Mixed amphetamine salts: Difference between revisions
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| starting_dose = 2.5 mg IR, 5 mg XR, or 12.5mg Mydayis | | starting_dose = 2.5 mg IR, 5 mg XR, or 12.5mg Mydayis | ||
| preparations = IR tabs 5, 7.5, 10, 12.5, 15, 20, 30 mg; XR caps 5, 10, 15, 20, 25, 30 mg; Mydayis caps 12.5, 25, 37.5, 50 mg | | preparations = IR tabs 5, 7.5, 10, 12.5, 15, 20, 30 mg; XR caps 5, 10, 15, 20, 25, 30 mg; Mydayis caps 12.5, 25, 37.5, 50 mg | ||
| fda_max = | | fda_max = XR = 40 or 60 mg/d; IR = 40 or 60 mg/d<ref name="carlat">S0</ref> | ||
| routes = Oral | | routes = Oral | ||
| onset = IR: 30–60 min; XR: 1–2 h to peak effect | | onset = IR: 30–60 min; XR: 1–2 h to peak effect | ||
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| mechanism = TAAR1 agonism, VMAT2 substrate, DAT/NET reverse transport — net release of dopamine and norepinephrine | | mechanism = TAAR1 agonism, VMAT2 substrate, DAT/NET reverse transport — net release of dopamine and norepinephrine | ||
| intro = '''Mixed amphetamine salts (MAS)''' — marketed primarily as '''Adderall''' — is a 3:1 mixture of dextroamphetamine and levoamphetamine salts (dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate). | | intro = '''Mixed amphetamine salts (MAS)''' — marketed primarily as '''Adderall''' — is a 3:1 mixture of dextroamphetamine and levoamphetamine salts (dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate). | ||
Amphetamine was first synthesized in 1887 by Lazăr Edeleanu, then developed as a | Amphetamine was first synthesized in 1887 by Lazăr Edeleanu, then developed as a med in the late 1920s. "Adderall" was approved by the FDA in 1996, and has since become one of the most popular meds in the United States. Adderall/MAS is FDA-approved for attention-deficit hyperactivity disorder and narcolepsy. It is listed in Schedule II of the Controlled Substances Act, and so is tightly regulated in the United States as well as many other countries around the world. | ||
| indications = < | | indications = <problem ref="adhd" author="MDElliottMD"/> | ||
< | <problem ref="narcolepsy" author="MDElliottMD"/> | ||
< | <problem ref="trd-augment" author="MDElliottMD"> | ||
Off-label. | Off-label. | ||
</ | </problem> | ||
< | <problem ref="shift-work" author="MDElliottMD"> | ||
Off-label. | Off-label. | ||
</ | </problem> | ||
< | <problem ref="chronic-illness-cog" author="MDElliottMD"> | ||
Off-label. | Off-label. | ||
</ | </problem> | ||
< | <problem ref="impulsivity" author="MDElliottMD"/> | ||
< | <problem ref="distractibility" author="MDElliottMD"> | ||
Impoved sustained attention by decreasing distractibility | Impoved sustained attention by decreasing distractibility | ||
</ | </problem> | ||
| dosing = <titration slug="typical-adult" title="Typical Adult" author="MDElliottMD"> | | dosing = <titration slug="typical-adult" title="Typical Adult" author="MDElliottMD"> | ||
Start at 5 mg XR; may increase by 5 mg each day until the desired effect is reached, up to 30 mg XR to start, and up to 60 mg XR eventually if necessary, in 10 mg increments. | Start at 5 mg XR; may increase by 5 mg each day until the desired effect is reached, up to 30 mg XR to start, and up to 60 mg XR eventually if necessary, in 10 mg increments. | ||
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* <effect ref="withdrawal" author="MDElliottMD">Low motivation, low mood, hypersomnia, increased appetite on abrupt discontinuation.</effect> | * <effect ref="withdrawal" author="MDElliottMD">Low motivation, low mood, hypersomnia, increased appetite on abrupt discontinuation.</effect> | ||
* <effect ref="urinary-retention" author="MDElliottMD">Difficult/slow urination</effect> | * <effect ref="urinary-retention" author="MDElliottMD">Difficult/slow urination</effect> | ||
<effect ref="focus-intensification"/> | |||
<effect ref="appetite-suppression"/> | |||
<effect ref="alertness"/> | |||
<effect ref="executive-functioning"/> | |||
| pk_absorption = Excellent oral bioavailability — sources report ">75%" to "~90%". Food does not significantly affect total absorption but can delay peak concentration. | | pk_absorption = Excellent oral bioavailability — sources report ">75%" to "~90%". Food does not significantly affect total absorption but can delay peak concentration. | ||
| pk_distribution = Volume of distribution ~4 L/kg; plasma protein binding less than 20%. Crosses the blood–brain barrier and placenta. | | pk_distribution = Volume of distribution ~4 L/kg; plasma protein binding less than 20%. Crosses the blood–brain barrier and placenta. | ||
| 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> | | 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>S1</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 purportedly works via several converging mechanisms at monoaminergic terminals: | | pharmacodynamics = Amphetamine purportedly works via several converging mechanisms at monoaminergic terminals: | ||
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| monitoring = * Baseline: cardiovascular history, weight/height, mental health history (especially for psychosis/bipolar/substance use risk), (optional) blood pressure, (optional) heart rate, | | monitoring = * Baseline: cardiovascular history, weight/height, mental health history (especially for psychosis/bipolar/substance use risk), (optional) blood pressure, (optional) heart rate, | ||
* At each visit: efficacy, side effects, general well-being | * At each visit: efficacy, side effects, general well-being | ||
* Periodically reassess continued need; consider | * Periodically reassess continued need; consider med holidays to assess ongoing benefit | ||
* Sleep quality (insomnia is dose-limiting) | * Sleep quality (insomnia is dose-limiting) | ||
| counseling = * Take first thing in the morning to minimize insomnia; avoid (late) afternoon dosing. | | counseling = * Take first thing in the morning to minimize insomnia; avoid (late) afternoon dosing. | ||
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| references = | | references = | ||
}} | }} | ||
[[Category:Psychostimulants]] | |||
[[Category:Amphetamines]] | |||