TAAR1 activation by methamphetamine in astrocytes appears to negatively modulate the membrane expression and function of EAAT2, a type of glutamate transporter.In addition to its effect on the plasma membrane monoamine transporters, methamphetamine inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the vesicles and promotes their release. This results in the outflow of monoamines from synaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent release into the synaptic cleft by the phosphorylated transporters. Other transporters that methamphetamine is known to inhibit are SLC22A3 and SLC22A5. SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter.Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma receptors with a greater affinity for σ1 than σ2, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Sigma receptor activation by methamphetamine may facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has stronger peripheral effects, a longer half-life, and longer perceived effects among addicts. At high doses, both enantiomers of methamphetamine can induce similar stereotypy and methamphetamine psychosis, but levomethamphetamine has shorter psychodynamic effects. Pharmacokinetics
The bioavailability of methamphetamine is 67% orally, 79% intranasally, 67 to 90% via inhalation (smoking), and 100% intravenously. Following oral administration, methamphetamine is well-absorbed into the bloodstream, with peak plasma methamphetamine concentrations achieved in approximately 3.13–6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration.
Bakers cysts arise between the tendons of the medial head of the gastrocnemius and the semimembranosus muscles. They are posterior to the medial femoral condyle. The synovial sac of the knee joint can, under certain circumstances, produce a posterior bulge, into the popliteal space, the space behind the knee. When this bulge becomes large enough, it becomes palpable and cystic. Most Bakers cysts maintain this direct communication with the synovial cavity of the knee, but sometimes, the new cyst pinches off. A Bakers cyst can rupture and produce acute pain behind the knee and in the calf and swelling of the calf muscles. Diagnosis
Diagnosis is by examination. A Bakers cyst is easier to see from behind with the patient standing with knees fully extended. It is most easily palpated (felt) with the knee partially flexed. Diagnosis is confirmed by ultrasonography, although if needed and there is no suspicion of a popliteal artery aneurysm then aspiration of synovial fluid from the cyst may be undertaken with care. An MRI image can reveal presence of a Bakers cyst. An infrequent but potentially life-threatening complication, which may need to be excluded by blood tests and ultrasonography, is a deep vein thrombosis (DVT). Quick assessment of the possibility of DVT may be required where a Bakers cyst has compressed vascular structures, causing leg edema, as this sets up conditions for a DVT to develop. A burst cyst commonly causes calf pain, swelling and redness that may mimic thrombophlebitis. Treatment
Bakers cysts usually require no treatment unless they are symptomatic.