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 id...
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)
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
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, SNRIs, TCAs - - SSRI Fluox = no NE
uptake inhib, **only high serot uptake inhib**
- SNRI Venlaf = some NE reup inhib, high serot reup inhib
- SNRI Dulox = high NE reup inhib, high serot reup inhib
- TCA Imipr = high NE reup inhib, mod-high serot reup inhib
- TCA Nortrip = high NE reup inhib, some serot inhib
Antidepressant Class Effects - - equiv effic when used @ comp doses so init choice is
empiric (NOT a single rec 1st line agent)
- Facs to consid = pt resp hx, fam AD resp hx, concur med illn+meds, pres sx (ie. insom
vs hypersom), drug-drug int pot, AEs, pt pref, med cost
- **BBW on all ADs = suic thoughts+behav**, NOT necessarily incr suic action; incr risk
child, adols, YAs <24y/o & decr risk >65y/o; mon all pts
- **CAUTION in bipol disord-rel depr b/c may cause switch to manic behav w/o having
mood-stab on board**
Antidepressant Response - - mod-sev depr --> benef deps on sev; more sev depr,
greater likely benefits; prob ineff for mild depr
- Find effect ag = pt-spec; failure to resp to 1 AD class/1 AD w/in class DOES NOT pred
failed resp to another class/another agent in same class
- Strats for poor resp = switch vs augm
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