B7 Pharmacology Final Exam (Lectures 12-22)

B7 Pharmacology Final Exam (Lectures 12-22) DSM5 Criteria for Major Depressive Disorder - 1+ maj depr eps w/o hx man/hypoman - 5+ SIGECAPS sx nearly everyday 2w per w/ change from prev func lev - MUST impair func/cause subst distr - 1 sx MUST be depr mood/anhed SIGECAPS sx of MDD - - Suic ideation w/ w/o plan; suic att; recur thoughts of death - Interest (loss int/pleas in activs; anhed) - Guilt (inappr/excess, feeling worthlessness) - Energy decr - Conc decr; diff making decis - Appet ch (typ decr, change 5% wt from basel) - Psychomot agit/retard - Sleep impair (typ insom but maybe hypersom) Pathophysiology of MDD (Biogenic Amine Hypothesis) - results from monoam NT def cort+limb brain areas - Dopa, 5-HT, and/or NE neurotransm abnorms -- decr cort resp to emo activ -- affective dysf+depr w/ impair serot NT - Noradr fibs proj from loc cerul to cer cort+dopa fibs innerv nuc accumb also reg mood - monoam def -- upreg postsynR Monoamine NT Neuronal Regulation & Antidepressant MOA - interf w/ transp mols inhib NT reup incr amts in synapse Monoamine System Feedback - DO NOT func indep ie. med enh NE transm may sec alter 5-HT+Dopa activ & 5-HT known to inhib NE+Dopa rel in cert brain areas NE Synthesis, Binding, Reuptake - - tyramine conv to NE, stored in vesics/degr by MAO - binds postsyn alpha/beta adrenR; binds/agonizes presyn alpha2R inhib NE rel - Recyc back presyn by NET transp Serotonin Synthesis, Binding, Reuptake - - tryp conv to 5HT - Binds many postsyn/presynR -- activ presynR to decr neur firing - SERT transp for reup Problems w/ Monoamine Hypothesis - antideps rap changing monoam concs have delayed onset to effic -- effs maybe sec to alter R dens/sensits OR sec sig PW (ie. inositol synth disr in bipol disord) Neurotropic Hypothesis of MDD - infl+overexc -- decr neuroplas+neur diff - n GF (ie. BDNF br-der neurotroph fac) reg neuron plasticity, resil, neurogen (incr syn conns)