Synthetic drug manufacture dominated by. ATS, methamphetamine. The majority (99%) of the detected clandestine syn- thetic drugs laboratories process. distinguish individual optical isomers of a substance (e.g. >amfetamine=, > dexamfetamine=, >levamfetamine=). In all other cases, where this distinction is not. The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader).
|Language:||English, Spanish, German|
|ePub File Size:||15.42 MB|
|PDF File Size:||13.36 MB|
|Distribution:||Free* [*Sign up for free]|
(Pemprofilan Bendasing Amfetamin dan Metamfetamin Menggunakan Kaedah Suruhanjaya Eropah bagi pemprofilan dadah amfetamin dan metamfetamin. 2_ Amfetamin and Cocain - Free download as PDF File .pdf), Text File .txt) or read online for free. jurnal. Treatment Amfetamin - Download as Word Doc .doc), PDF File .pdf), Text File . txt) or jurnal 5. Uploaded by. mohd ikram · Staying Alert at the Whell.
This article has been cited by other articles in PMC. Abstract Background and objectives Central nervous system CNS stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. Methods Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine.
Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review Influence of age and time interval between death and autopsy on dopamine and 3-methoxytyramine levels in human basal ganglia. Methamphetamine or 2-n-methylphenyl-propanamine or metamfetamine is a highly addictive, psychostimulant, and sympathomimetic drug, illicitly used in many countries [ 3 ].
It is not known if amgetamin are similar alterations in the dopaminergic system of humans receiving long courses of prescription amphetamines View at Google Scholar G.
Upon arrival to the hospital, she was in stable condition, alert and oriented, with no visual or other neurological symptoms, and negative review of systems.
Pu C, Vorhees CV. Methamphetamine is actually the hydrochloric HCl salt of methamphetamine [ 16 ] because the synthesis includes the pumping of hydrochloric acid gas through the solution to crystallize the amferamin.
A potential animal model of adolescent alcohol drinking. Growth on stimulant medication; clarifying the confusion: An association between childhood ADHD and increased risk for substance abuse has been described, although some argue that the relationship may reflect the common comorbid problems of oppositional defiant disorder, conduct disorder, or antisocial personality disorder, rather than ADHD per se.
Size deficits have generally been interpreted as representing cell loss and enlarged areas thought to result from inflammation and possible reactive gliosis, although it has been suggested that volume increases in striatal volume may be compensatory In the very few studies that have compared the efficacy and safety of amphetamine directly to those of methylphenidate, amphetamine was equivalent or superior to methylphenidate on standard efficacy endpoints.
Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models. An oral once-a-day osmotic delayed-release formulation of methylphenidate produced lower subject ratings of both detectability and likeability than an immediate-release formulation that was associated with equivalent plasma concentration and dopamine transporter occupancy Is there a threshold of amphetamine exposure jyrnal which persistent changes in the dopamine system are induced?
To our knowledge, neither atomoxetine nor its metabolites, have previously been reported in the literature to cause a false-positive result for amphetamines on urine drug screen. Thus, the appeal of a particular drug as a recreational substance of abuse is to a large extent determined by its ability to produce its desired effects within minutes, for example the cocaine rush.
The kinetics of d-amphetamine when taken orally make it less rewarding pleasurable than cocaine or methamphetamine. Cocaine, whether snorted or smoked as crack in particular, enters the brain very quickly, and appears even to be concentrated in the brain relative to plasma; this explains the high rewarding potential of this drug: faster brain entry leads to a greater high.
Methamphetamine enters more slowly and its peak effects are delayed by min compared with cocaine Fowler et al. Although damphetamine sulphate has not been studied in an exactly comparable way, we can predict from its physico-chemical properties that after oral ingestion d-amphetamine would have even slower rate of uptake into the brain than methamphetamine.
Having said that, the abuse of d-amphetamine is not a cause for complacency. Although amphetamine abuse peaked in the s Rasmussen, , the misuse of amphetamine is a persistent social, legal and medical problem Das-Douglas et al.
The intravenous use of damphetamine and other stimulants still pose major safety risks to the individuals indulging in this practice Charnaud and Griffiths, ; Das-Douglas et al.
Some of this intravenous abuse is derived from the diversion of ampoules of d-amphetamine, which are still occasionally prescribed in the UK for the control of severe narcolepsy and other disorders of excessive sedation. However, most intravenous d-amphetamine use is from local illicit production. Some abusers will use solvents to extract the active ingredient from tablets or capsules, which can then be concentrated and injected intravenously.
The development of tamperdeterrent d-amphetamine formulations has been a major objective of the pharmaceutical industry to prevent this type of abuse. Several new once-daily d-amphetamine-containing prescription drugs have emerged that have a high degree of tamper deterrence, for example Adderall XR. In addition, lisdexamfetamine as a prodrug of d-amphetamine, is a further advance in reducing diversion risk since it provides a more gradual increase in brain drug concentration, thereby further reducing the pleasurable effects of the damphetamine.
These topics will be revisited later in this review. Volkow and colleagues have performed an enormous body of research using PET and other brain imaging techniques to explore the relationship between DAT occupancy, synaptic dopamine concentration and dopamine D2 receptor occupancy for psychostimulant drugs of abuse. Although the dopamine release hypothesis of drug reinforcement proposed by Di Chiara and Imperato based on experiments performed in rats and then extended in humans by Volkow and colleagues , a has its limitations, it is now well accepted that euphoria, psychostimulation and reinforcement produced by stimulant drugs occur when there are rapid and substantial increases in the synaptic concentrations of dopamine in the basal striatum and mesolimbic system of the human brain.
These researchers have also demonstrated that the rate of DAT occupancy by drugs such as cocaine and methylphenidate is critical to their ability to produce highs in human subjects Volkow and Swanson, ; Volkow et al. Although d-amphetamine is a competitive substrate for DAT rather than a classical reuptake inhibitor, these same principles apply to its pharmacological action. Thus, the rate and magnitude of neuronal dopamine release produced by amphetamine is absolutely dependent on the rate and concentration of drug that reaches DAT sites in the brain Heal et al.
There has been little research conducted in humans on this kinetic course using brain imaging, but it seems likely that the same rules apply. Consistent with the findings in microdialysis experiments, d-amphetamine has greater potency than l-amphetamine to evoke stimulant-like subjective effects in rats Schechter, and behavioural activation in primates Scraggs and Ridley, Crossgeneralisation occurs between the subjective cues evoked by amphetamines d- and lisomers, indicating a common neurochemical mechanism Schechter, Both amphetamine isomers have been shown to serve as positive reinforcers in animals i.
The same is true for human subjects Smith and Davis, ; Van Kammen and Murphy, , with the d-isomer once again being two to threefold more potent than the l-isomer Risner, ; Smith and Davis, ; Van Kammen and Murphy, ; Yokel and Pickens, On the basis that the subjective and reinforcing effects of amphetamines isomers translate well from animals to humans, and with the assumption that the neurochemical mediators are similarly consistent across species, we can employ the findings from the microdialysis experiments to draw some conclusions on this subject.
The results in Figure 4, which reveal that both isomers are equally potent noradrenaline releasers, but d-amphetamine is around threefold more potent than lamphetamine as a dopamine releaser, point to dopamine as the primary neurochemical mediator of amphetamines stimulant and euphoriant properties. As indicated above, it is the combination of the rapid rate of increase and magnitude of effect that accounts for the powerful stimulant effects of amphetamine.
Although l-amphetamine is the less potent of the two isomers, its pharmacological efficacy should not be underestimated.
Cheetham et al. In contrast, the maximum increases in dopamine efflux achieved by classical dopamine reuptake inhibitors e.
The importance of the rate of increase of synaptic dopamine concentrations to the induction of stimulation and euphoria is exemplified by the observation that bupropion and GBR were not experienced as stimulant or euphoriant by normal volunteers Hamilton et al. In those bupropion and GBR trials where damphetamine was employed as the positive control, its stimulant, energising and reinforcing effects were unequivocally recognised by normal subjects and recreational drug users Hamilton et al.
Once-daily formulations In previous reviews, we have extensively described the efficacy and safety of stimulant and non-stimulant drugs used in the management of ADHD and compared the relative merits of each Heal et al. This analysis has revealed that the stimulants, including amphetamine, are still accepted to be the most efficacious drugs available. Some attempts to introduce new medications, for example guanfacine XR Intuniv have been successful, but many other new pharmacological approaches have failed see Heal et al.
On the other hand, the innovations in formulation technology and drug delivery systems have made significant strides forward in improving the clinical management of ADHD.
All of the stimulants have biological half-lives that require at least twice-daily dosing to deliver efficacy over h. ADHD is characterised by inattention, distractibility, working memory deficits and impulsivity, and as such, subjects with this disorder are particularly unsuited to compliance with rigid dosing schedules. One of the additional benefits of these new formulations is their tamper deterrence, making it difficult for abusers to extract amphetamine for self-administration by hazardous routes, such as smoking, snorting or intravenous injection.
Examples of once-daily amphetamine medications include MESamphetamine XR and the d-amphetamine prodrug, lisdexamfetamine. Lisdexamfetamine As briefly discussed earlier in the review, lisdexamfetamine is the first amphetamine prodrug to have been approved for use in treating ADHD. This profile is consistent with lisdexamfetamine being pharmacologically inactive. Although there is no definitive information on the subject, the large molecular size and polar characteristics of lisdexamfetamine predict that the parent molecule is unlikely to cross the bloodbrain barrier.
In vitro experiments revealed that the metabolism of lisdexamfetamine to d-amphetamine occurs in red blood cells by rate-limited enzymatic hydrolysis Pennick, Table 3. The locomotor activity of the rats was also simultaneously monitored.
After administration of equivalent doses of lisdexamfetamine and IR d-amphetamine 1. These observations are entirely consistent with the postulated rate-limited enzymatic conversion of lisdexamfetamine to d-amphetamine. This difference in PK characteristics had a profound impact on the pharmacological effects of these two compounds in rats Figure 5.
Lisdexamfetamine produced a gradual and sustained increase in striatal dopamine efflux, whereas the increase produced by IR d-amphetamine was faster in onset, reaching a peak at 30 min, and it subsequently declined more rapidly Figure 5. In the case of lisdexamfetamine, the more gradual and sustained increase in dopamine efflux was associated with a much smaller and visibly delayed locomotor response.
Using the hysteresis analysis in a more conventional way to explore the relationship between the plasma concentration of d-amphetamine and the functional response, there was a clear difference between the two compounds with an anticlockwise hysteresis for lisdexamfetamine and no hysteresis for IR d-amphetamine Rowley et al.
The anticlockwise hysteresis shows that the functional effect of lisdexamfetamine was greater as the plasma concentration of d-amphetamine was falling, whilst the lack of hysteresis with IR d-amphetamine demonstrates that as soon as the plasma concentration of the drug starts to decline, so does its pharmacological effect. The clinical importance of these findings will be discussed in the following section. Implications of pharmacokinetics of lisdexamfetamine for efficacy, safety and recreational abuse liability The efficacy of lisdexamfetamine has been demonstrated in a number of randomised, double-blind, placebo-controlled clinical trials in ADHD in children, adolescents Biederman et al.
Since lisdexamfetamine has been the subject of several reviews Dew and Kollins, ; Heal et al. Biederman et al. Following a 3-week, open-label run-in period where the dose of MES-amphetamine XR was optimised to 10, 20 or 30 mg once a day, subjects were then randomised into a 3-way double-blind, placebo-controlled crossover trial. They received their optimal dose of MES-amphetamine XR, an equivalent dose of lisdexamfetamine in terms of d-amphetamine base, or placebo.
On the primary and secondary efficacy variables of behaviour, attention and problem solving, lisdexamfetamine delivered equivalent or better efficacy than MES-amphetamine XR with both drugs being maximally effective at 2 h post-dose Biederman et al.
However, on the problem-solving endpoints, it was also evident that lisdexamfetamine maintained its maximum effect for at least 12 h, whereas the effect of MES-amphetamine XR showed a clear decline after 68 h Biederman et al. An exceptionally long duration of effect of lisdexamfetamine was observed by Wigal et al. A posthoc analysis of the data also showed that the sex and age of the subjects had no significant influence on the efficacy of lisdexamfetamine Wigal et al.
These observations fit well with the PD profile of lisdexamfetamine in the microdialysis experiments. Another way to produce a more gentle increase of brain dopamine is to bind damphetamine to a support.
MES-amphetamine XR employs a bead technology to deliver two bolus doses of amphetamine, the first immediately and the second approximately 4 h later, giving a Cmax for amphetamines d- and l-isomers 68 h Adderall XR, US Product Label.
Another factor that almost certainly contributes to the consistently high level of therapeutic efficacy observed with lisdexamfetamine treatment is the very low inter- and intra-subject variability in the plasma concentration of d-amphetamine observed after administration of the prodrug compared with traditionally formulated stimulants, including beaded and osmotic-release formulations.
Once again, the reproducible pharmacokinetics of its active metabolite, d-amphetamine, are probably due to the ratelimited, enzymatic cleavage of the precursor molecule that occurs primarily in red blood cells Ermer et al. In two earlier published studies, Jasinski and Krishnan compared the subjective effects of lisdexamfetamine and IR d-amphetamine in drug-experienced human volunteers when these compounds were administered intravenously Jasinski and Krishnan, a and orally Jasinski and Krishnan, b.
In the trial where they compared these compounds after oral administration, IR d-amphetamine 40 mg Furthermore, the time of lisdexamfetamines peak pharmacological effect was substantially delayed compared with IR d-amphetamine, at 3.
When lisdexamfetamine was given at an increased dose of mg, it significantly increased the DQRS Drug liking score to an equivalent extent to IR d-amphetamine 40 mg oral. However, the peak effect of the higher dose of lisdexamfetamine was even more delayed, at 4.
When the intravenous route was explored, IR d-amphetamine 20 mg intravenous produced a peak Drug liking score 20 min after dosing, which coincided with plasma Cmax Jasinsky and Krishnan, b. In contrast, the equivalent dose of lisdexamfetamine 50 mg intravenous did not significantly increase Dug liking relative to placebo, and the Cmax of plasma d-amphetamine occurred considerably later at 2. Both compounds yielded equivalent AUCh values, but compared with the equivalent dose of IR d-amphetamine, the Cmax for plasma d-amphetamine was threefold smaller for lisdexamfetamine and the tmax was threefold greater Jasinski and Krishnan, b.
From these results, it can be concluded that although in terms of d-amphetamine base equivalents lisdexamfetamine is clearly less potent than IR d-amphetamine, it does nonetheless produce d-amphetamine-like subjective effects in man. It is also reasonable to assume that if the intravenous dose of lisdexamfetamine had been increased, its Drug liking effect would have separated from placebo.
However, when considering any drugs potential for recreational abuse, the time required for it to produce its peak response is likely to be as important as its magnitude. In the case of IR d-amphetamine, its maximum subjective effect occurred much earlier than lisdexamfetamine, and switching to the intravenous route speeded up IR d-amphetamines onset of action and increased its potency. Although increasing the dose of lisdexamfetamine enhanced its efficacy, it also progressively delayed its time of peak effect.
Furthermore, switching to the intravenous route for lisdexamfetamine appeared to have relatively little influence on the abuse potential of the prodrug. To explore this possibility further, we performed a post-hoc analysis on the data in the original clinical study reports Jasinski, , NRP A02; Jasinski, , NRP A03 to compare pharmacodynamics and pharmacokinetics of lisdexamfetamine when given by the clinical route oral versus one of those favoured by recreational abusers intravenous.
This topic is of particular importance because lisdexamfetamine has very high aqueous solubility, making the prodrug very easy to extract.
In fact, breaking the capsule open and dissolving the contents in water is stated as a dosing route for patients who are unable to swallow capsules Vyvanse, US Product Label. As shown in Table 4, the average maximum scores on the DQRS and Drug Rating Questionnaire Observer DRQO scales for Liking, Feel drug effect, and Disliking reveal that the subjective effects of lisdexamfetamine 50 mg were not significantly different when the prodrug was administered orally or intravenously.
This result shows that the subjective effects of lisdexamfetamine were not enhanced when the drug was given intravenously. Blood pressure measurements are useful objective measures of the PD effects of sympathomimetic drugs. Compared with placebo, 50 mg lisdexamfetamine significantly increased the peak systolic blood pressure when administered both orally and intravenously and diastolic blood pressure when given orally Figure 6. What is also evident from the data in Figure 6 is that the magnitude of increases in systolic and diastolic blood pressures was not statistically different after oral or intravenous administration of lisdexamfetamine.
Table 4. A comparison of the pharmacodynamics and pharmacokinetics of orally versus intravenously administered 50 mg lisdexamfetamine. Figure 6. A comparison of the mean peak increases in systolic and diastolic blood pressure produced by intravenous versus oral administration of 50 mg lisdexamfetamine. The PK parameters for plasma d-amphetamine observed after oral versus intravenous administration of lisdexamfetamine 50 mg are also summarised in Table 4.
The AUC0infinity shows that the overall drug exposure was identical irrespective of the route of administration. Ann Emerg Med Apr;53 4 — Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia. Harm Reduct J ; Stats and Facts. National Drug Threat Assessment Washington, DC: National Methamphetamine Threat Assessment Ellenhorn, MJ. Ellenhorn's medical toxicology: diagnosis and treatment of human poisoning.
Baltimore: Williams and Wilkins; Ciccarone Page 11 Patterns of methamphetamine abuse and their consequences. J Addict Dis ;21 1 — Use of stimulants in the medically ill. Psychiatr Clin North Am Sep; 19 3 — Warner M. A jolt of caffeine, by the can. New York Times. Medical use, illicit use and diversion of prescription stimulant medication. J Psychoactive Drugs Mar;38 1 — Does childhood treatment of ADHD with stimulant medication affect substance abuse in adulthood?
Am J Psychiatry May; 5 — Effect of fenfluramine-derivative diet pills on cardiac valves: a meta-analysis of observational studies. Am Heart J Dec; 6 — Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med Dec 21; 25 — New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol ;— Monoamine transporters and psychostimulant addiction. Biochem Pharmacol Jan 1;75 1 — Imaging dopamine's role in drug abuse and addiction. Neuropharmacology ;56 Suppl —8.
A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants. Neuropsychopharmacology Feb;31 2 — Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter.
Lack of self-administration of cocaine in dopamine D1 receptor knock-out mice. J Neurosci Nov 28;27 48 — Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys. Pharmacol Biochem Behav Jan;86 1 — The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci Jul;14 7 — The serotonergic system and its role in cocaine addiction. Pharmacol Rep Nov—Dec;57 6 — Amphetamine-type central nervous system NIH-PA Author Manuscript stimulants release norepinephrine more potently than they release dopamine and serotonin.
Synapse Jan;39 1 — Glutamatergic substrates of drug addiction and alcoholism. Williams MJ, Adinoff B. The role of acetylcholine in cocaine addiction. Neuropsychopharmacology Jul;33 8 — Romanelli F, Smith KM. Clinical effects and management of methamphetamine abuse. Pharmacotherapy Aug;26 8 — Angrist, B. Clinical effects of central nervous system stimulants: a selective update. New York: Raven Press; Brain reward systems and abuse Amphetamine-related harms and treatment preferences of regular amphetamine users in Sydney, Australia.