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) B7 Pharmacology Final Exam (Lectures 12-22) - depr assoc w/ decr BDNF --> decr neurotroph supp (also assoc w/ DM+other nonneuro/psych dis) - sust NE/5HT sig incr BDNF expr - antideps incr neurogen+syn conn cort areas (ie. hippocamp) Altered Glutamate Neurotransmission in MDD - overexcit in cert brain areas Neuroendocrine Factors in MDD - hypoT+low sex sters (estrog in menop, testos) assoc w/ depr - neuroactive steroids like progest metabolite Allopregnanolone def correl w/ PPD Goals of Treatment in Depression - - ac depr sx resol - prev func lev return - suic prev - fut depr eps (recur/relapse) prev Nonpharmacologic Interventions for MDD - - Psychother = **1st LINE for mild-mod** depr, addit effs w/ pharm ther, maybe cost+resource prohib - ECT = **LAST LINE** for refrac MDD - Exercise --> incr BDNF **Use pharm ther+CBT for mod-sev depr** Acne treatment that may Exacerbate Depression - Isotretinoin - mon psych sx per REMS program iPledge CV Meds that may Exacerbate Depression - - Reserpine = depl symp biogen amines NE+Dopa; used for HTN but pulled from market due to fatigue, decr energ, sex dysf? - ARBs - BBs = classically linked to depr but evid supps just phys sx fatigue+low energ - CCBs - Clonidine - Methyldopa CNS Agents that May Exacerbate Depression - - Deutetrabenazine & Tetrabenazine = depl syn monamines by decr vesic presyn neur transp; **BBW depr+suicidality** - Valbenazine Hormonal Therapy that may Exacerbate Depression - - GRH & OCPs = progest+estrog alters poss link to monoam oxid activ - Steroids (ie. Prednis) = poss assoc w/ infl+HPA axis changes of depr Immunologic Agent that may Exacerbate Depression - Interferons B7 Pharmacology Final Exam (Lectures 12-22) Smoking Cessation Drug that may Exacerbate Depression - Varenicline Line of Pharmacotherapy for Mod-Sev Depression - FIRST LINE w/ antideps in top 3 classes Rx meds 3 Phases & Goals of Depression Pharm Treatment - - Acute ph (6-12w) = sx remis/abs - Cont (next 4-9m after remis) = resid sx elim/relapse (sx ret w/in 6m) prev - Maint (@least 12-36m) = recur (sep depr ep) prev Duration of Pharmacotherapy for Depression - pt-dep based on # past depr eps Classes of Antidepressants - - SSRIs - SNRIs (newer gen & TCA) - Atypical Antideps - MAOIs Examples of SSRIs - - Citalopram - Escitalopram - Fluoxetine - Fluvoxamine - Paroxetine - Sertraline Examples of Newer Generation SNRIs - - Desvenlafaxine - Duloxetine - Venlafaxine - Levomilnacipran Examples of TCAs (class of SNRIs) - - Amitriptyline - Desipramine - Doxepin - Imipramine - Nortriptyline Examples of Atypical Antidepressants - - Bupropion - Nefazodone - Trazodone - Vilazodone - Vortioxetine - Mirtazapine Examples of MAOIs - - Phenelzine - Selegiline B7 Pharmacology Final Exam (Lectures 12-22) - Tranylcypromine - Isocarboxazid General MOA of TCAs - block reuptake both serot+NE @ SERT+NET but **nonspec+promisc** @ other rec sites - block serot reup & incr syn conc - cont use --> incr syn serot conc downreg presyn autoR+incr raphe neur firing rate General MOA of SNRIs - block serot+NE reup but **don't additionally block other R like TCA** - cont use --> incr syn serot conc downreg presyn autoR+incr raphe neur firing rate General MOA of SSRIs - inhib only serot reup on 5HT terms - cont use --> incr syn serot conc downreg presyn autoR+incr raphe neur firing rate General MOA of MAOIs - irrev bind MAO mit metab serot+NE --> inhib NE, serot, Dopa degr General MOA of NSRIs - NE-sel reup inhibs NOT yet dev for depr treatment but stim Atomoxetine known as NSRI NE & Serotonin Uptake Inhibition by SSRIs, SN