Stimulants Amfetamines

Six healthy volunteers learned to recognize the effects of oral D-amfetamine 15 mg and then the effects of a range of doses of D-amfetamine (0, 2.5, 5,10, and 15 mg), alone and after pre-treatment with alprazolam (0 and 0.5 mg), were assessed (36). Amfetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported drug effects related to dose. Alprazolam alone did not have amfetamine-like discriminative stimulus effects, nor did it increase ratings of sedation or impair performance. Alprazolam pre-treatment significantly attenuated the discriminative stimulus effects of amfetamine, and some of the self-reported drug effects. The authors suggested that... 

Adverse effects of catecholaminergic stimulants, such as amfetamine and cocaine, fall into several categories, based on dose, time after dose, chronicity of use, and pattern of use/abuse (for example 4-5 day bingeing episodes). Adverse effects include not only responses during the period of use but also intermediate and longterm residual effects after withdrawal. For example, in some abusers once an amfetamine psychosis has developed with chronic abuse, only one or two moderate doses are required to induce the full-blown psychosis in its original form, even long after withdrawal (1). This is also evidenced by the precipitous slide to severe re-addic-tion in former abusers who are re-introduced to stimulants. 

A type of automatic behavior, which can continue for hours, has been observed in addicts who inject large doses of central nervous system stimulants. Dyskinesias can occur, with strange facial and tongue movements or jerky motions of the arms and legs and a never-ending repetition of certain actions. Such stereotyped activity is induced in laboratory animals with high doses of amfetamine. 

In other studies, volunteers previously dependent on amphetamines were dosed to a level at which amfetamine psychosis was produced, in order to examine the mechanism of action and pharmacokinetics of amfetamine and its possible relation to schizophrenia (64,65). Psychosis was induced by moderately high doses of amfetamine and the psychotic symptoms were often a replication of the chronic amfetamine psychosis, raising the question of whether the establishment of chronic stimulant psychosis leaves residual vulnerability to psychosis precipitated by stimulants. The mechanism might be similar to that which operates in the reverse tolerance that has been seen in experimental animals (66). In some cases an underlying psychosis can be precipitated an increase in schizophrenic symptoms (SED-8, 12) was observed in 17 actively ill schizophrenic patients after a single injection of amfetamine. 

Acute transient urinary retention associated with metamfetamine and ecstasy (3,4 methylenedioxymetamfeta-mine, MDMA) in an 18-year-old man has been described (76). Analysis by gas chromatography-mass spectrometry confirmed the presence of metamfetamine (>25 pg/ml), MDMA (> 5 pg/ml), amfetamine (1.4 pg/ml), and methylenedioxyamfetamine (3.7 pg/ml) in the urine. Bladder dysfunction resulting from alpha-adrenergic stimulation of the bladder neck may have explained the observed effect. 

An anaphylactic reaction after the injection of crushed tablets equivalent to 45 mg of amfetamine occurred in a young woman in others injected with the same solution and at the same time there were no adverse effects (SED-9, 8). The reaction may have involved amfetamine or excipients. Scleroderma is a potential consequence of various stimulants used for appetite control (79). 

Dexamfetamine or (+)-amfetamine is significantly more potent than (—)-amfetamine. The use of dexamfetamine as an appetite suppressant has rapidly declined, because of appreciation of its potential for abuse and addiction. These arise mainly from euphoria, which may be followed by depression as the effect of the drug wears off. Stimulant effects were reported in 23% of 347 patients using dexamfetamine as an appetite suppressant (SED-9,10). 

Noradrenaline is synthesised and stored in adrenergic nerve terminals and can be released from these stores by stimulating the nerve or by drugs (ephedrine, amfetamine). These noradrenaline stores may be replenished by i.v. infusion of noradrenaline, and abolished by reserpine or by cutting the sympathetic neuron. 

Anorectic drugs act mainly on the satiety centre in the hypothalamus (1). They also have metabohc effects involving fat and carbohydrate metaboUsm. Most of them are structurally related to amfetamine and increase physical activity. Their therapeutic effect tends to abate after some months, and part of this reduction in effect may be due to chemical alterations in the brain. Fenfluramine commonly produces drowsiness in normal doses, but has stimulaut effects in overdosage. Dexamfetamine, phenmetrazine, and benzfetamine all tend to cause euphoria, with a risk of addiction. Euphoria occasionally occurs with amfepramone (diethylpropion), phentermine, and chlorphentermine, but to a much lesser extent. Some adverse effects are due to sympathetic stimulation and gastrointestinal irritation these may necessitate withdrawal but are never serious. There are interactions with monoamine oxidase inhibitors and antihypertensive drugs. 

Although it resembles amfetamine structurally, the appetite suppressant fenfluramine does not produce central nervous system stimulation in therapeutic doses. 

Phentermine is a central nervous system stimulant that can increase brain dopamine concentrations and has a structure similar to amfetamine. 

Two reviews have addressed the diagnosis and management of ADHD and have summarized the effects of stimulants, including those of methylphenidate and AdderaU (a mixture of equal components of D-amfeta-mine saccharate, D,L-amfetamine aspartate, D-amfeta-mine sulfate, and D,L-amfetamine sulfate, which seems to be gaining popularity in the treatment of ADHD) (6,7). 

Ambulatory blood pressure monitoring showed changes in blood pressure and heart rate in boys aged 7-11 years taking stimulant therapy (13). This preliminary study with chronic methylphenidate or AdderaU (dex-amfetamine + levamfetamine) for ADHD showed alterations in awake and asleep blood pressures, with profound nocturnal dipping. Modified-release formulations of methylphenidate and AdderaU now allow more sustained blood concentrations in children. The effects of these newer formulations on cardiovascular indices should be evaluated. 

Prolintane, an amfetamine-related substance, is a central nervous system stimulant with similar structure and properties to dexamfetamine. Prolintane hydrochloride is available mainly in many formulations with multivitamin supplements in many European countries, Australia, and South Africa. 

Possession and supply illegal except by Home Office Licence Drugs of high abuse potential with medicinal use, opiates and major stimulants, for example amfetamines and cocaine Subject to full controlled drug requirements under the law Drugs of lesser abuse potential with medicinal use for example minor stimulants and barbiturates Subject to special prescription requirements, but not other requirements under the law Anabolic steroids and related hormones Most benzodiazepines and zolpidem Subject to minimal control requirements Sale and supply and possession without a prescription for personal use an offence... 

Class A All opiates, hallucinogens, cocaine, injectable amfetamines, cannabinol and coca leaf Class B Amfetamines, codeine, pholcodeine and barbiturates Class C Milder stimulants and tranquilizers, benzfetamine, benzodiazepines, cannabis and anabolic steroids and related hormones... 

Alemtuzumab - monoclonal antibody leukaemia treatment Allopurinol - prevention of uric acid production, gout treatment Alteplase - fibrinolytic thrombosis Amantadine - antiviral Parkinson s disease Amfetamine (amphetamine) - CNS stimulant (little therapeutic use)... 

Not understood. Although alcohol is a CNS depressant and the amfetamines are CNS stimulants, there is no simple antagonism between the... 

A 16-year-old boy developed unsteadiness and double vision 5 minutes after intranasal inhalation of a small amount of amfetamine cut with cocaine. Cranial MRI (magnetic resonance imaging) revealed a mesencephalic lesion that was seen to have decreased 12 days later, and he became symptom-free after 3 weeks. The ischaemic lesion was thought to be due to vasospasm caused by synergistic stimulation of the sympathetic nervous system amfetamine causes the release of adrenaline (epinephrine) and noradrenaline (norepinephrine), while cocaine prevents their reuptake. ... 

The stimulant and/or cardiovascular effects of the amfetamines have been shown to be opposed by lithium in some, but not other studies. 

Established interactions. These reports suggest that it is not beneficial to attempt to treat patients taking chlorpromazine with amfetamines, such as dexamfetamine, or other central stimulants such as phenmetrazine. In one study, thioridazine also appeared to interact. However, it is not clear whether this interaction takes place with antipsychotics other than chlorpromazine, but it seems possible with the phenothiazines, especially if the suggested mechanism is correct. Note that central stimulants are no longer recommended for the treatment of obesity. 

Amfetamine (Amphetamine) Alpha and beta - also central stimulant... 

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