Pharmacokinetics amphetamine

Pharmacokinetics Amphetamines are completely absorbed from the gastrointestinal tract, metabolized by the liver, and excreted in the urine. Amphetamine abusers often administer the drugs by intravenous injection and by smoking. The euphoria caused by amphetamine lasts 4 to 6 hours, or 4 to 8 times longer than the effects of cocaine. The amphetamines produce addiction—dependence, tolerance and drug-seeking behavior. 

Some, but not all of ibogaine s effects may involve pharmacokinetic actions. Although ibogaine does not alter brain morphine or alcohol levels, it does alter amphetamine levels, suggesting a possible hepatic interaction (Click et al. 1992a Rezvani et al. 1995). 

Kramer WQ Read SC, Tran BV, Zhang Y, Tnlloch SJ. (2005) Pharmacokinetics of mixed amphetamine salts extended release in adolescents with ADHD. CNS Spectrums 10 6-13. 

Pharmacology Amphetamines are sympathomimetic amines with CNS stimulant activity. CNS effects are mediated by release of norepinephrine from central noradrenergic neurons. Peripheral activities include elevation of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. Pharmacokinetics ... 

Amphetamine mixture - Peak plasma concentrations occur in about 3 hours (Adderall) and 7 hours (Adderall XR). Elimination half-life is 10 to 13 hours in adults and 9 to 11 hours in children. Extended-release amphetamine mixture capsules demonstrate linear pharmacokinetics. There is no unexpected accumulation at steady state. Food does not affect the extent of absorption of extended-release amphetamine mixture capsules, but prolongs T ax by 2.5 hours. 

Mecfianism of Action A phenylalkylamine sympathomimetic with activity similar to amphetamines that stimulates the central nervous system (CNS) and elevates blood pressure (BP) most likely mediated via norepinephrine and dopamine metabolism. Causes stimulation of the hypothalamus. Therapeutic Effect Decreases appetite. Pharmacokinetics The pharmacokinetics of phendimetrazine tartrate has not been well established. Metabolized to active metabolite, phendimetrazine. Excreted in urine. Half-life 2-4 hr. 

Pharmacokinetics Rapidly absorbed from the G1 tract. Crosses the blood-brain barrier. Metabolized in the liver to the active metabolites. Primarily excreted in urine. Half-life 17hr (amphetamine), 20 hr (methamphetamine). 

Amphetamine is a racemic mixture of phenylisopropylamine (Figure 9-4) that is important chiefly because of its use and misuse as a central nervous system stimulant (see Chapter 32). Pharmacokinetically, it is similar to ephedrine however, amphetamine even more... 

Amphetamine and methamphetamine occur as structural isomers and stereoisomers. Structural isomers are compounds with the same empirical formula but a different atomic arrangement, e.g., methamphetamine and phentermine. Stereoisomers differ in the three-dimensional arrangement of the atoms attached to at least one asymmetric carbon and are nonsuperimposable mirror images. Therefore, amphetamine and methamphetamine occur as both d- and L-isomeric forms. The two isomers together form a racemic mixture. The D-amphetamine form has significant stimulant activity, and possesses approximately three to four times the central activity of the L-form. It is also important to note that the d- and L-enantiomers may have not only different pharmacological activity but also varying pharmacokinetic characteristics. 

Schepers, R.J.F., Oyler, J.M., Joseph, R.E., Cone, E.J., Moolchan, E.T., and Huestis, M.A., Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers, Clin. Chem., 49(1), 121-132, 2003. 

Desmethylselegiline is also an irreversible inhibitor of monoamine oxidase B in humans. There is evidence that the 1-stereoisomers of 1-amphetamine and 1-methamphetamine may have some qualitatively different actions from their d-isomer counterparts, which might result in beneficial clinical effects and could complement any beneficial clinical actions of selegiline itself. Food has no effect on the pharmacokinetics of desmethylselegiline, methamphetamine, and amphetamine. At a dose of 10 mg per day, selegiline is devoid of the cheese effect that is, it does not cause hypertension when taken with tyramine-containing foods such as cheese. 

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. 

Disposition in the Body. Well absorbed after oral administration. It is approximately twice as potent as amphetamine. For information on metabolism, excretion, and pharmacokinetics, see under Amphetamine. 

Clinical duration of action often differs from pharmacokinetic half-life Immediate release d,l-amphetamine has 3-6 hour duration of clinical action Extended release d,l-amphetamine has up to 8-hour duration of clinical action... 

The Coca Leaf Early Use of Cocaine The Amphetamines Cocaine Epidemic II The Return of Meth Pharmacokinetics of Stimulants Mechanism of Stimulant Action Acute Effects at Low and Moderate Doses... 

The pharmacokinetic and toxicokinetic behavior of any isomer cannot be used to predict that of any other ephedrine isomer. The (+) isomer of meth-amphetamine, for example, is a potent CNS stimulant, but the (-)-isomer is merely a decongestant. There is a tendency in the literature to lump together all ephedrine alkaloids and use the term class effect to assume that all the different drugs in that class exert the same effects on the same biological targets. In fact, some of the drugs in the class will be similar in some regards and different in others. 

A number of drugs of abuse are known substrates (e.g., codeine, hydrocodone, p-methoxyamphetamine, amphetamine) or inhibitors (e g., (-)-cocaine, pentazocine) of CYP2D6. For some of these drugs, the pharmacokinetic differences due to the polymorphism will be so profound that they are likely to exceed pharmacodynamic sources of variation in response. For other drugs (e.g., hydrocodone to hydromorphone, codeine to morphine, oxycodone to oxymorphone), CYP2D6 may not contribute importantly to the overall clearance of the drug, but may catalyze the formation of highly active metabolites. 

Mascher HJ, Kikuta C, Millendorfer A, et al. Pharmacokinetics and bioequivalence of the main metabolites of selegiline desmethylselegiline, methamphetamine and amphetamine after oral administration of selegiline. Int J Clin Pharmacol Ther 1997 35 9-13. 

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