Amphetamine

Class Recreational sympathomimetic
Chemistry

Phenylethylamine

Routes of administration

oral, nasal, IM, s.c, IV

Absorption

Good oral bioavailability (about 75%)

Solubility

pKa = 9.9, poor water solubility; good lipid solubility

Distribution

VOD= 4L/kg, 20% protein-bound

Metabolism

Undergoes hepatic metabolism primarily by CYP2D6; CYP1A2, CYP3A4, and CYP2B6 involved to a lesser extent. First step may be oxidative deamination, beta-hydroxylation, or para-hydroxylation. Some metabolites are also psychoactive. A significant amount, estimated to be around a quarter, is excreted unchanged in urine.

Elimination

Minimal free drug is eliminated in the urine

Time course of action

Half-life 4-12 hours

Target receptor

The intracellular receptor TAAR1, which is activated and causes the internalisation or transporter reversal of DAT, NET and SERT (as well as vesicular monoamine transporter VMAT2 and MAO which are inhibited)

Mechanism of action

By increasing the synaptic concentration of noradrenaline and dopamine, amphetamine-like drugs acts as indirect sympathomimetics. Because they act centrally, this effect translates into increased alertness and arousal, as well as broadly adrenaline-like peripheral effects.

Clinical effects

Increased alertness as well as nausea, vomiting, abdominal cramps, hypertension, tachycardia, exacerbation of motor tics, lower seizure threshold

Literature reference

Heal et al (2013)

CICM details of understanding Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
Related SAQs