B6 Pharm Exam 1 (Lectures 1-7)
Adenohypophyseal Physio - - 3 func anat components = hypoth, adenohypophysis (ant
pit), periph endoc gl/tiss
- hypoth secr 2 horm types to hypoth-hypoph port sys in med emin = rel horms (RH,
liberins) & rel-inhib horms (IH, statins)
w/ hypoth-hypoph port sys carrying horms to ant pit
Synthesis & Regulation of Growth Hormone (GH, somatotropin) - - synth by ant pit
somatotropes (30-40% ant pit c)
- +by hypoth GHRH & Dopa
- -by GH, IGF-1, hypoth GHIH/somatostatin
Receptor, Target Organs, Peripheral Hormone Released by GH - -GH-r = tyr kin-assoc
R, memb JAK/STAT superfam
- Targets = liv, bone, musc, adip, kidney
- Periph horm = IGF-1
Physiologic & Pharmacologic Stimulation of GH - - Physio = GHRH, ghrelin, ADH,
GABA, NE, Dopa, serot, estrog, sleep, stress, exerc
- Pharm = alpha-ag, BB, Dopa ags (ie. Bromocriptine), GABA ag
Physiologic & Pharmacologic Inhibition of GH - - Physio = somatostatin, elev IGF-1, GH,
progest, GCs, postprand hypergly, elev FFAs
- Pharm = Dopa antag, alpha antag, beta ag, serot antag
General Effects of GH p- p(+) pvisc+sk pgrowth, plipolysis, pprot psynth, pIGF-1 pprod p-->
psuppr pliv pgluc pprod, pincr pperiph pgluc putil, pinhib pinsul psecr
(-) pinsul psensit p--> phypergly
Features pof pGH pDeficiency p(hypopituitarism) pin pChildren p& pAdults p- p- pChildren p&
padols p= pcongen/acq pdef p--> pgrowth pstunt, pdwarf, p+fat-musc pmass pratio, phypogly
pby punopp pinsul
- Adult p= p-lean pbod pmass, p+body pfat pto pobes, p-musc pmass, pasthenia p(phys
pweak), p-BMD, pdyslip, p-CO
Examples, pMOA, pAdministration, pPK pof pRecombinant phuman pGH p(rhGH) p- pincl
pSomatrem p(protropin) p& pSomatropin p(10 pdiff pbrand pnames)
- MOA p= pmimic pGH pphysio pactions
- Admin p= p6-7x/wk
- PK p= ppeak ppl plevs p2-4hrs pw/ p36hr ppersis
- Route p= pIM p& pSQ, pmust pbe pinjec pb/c pis pprot p& pnot pabs porally
Indications pfor prhGH p- p- pChildren p& pAdols p= pidiop pshort pstat p(ISS); p**many
pgrowth pfail pindics pNOT passoc pw/ pGH pdef**
- Adults p= pAIDS-assoc pwasting psynd p(cachex); pUNSUBST pfor p"anti-aging" por
pathletic pperf penh
,B6 Pharm Exam 1 (Lectures 1-7)
AEs p& pCIs pfor prhGH p- p- pAEs p= prare ppseudotum pcerebri p(idiop pintracran pHTN),
pslipped pcap pfem pepiph, phypergly, pDM, p**asphyx pin psev pobese/resp pimpaired
pPrader-Willi psynd** pin pchildren+adols; pmore pcomm pperiph ped, pmyalg, parthralg, pCTS
pin padults
- CIs p= pPrader-Willi pw/ pairw pobstr/sleep pap/sev pobes; pactive pmalig/neop, pac pcrit
pillness, pac presp pfail p--> pincr pmort; pactive/sev pdiab pretinop, pclosed pepiph pin ppeds
Clinical pNotes pfor prhGH p- p- pGCs pmay pinhib pgrowth-prom peffs
- concom pandrog, pestrog, pthyr phorm, panab psters pmay paccel pepiph pclos
pcomprom pfinal pheight
- GH ptreat pcrit pill ppts pincr pmort
Examples, pMOA, pIndications pof pRecombinant phuman pIGF-1 p(rhIGF-1) p- pincl
pMecasermin p(increlex, pplain pIGF1) p& pMecasermin prinfabate p(Iplex,
prhIGF1+rhIGFBP-3)
- MOA p= pmimic pIGF1 pphysio pactions
- Indics p= pSQ p2x/d pfor pIGF1 pdef, ppts pnonresp pto pGH p(ie. pGHR pmuts, pGH pABs)
Description p& pTreatment pOptions pfor pExcess pGH p(hyperpituitarism) p-
pacromeg/gigantism pby pincr pGH pand/or pGH-secr ppit padeno
- Nonpharm p= ptransphen psrug presec pGH-secr padeno p(rare pcomplics pCSF pleak,
pmening, parachnoiditis, pDI, ppit pfail), prad pther pfor ppoor psurg pcandids, pfail
psurg/med pther presp
- Pharm p= pSomatostatin pAnalogs p(ocreotide, planreotide, ppasireotide), pGHR
pAntag p(pegvisomant), pDopa pAgs p(bromocriptine, pcabergoline) pfor psurg/rad
pCI, ppoor psurg psuccess plikelihood, prap psx pcontrol, pther pfail
Categories p& pExamples pof pGH pAntagonists pfor pGH pExcess p- p- pSomatostatin
panalogs p(somato pR pligs) p= pOcreotide, pOcreotide pLAR p(long-ac prel), pLanreotide,
pPasireotide
- GH-R pantag p= pPegvisomant
- Dopa pags p= pBromocriptine, pCabergoline
Examples, pMOA, pIndications pof pSomatostatin pRec pLigands p(SRL) p- pincl pOcreotide,
pOcreotide pLAR p(long-ac prel), pLanreotide, pPasireotide
- MOA p= p-GH prel p(same pas pendog psomatost)
- Admin p= pSQ pOcreo pq8h, pIM pOcreo pLAR pq28d p(1mt pIM pdose), pdeep pSQ
pLanreo pDepot pq28d
- Indics p= pOcreo p1st pline pfor pacromeg, palso pcarcinoid psynd, pVIPoma, pesoph
pvarices; pLanreo p1st pline pfor pacromeg
AEs, pAdvantages, pDisadvantages, pClinical pNotes pfor pSRLs p- p- pAEs p= pGI pn/d, pabd
pcramp, pflatul, psteat; pinjec psite pp; pgallst pw/ plong-term; pbradyarrhyth
- Adv p= pgood p@ pdecr pGH, pnormalizing pIGF1 pmost ppts
- Disad p= pcost, pweekly pIM/deep pSQ pinjec
- Notes p= psuppr pGH, pnormaliz pIGF1 p(might pbe psecondarily pelev pb/c pGH pincr), psx
pcontrol
MOA, pIndications, pAEs, pAdvantages, pDisadvantages pof pPegvisomant pfor pGH
pExcess p- p- pMOA p= pdaily pSQ pGH-R pantag pnormaliz pIGF1 plevels; pmodif pGH
,B6 Pharm Exam 1 (Lectures 1-7)
pblocking pactual pGH pbinding pto prec
, B6 Pharm Exam 1 (Lectures 1-7)
- Indics p= p2nd pline pfor pacromeg pin pfail pIGF1 preduction pw/ pSRL
- AEs p= pinjec psite pp, pGI pn/d, pelev phep paminotransf plevels p(LFTs pto pbreakdown
pGH pnot pbinding prec panymore)
- Adv p= pvery peffec pIGF1 pred
- Disad p= pexpensive, pLT peffic+safety pnot pdet
- Notes p= pMONITOR pb/c pdoesn't pred pGH, pnormaliz pIGF1, psx pcontrol, phep pfunc ptests
Examples, pMOA, pIndications pof pDopamine pAgonists pfor pGH pExcess p- pincl pBromocrip
p& pCabergoline
- MOA p= pD2 pR pantag pw/ pnon-sel pbromo, plong-acting pselec pcaberg; p**paradox
pdecr pGH pprod pin pacromeg**
- Indics p= p2nd pline pfor pacromeg p(Caberg pover pBromo); phyperprolactinemia p(esp
pBromo)
AE, pCI, pDI, pAdvantages pof pDopamine pAgonists pfor pGH pExcess p- p- pAE p= pGI
pupset pso ptake pw/ pfood, portho phypoTN
- CI p= puncontr pHTN; pbreastfeed, psync pmigr pw/ pbromo; pcard
pvalv pdis, ppulm/pericard/retroperit pfibr pdisords pw/ pcaberg
- DI p= p**bromo pw/ pantimigr pTriptans p--> p+prol pvasospastic prxns pby pfurther
pnarrowing pcer pBVs**
- Adv p= pcost pcheaper pthan pSRLs, pPO padmin
ACTH pSynthesis p& pRelease p- p- psynth pby pant ppit pcorticotropes pw/ p10mins pcirc
pt1/2 p(short pacting)
- pulsat prel ppeaking pin pmorning
Difference pb/w pPeptide p& pSteroid pHormone pBinding pand pAction p- p- pPep phorms
pbind prec palready psynth+expr pon pcell psurf pfor pquick prapid paction
- Steroid phorms pbind pintracell/nucl prec pto pincr pDNA ptranscr+prot psynth pas pTFs pfor
pslower paction pbut psust peff
Results pof pAdrenal pHyperactivation p(Cushing psynd) p- p- pz pglom p--> p+aldost p-->
pdecr pK+&H+ pcausing phypokal+metab palk, phigh pNa+, phigh pBP
- z pfasc p--> p+cort p--> pincr pgluc pfor phypergly
- z pretic p--> p+androg/testost p--> phigh ptestost pcausing pviriliz+hirsut pin pfemales
Results pof pAdrenal pHypoactivation p(Addison's pdis) p- p- pz pglom p--> p-aldost p--> pincr
pK+&H+ pfor phyperkal+metab pacid, phyponat, plow pBP
- z pfasc p--> p-cort pfor pdecr pgluc+hypogly
- z pretic p--> p-androg p--> pdecr psex pdrive
Physiological pEffects pof pMineralocorticoids p- p- pNa+ pabs preg pin pkid, pcol, psw+saliv pgl
- aldost p--> p+Na pret, pK+ pexcr pby pincr pENaC papic pmemb p& pNa/K pATPase pbasolat
pmemb pin pkid pcoll pd
Aldosterone pRegulation p- p- p+by pincr pK+ p& pAngiotensin
- min p+ pby pACTH
Adenohypophyseal Physio - - 3 func anat components = hypoth, adenohypophysis (ant
pit), periph endoc gl/tiss
- hypoth secr 2 horm types to hypoth-hypoph port sys in med emin = rel horms (RH,
liberins) & rel-inhib horms (IH, statins)
w/ hypoth-hypoph port sys carrying horms to ant pit
Synthesis & Regulation of Growth Hormone (GH, somatotropin) - - synth by ant pit
somatotropes (30-40% ant pit c)
- +by hypoth GHRH & Dopa
- -by GH, IGF-1, hypoth GHIH/somatostatin
Receptor, Target Organs, Peripheral Hormone Released by GH - -GH-r = tyr kin-assoc
R, memb JAK/STAT superfam
- Targets = liv, bone, musc, adip, kidney
- Periph horm = IGF-1
Physiologic & Pharmacologic Stimulation of GH - - Physio = GHRH, ghrelin, ADH,
GABA, NE, Dopa, serot, estrog, sleep, stress, exerc
- Pharm = alpha-ag, BB, Dopa ags (ie. Bromocriptine), GABA ag
Physiologic & Pharmacologic Inhibition of GH - - Physio = somatostatin, elev IGF-1, GH,
progest, GCs, postprand hypergly, elev FFAs
- Pharm = Dopa antag, alpha antag, beta ag, serot antag
General Effects of GH p- p(+) pvisc+sk pgrowth, plipolysis, pprot psynth, pIGF-1 pprod p-->
psuppr pliv pgluc pprod, pincr pperiph pgluc putil, pinhib pinsul psecr
(-) pinsul psensit p--> phypergly
Features pof pGH pDeficiency p(hypopituitarism) pin pChildren p& pAdults p- p- pChildren p&
padols p= pcongen/acq pdef p--> pgrowth pstunt, pdwarf, p+fat-musc pmass pratio, phypogly
pby punopp pinsul
- Adult p= p-lean pbod pmass, p+body pfat pto pobes, p-musc pmass, pasthenia p(phys
pweak), p-BMD, pdyslip, p-CO
Examples, pMOA, pAdministration, pPK pof pRecombinant phuman pGH p(rhGH) p- pincl
pSomatrem p(protropin) p& pSomatropin p(10 pdiff pbrand pnames)
- MOA p= pmimic pGH pphysio pactions
- Admin p= p6-7x/wk
- PK p= ppeak ppl plevs p2-4hrs pw/ p36hr ppersis
- Route p= pIM p& pSQ, pmust pbe pinjec pb/c pis pprot p& pnot pabs porally
Indications pfor prhGH p- p- pChildren p& pAdols p= pidiop pshort pstat p(ISS); p**many
pgrowth pfail pindics pNOT passoc pw/ pGH pdef**
- Adults p= pAIDS-assoc pwasting psynd p(cachex); pUNSUBST pfor p"anti-aging" por
pathletic pperf penh
,B6 Pharm Exam 1 (Lectures 1-7)
AEs p& pCIs pfor prhGH p- p- pAEs p= prare ppseudotum pcerebri p(idiop pintracran pHTN),
pslipped pcap pfem pepiph, phypergly, pDM, p**asphyx pin psev pobese/resp pimpaired
pPrader-Willi psynd** pin pchildren+adols; pmore pcomm pperiph ped, pmyalg, parthralg, pCTS
pin padults
- CIs p= pPrader-Willi pw/ pairw pobstr/sleep pap/sev pobes; pactive pmalig/neop, pac pcrit
pillness, pac presp pfail p--> pincr pmort; pactive/sev pdiab pretinop, pclosed pepiph pin ppeds
Clinical pNotes pfor prhGH p- p- pGCs pmay pinhib pgrowth-prom peffs
- concom pandrog, pestrog, pthyr phorm, panab psters pmay paccel pepiph pclos
pcomprom pfinal pheight
- GH ptreat pcrit pill ppts pincr pmort
Examples, pMOA, pIndications pof pRecombinant phuman pIGF-1 p(rhIGF-1) p- pincl
pMecasermin p(increlex, pplain pIGF1) p& pMecasermin prinfabate p(Iplex,
prhIGF1+rhIGFBP-3)
- MOA p= pmimic pIGF1 pphysio pactions
- Indics p= pSQ p2x/d pfor pIGF1 pdef, ppts pnonresp pto pGH p(ie. pGHR pmuts, pGH pABs)
Description p& pTreatment pOptions pfor pExcess pGH p(hyperpituitarism) p-
pacromeg/gigantism pby pincr pGH pand/or pGH-secr ppit padeno
- Nonpharm p= ptransphen psrug presec pGH-secr padeno p(rare pcomplics pCSF pleak,
pmening, parachnoiditis, pDI, ppit pfail), prad pther pfor ppoor psurg pcandids, pfail
psurg/med pther presp
- Pharm p= pSomatostatin pAnalogs p(ocreotide, planreotide, ppasireotide), pGHR
pAntag p(pegvisomant), pDopa pAgs p(bromocriptine, pcabergoline) pfor psurg/rad
pCI, ppoor psurg psuccess plikelihood, prap psx pcontrol, pther pfail
Categories p& pExamples pof pGH pAntagonists pfor pGH pExcess p- p- pSomatostatin
panalogs p(somato pR pligs) p= pOcreotide, pOcreotide pLAR p(long-ac prel), pLanreotide,
pPasireotide
- GH-R pantag p= pPegvisomant
- Dopa pags p= pBromocriptine, pCabergoline
Examples, pMOA, pIndications pof pSomatostatin pRec pLigands p(SRL) p- pincl pOcreotide,
pOcreotide pLAR p(long-ac prel), pLanreotide, pPasireotide
- MOA p= p-GH prel p(same pas pendog psomatost)
- Admin p= pSQ pOcreo pq8h, pIM pOcreo pLAR pq28d p(1mt pIM pdose), pdeep pSQ
pLanreo pDepot pq28d
- Indics p= pOcreo p1st pline pfor pacromeg, palso pcarcinoid psynd, pVIPoma, pesoph
pvarices; pLanreo p1st pline pfor pacromeg
AEs, pAdvantages, pDisadvantages, pClinical pNotes pfor pSRLs p- p- pAEs p= pGI pn/d, pabd
pcramp, pflatul, psteat; pinjec psite pp; pgallst pw/ plong-term; pbradyarrhyth
- Adv p= pgood p@ pdecr pGH, pnormalizing pIGF1 pmost ppts
- Disad p= pcost, pweekly pIM/deep pSQ pinjec
- Notes p= psuppr pGH, pnormaliz pIGF1 p(might pbe psecondarily pelev pb/c pGH pincr), psx
pcontrol
MOA, pIndications, pAEs, pAdvantages, pDisadvantages pof pPegvisomant pfor pGH
pExcess p- p- pMOA p= pdaily pSQ pGH-R pantag pnormaliz pIGF1 plevels; pmodif pGH
,B6 Pharm Exam 1 (Lectures 1-7)
pblocking pactual pGH pbinding pto prec
, B6 Pharm Exam 1 (Lectures 1-7)
- Indics p= p2nd pline pfor pacromeg pin pfail pIGF1 preduction pw/ pSRL
- AEs p= pinjec psite pp, pGI pn/d, pelev phep paminotransf plevels p(LFTs pto pbreakdown
pGH pnot pbinding prec panymore)
- Adv p= pvery peffec pIGF1 pred
- Disad p= pexpensive, pLT peffic+safety pnot pdet
- Notes p= pMONITOR pb/c pdoesn't pred pGH, pnormaliz pIGF1, psx pcontrol, phep pfunc ptests
Examples, pMOA, pIndications pof pDopamine pAgonists pfor pGH pExcess p- pincl pBromocrip
p& pCabergoline
- MOA p= pD2 pR pantag pw/ pnon-sel pbromo, plong-acting pselec pcaberg; p**paradox
pdecr pGH pprod pin pacromeg**
- Indics p= p2nd pline pfor pacromeg p(Caberg pover pBromo); phyperprolactinemia p(esp
pBromo)
AE, pCI, pDI, pAdvantages pof pDopamine pAgonists pfor pGH pExcess p- p- pAE p= pGI
pupset pso ptake pw/ pfood, portho phypoTN
- CI p= puncontr pHTN; pbreastfeed, psync pmigr pw/ pbromo; pcard
pvalv pdis, ppulm/pericard/retroperit pfibr pdisords pw/ pcaberg
- DI p= p**bromo pw/ pantimigr pTriptans p--> p+prol pvasospastic prxns pby pfurther
pnarrowing pcer pBVs**
- Adv p= pcost pcheaper pthan pSRLs, pPO padmin
ACTH pSynthesis p& pRelease p- p- psynth pby pant ppit pcorticotropes pw/ p10mins pcirc
pt1/2 p(short pacting)
- pulsat prel ppeaking pin pmorning
Difference pb/w pPeptide p& pSteroid pHormone pBinding pand pAction p- p- pPep phorms
pbind prec palready psynth+expr pon pcell psurf pfor pquick prapid paction
- Steroid phorms pbind pintracell/nucl prec pto pincr pDNA ptranscr+prot psynth pas pTFs pfor
pslower paction pbut psust peff
Results pof pAdrenal pHyperactivation p(Cushing psynd) p- p- pz pglom p--> p+aldost p-->
pdecr pK+&H+ pcausing phypokal+metab palk, phigh pNa+, phigh pBP
- z pfasc p--> p+cort p--> pincr pgluc pfor phypergly
- z pretic p--> p+androg/testost p--> phigh ptestost pcausing pviriliz+hirsut pin pfemales
Results pof pAdrenal pHypoactivation p(Addison's pdis) p- p- pz pglom p--> p-aldost p--> pincr
pK+&H+ pfor phyperkal+metab pacid, phyponat, plow pBP
- z pfasc p--> p-cort pfor pdecr pgluc+hypogly
- z pretic p--> p-androg p--> pdecr psex pdrive
Physiological pEffects pof pMineralocorticoids p- p- pNa+ pabs preg pin pkid, pcol, psw+saliv pgl
- aldost p--> p+Na pret, pK+ pexcr pby pincr pENaC papic pmemb p& pNa/K pATPase pbasolat
pmemb pin pkid pcoll pd
Aldosterone pRegulation p- p- p+by pincr pK+ p& pAngiotensin
- min p+ pby pACTH
