Amfetamine

Tranylcypromine is a non-hydrazine monoamine oxidase (MAO) inhibitor with actions and uses similar to those of phenelzine, but with less prolonged inhibition. Its half-life is 90-190 minutes. It is structurally related to amfetamine, to which it is metabolized in overdose (1). 

Four cases of addiction to tranylcypromine have been described, in addition to the three reported since 1965 (2). The dosage was 150-300 mg/day. The mild euphoriant properties of tranylcypromine reflect its structural resemblance to amfetamine, and probably account for tolerance and addiction in predisposed individuals. Tranylcypromine abuse in 18 patients has been reviewed (3), and two further reports have appeared (SEDA-17,17) (4). In one case (5), the patient took 440 mg/day without any adverse effects. The patient reported that she was longing for the energizing effect of the drug and for the feeling of freedom and power. Withdrawal resulted in repeated generalized seizures and status epilepticus. 

When metamfetamine and amfebutamone (bupropion) were co-administered to 26 subjects, 20 of whom completed the protocol, there was no evidence of additive cardiovascular effects [32], The subjects received metamfetamine 0,15, and 30 mg intravenously before and after randomization to bupropion 150 mg bd in a modified-release formulation or matched placebo. There was a non-significant trend for amfebutamone to reduce metamfetamine-associated increases in blood pressure and a significant reduction in the metamfetamine-associated increase in heart rate. Amfebutamone reduced the plasma clearance of metamfetamine and the appearance of amfetamine in the plasma. Metamfetamine did not alter the peak and trough concentrations of amfebutamone or its metabolites. These findings are relevant to the potential use of amfebutamone in ameliorating acute abstinence in metamfetamine users. However, the risk of seizures during amfebutamone treatment for metamfetamine abuse has not been estimated. 

Chlorpromazine has sometimes been used to treat amfetamine psychosis, for example due to acute poisoning in children who did not respond to barbiturates (14). 

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. 

The relative reinforcing effects or abuse potential of these drugs is thought to be related to their potency in releasing dopamine from nerve terminals, compared with serotonin release. Amfetamine, metamfetamine, and phenmetrazine are potent dopamine releasers with high... 

In a study of extended treatment (15 months) of ADHD, amfetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavioral problems. The treatment failure rate was considerably lower and the time to treatment failure was longer in the treated group adverse effects were few and relatively mild (11). 

Tachycardia, dysrhythmias, and a rise in blood pressure have been described after the administration of centrally acting sympathomimetic amines. Amfetamine acutely administered to men with a history of amfetamine abuse enhanced the pressor effects of tyramine and noradrenaline, while continuous amfetamine led to tolerance of the pressor response to tyramine. As with intravenous amphetamines, cardiomyopathy, cardiomegaly, and pulmonary edema have been reported with smoking of crystal metamfetamine (15-17). 

The cardiovascular response to an oral dose of d-amfe-tamine 0.5 mg/kg has been determined in 81 subjects with schizophrenia, 8 healthy controls who took amfetamine, and 7 subjects with schizophrenia who took a placebo (18). Blood pressure increased in both amphetamine groups, whereas placebo had no effect. However, pulse... 

Two cases of myocardial infarction after the use of amfetamine have been reported (19,20). 

A 34-year-old man who smoked a pack of cigarettes a day took amfetamine for mild obesity. He developed an acute myocardial infarction 1 week later. Echocardiography showed inferior left ventricular hypokinesia and a left ventricular ejection fraction of 50%. Coronary cineangiography showed normal coronary arteries but confirmed the inferior left ventricular hypokinesia. Blood and urine toxicology were positive only for amfetamine. 

A 31-year-old man developed generalized discomfort after injecting four doses of amfetamine and metamfetamine over 48 hours, but no chest pain or tightness or shortness of breath. Electrocardiography showed inverted T-waves and left bundle branch block. Echocardiography showed reduced anterior wall motion. 

Coronary artery rupture has been associated with amfetamine abuse (21). 

An uncommon presentation of amfetamine-related acute myocardial infarction due to coronary artery spasm has been reported (22). 

These findings suggest that coronary artery plaques played a role in endothelial dysfunction resulting from amfetamine use, and that induction of coronary artery spasm, a finding not reported before, was the likely mechanism of amfetamine-related acute myocardial infarction. 

Vertebral artery dissection has been described in a previously healthy man with a 3-year history of daily oral amfetamine abuse (26). 

Since this patient had no known risk factors for vertebral artery dissection and had abused amfetamine daily for 3 years with escalating amounts, an association between metamfetamine and vertebral artery dissection cannot be excluded. The local and systemic vascular impacts of amfetamine could have contributed to initial changes (along with smoking), resulting in dissection. 

Concentrations of metamfetamine and its metabolite amfetamine were measured in autopsied brain regions of 14 human metamfetamine abusers (31). There was no evidence of variation in the regional distribution of amphetamines in the brain. Post-mortem redistribution of metamfetamine in the heart and lung has been reported before, although peripheral blood concentrations appear to remain constant (32,33). 

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. 

A previously healthy 16-year-old schoolboy had mesencephalic ischemia, most probably caused by vasospasm, after combined abuse of amfetamine and cocaine (51). There was a close temporal relation between intake of the drug and the onset of symptoms. Thus, combining these drugs, even in small amounts, may be harmful. 

A 22-year-old man who had had ADHD since the age of 8 years took methylphenidate, and had an adequate response for 14 years (52). However, his symptoms worsened and he switched from methylphenidate to mixed amfetamine salts 20 mg bd. A month later he continued to have difficulty in focusing on tasks, and the dosage was eventually increased to 45 mg tds over several weeks, with symptomatic improvement. However, 5 days later, he awoke feeling nauseated and agitated and had choreiform movements of his face, trunk, and limbs. He had also taken escitalopram 10 mg/day for anxiety and depression for 2 months before any changes in his ADHD medications. He was treated with intravenous diphenhydramine, lora-zepam, and diazepam without improvement in the chorea. Amfetamine was withdrawn and 3 days later his chorea abated. He restarted methylphenidate and the movement disorders did not recur. 

A koro-like syndrome has been related to amfetamine abuse (56). 

A 17-year-old man who had been abusing amfetamine and cannabis for 2 years took amfetamine 1 g orally over the course of an evening and suddenly felt an uncomfortable sensation in his groin and thought that his penis was being sucked into his abdomen. Physical examination was normal. The serum prolactin and bilirubin concentrations were raised. He had normal sexual function, and was able to attain and sustain an erection. He described the phenomenon of penile shrinkage as Whizz-Dick and stated that all the amfetamine users with whom he was in contact were... 

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