APNA 29th Annual Conference Session 2026: October 29, 2015 T he - PDF document

APNA 29th Annual Conference Session 2026: October 29, 2015 T he Huma n Ge no me Pro je c t (1990-2003) Clinic a l Applic a tio n o f Pha rma c o g e no mic s T e sting :  Co mprise d o f 20 I ntuitio ns fro m 6 c o untrie s 1 A T o o l fo r the Nurse Pra c titio ne r in the tre a tme nt Co -Oc c urring Diso rde rs  13 ye a rs to c o mple te 1  Co st ~ $2.7 b illo n 1 Pa tric ia M. Alle n, MSN PMHNP-BC  I de ntifie d ~ 3 b illo n b a se -pa irs 1 Gre g Gilb e rt RN, BSN  I de ntifie d ~ 20,500 huma n g e ne s 1  3.7 millio n ma ppe d huma n sing le nuc le o tide po lymo rphism (SNPs) 1 T he Spe a ke rs ha ve no c o nflic ts o f inte re st to disc lo se T he Huma n Ge no me Pro je c t Adva nc e me nts Why do some me dic ations wor k for some patie nts, but not othe r s? On a ve ra g e , 40% o f pa tie nts who ta ke a g ive n me dic a tio n will  F ue le d disc o ve ry o f >1,800 dise a se no t re spo nd to tre a tme nt. K no wing a pa tie nt’ s g e ne tic pro file c a n g e ne s 1 he lp. 2  De c re a se d time to sc re e n g e ne s Ge no mic va ria nc e s in a p a tie nt’ s me ta b o lic pa thwa y de te rmine ho w suspe c te d o f c a using a n inhe rite d a pa tie nt will re spo nd to pre sc rib e d me dic a tio ns. Pha rma c o g e ne tic d ise a se to d a ys ra the r tha n ye a rs 1 te sting pro vide s p hysic ia ns with insig ht into individua l g e ne tic  > 350 Bio te c h-b a se d pro duc ts a re diffe re nc e s in the ir pa tie nts' drug pro c e ssing a b ility. Arme d with this c urre ntly in c linic a l tria ls 1 kno wle d g e , physic ia ns c o uld pre d ic t the p a tie nt’ s re spo nse to the ma jo rity o f c o mmo nly p re sc rib e d me dic a tio ns a llo wing fo r p re c isio n  > 2,000 g e ne tic te sts fo r huma n pre sc riptio n writing a nd b e tte r pa tie nt o utc o me s. c o nditio ns a va ila b le 1  Pro vide d the sc ie nc e fo r Pha rma c o g e no mic s & Pha rma c o g e ne tic (PGx) T e sting 1 “One -Size -F its-All” mo de l Wha t is Pha rma c o g e ne tic s ?  Ave ra g e pa tie nt wa ste s $800- $1,200/ ye a r o n me d ic a tio ns tha t d o Pha rma c o g e ne tic s is the stud y o f g e ne tic va ria tio ns the y d o no t re spo nd to OR the y tha t influe nc e ind ividua l re spo nse to d rug s. c a nno t to le ra te . (Insura nc e Ave ra g e )  On a ve ra g e , a pa tie nt will ta ke 3 o r 4 K no wing whe the r a pa tie nt c a rrie s a ny o f the se d iffe re nt me d ic a tio ns b e fo re re po rting g e ne tic va ria tio ns c a n he lp: a d e q ua te sympto m re d uc tio n (Me nta l He a lth) 4  Pre sc rib e rs ind ivid ua lize d rug the ra py 3  De c re a se the c ha nc e fo r a d ve rse d rug e ve nts  33%-55% Ra te o f me d ic a tio n no n- s) 3 a d he re nc e (Me nta l He a lth) 4 (ADE  Inc re a se the e ffe c tive ne ss o f d rug s. 3  On a ve ra g e , 40% o f pa tie nts who ta ke a g ive n me d ic a tio n will no t re spo nd to tre a tme nt (Me nta l He a lth) 4 http:/ / www.a ma -a ssn.o rg / a ma / pub / physic ia n-re so urc e s/ me d ic a l-sc ie nc e / g e ne tic s-mo le c ula r-me d ic ine / ne ws.pa g e Allen 1

APNA 29th Annual Conference Session 2026: October 29, 2015 Pa tie nt Sa fe ty Me dic a tio n Co mplia nc e Adve rse Drug E ve nts (ADEs)  49% sto ppe d a t 16 we e ks 6  ~850,000 ADE s a nnua lly 5  59% sto ppe d a t 32 we e k 6  >125,000 ADE d e a ths a nnua lly 5  “T he Antid e pre ssa nt wa sn’ t he lping ” 6  ~100,000 E me rg e nc y ho spita liza tio ns a nnua lly a mo ng >65 ye a rs o ld 5  “I wa s ha ving sid e e ffe c ts” 6  $289 Billio n pe r ye a r spe nt o n ADE s 5 Pe rso na lize d mo de l Pe rso na lize d Me dic ine Appro a c h Go a ls o f Pe rso na lize d Mo d e l  Re d uc tio n in ADE s “ Pe rso nalize d me dic ine aims to stre amline c linic al de c isio n making by using bio lo g ic al info rmatio n available thro ug h a  Inc re a se T he ra pe utic g e ne tic te st o r bio marke r, and the n saying, ‘ base d o n this pro file , Re spo nse (Sta b iliza tio n time ) I think yo u're mo re like ly to re spo nd to Drug A o r Drug B, o r le ss like ly to have an adve rse re ac tio n with Drug C.’ T he ide a is to g e t  Inc re a se Me d ic a tio n patie nts o n the rig ht me dic atio n and to g e t the m o n it so o ne r.” Co mplia nc e  Re d uc e Ove ra ll He a lthc a re – Dr. Issa m Zine h, Dir o f Clinic a l Pha rma c o lo g y, F DA Co st (ie , RX, E R & o ffic e visits) Wha t Ge ne s Are Ana lyze d ? Cyto c hro me P450 (CYP450)  F a mily o f live r e nzyme s re spo nsib le fo r  CYP450 – Re spo nsib le fo r drug me ta b o lism me ta b o lizing ~85% o f pre sc rib e d me dic a tio ns  COMT – Re g ula te s Ca te c ho la mine Ne uro tra nsmitte rs  50+ I de ntifie d, b ut 6 a re re spo nsib le fo r  S L C6A2 – No re pine phrine T ra nspo rt Pro te in (NE T ) re spo nsib le fo r the ma jo rity o f me ta b o lism  S L C6A4 – Se ro to nin T ra nspo rt Pro te in (SE RT )  Va ria tio ns in the CYP450 c a n c a use the b o dy  HT R2A – Se ro to nin Re c e pto r Site to b re a k do wn drug s mo re ra pidly, o r to b re a k the m do wn mo re slo wly R2C – Se ro to nin Re c e pto r Site  HT - De c re a se d drug c o nc e ntra tio n  OPRM1 – Mu-Opio id Re c e pto r - I nc re a se d drug c o nc e ntra tio n  MT HF R - K e y re g ula to ry e nzyme in the me ta b o lism o f fo la te Allen 2

APNA 29th Annual Conference Session 2026: October 29, 2015 Clinic a l sig nific a nc e Se ro to nin (SE RT s) & No re pine phrine (NE T s) T ra nspo rte r Pro te ins  He lp to re g ula te the e ffe c t o f ne uro tra nsmitte rs in the CNS  Are the ta rg e t fo r e a c h ma jo r c la ss o f Antide pre ssa nts: SNRIs, SSRIs & T CAs  Muta tio ns in the SE RT a nd NE T g e ne s c a n a lte r the e ffe c tive ne ss o f c e rta in SSRIs & SNRIs c a using a re d uc e d , Pa tie nt A: Ultra -Ra pid Me ta b o lize r –do se ma y ha ve little to no the ra pe utic e ffe c t 6 slo we r o r a typic a l re spo nse to the me d ic a tio n s 6 Pa tie nt B: Po o r Me ta b o lize r –do se ma y b e to xic o r c a use ADE xte nsive Me ta b o lize r –fa ll within the drug ’ s the ra pe utic windo w 6 Pa tie nt C: E Re trie ve d fro m www.pha rmg kb .c o m Ca te c ho l-O-me thyl tra nsfe ra se (COMT ) Se ro to nin Re c e pto rs: HT R2A a nd HT R2C  Wo rk a s pa rt o f a fe e db a c k lo o p  L o c a l me ta b o lizing e nzyme tha t re g ula te s Se ro to nin c o nc e ntra tio ns within the syna ptic  Re g ula te s e xtra c e llula r c le ft ne uro tra nsmitte r c o nc e ntra tio ns  I nvo lve d in the re spo nse to va rio us  Muta tio ns in the COMT g e ne ha s b e e n a sso c ia te d with de c re ase d r drug s use d to tre a t Anxie ty, e sponse to va rio us ADHD & Antide pre ssa nts De pre ssio n & Psyc ho sis me d ic a tio n  Muta tio ns in the HT R2A o r HT R2C  Has be e n assoc iate d with ha ve b e e n a sso c ia te d lo we r sc hizo phre nia , d e pre ssio n, a nxie ty, re spo nse ra te to a nd hig he r ra te o f a nd b ipo la r d iso rd e r . side e ffe c ts Re trie ve d fro m www.pha rmg kb .c o m Re trie ve d fro m www.pha rmg kb .c o m Opio id Re c e pto r Mu-1 (OPRM1) Re sults o f PGx Guide d T re a tme nt  OPRM1 c o d e s fo r the Mu-Opio id QIDS-C16 Sc o re re c e pto r 7.2% re d uc tio n in the ung uid e d g ro up 7  31.2% re d uc tio n in the g uid e d g ro up 7   Ma in ta rg e t o f o pio id s suc h a s Mo rphine & F e nta nyl HAM-D17 ra ting s  18.2% re d uc tio n in the ung uid e d g ro up 7  Affe c ts me c ha nisms re la te d to pa in, o pio id e ffic a c y, a nd o pio id -re la te d  30.8% re d uc tio n in the g uid e d g ro up 7 sid e e ffe c ts, to le ra nc e , d e pe nd e nc e & re wa rd E c o no mic Impa c t $1,036 in Rx sa ving s 7   Muta tio ns in the OPRM1 g e ne c a n $1,556 in o ffic e / E R visits 7  e sponse to c e rta in de c r e ase r me d ic a tio ns inc lud ing Na ltre xo ne  $2,592 in to ta l a nnua l sa ving s 7 a nd Bupre no rphine Translational Psychiatry (2012) 2, e172; doi:10.1038/tp.2012.99 Allen 3