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 k--> kactiv kpresynR kto kdecr kneur kfiring
- SERT ktransp kfor kreup
Problems kw/ kMonoamine kHypothesis k- kantideps krap kchanging kmonoam kconcs khave
kdelayed konset kto keffic k--> keffs kmaybe ksec kto kalter kR kdens/sensits kOR ksec ksig kPW
k(ie. kinositol ksynth kdisr kin kbipol kdisord)
Neurotropic kHypothesis kof kMDD k- kinfl+overexc k--> kdecr kneuroplas+neur kdiff
- n kGF k(ie. kBDNF kbr-der kneurotroph kfac) kreg kneuron kplasticity, kresil, kneurogen
k(incr ksyn kconns)
,B7 Pharmacology Final Exam (Lectures
12-22)
- depr kassoc kw/ kdecr kBDNF k--> kdecr kneurotroph ksupp k(also kassoc kw/
kDM+other knon- kneuro/psych kdis)
- sust kNE/5HT ksig kincr kBDNF kexpr
- antideps kincr kneurogen+syn kconn kcort kareas k(ie. khippocamp)
Altered kGlutamate kNeurotransmission kin kMDD k- koverexcit kin kcert kbrain kareas
Neuroendocrine kFactors kin kMDD k- khypoT+low ksex ksters k(estrog kin kmenop, ktestos)
kassoc kw/ kdepr
- neuroactive ksteroids klike kprogest kmetabolite kAllopregnanolone kdef kcorrel kw/ kPPD
Goals kof kTreatment kin kDepression k- k- kac kdepr ksx kresol
- prev kfunc klev kreturn
- suic kprev
- fut kdepr keps k(recur/relapse) kprev
Nonpharmacologic kInterventions kfor kMDD k- k- kPsychother k= k**1st kLINE kfor kmild-
mod** kdepr, kaddit keffs kw/ kpharm kther, kmaybe kcost+resource kprohib
- ECT k= k**LAST kLINE** kfor krefrac kMDD
- Exercise k--> kincr kBDNF
**Use kpharm kther+CBT kfor kmod-sev kdepr**
Acne ktreatment kthat kmay kExacerbate kDepression k- kIsotretinoin
- mon kpsych ksx kper kREMS kprogram kiPledge
CV kMeds kthat kmay kExacerbate kDepression k- k- kReserpine k= kdepl ksymp kbiogen
kamines kNE+Dopa; kused kfor kHTN kbut kpulled kfrom kmarket kdue kto kfatigue, kdecr
kenerg, ksex kdysf?
- ARBs
- BBs k= kclassically klinked kto kdepr kbut kevid ksupps kjust kphys ksx kfatigue+low kenerg
- CCBs
- Clonidine
- Methyldopa
CNS kAgents kthat kMay kExacerbate kDepression k- k- kDeutetrabenazine k& kTetrabenazine
k= kdepl ksyn kmonamines kby kdecr kvesic kpresyn kneur ktransp; k**BBW kdepr+suicidality**
- Valbenazine
Hormonal kTherapy kthat kmay kExacerbate kDepression k- k- kGRH k& kOCPs k=
kprogest+estrog kalters kposs klink kto kmonoam koxid kactiv
- Steroids k(ie. kPrednis) k= kposs kassoc kw/ kinfl+HPA kaxis kchanges kof kdepr
Immunologic kAgent kthat kmay kExacerbate kDepression k- kInterferons
,B7 Pharmacology Final Exam (Lectures
12-22)
Smoking kCessation kDrug kthat kmay kExacerbate kDepression k- kVarenicline
Line kof kPharmacotherapy kfor kMod-Sev kDepression k- kFIRST kLINE kw/ kantideps kin
ktop k3 kclasses kRx kmeds
3 kPhases k& kGoals kof kDepression kPharm kTreatment k- k- kAcute kph k(6-12w) k= ksx
kremis/abs
- Cont k(next k4-9m kafter kremis) k= kresid ksx kelim/relapse k(sx kret kw/in k6m) kprev
- Maint k(@least k12-36m) k= krecur k(sep kdepr kep) kprev
Duration kof kPharmacotherapy kfor kDepression k- kpt-dep kbased kon k# kpast kdepr keps
Classes kof kAntidepressants k- k- kSSRIs
- SNRIs k(newer kgen k& kTCA)
- Atypical kAntideps
- MAOIs
Examples kof kSSRIs k- k- kCitalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
Examples kof kNewer kGeneration kSNRIs k- k- kDesvenlafaxine
- Duloxetine
- Venlafaxine
- Levomilnacipran
Examples kof kTCAs k(class kof kSNRIs) k- k- kAmitriptyline
- Desipramine
- Doxepin
- Imipramine
- Nortriptyline
Examples kof kAtypical kAntidepressants k- k- kBupropion
- Nefazodone
- Trazodone
- Vilazodone
- Vortioxetine
- Mirtazapine
Examples kof kMAOIs k- k- kPhenelzine
- Selegiline
, B7 Pharmacology Final Exam (Lectures
12-22)
- Tranylcypromine
- Isocarboxazid
General kMOA kof kTCAs k- kblock kreuptake kboth kserot+NE k@ kSERT+NET kbut
**nonspec+promisc** k@ kother krec ksites
- block kserot kreup k& kincr ksyn kconc
- cont kuse k--> kincr ksyn kserot kconc kdownreg kpresyn kautoR+incr kraphe kneur kfiring krate
General kMOA kof kSNRIs k- kblock kserot+NE kreup kbut k**don't kadditionally kblock kother kR
klike kTCA**
- cont kuse k--> kincr ksyn kserot kconc kdownreg kpresyn kautoR+incr kraphe kneur kfiring krate
General kMOA kof kSSRIs k- kinhib konly kserot kreup kon k5HT kterms
- cont kuse k--> kincr ksyn kserot kconc kdownreg kpresyn kautoR+incr kraphe kneur kfiring krate
General kMOA kof kMAOIs k- kirrev kbind kMAO kmit kmetab kserot+NE k--> kinhib kNE, kserot,
kDopa kdegr
General kMOA kof kNSRIs k- kNE-sel kreup kinhibs kNOT kyet kdev kfor kdepr ktreatment kbut
kstim kAtomoxetine kknown kas kNSRI
NE k& kSerotonin kUptake kInhibition kby kSSRIs, kSNRIs, kTCAs k- k- kSSRI kFluox k= kno
kNE kuptake kinhib, k**only khigh kserot kuptake kinhib**
- SNRI kVenlaf k= ksome kNE kreup kinhib, khigh kserot kreup kinhib
- SNRI kDulox k= khigh kNE kreup kinhib, khigh kserot kreup kinhib
- TCA kImipr k= khigh kNE kreup kinhib, kmod-high kserot kreup kinhib
- TCA kNortrip k= khigh kNE kreup kinhib, ksome kserot kinhib
Antidepressant kClass kEffects k- k- kequiv keffic kwhen kused k@ kcomp kdoses kso kinit
kchoice kis kempiric k(NOT ka ksingle krec k1st kline kagent)
- Facs kto kconsid k= kpt kresp khx, kfam kAD kresp khx, kconcur kmed killn+meds, kpres ksx
k(ie. kinsom kvs khypersom), kdrug-drug kint kpot, kAEs, kpt kpref, kmed kcost
- **BBW kon kall kADs k= ksuic kthoughts+behav**, kNOT knecessarily kincr ksuic kaction;
kincr krisk kchild, kadols, kYAs k<24y/o k& kdecr krisk k>65y/o; kmon kall kpts
- **CAUTION kin kbipol kdisord-rel kdepr kb/c kmay kcause kswitch kto kmanic kbehav kw/o
khaving kmood-stab kon kboard**
Antidepressant kResponse k- k- kmod-sev kdepr k--> kbenef kdeps kon ksev; kmore ksev
kdepr, kgreater klikely kbenefits; kprob kineff kfor kmild kdepr
- Find keffect kag k= kpt-spec; kfailure kto kresp kto k1 kAD kclass/1 kAD kw/in kclass kDOES
kNOT kpred kfailed kresp kto kanother kclass/another kagent kin ksame kclass
- Strats kfor kpoor kresp k= kswitch kvs kaugm
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 k--> kactiv kpresynR kto kdecr kneur kfiring
- SERT ktransp kfor kreup
Problems kw/ kMonoamine kHypothesis k- kantideps krap kchanging kmonoam kconcs khave
kdelayed konset kto keffic k--> keffs kmaybe ksec kto kalter kR kdens/sensits kOR ksec ksig kPW
k(ie. kinositol ksynth kdisr kin kbipol kdisord)
Neurotropic kHypothesis kof kMDD k- kinfl+overexc k--> kdecr kneuroplas+neur kdiff
- n kGF k(ie. kBDNF kbr-der kneurotroph kfac) kreg kneuron kplasticity, kresil, kneurogen
k(incr ksyn kconns)
,B7 Pharmacology Final Exam (Lectures
12-22)
- depr kassoc kw/ kdecr kBDNF k--> kdecr kneurotroph ksupp k(also kassoc kw/
kDM+other knon- kneuro/psych kdis)
- sust kNE/5HT ksig kincr kBDNF kexpr
- antideps kincr kneurogen+syn kconn kcort kareas k(ie. khippocamp)
Altered kGlutamate kNeurotransmission kin kMDD k- koverexcit kin kcert kbrain kareas
Neuroendocrine kFactors kin kMDD k- khypoT+low ksex ksters k(estrog kin kmenop, ktestos)
kassoc kw/ kdepr
- neuroactive ksteroids klike kprogest kmetabolite kAllopregnanolone kdef kcorrel kw/ kPPD
Goals kof kTreatment kin kDepression k- k- kac kdepr ksx kresol
- prev kfunc klev kreturn
- suic kprev
- fut kdepr keps k(recur/relapse) kprev
Nonpharmacologic kInterventions kfor kMDD k- k- kPsychother k= k**1st kLINE kfor kmild-
mod** kdepr, kaddit keffs kw/ kpharm kther, kmaybe kcost+resource kprohib
- ECT k= k**LAST kLINE** kfor krefrac kMDD
- Exercise k--> kincr kBDNF
**Use kpharm kther+CBT kfor kmod-sev kdepr**
Acne ktreatment kthat kmay kExacerbate kDepression k- kIsotretinoin
- mon kpsych ksx kper kREMS kprogram kiPledge
CV kMeds kthat kmay kExacerbate kDepression k- k- kReserpine k= kdepl ksymp kbiogen
kamines kNE+Dopa; kused kfor kHTN kbut kpulled kfrom kmarket kdue kto kfatigue, kdecr
kenerg, ksex kdysf?
- ARBs
- BBs k= kclassically klinked kto kdepr kbut kevid ksupps kjust kphys ksx kfatigue+low kenerg
- CCBs
- Clonidine
- Methyldopa
CNS kAgents kthat kMay kExacerbate kDepression k- k- kDeutetrabenazine k& kTetrabenazine
k= kdepl ksyn kmonamines kby kdecr kvesic kpresyn kneur ktransp; k**BBW kdepr+suicidality**
- Valbenazine
Hormonal kTherapy kthat kmay kExacerbate kDepression k- k- kGRH k& kOCPs k=
kprogest+estrog kalters kposs klink kto kmonoam koxid kactiv
- Steroids k(ie. kPrednis) k= kposs kassoc kw/ kinfl+HPA kaxis kchanges kof kdepr
Immunologic kAgent kthat kmay kExacerbate kDepression k- kInterferons
,B7 Pharmacology Final Exam (Lectures
12-22)
Smoking kCessation kDrug kthat kmay kExacerbate kDepression k- kVarenicline
Line kof kPharmacotherapy kfor kMod-Sev kDepression k- kFIRST kLINE kw/ kantideps kin
ktop k3 kclasses kRx kmeds
3 kPhases k& kGoals kof kDepression kPharm kTreatment k- k- kAcute kph k(6-12w) k= ksx
kremis/abs
- Cont k(next k4-9m kafter kremis) k= kresid ksx kelim/relapse k(sx kret kw/in k6m) kprev
- Maint k(@least k12-36m) k= krecur k(sep kdepr kep) kprev
Duration kof kPharmacotherapy kfor kDepression k- kpt-dep kbased kon k# kpast kdepr keps
Classes kof kAntidepressants k- k- kSSRIs
- SNRIs k(newer kgen k& kTCA)
- Atypical kAntideps
- MAOIs
Examples kof kSSRIs k- k- kCitalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
Examples kof kNewer kGeneration kSNRIs k- k- kDesvenlafaxine
- Duloxetine
- Venlafaxine
- Levomilnacipran
Examples kof kTCAs k(class kof kSNRIs) k- k- kAmitriptyline
- Desipramine
- Doxepin
- Imipramine
- Nortriptyline
Examples kof kAtypical kAntidepressants k- k- kBupropion
- Nefazodone
- Trazodone
- Vilazodone
- Vortioxetine
- Mirtazapine
Examples kof kMAOIs k- k- kPhenelzine
- Selegiline
, B7 Pharmacology Final Exam (Lectures
12-22)
- Tranylcypromine
- Isocarboxazid
General kMOA kof kTCAs k- kblock kreuptake kboth kserot+NE k@ kSERT+NET kbut
**nonspec+promisc** k@ kother krec ksites
- block kserot kreup k& kincr ksyn kconc
- cont kuse k--> kincr ksyn kserot kconc kdownreg kpresyn kautoR+incr kraphe kneur kfiring krate
General kMOA kof kSNRIs k- kblock kserot+NE kreup kbut k**don't kadditionally kblock kother kR
klike kTCA**
- cont kuse k--> kincr ksyn kserot kconc kdownreg kpresyn kautoR+incr kraphe kneur kfiring krate
General kMOA kof kSSRIs k- kinhib konly kserot kreup kon k5HT kterms
- cont kuse k--> kincr ksyn kserot kconc kdownreg kpresyn kautoR+incr kraphe kneur kfiring krate
General kMOA kof kMAOIs k- kirrev kbind kMAO kmit kmetab kserot+NE k--> kinhib kNE, kserot,
kDopa kdegr
General kMOA kof kNSRIs k- kNE-sel kreup kinhibs kNOT kyet kdev kfor kdepr ktreatment kbut
kstim kAtomoxetine kknown kas kNSRI
NE k& kSerotonin kUptake kInhibition kby kSSRIs, kSNRIs, kTCAs k- k- kSSRI kFluox k= kno
kNE kuptake kinhib, k**only khigh kserot kuptake kinhib**
- SNRI kVenlaf k= ksome kNE kreup kinhib, khigh kserot kreup kinhib
- SNRI kDulox k= khigh kNE kreup kinhib, khigh kserot kreup kinhib
- TCA kImipr k= khigh kNE kreup kinhib, kmod-high kserot kreup kinhib
- TCA kNortrip k= khigh kNE kreup kinhib, ksome kserot kinhib
Antidepressant kClass kEffects k- k- kequiv keffic kwhen kused k@ kcomp kdoses kso kinit
kchoice kis kempiric k(NOT ka ksingle krec k1st kline kagent)
- Facs kto kconsid k= kpt kresp khx, kfam kAD kresp khx, kconcur kmed killn+meds, kpres ksx
k(ie. kinsom kvs khypersom), kdrug-drug kint kpot, kAEs, kpt kpref, kmed kcost
- **BBW kon kall kADs k= ksuic kthoughts+behav**, kNOT knecessarily kincr ksuic kaction;
kincr krisk kchild, kadols, kYAs k<24y/o k& kdecr krisk k>65y/o; kmon kall kpts
- **CAUTION kin kbipol kdisord-rel kdepr kb/c kmay kcause kswitch kto kmanic kbehav kw/o
khaving kmood-stab kon kboard**
Antidepressant kResponse k- k- kmod-sev kdepr k--> kbenef kdeps kon ksev; kmore ksev
kdepr, kgreater klikely kbenefits; kprob kineff kfor kmild kdepr
- Find keffect kag k= kpt-spec; kfailure kto kresp kto k1 kAD kclass/1 kAD kw/in kclass kDOES
kNOT kpred kfailed kresp kto kanother kclass/another kagent kin ksame kclass
- Strats kfor kpoor kresp k= kswitch kvs kaugm
