Mixed amphetamine salts: Difference between revisions
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| pk_metabolism = Amphetamine is oxidized to 4-hydroxyamphetamine, α-hydroxyamphetamine, or norephedrine. Norephedrine and 4-hydroxyamphetamine are active metabolites and are further metabolized to 4-hydroxy-norephedrine. Deamination of α-hydroxyamphetamine yields phenylacetone, which is metabolized to benzoic acid and conjugated to its glucuronide and hippuric acid. '''CYP2D6''' is crucial for amphetamine metabolism; genetic polymorphism causes significant inter-patient variability in clearance. Amphetamine itself inhibits monoamine oxidase (MAO), and both CYP1A2 and CYP3A4 contribute to its metabolism.<ref>https://www.ncbi.nlm.nih.gov/sites/books/NBK507808/</ref> | | pk_metabolism = Amphetamine is oxidized to 4-hydroxyamphetamine, α-hydroxyamphetamine, or norephedrine. Norephedrine and 4-hydroxyamphetamine are active metabolites and are further metabolized to 4-hydroxy-norephedrine. Deamination of α-hydroxyamphetamine yields phenylacetone, which is metabolized to benzoic acid and conjugated to its glucuronide and hippuric acid. '''CYP2D6''' is crucial for amphetamine metabolism; genetic polymorphism causes significant inter-patient variability in clearance. Amphetamine itself inhibits monoamine oxidase (MAO), and both CYP1A2 and CYP3A4 contribute to its metabolism.<ref>https://www.ncbi.nlm.nih.gov/sites/books/NBK507808/</ref> | ||
| pk_elimination = Primarily renal — ~30–40% recovered as unchanged amphetamine, the rest as metabolites. Due to its pK<sub>a</sub> of 9.9, urinary elimination is highly pH-dependent: alkaline urine reduces ionization and decreases renal clearance, while acidic urine and high flow rates accelerate clearance via active tubular secretion. '''Half-life:''' D-enantiomer 9 h (children 6–12 y), 11 h (adolescents 13–17 y), 10 h (adults); L-enantiomer 11 h, 13–14 h, 13 h respectively. | | pk_elimination = Primarily renal — ~30–40% recovered as unchanged amphetamine, the rest as metabolites. Due to its pK<sub>a</sub> of 9.9, urinary elimination is highly pH-dependent: alkaline urine reduces ionization and decreases renal clearance, while acidic urine and high flow rates accelerate clearance via active tubular secretion. '''Half-life:''' D-enantiomer 9 h (children 6–12 y), 11 h (adolescents 13–17 y), 10 h (adults); L-enantiomer 11 h, 13–14 h, 13 h respectively. | ||
| pharmacodynamics = Amphetamine | | pharmacodynamics = Amphetamine purportedly works via several converging mechanisms at monoaminergic terminals: | ||
* '''Trace amine-associated receptor 1 (TAAR1) agonism''' — activates TAAR1 in monoaminergic neurons, triggering PKA/PKC signaling that phosphorylates the dopamine and norepinephrine transporters (DAT, NET), causing them to internalize and reverse direction. | * '''Trace amine-associated receptor 1 (TAAR1) agonism''' — activates TAAR1 in monoaminergic neurons, triggering PKA/PKC signaling that phosphorylates the dopamine and norepinephrine transporters (DAT, NET), causing them to internalize and reverse direction. | ||
* '''VMAT2 substrate''' — enters the presynaptic terminal, displaces dopamine and norepinephrine from vesicles into the cytoplasm. | * '''VMAT2 substrate''' — enters the presynaptic terminal, displaces dopamine and norepinephrine from vesicles into the cytoplasm. | ||
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* History of substance use disorder (relative contraindication; careful risk-benefit) | * History of substance use disorder (relative contraindication; careful risk-benefit) | ||
* Caution: structural cardiac abnormalities, bipolar disorder, psychotic disorders, Tourette syndrome / tic disorders | * Caution: structural cardiac abnormalities, bipolar disorder, psychotic disorders, Tourette syndrome / tic disorders | ||
| interactions = | | interactions = Minimal in practice. Caution with other psychostimulants, including caffeine. metabolized by 2D6, so relevant caution applies. | ||
| pregnancy_details = [https://www.ncbi.nlm.nih.gov/books/NBK501307/ Category C]. Crosses the placenta. Prenatal amphetamine exposure has been associated with low birth weight, premature delivery, and neonatal withdrawal (agitation, dysphoria, lassitude). Long-term neurodevelopmental outcomes from prescribed therapeutic exposure are less clear and likely modest, but illicit-dose exposure is associated with significant developmental impact. Decision should be individualized; many patients defer ADHD treatment during pregnancy. Excreted in breast milk in clinically significant amounts — breastfeeding generally discouraged. | |||
| pregnancy_details = Category C. Crosses the placenta. Prenatal amphetamine exposure has been associated with low birth weight, premature delivery, and neonatal withdrawal (agitation, dysphoria, lassitude). Long-term neurodevelopmental outcomes from prescribed therapeutic exposure are less clear and likely modest, but illicit-dose exposure is associated with significant developmental impact. Decision should be individualized; many patients defer ADHD treatment during pregnancy. Excreted in breast milk in clinically significant amounts — breastfeeding generally discouraged. | |||
| monitoring = * Baseline: cardiovascular history, blood pressure, heart rate, weight/height, mental health history (especially for psychosis/bipolar/substance use risk) | | monitoring = * Baseline: cardiovascular history, blood pressure, heart rate, weight/height, mental health history (especially for psychosis/bipolar/substance use risk) | ||
* Consider ECG if cardiac risk factors present | * Consider ECG if cardiac risk factors present | ||