RT Book, Section
A1 Rollins, Douglas E.
A1 Blumenthal, Donald K.
SR Print(0)
ID 1140224101
T1 Histamine, Bradykinin, and Their Antagonists
T2 Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics
YR 2016
FD 2016
PB McGraw-Hill Education
PP New York, NY
SN 9780071793360-qa
LK accesspharmacy.mhmedical.com/content.aspx?aid=1140224101
RD 2024/04/19
AB CASE  21-1A  24-year-old  woman  has  seasonal  allergies  in  the  summer  due  to  various  pollens  and  grasses.  Her  symptoms  include  a  runny  nose  and  itchy,  watery  eyes.  At  the  beginning  of  the  summer  she  takes  over-the-counter  (OTC)  diphenhydramine  for  relief  of  symptoms.What  is  the  mechanism  of  action  of  diphenhydramine  in  treating  this  patient’s  symptoms?Diphenhydramine  is  a  first-generation  H1-receptor  antagonist.  H1  antagonists  are  most  useful  in  acute  types  of  allergy  that  present  with  symptoms  of  rhinitis,  urticaria,  and  conjunctivitis.  Their  effect  is  confined  to  the  suppression  of  symptoms  attributable  to  the  histamine  released  by  the  antigen-antibody  reaction.  These  drugs  relieve  the  sneezing,  rhinorrhea,  and  itching  of  eyes,  nose,  and  throat.  A  gratifying  response  is  obtained  in  most  patients,  especially  at  the  beginning  of  the  season  when  pollen  counts  are  low;  however,  the  drugs  are  less  effective  when  the  allergens  are  most  abundant,  when  exposure  to  them  is  prolonged,  and  when  nasal  congestion  is  prominent.She  finds  the  diphenhydramine  causes  her  to  be  drowsy.  Why  does  this  agent  cause  drowsiness?The  first-generation  H1  antagonists  can  cross  the  blood-brain  barrier  and  can  both  stimulate  and  depress  the  CNS.  The  most  frequent  side  effect  in  first-generation  H1  antagonists  is  sedation  and  usually  accompanies  therapeutic  doses  of  the  older  H1  antagonists.  Diminished  alertness,  slowed  reaction  times,  and  somnolence  are  common  manifestations  of  the  central  CNS  depression  caused  by  these  agents.  Concurrent  ingestion  of  alcohol  or  other  CNS  depressants  produces  an  additive  effect  that  impairs  motor  skills.  Patients  vary  in  their  susceptibility  and  responses  to  individual  drugs.  The  ethanolamines,  which  include  diphenhydramine,  are  particularly  prone  to  causing  sedation.  Because  of  the  sedation  that  occurs  with  first-generation  antihistamines,  these  drugs  cannot  be  tolerated  or  used  safely  by  many  patients  except  at  bedtime.  Even  then,  patients  may  experience  an  antihistamine  “hangover”  in  the  morning,  resulting  in  sedation  with  or  without  psychomotor  impairment.  CNS  stimulation  occasionally  is  encountered  in  patients  given  conventional  doses  of  first-generation  H1  antagonists;  they  become  restless,  nervous,  and  unable  to  sleep.  Central  excitation  also  is  a  striking  feature  of  overdose,  which  commonly  results  in  convulsions,  particularly  in  infants.  Other  untoward  central  actions  caused  by  first-generation  H1  antagonists  include  dizziness,  tinnitus,  lassitude,  incoordination,  fatigue,  blurred  vision,  diplopia,  euphoria,  nervousness,  insomnia,  and  tremors.What  alternatives  does  she  have  to  treat  her  allergy  symptoms  without  getting  drowsy?The  second-generation  H1  antagonists  (eg,  levocetirizine,  cetirizine,  loratadine,  desloratadine,  fexofenadine)  are  largely  devoid  of  these  side  effects  because  they  do  not  penetrate  the  central  nervous  system  (CNS).  Thus,  they  usually  are  the  drugs  of  choice  for  the  treatment  of  allergic  disorders.She  plans  to  get  pregnant  and  is  concerned  about  whether  she  can  treat  her  allergies  when  she  is  pregnant.  What  are  her  options?Caution  should  be  used  in  treating  pregnant  or  lactating  women  with  certain  H1  antihistamines,  especially  first-generation  drugs,  because  of  their  possible  teratogenic  effects  or  symptomatic  effects  on  infants  resulting  from  secretion  of  the  drug  into  breast  milk.  Cetirizine  and  loratadine  are  preferred  if  H1  antihistamines  are  required,  but  if  they  are  not  effective,  diphenhydramine  can  be  used  safely  in  pregnant  (but  not  breast-feeding)  women.