Methamphetamine may decrease the effects of sedatives and depressants and increase the effects of antidepressants and other stimulants as well. Methamphetamine may counteract the effects of antihypertensives and antipsychotics due to its effects on the cardiovascular system and cognition respectively. The pH of gastrointestinal content and urine affects the absorption and excretion of methamphetamine. Specifically, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite. Due to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine. Pharmacology
Pharmacodynamics
Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems. Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). When methamphetamine binds to TAAR1, it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or reverse function of monoamine transporters. Methamphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn producing dopamine efflux. TAAR1 has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels.
In edentulous persons, a lack of teeth leaves more room for the tongue to expand into laterally, which can create problems with wearing dentures and may cause pseudomacroglossia.Amyloidosis is an accumulation of insoluble proteins in tissues that impedes normal function. This can be a cause of macroglossia if amyloid is deposited in the tissues of the tongue, which gives it a nodular appearance. Beckwith–Wiedemann syndrome is a rare hereditary condition, which may include other defects such as omphalocele, visceromegaly, gigantism or neonatal hypoglycemia. The tongue may show a diffuse, smooth generalized enlargement. The face may show maxillary hypoplasia causing relative mandibular prognathism. Apparent macroglossia can also occur in Down syndrome. The tongue has a papillary, fissured surface. Macroglossia may be a sign of hypothyroid disorders. Other causes include mucopolysaccharidosis, neurofibromatosis, multiple endocrine neoplasia type 2B, myxedema, acromegaly, angioedema, tumors (e.g. carcinoma), Glycogen storage disease type 2, Simpson–Golabi–Behmel syndrome, Triploid syndrome, trisomy 4p, fucosidosis, alpha-mannosidosis, Klippel–Trénaunay syndrome, cardiofaciocutaneous syndrome, Ras pathway disorders, transient neonatal diabetes, and lingual thyroid. Diagnosis
Macroglossia is usually diagnosed clinically. Sleep endoscopy and imaging may be used for assessment of obstructive sleep apnea. The initial evaluation of all patients with macroglossia may involve abdominal ultrasound and molecular studies for Beckwith–Wiedemann syndrome. Classification
The ICD-10 lists macroglossia under "other congenital malformations of the digestive system". Definitions of macroglossia have been proposed, including "a tongue that protrudes beyond the teeth during [the] resting posture" and "if there is an impression of a tooth on the lingual border when the patients slightly open their mouths".