NR 565 MIDTERM QUESTIONS AND
ANSWERS
G-Protien65coupled65receptors65and65how65they65interact65with65drugs65-65answer--G-
protein65coupled65receptors65(GPCR)65interact65with65drugs65through65765regions65of65pr
oteins65that65span65and65innervate65the65cell65membrane65and65trap65the65molecule65int
o65the65receptor65site65like65an65interwoven65basket65(Insel65&65Sriram,652018).65Drugs6
5can65then65enter65this65space65and65interact65with65the65GRCP.65A65specific65interactio
n65and65binding65with65a65site65on65one65or65more65of65the65regions65of65proteins65within
65the65GPCR,65and65drugs65bound65with65the65GRCP65can65stimulate65the65release65of6
5G65proteins65that65can65interact65with65various65effector65proteins65to65create65physiolo
gical65responses65within65the65body65(Insel65&65Sriram,652018).65This65process65occurs6
5through65secondary65messengers65(such65as65cAMP)65which65creates65the65extracellul
ar65interactions65produced65by65the65drug65binding65to65the65GRCP.
What65neurotransmitters65are65excitatory?65-65answer--
amino65acids65such65as65glycine,65aspartate,65and65glutamate65are65excitatory65(Woo65
&65Robinson,65p.16,652016).
Which65is65the65most65common65CYP65enzyme65in65the65body?
65What65role65does65it65play?65-65answer--
According65to65the65textbook,65the65CYP3A465is65the65most65important65enzyme65in65the
65body.65CYP3A465is65responsible65for65the65metabolism65of65more65than6550%65of65me
dications65and65is65considered65a65major65drug65metabolizing65enzyme.65CYP3A465can6
5be65found65in65the65liver,65as65well65as65the65lining65of65the65GI65tract.65Due65to65this65lo
cation,65food65can65also65influence65this65CYP.65One65example65of65this65is65grapefruit65
juice,65which65can65inhibit65CYP3A4.65Medications65that65are65metabolized65by65CYP3A
465include65antimicrobials,65calcium65channel65blockers,65antihistamines,65anticonvulsan
ts,65azole65antifungals,65and65corticosteroids65(Woo,65&65Robinson,652016).
What65is65the65clinical65significance65of65being65an65ultra-rapid65CYP2D665metabolizer?
65-65answer--People65who65are65ultra-
rapid65metabolizers65have65high65activity65of65CYP2D665enzymes65that65break65down65c
ertain65medicines65rapidly65and65are65likely65to65need65different65doses65or65even65a65dif
ferent65medicine.65Drug65dose,65response,65and65toxicity65risk65of65beta-
blockers,65antidepressants,65antiarrhythmics,65and65opioid65analgesics65are65dependent
65on65CYP2D665pharmacogenetics65(Ayazseven65et65al.,652020).65Knowing65the65result6
5of65the65CYP2D665test65and65which65group65the65patient65falls65into65such65as65poor65
, metabolizers,65intermediate65metabolizers,65or65ultra-
rapid65metabolizers,65will65help65nurse65practitioners65prescribe65the65right65medication6
5and65dosage65for65the65patient.
What65would65be65the65concern65if65a65drug65is65a65CYP450indicer?
65How65that65might65affect65the65metabolism65of65another65drug65the65patient65is65taking
?65-65answer--
Cytochrome65P45065enzymes65are65in65cells65throughout65the65body,65primarily65found6
5in65liver65cells65(Girvan65&65Munro,652016).65These65enzymes65are65essential65for65the6
5metabolism65of65many65medications.65Cytochrome65P45065enzymes65can65act65as65an
65inducer65or65inhibitor65of65metabolism.65When65a65medication65induces65the65CYP4506
5enzyme65that65increases65the65rate65of65metabolism65(Girvan65&65Munro,652016).65This
65can65impact65the65effectiveness65of65other65medications.65For65example,65medication6
5A65induces65CYP45065enzyme65activity,65therefore65medication65B65will65be65metaboliz
ed65quicker65and65have65a65less65therapeutic65effect.
Explain65the65significance65of65a65drug65being65an65inhibitor65of65P-glycoprotein?
65(see65text)65-65answer--P-glycoprotein65(P-
gp)65is65the65main65barrier65of65the65body65and65it65affects65the65proper65delivery65of65dr
ugs65and65causes65drug65resistance65in65our65body.65P-
gp65is65an65efflux65membrane65transporter,65that65can65be65found65throughout65the65bod
y65and65it65controls65the65cellular65uptake65and65the65distribution65of65synthetic65substan
ces,65chemicals,65and65toxins.65Drugs65are65chemicals65and65P-
gp65hinders65the65absorption,65permeability,65and65retention65of65the65drugs,65extruding6
5them65out65of65the65cells.65This65adversely65affects65drug65therapies65and65fails65to65yie
ld65good65results,65for65example65in65therapies65like65using65chemo65agents65in65cancer
65treatments.65In65this65case,65proper65inhibition65of65P-
gp65is65important65to65increase65cellular65uptake,65transport,65and65half-
lives65of65drugs.65The65drug65is65an65inhibitor65of65P-
gp65that65would65help65in65the65cost-
effective65treatment65for65disease65conditions65without65wasting65an65extra65amount65of6
5medicines.65It65will65help65to65shorten65the65treatment65time65and65speedy65recovery65o
f65the65patient65(Abebe65et65al.,652019;65Woo65&65Robinson,652016).
Significance65of65a65VCORC165mutation65for65patients65taking65warfarin?65-65answer--
In652008,65the65U.S65Food65and65Drug65Administration65updated65the65dosing65of65warfa
rin65to65include65the65application65of65pharmacogenomics.65Variable65metabolism65by65
CYP2C965was65once65known65as65the65major65contributor65to65the65variable65response6
5to65warfarin.65However,65a65mutation65in65VCORC165has65been65found65to65account65f
or65much65more65variability65in65warfarin65responses65and65can65cause65a65rare65syndro
me65of65warfarin65resistance.65A65mutation65in65VCORC165encodes65a65subunit65of65the
65vitamin65K65epoxide65reductase65complex65,the65pharmacological65target65for65warfari
n,65and65increases65the65chances65of65uncontrolled65bleeding65(Woo65&65Robinson,6520
16).65Therefore,65if65providers65have65information65about65the65presence65of65this65muta
tion,65they65may65decide65to65decrease65the65dosage65of65Coumadin65for65their65patient.
ANSWERS
G-Protien65coupled65receptors65and65how65they65interact65with65drugs65-65answer--G-
protein65coupled65receptors65(GPCR)65interact65with65drugs65through65765regions65of65pr
oteins65that65span65and65innervate65the65cell65membrane65and65trap65the65molecule65int
o65the65receptor65site65like65an65interwoven65basket65(Insel65&65Sriram,652018).65Drugs6
5can65then65enter65this65space65and65interact65with65the65GRCP.65A65specific65interactio
n65and65binding65with65a65site65on65one65or65more65of65the65regions65of65proteins65within
65the65GPCR,65and65drugs65bound65with65the65GRCP65can65stimulate65the65release65of6
5G65proteins65that65can65interact65with65various65effector65proteins65to65create65physiolo
gical65responses65within65the65body65(Insel65&65Sriram,652018).65This65process65occurs6
5through65secondary65messengers65(such65as65cAMP)65which65creates65the65extracellul
ar65interactions65produced65by65the65drug65binding65to65the65GRCP.
What65neurotransmitters65are65excitatory?65-65answer--
amino65acids65such65as65glycine,65aspartate,65and65glutamate65are65excitatory65(Woo65
&65Robinson,65p.16,652016).
Which65is65the65most65common65CYP65enzyme65in65the65body?
65What65role65does65it65play?65-65answer--
According65to65the65textbook,65the65CYP3A465is65the65most65important65enzyme65in65the
65body.65CYP3A465is65responsible65for65the65metabolism65of65more65than6550%65of65me
dications65and65is65considered65a65major65drug65metabolizing65enzyme.65CYP3A465can6
5be65found65in65the65liver,65as65well65as65the65lining65of65the65GI65tract.65Due65to65this65lo
cation,65food65can65also65influence65this65CYP.65One65example65of65this65is65grapefruit65
juice,65which65can65inhibit65CYP3A4.65Medications65that65are65metabolized65by65CYP3A
465include65antimicrobials,65calcium65channel65blockers,65antihistamines,65anticonvulsan
ts,65azole65antifungals,65and65corticosteroids65(Woo,65&65Robinson,652016).
What65is65the65clinical65significance65of65being65an65ultra-rapid65CYP2D665metabolizer?
65-65answer--People65who65are65ultra-
rapid65metabolizers65have65high65activity65of65CYP2D665enzymes65that65break65down65c
ertain65medicines65rapidly65and65are65likely65to65need65different65doses65or65even65a65dif
ferent65medicine.65Drug65dose,65response,65and65toxicity65risk65of65beta-
blockers,65antidepressants,65antiarrhythmics,65and65opioid65analgesics65are65dependent
65on65CYP2D665pharmacogenetics65(Ayazseven65et65al.,652020).65Knowing65the65result6
5of65the65CYP2D665test65and65which65group65the65patient65falls65into65such65as65poor65
, metabolizers,65intermediate65metabolizers,65or65ultra-
rapid65metabolizers,65will65help65nurse65practitioners65prescribe65the65right65medication6
5and65dosage65for65the65patient.
What65would65be65the65concern65if65a65drug65is65a65CYP450indicer?
65How65that65might65affect65the65metabolism65of65another65drug65the65patient65is65taking
?65-65answer--
Cytochrome65P45065enzymes65are65in65cells65throughout65the65body,65primarily65found6
5in65liver65cells65(Girvan65&65Munro,652016).65These65enzymes65are65essential65for65the6
5metabolism65of65many65medications.65Cytochrome65P45065enzymes65can65act65as65an
65inducer65or65inhibitor65of65metabolism.65When65a65medication65induces65the65CYP4506
5enzyme65that65increases65the65rate65of65metabolism65(Girvan65&65Munro,652016).65This
65can65impact65the65effectiveness65of65other65medications.65For65example,65medication6
5A65induces65CYP45065enzyme65activity,65therefore65medication65B65will65be65metaboliz
ed65quicker65and65have65a65less65therapeutic65effect.
Explain65the65significance65of65a65drug65being65an65inhibitor65of65P-glycoprotein?
65(see65text)65-65answer--P-glycoprotein65(P-
gp)65is65the65main65barrier65of65the65body65and65it65affects65the65proper65delivery65of65dr
ugs65and65causes65drug65resistance65in65our65body.65P-
gp65is65an65efflux65membrane65transporter,65that65can65be65found65throughout65the65bod
y65and65it65controls65the65cellular65uptake65and65the65distribution65of65synthetic65substan
ces,65chemicals,65and65toxins.65Drugs65are65chemicals65and65P-
gp65hinders65the65absorption,65permeability,65and65retention65of65the65drugs,65extruding6
5them65out65of65the65cells.65This65adversely65affects65drug65therapies65and65fails65to65yie
ld65good65results,65for65example65in65therapies65like65using65chemo65agents65in65cancer
65treatments.65In65this65case,65proper65inhibition65of65P-
gp65is65important65to65increase65cellular65uptake,65transport,65and65half-
lives65of65drugs.65The65drug65is65an65inhibitor65of65P-
gp65that65would65help65in65the65cost-
effective65treatment65for65disease65conditions65without65wasting65an65extra65amount65of6
5medicines.65It65will65help65to65shorten65the65treatment65time65and65speedy65recovery65o
f65the65patient65(Abebe65et65al.,652019;65Woo65&65Robinson,652016).
Significance65of65a65VCORC165mutation65for65patients65taking65warfarin?65-65answer--
In652008,65the65U.S65Food65and65Drug65Administration65updated65the65dosing65of65warfa
rin65to65include65the65application65of65pharmacogenomics.65Variable65metabolism65by65
CYP2C965was65once65known65as65the65major65contributor65to65the65variable65response6
5to65warfarin.65However,65a65mutation65in65VCORC165has65been65found65to65account65f
or65much65more65variability65in65warfarin65responses65and65can65cause65a65rare65syndro
me65of65warfarin65resistance.65A65mutation65in65VCORC165encodes65a65subunit65of65the
65vitamin65K65epoxide65reductase65complex65,the65pharmacological65target65for65warfari
n,65and65increases65the65chances65of65uncontrolled65bleeding65(Woo65&65Robinson,6520
16).65Therefore,65if65providers65have65information65about65the65presence65of65this65muta
tion,65they65may65decide65to65decrease65the65dosage65of65Coumadin65for65their65patient.
