had placed himself under the care of a surgeon apothecary, this diagnosis seems to have been his own. Near the end of March 1801, he announced he had "a sort of irregular gout" (Griggs, ii, 719). In quick succession, he reported "three paroxysms of decided gout" (Griggs, ii, 739). His symptoms were "Swoln knees, a knotty fingers, a loathy Stomach, & a dizzy head" (Griggs, ii, 739). But the symptoms which caused him most suffering were stomach symptoms: as he told Sara Hutchinson in the summer, "for the first 10 days after my arrival at Stowey, I had every evening a Bowel attack-which layed my spirits prostrate-but by a severe adherence to a certain regular Diet & Regimen, I have, I hope, entirely got the better" (Griggs, ii, 780). To Southey, he complained that he was "often literally sick with pain" (Griggs, ii, 748). In a rueful letter written some 13 years after these events, Coleridge described how he treated himself with opium: I had been almost bed-ridden for many months with swellings in my knees-in a medical Journal I unhappily met with an account of a cure performed in a similar 334 Neil Vickers case. Brown claimed to have formulated his discoveries while treating himself for this same condition: the universal rule, suggested by the principles, and confirmed by the practice of this new doctrine, is to invigorate the whole system, and apply any diffusible stimulus, particularly laudanum, to the pained parts. By that practice I know not one cure, of some hundreds, that either I or my pupils have performed, that has failed. The effectual method of cure is to apply rags dipped in laudanum, volatile alkali, or ether, and renew them as often as they become dry, and to support [the patient] internally with durable and diffusible stimuli, proportioned in kind and quantity to the exigence of the case. Thus, he talked of "ripening" his gout into a "fair Paroxysm" (Griggs, ii, 721) by undertaking a long walking tour, a cure endorsed by Sydenham in his famous essay on gout. And so we come full circle to the quotation at the beginning of this paper in which Coleridge urged Tom Wedgwood to try "large doses of opium in a hot climate," so as to "produce the Gout, & that a violent Pain and Inflammation in the Extremities might produce new trains of motion & feeling in your Stomach and the Organs connected with it, the Stomach known and unknown All of this is consistent with what he knew of irritability treatments and with what he knew of stimulants. Opium as a Literary Stimulant 335 In August of 1803, Coleridge went on a walking tour of Scotland with William and Dorothy Wordsworth during which he tried to use walking as a substitute for opium. I have argued elsewhere that he probably thought that his "gout" was taking on an epileptic dimension. He spoke, for instance, of "Epileptic winds and breezes, gusts from the bowels of the volcano upwards to the Crater of the Brain, rushings & brain horrors" (Coburn, i, 1822) and complained of "frequent paralytic feelings-sometimes approaches to Convulsion fit" (Griggs, ii, 975). Coleridge found that they stopped when he took opium again (though the nightmares and the hallucinations resumed). Here, we come to one of the thorniest issues that beset historic analyses of addictions to psychostimulants. It is undeniable that some of the elements of what would subsequently become the theory of addiction had been discussed in detail by the close of the eighteenth century.
Proceedings of the National Academy of Sciences of the United States of America allergy medicine in pregnancy order fml forte, 97(8), 43214326. Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization. Stimulants can enhance stamina and improve performance in tasks that have been impaired by fatigue or boredom. These agents also possess potent reinforcing properties that can result in excessive self-administration and abuse. Chronic use is associated with adverse effects including psychosis, seizures, and cerebrovascular accidents, though these complications usually occur in individuals with preexisting risk factors. This chapter reviews the adverse neurologic consequences of chronic psychomotor stimulant use and abuse, with a focus on two prototypical stimulants methamphetamine and cocaine. Khat is an evergreen plant that grows at high altitudes in East Africa and the Arabian Peninsula. Users of khat report increased levels of energy, alertness, and self-esteem, a sensation of elation, enhanced imaginative ability, and a higher capacity to detect patterns of connectivity (Carvalho, 2003). Some other less-potent amphetamines may also be present in khat, namely norpseudoephedrine (cathine) and norephedrine. One of the oldest medicinal herbs known to mankind is probably ´ ´ Ephedra, or ma huang as it is known in Traditional Chinese Medicine. The amphetamines ephedrine and pseudoephedrine are the main psychoactive constituents of the plant, the others being their optical isomers and N-methylated derivatives (Abourashed, El-Alfy, Khan, & Walker, 2003). Before the abuse potential of methamphetamine was recognized, its clinical effects were considered to be ideal for warfare. Combat capability was markedly enhanced by a drug-induced state of alertness and aggression, as well as decreased hunger and need to sleep. After the war, Japan experienced an epidemic of methamphetamine abuse as army surplus flooded the market. Its usage declined in the 1960s, only for a resurgence to occur in the 1970s and continues to be a problem in Japan today (Suwaki, Fukui, & Konuma, 1997). Also depicted are the natural amphetamines pseudoephedrine, ephedrine, cathinone, and cathine (norpseudoephedrine). The neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) are based on the same phenylethylamine structure. When pharmaceutical companies terminated their injectable formulations in the early 1960s, methamphetamine manufacturing was taken up in clandestine labs and distributed by west coast motorcycle gangs to meet the demand for the drug (Gonzales, Mooney, & Rawson, 2010). At that time, methamphetamine was produced primarily from the precursors phenyl-2propanone and methylamine (the P-2-P method) (Anglin et al. In the 1980s, a crystalline form of methamphetamine that could be smoked, called "ice," began to be imported from Asia to Hawaii (Gonzales et al. Hydrolysis of cocaine yields benzoylecgonine, and the action of serum and liver esterases produces ecgonine methyl ester. Cocaine is also N-demethylated by the liver cytochrome P450 system into norcocaine. By 1990, methamphetamine had replaced cocaine as the stimulant of choice among drug users in many areas of California (Derlet & Heischober, 1990). When done by those without chemistry backgrounds in poorly ventilated areas, fires and explosions were not uncommon. This led to the closure of large numbers of small and medium-sized clandestine laboratories resulting in a Neurologic Complications 135 decrease in numbers of methamphetamine abusers in 2006-the first time for 10 years (Gonzales et al. Despite the decline in illicit use of amphetamines, they remain important and useful treatments in medicine. It was first extracted from the plant Erythroxylum coca in the mid-nineteenth century. Leaves of the plant were used by the indigenous population of the Andes for centuries before the European conquest and formed an integral part of Inca rites and customs. Coca leaves continue to be chewed by natives of the altiplano to alleviate the diminish fatigue and alleviate altitude sickness. The leaves are sprinkled with lime alkali (or nowadays readily available baking soda-sodium bicarbonate) to facilitate extraction of the base and absorption into the blood stream by the oral mucosa. Among many potential applications suggested by Freud (including treatment of alcohol and opiate dependence), its use as a local anesthetic was widely adopted by physicians. Its stimulant effects were also considered to be of potential value as a treatment for neurasthenia and depression by many eminent physicians, and the popular press extolled its use for innumerable ailments from the common cold to impotence. Cocaine was added to many tonics and popular alcohol and nonalcoholic beverages such as Vin Mariani and Coca Cola. Such publicity and widespread use inevitably led to reports of cocaine intoxication and addiction. Opposition by the medical profession then followed, with sensationalized newspaper stories describing the dangers and violence associated with cocaine use by "black dope fiends. Despite its criminalization as a recreational drug, its use was resurrected by 136 Juan Sanchez-Ramos bohemians and artists and jazz musicians in the 1950s, and its use and abuse gradually spread over the next decade to all echelons of society. In 1980s, the drug became available in a smokable form known as "crack," supposedly because of the sound made by popping cocaine crystals during heating. Crack could be synthesized readily from cocaine hydrochloride, and because of its relatively lower price, soon it became the stimulant of choice among the urban American poor. Cocaine and amphetamines have alternated in abuse prevalence during the past 70 years, with peaks in amphetamine abuse roughly corresponding to troughs of cocaine abuse. The most recent data from 2007 to 2012 indicate methamphetamine use has remained steady, from 530,000 current users in 2007 to 440,000 in 2012. In contrast over the same period, cocaine use has gone down, the number of current users aged 12 or older having dropped from 2. Amphetamines without ring substitutions have sympathomimetic, antifatigue, and strong reinforcing effects, those with side-chain substitutions may cause anorexia, while those derivatives with terminal amine substitutions have psychomotor stimulant effects at low doses and hallucinogenic activity at higher doses (Young & Glennon, 1986).