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, wReuptake w- w- wtyramine wconv wto wNE, wstored win wvesics/degr
wby wMAO
- binds wpostsyn walpha/beta wadrenR; wbinds/agonizes wpresyn walpha2R winhib wNE wrel
- Recyc wback wpresyn wby wNET wtransp
Serotonin wSynthesis, wBinding, wReuptake w- w- wtryp wconv wto w5HT
- Binds wmany wpostsyn/presynR w--> wactiv wpresynR wto wdecr wneur wfiring
- SERT wtransp wfor wreup
Problems ww/ wMonoamine wHypothesis w- wantideps wrap wchanging wmonoam wconcs
whave wdelayed wonset wto weffic w--> weffs wmaybe wsec wto walter wR wdens/sensits wOR
wsec wsig wPW w(ie. winositol wsynth wdisr win wbipol wdisord)
Neurotropic wHypothesis wof wMDD w- winfl+overexc w--> wdecr wneuroplas+neur wdiff
- n wGF w(ie. wBDNF wbr-der wneurotroph wfac) wreg wneuron wplasticity, wresil, wneurogen
w(incr wsyn wconns)
,B7 Pharmacology Final Exam (Lectures
12-22)
- depr wassoc ww/ wdecr wBDNF w--> wdecr wneurotroph wsupp w(also wassoc ww/
wDM+other wnon- wneuro/psych wdis)
- sust wNE/5HT wsig wincr wBDNF wexpr
- antideps wincr wneurogen+syn wconn wcort wareas w(ie. whippocamp)
Altered wGlutamate wNeurotransmission win wMDD w- woverexcit win wcert wbrain wareas
Neuroendocrine wFactors win wMDD w- whypoT+low wsex wsters w(estrog win wmenop,
wtestos) wassoc ww/ wdepr
- neuroactive wsteroids wlike wprogest wmetabolite wAllopregnanolone wdef wcorrel ww/ wPPD
Goals wof wTreatment win wDepression w- w- wac wdepr wsx wresol
- prev wfunc wlev wreturn
- suic wprev
- fut wdepr weps w(recur/relapse) wprev
Nonpharmacologic wInterventions wfor wMDD w- w- wPsychother w= w**1st wLINE wfor wmild-
mod** wdepr, waddit weffs ww/ wpharm wther, wmaybe wcost+resource wprohib
- ECT w= w**LAST wLINE** wfor wrefrac wMDD
- Exercise w--> wincr wBDNF
**Use wpharm wther+CBT wfor wmod-sev wdepr**
Acne wtreatment wthat wmay wExacerbate wDepression w- wIsotretinoin
- mon wpsych wsx wper wREMS wprogram wiPledge
CV wMeds wthat wmay wExacerbate wDepression w- w- wReserpine w= wdepl wsymp wbiogen
wamines wNE+Dopa; wused wfor wHTN wbut wpulled wfrom wmarket wdue wto wfatigue, wdecr
wenerg, wsex wdysf?
- ARBs
- BBs w= wclassically wlinked wto wdepr wbut wevid wsupps wjust wphys wsx wfatigue+low wenerg
- CCBs
- Clonidine
- Methyldopa
CNS wAgents wthat wMay wExacerbate wDepression w- w- wDeutetrabenazine w&
wTetrabenazine w= wdepl wsyn wmonamines wby wdecr wvesic wpresyn wneur wtransp;
w**BBW wdepr+suicidality**
- Valbenazine
Hormonal wTherapy wthat wmay wExacerbate wDepression w- w- wGRH w& wOCPs w=
wprogest+estrog walters wposs wlink wto wmonoam woxid wactiv
- Steroids w(ie. wPrednis) w= wposs wassoc ww/ winfl+HPA waxis wchanges wof wdepr
Immunologic wAgent wthat wmay wExacerbate wDepression w- wInterferons
,B7 Pharmacology Final Exam (Lectures
12-22)
Smoking wCessation wDrug wthat wmay wExacerbate wDepression w- wVarenicline
Line wof wPharmacotherapy wfor wMod-Sev wDepression w- wFIRST wLINE ww/ wantideps
win wtop w3 wclasses wRx wmeds
3 wPhases w& wGoals wof wDepression wPharm wTreatment w- w- wAcute wph w(6-12w) w= wsx
wremis/abs
- Cont w(next w4-9m wafter wremis) w= wresid wsx welim/relapse w(sx wret ww/in w6m) wprev
- Maint w(@least w12-36m) w= wrecur w(sep wdepr wep) wprev
Duration wof wPharmacotherapy wfor wDepression w- wpt-dep wbased won w# wpast wdepr weps
Classes wof wAntidepressants w- w- wSSRIs
- SNRIs w(newer wgen w& wTCA)
- Atypical wAntideps
- MAOIs
Examples wof wSSRIs w- w- wCitalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
Examples wof wNewer wGeneration wSNRIs w- w- wDesvenlafaxine
- Duloxetine
- Venlafaxine
- Levomilnacipran
Examples wof wTCAs w(class wof wSNRIs) w- w- wAmitriptyline
- Desipramine
- Doxepin
- Imipramine
- Nortriptyline
Examples wof wAtypical wAntidepressants w- w- wBupropion
- Nefazodone
- Trazodone
- Vilazodone
- Vortioxetine
- Mirtazapine
Examples wof wMAOIs w- w- wPhenelzine
- Selegiline
, B7 Pharmacology Final Exam (Lectures
12-22)
- Tranylcypromine
- Isocarboxazid
General wMOA wof wTCAs w- wblock wreuptake wboth wserot+NE w@ wSERT+NET wbut
**nonspec+promisc** w@ wother wrec wsites
- block wserot wreup w& wincr wsyn wconc
- cont wuse w--> wincr wsyn wserot wconc wdownreg wpresyn wautoR+incr wraphe wneur wfiring
wrate
General wMOA wof wSNRIs w- wblock wserot+NE wreup wbut w**don't wadditionally wblock
wother wR wlike wTCA**
- cont wuse w--> wincr wsyn wserot wconc wdownreg wpresyn wautoR+incr wraphe wneur wfiring
wrate
General wMOA wof wSSRIs w- winhib wonly wserot wreup won w5HT wterms
- cont wuse w--> wincr wsyn wserot wconc wdownreg wpresyn wautoR+incr wraphe wneur wfiring
wrate
General wMOA wof wMAOIs w- wirrev wbind wMAO wmit wmetab wserot+NE w--> winhib wNE,
wserot, wDopa wdegr
General wMOA wof wNSRIs w- wNE-sel wreup winhibs wNOT wyet wdev wfor wdepr wtreatment
wbut wstim wAtomoxetine wknown was wNSRI
NE w& wSerotonin wUptake wInhibition wby wSSRIs, wSNRIs, wTCAs w- w- wSSRI wFluox w=
wno wNE wuptake winhib, w**only whigh wserot wuptake winhib**
- SNRI wVenlaf w= wsome wNE wreup winhib, whigh wserot wreup winhib
- SNRI wDulox w= whigh wNE wreup winhib, whigh wserot wreup winhib
- TCA wImipr w= whigh wNE wreup winhib, wmod-high wserot wreup winhib
- TCA wNortrip w= whigh wNE wreup winhib, wsome wserot winhib
Antidepressant wClass wEffects w- w- wequiv weffic wwhen wused w@ wcomp wdoses wso winit
wchoice wis wempiric w(NOT wa wsingle wrec w1st wline wagent)
- Facs wto wconsid w= wpt wresp whx, wfam wAD wresp whx, wconcur wmed willn+meds, wpres
wsx w(ie. winsom wvs whypersom), wdrug-drug wint wpot, wAEs, wpt wpref, wmed wcost
- **BBW won wall wADs w= wsuic wthoughts+behav**, wNOT wnecessarily wincr wsuic
waction; wincr wrisk wchild, wadols, wYAs w<24y/o w& wdecr wrisk w>65y/o; wmon wall wpts
- **CAUTION win wbipol wdisord-rel wdepr wb/c wmay wcause wswitch wto wmanic wbehav
ww/o whaving wmood-stab won wboard**
Antidepressant wResponse w- w- wmod-sev wdepr w--> wbenef wdeps won wsev; wmore wsev
wdepr, wgreater wlikely wbenefits; wprob wineff wfor wmild wdepr
- Find weffect wag w= wpt-spec; wfailure wto wresp wto w1 wAD wclass/1 wAD ww/in wclass
wDOES wNOT wpred wfailed wresp wto wanother wclass/another wagent win wsame wclass
- Strats wfor wpoor wresp w= wswitch wvs waugm
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, wReuptake w- w- wtyramine wconv wto wNE, wstored win wvesics/degr
wby wMAO
- binds wpostsyn walpha/beta wadrenR; wbinds/agonizes wpresyn walpha2R winhib wNE wrel
- Recyc wback wpresyn wby wNET wtransp
Serotonin wSynthesis, wBinding, wReuptake w- w- wtryp wconv wto w5HT
- Binds wmany wpostsyn/presynR w--> wactiv wpresynR wto wdecr wneur wfiring
- SERT wtransp wfor wreup
Problems ww/ wMonoamine wHypothesis w- wantideps wrap wchanging wmonoam wconcs
whave wdelayed wonset wto weffic w--> weffs wmaybe wsec wto walter wR wdens/sensits wOR
wsec wsig wPW w(ie. winositol wsynth wdisr win wbipol wdisord)
Neurotropic wHypothesis wof wMDD w- winfl+overexc w--> wdecr wneuroplas+neur wdiff
- n wGF w(ie. wBDNF wbr-der wneurotroph wfac) wreg wneuron wplasticity, wresil, wneurogen
w(incr wsyn wconns)
,B7 Pharmacology Final Exam (Lectures
12-22)
- depr wassoc ww/ wdecr wBDNF w--> wdecr wneurotroph wsupp w(also wassoc ww/
wDM+other wnon- wneuro/psych wdis)
- sust wNE/5HT wsig wincr wBDNF wexpr
- antideps wincr wneurogen+syn wconn wcort wareas w(ie. whippocamp)
Altered wGlutamate wNeurotransmission win wMDD w- woverexcit win wcert wbrain wareas
Neuroendocrine wFactors win wMDD w- whypoT+low wsex wsters w(estrog win wmenop,
wtestos) wassoc ww/ wdepr
- neuroactive wsteroids wlike wprogest wmetabolite wAllopregnanolone wdef wcorrel ww/ wPPD
Goals wof wTreatment win wDepression w- w- wac wdepr wsx wresol
- prev wfunc wlev wreturn
- suic wprev
- fut wdepr weps w(recur/relapse) wprev
Nonpharmacologic wInterventions wfor wMDD w- w- wPsychother w= w**1st wLINE wfor wmild-
mod** wdepr, waddit weffs ww/ wpharm wther, wmaybe wcost+resource wprohib
- ECT w= w**LAST wLINE** wfor wrefrac wMDD
- Exercise w--> wincr wBDNF
**Use wpharm wther+CBT wfor wmod-sev wdepr**
Acne wtreatment wthat wmay wExacerbate wDepression w- wIsotretinoin
- mon wpsych wsx wper wREMS wprogram wiPledge
CV wMeds wthat wmay wExacerbate wDepression w- w- wReserpine w= wdepl wsymp wbiogen
wamines wNE+Dopa; wused wfor wHTN wbut wpulled wfrom wmarket wdue wto wfatigue, wdecr
wenerg, wsex wdysf?
- ARBs
- BBs w= wclassically wlinked wto wdepr wbut wevid wsupps wjust wphys wsx wfatigue+low wenerg
- CCBs
- Clonidine
- Methyldopa
CNS wAgents wthat wMay wExacerbate wDepression w- w- wDeutetrabenazine w&
wTetrabenazine w= wdepl wsyn wmonamines wby wdecr wvesic wpresyn wneur wtransp;
w**BBW wdepr+suicidality**
- Valbenazine
Hormonal wTherapy wthat wmay wExacerbate wDepression w- w- wGRH w& wOCPs w=
wprogest+estrog walters wposs wlink wto wmonoam woxid wactiv
- Steroids w(ie. wPrednis) w= wposs wassoc ww/ winfl+HPA waxis wchanges wof wdepr
Immunologic wAgent wthat wmay wExacerbate wDepression w- wInterferons
,B7 Pharmacology Final Exam (Lectures
12-22)
Smoking wCessation wDrug wthat wmay wExacerbate wDepression w- wVarenicline
Line wof wPharmacotherapy wfor wMod-Sev wDepression w- wFIRST wLINE ww/ wantideps
win wtop w3 wclasses wRx wmeds
3 wPhases w& wGoals wof wDepression wPharm wTreatment w- w- wAcute wph w(6-12w) w= wsx
wremis/abs
- Cont w(next w4-9m wafter wremis) w= wresid wsx welim/relapse w(sx wret ww/in w6m) wprev
- Maint w(@least w12-36m) w= wrecur w(sep wdepr wep) wprev
Duration wof wPharmacotherapy wfor wDepression w- wpt-dep wbased won w# wpast wdepr weps
Classes wof wAntidepressants w- w- wSSRIs
- SNRIs w(newer wgen w& wTCA)
- Atypical wAntideps
- MAOIs
Examples wof wSSRIs w- w- wCitalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
Examples wof wNewer wGeneration wSNRIs w- w- wDesvenlafaxine
- Duloxetine
- Venlafaxine
- Levomilnacipran
Examples wof wTCAs w(class wof wSNRIs) w- w- wAmitriptyline
- Desipramine
- Doxepin
- Imipramine
- Nortriptyline
Examples wof wAtypical wAntidepressants w- w- wBupropion
- Nefazodone
- Trazodone
- Vilazodone
- Vortioxetine
- Mirtazapine
Examples wof wMAOIs w- w- wPhenelzine
- Selegiline
, B7 Pharmacology Final Exam (Lectures
12-22)
- Tranylcypromine
- Isocarboxazid
General wMOA wof wTCAs w- wblock wreuptake wboth wserot+NE w@ wSERT+NET wbut
**nonspec+promisc** w@ wother wrec wsites
- block wserot wreup w& wincr wsyn wconc
- cont wuse w--> wincr wsyn wserot wconc wdownreg wpresyn wautoR+incr wraphe wneur wfiring
wrate
General wMOA wof wSNRIs w- wblock wserot+NE wreup wbut w**don't wadditionally wblock
wother wR wlike wTCA**
- cont wuse w--> wincr wsyn wserot wconc wdownreg wpresyn wautoR+incr wraphe wneur wfiring
wrate
General wMOA wof wSSRIs w- winhib wonly wserot wreup won w5HT wterms
- cont wuse w--> wincr wsyn wserot wconc wdownreg wpresyn wautoR+incr wraphe wneur wfiring
wrate
General wMOA wof wMAOIs w- wirrev wbind wMAO wmit wmetab wserot+NE w--> winhib wNE,
wserot, wDopa wdegr
General wMOA wof wNSRIs w- wNE-sel wreup winhibs wNOT wyet wdev wfor wdepr wtreatment
wbut wstim wAtomoxetine wknown was wNSRI
NE w& wSerotonin wUptake wInhibition wby wSSRIs, wSNRIs, wTCAs w- w- wSSRI wFluox w=
wno wNE wuptake winhib, w**only whigh wserot wuptake winhib**
- SNRI wVenlaf w= wsome wNE wreup winhib, whigh wserot wreup winhib
- SNRI wDulox w= whigh wNE wreup winhib, whigh wserot wreup winhib
- TCA wImipr w= whigh wNE wreup winhib, wmod-high wserot wreup winhib
- TCA wNortrip w= whigh wNE wreup winhib, wsome wserot winhib
Antidepressant wClass wEffects w- w- wequiv weffic wwhen wused w@ wcomp wdoses wso winit
wchoice wis wempiric w(NOT wa wsingle wrec w1st wline wagent)
- Facs wto wconsid w= wpt wresp whx, wfam wAD wresp whx, wconcur wmed willn+meds, wpres
wsx w(ie. winsom wvs whypersom), wdrug-drug wint wpot, wAEs, wpt wpref, wmed wcost
- **BBW won wall wADs w= wsuic wthoughts+behav**, wNOT wnecessarily wincr wsuic
waction; wincr wrisk wchild, wadols, wYAs w<24y/o w& wdecr wrisk w>65y/o; wmon wall wpts
- **CAUTION win wbipol wdisord-rel wdepr wb/c wmay wcause wswitch wto wmanic wbehav
ww/o whaving wmood-stab won wboard**
Antidepressant wResponse w- w- wmod-sev wdepr w--> wbenef wdeps won wsev; wmore wsev
wdepr, wgreater wlikely wbenefits; wprob wineff wfor wmild wdepr
- Find weffect wag w= wpt-spec; wfailure wto wresp wto w1 wAD wclass/1 wAD ww/in wclass
wDOES wNOT wpred wfailed wresp wto wanother wclass/another wagent win wsame wclass
- Strats wfor wpoor wresp w= wswitch wvs waugm
