Amphetamine cardiovascular effects

Acute intoxication with amphetamine is associated with tremor, confusion, irritability, hallucinations and paranoid behaviour, hypertension, sweating and occasionally cardiac arrhythmias convulsions and death may occur. The cardiovascular effects of the stimulants may be treated by beta-blockers, or by the combined alpha- and beta-blocker labetalol calcium channel antagonists such as nifedipine may correct the arrhythmias, while intravenous diazepam is of value in attenuating seizures. 

Angrist B, Sanfilipo M, Wolkin A. Cardiovascular effects of 0.5 milligrams per kilogram oral d-amphetamine and possible attenuation by haloperidol Clin Neuropharmacol 2001 24(3) 139-44. 

Findling RL, Biederman J, Wilens TE, Spencer TJ, McGrough JJ, Lopez FA, Tulloch SJ, on behalf of the SL1381.301 and. 302 Study Groups. Short- and longterm cardiovascular effects of mixed amphetamine salts extended release in children. J Pediatr 2005 147 348-54. 

AMPHETAMINES TCAs Risk of severe and life-threatening hypertension and arrhythmias. May give false-positive urine tests for amphetamines Additive effects on cardiovascular system due to enhanced noradrenergic activity Avoid concurrent use... 

Desipramine and protryptiline can cause striking and sustained increases in brain concentrations of d-amphetamine and may also add to d-amphetamine s cardiovascular effects... 

Theoretically, other agents with norepinephrine reuptake blocking properties, such as venlafaxine, duloxetine, atomoxetine, milnacipran, and reboxetine, could also add to amphetamine s CNS and cardiovascular effects... 

Chewing the leaves of Catha edulis (khat, qat) results in subjective mental stimulation, increased physical endurance, and increased self-esteem and social interaction. Until recently, this habit was confined to Arabian and East African countries, because only fresh leaves are active, but because of increased air transportation, khat is now also chewed in other parts of the world. Although cathine (norpseudoephedrine) is quantitatively the main alkaloid, the amphetamine-hke euphorigenic and sympathomimetic cardiovascular effects of khat are primarily attributed to cathinone (1). In Yemen chewers of khat produced in fields where chemical pesticides are used regularly have more sjmptoms than chewers of khat produced in fields where chemical pesticides are rarely or never used (2). 

Rush, Roll, Higgins, 1998). The combination of cocaine (or amphetamine) and heroin (or other opiate) is called a speedbair and is particularly popular among heroin addicts. Morphine and cocaine combinations have been studied in the laboratory, and as with alcohol, morphine appeared to enhance the pleasurable effects of cocaine but also increased the cardiovascular effects. Combinations of cocaine and heroin have sometimes been blamed for drug overdose deaths (as in the deaths of comedian John Belushi and actor River Phoenix), and the synergistic effects on blood pressure and heart rate may be a factor (Foltin Fischman, 1992 Rush et al., 1998). 

Amphetamine Sulfate, USP. Amphetamine. ( )-l-phenyl-2-uminopropane (Benzedrine), as the racemic mix-litre has a higher proportion of cardiovascular effects than ihedertro isomer. For most medical uses, the dextrorotatory lioiner is preferred. 

Thus it may be concluded that in this group of compounds molecular modification of the amphetamine structure achieved a distinct selectivity of action with regard to psychomotor stimulation and a considerably lessened incidence of the usual amphetamine side effects such as anorexia, jitteriness, apprehension, cardiovascular effects, insomnia, tolerance, and postdrug depression. 

Steifel G, Besag FMC. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf 2010 33 821 2. 

An N-cyanoethyl derivative (IVc) of amphetamine has been examined clinically and reported to be effective in reducing appetite. It has no cardiovascular effects, caused little central stimulation and did not cause insomnia. 7 A series of azetidine derivatives has been described, and one of these (IX) was reported to have about one-third the activity of methamphetamine. 8... 

Metamfetamine The results of a doubleblind study of potential interactions of intravenous metamfetamine (15 and 30 mg) with oral aripiprazole (15 mg) have been published [72 ]. The effects of aripiprazole on abstinence-related craving and cue-induced craving were also evaluated. Participants included non-treatment-seeking metamfetamine-dependent patients who took aripiprazole (n = 8) or placebo (n = 8) for 2 weeks. Aripiprazole had no effect on cue-induced metamfetamine craving, but was associated with increased craving independent of metamfetamine dose, euphoria, and amphetamine-like effects after metamfetamine. Aripiprazole reduced the increase in systolic blood pressure after metamfetamine, but it had no other effects on cardiovascular responses to metamfetamine. Aripiprazole did not alter the pharmacokinetics of metamfetamine. The adverse events tended to be equally distributed between the two groups, except for tremor (n = 4) and restlessness n = 3), which were more common in those who took aripiprazole. 

Chemical Structures. Figure 1 shows the chemical structures for 14 phenylethylamine compounds. Nine of these compounds are used clinically as anorectics (ii-amphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, clotermine, chlorphentermine, benzphetamine, and fenfluramine). Four of these compounds are not approved for clinical use and are reported to have hallucinogenic properties (MDA, PMA, DOM, and DOET). The final compound ( /-ephedrine) is used clinically for bronchial muscle relaxation, cardiovascular, and mydriatic effects. Figure 2 shows the chemical structure for MDMA, the methyl analog of MDA. MDMA is not approved for clinical use and has been reported to produce both LSD-like and cocaine-like effects. 

A series of 1-substituted 3-phenylbenzazepines have been evaluated. It was found that the aminopropyl derivative (6, n = 3 R1 = R2 = Et) counteracted amphetamine toxicity, and that the piperazinyl derivative (6) (n = 2 NR R2 = N(CH2CH2)2 = NCH2CH2OH) gave protection against maximal electroshock seizures (MES) [12]. None of the other derivatives such as the 2-oxo derivatives showed any significant effects on the central nervous or cardiovascular system, nor did any of them exhibit any diuretic or hypo-glycaemic activity [12]. Several similar compounds possess antiarrhythmic and antihypertensive effects this will be mentioned in a later section. 

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