TY  - CHAP
M1  - Book, Section
TI  - Pulmonary Arterial Hypertension
A1  - Moote, Rebecca
A1  - Attridge, Rebecca L.
A1  - Levine, Deborah J.
A2  - DiPiro, Joseph T.
A2  - Talbert, Robert L.
A2  - Yee, Gary C.
A2  - Matzke, Gary R.
A2  - Wells, Barbara G.
A2  - Posey, L. Michael
PY  - 2017
T2  - Pharmacotherapy: A Pathophysiologic Approach, 10e
AB  - KEY  CONCEPTS  Pulmonary  arterial  hypertension  (PAH)  is  defined  as  a  mean  pulmonary  artery  pressure  (mPAP)  more  than  or  equal  to  25  mm  Hg  at  rest  with  a  pulmonary  wedge  pressure  or  left  ventricular  end-diastolic  pressure  (LVEDP)  less  than  or  equal  to  15  mm  Hg  and  a  pulmonary  vascular  resistance  (PVR)  more  than  3  Wood  units  (WU)  measured  by  right  cardiac  catheterization.  Diagnosis  of  PAH  is  growing  because  of  increased  awareness  and  knowledge  of  the  disease  state,  leading  to  earlier  and  improved  evaluation  and  identification.  Regardless  of  the  etiology,  be  it  unknown  or  related  to  an  associated  medical  condition,  subgroups  of  PAH  are  based  on  similar  clinical  and  pathologic  physiology.  The  underlying  cause  of  PAH  is  a  complicated  amalgam  of  endothelial  cell  dysfunction,  a  procoagulant  state,  platelet  activation,  vasoconstriction,  loss  of  relaxing  factors,  cellular  proliferation,  hypertrophy,  fibrosis,  and  inflammation.  Patients  with  PAH  present  with  exertional  dyspnea,  fatigue,  weakness,  and  exertion  intolerance.  As  the  disease  progresses,  symptoms  of  right  heart  dysfunction  and  failure,  such  as  dyspnea  at  rest,  lower  extremity  edema,  chest  pain,  and  syncope,  are  seen.  The  only  way  to  make  a  definitive  diagnosis  of  PAH  is  by  right  heart  catheterization.  The  right  heart  catheterization  provides  important  prognostic  information  and  can  be  used  to  assess  pulmonary  vasoreactivity  prior  to  initiating  therapy.  The  goals  of  treatment  are  to  alleviate  symptoms,  improve  the  quality  of  life,  slow  the  progression  of  the  disease,  and  improve  survival.  A  general  goal  of  PAH  treatment  is  to  correct  the  imbalance  between  vasoconstriction  and  vasodilation  and  prevent  adverse  thrombotic  events  to  improve  oxygenation,  functional  class,  exercise  capacity,  and  quality  of  life.  Nonpharmacologic  therapy  is  frequently  used  to  address  comorbid  conditions  that  often  accompany  PAH.  Conventional  therapy  of  PAH  includes  oral  anticoagulants,  diuretics,  oxygen,  and  digoxin.  Prostacyclin  analogs  such  as  epoprostenol,  treprostinil,  and  iloprost  induce  potent  vasodilation  of  pulmonary  vascular  beds.  Only  epoprostenol  has  demonstrated  improved  survival.  Endothelin  receptor  antagonists,  bosentan,  ambrisentan  and  macitentan,  improve  exercise  capacity,  hemodynamics,  and  functional  class  in  PAH.  Macitentan  also  significantly  decreases  the  composite  end  point  of  events  related  to  PAH  or  death.  Phosphodiesterase-5  inhibitors,  including  sildenafil  and  tadalafil,  are  potent  and  highly  specific  drugs  that  have  been  shown  to  reduce  mPAP  and  improve  functional  class.  Riociguat  is  a  novel  soluble  guanylate  cyclase  stimulator  shown  to  improve  exercise  capacity,  hemodynamic  parameters,  and  functional  class.  Calcium  channel  blockers  may  be  considered  in  a  small  number  of  patients  who  have  a  positive  response  on  acute  vasoreactivity  testing.  Combination  therapy  in  PAH  may  address  more  than  one  mechanism  causing  this  disease.  Combination  therapy  may  be  initiated  sequentially  or  as  the  initial  regimen  in  patients  with  worse  functional  classes.  Recent  evidence  demonstrated  that  initial  combination  therapy  was  associated  with  a  significant  reduction  in  time  to  clinical  failure  and  PAH  hospitalizations.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/20
UR  - accesspharmacy.mhmedical.com/content.aspx?aid=1145180553
ER  -