Exam 3 (CNS Stimulants, Antihistamines, Antithrombotics)
-mainly in liver -aromatic hydroxylation -N-dealkylation -deamination -hydroxylation at benzylic pos urinary excretion of unchanged drug is pH-dpd give *NH4Cl for overdose > convert to urea and H3O+ in liver > decr pH > amines protonated and eliminated more readily in urine (vs neutral: rebaosrbed > incr drug conc, longer effects)*
B-phenethylamine met
-MAO is a class of flavin-containing enzymes primarily responsible for inactivating biogenic amines (NE, 5-HT3, DA, tryptamine, tyramine) -convert amine > aldehyde >COOH or OH MAO-A prefer serotonin, NE, E MAO-B prefer phenylethylamine and benzylamine DA and tyramine metabolized by both not selective for MAO in brain (also inhibit liver) MAOI mainly used for atypical dep, not 1st choice -*mechanism-based inhib (suicide substrates)*: 1st act as substrate for enzy, then create free radical > generate electrophiles so MAO can attack and covalently modify enzyme -irreversible inhib (react covalently)
MOAI
o GPCR H1: IP3 H2-H4: cAMP
histamine recep
o Histamine stored in secretory granules in mast cells as complex w/*proteoglycan* and in basophils as complex w/*chrondroitin*
histamine storage
