Healthcare and Medicine Reference
In-Depth Information
sensitivity  to  opioids. 175   The  limited  PSG  data  available 
indicate that opioids used acutely in young healthy volun-
teers markedly decrease SWS but have no effect on TST 
or wake after sleep onset. 176  REM sleep may be decreased 
with higher doses. 177  In current or former addicts, opioids 
also decrease TST and  increase wake after sleep onset. 178
Subjective quality of  sleep may be  improved, presumably 
because  of  improved  pain  control. 179   Cognitive  and  psy-
chomotor  function  are  impaired,  at  least  initially,  with 
opioids, 173 , 180   but  there  are  no  well-controlled  studies  to 
confirm whether these effects improve over time. Patients 
using  opioids  chronically  do  show  cognitive  impairment, 
but comorbid medical or psychiatric disease may be more 
predictive  of  impairment  than  frequency  or  dose  of 
medication. 181
The most serious adverse effect of opioids is respiratory 
depression,  particularly  during  sleep  or  after  surgery. 
Opioids  act directly on  the brainstem  respiratory  centers 
through  mu  and  delta  receptors  and  at  chemoreceptors 
through mu receptors, resulting in a shift to the right and 
a change in slope of the carbon dioxide response curve. 182
Opioids depress the pontine and medullary centers involved 
in  the  regulation  of  respiratory  rhythmicity,  resulting  in 
increased  respiratory  pauses,  irregular  breathing,  and 
decreased tidal volume. 183  Respiratory depression increases 
with  increase  in  opioid  dose.  Limited  data  suggest  that 
clinically  significant  respiratory  depression  rarely  occurs 
with  standard  opioid  doses  used  acutely  in  healthy  indi-
viduals. 184 , 185   However,  with  chronic  opioid  use,  central 
sleep  apnea  is  common. 186   Individuals  with  pulmonary 
disease  or  obstructive  sleep  apnea  are  at  greater  risk  for 
sustained hypoxemia during  sleep. 187  Concomitant use of 
other  sedatives  including  sleep  aids  increases  the  risk  for 
potentially  fatal  respiratory  depression.  After  surgery, 
individuals with obstructive sleep apnea receiving intrave-
nous  morphine  have  been  shown  to  have  pronounced 
oxygen  desaturation,  paradoxical  breathing,  and  slow 
ventilation. 188
Triptans, which are selective serotonin 1B/1D agonists, 
are  currently  the  primary  treatment  of  acute  migraine. 
Somnolence  is  a  common  side  effect,  but  its  incidence 
varies  among  drugs,  probably  the  result  of  differences  in 
lipophilicity and the presence of active metabolites. Som-
nolence is highest with eletriptan, zolmitriptan, and rizat-
riptan,  all  of  which  are  highly  lipophilic  and  have  active 
metabolites, and lowest with almotriptan, sumatriptan, and 
naratriptan, which have lipophilicity and no active metabo-
lites. 189  There are no PSG or MSLT data or studies evalu-
ating cognition.
Nonsteroidal  antiinflammatory  drugs  (NSAIDs)  may 
affect sleep because they decrease the synthesis of prosta-
glandin D 2 , suppress the normal nocturnal surge in mela-
tonin  synthesis,  and  attenuate  the  normal  nocturnal 
decrease in body temperature. 190  Prostaglandin D 2  increases 
proportionately with increased duration of wake and may 
be involved in sleep initiation. 191  NSAIDs inhibit cyclooxy-
genase  (COX),  blocking  the  synthesis  of  inflammatory 
prostaglandins. The classic NSAIDs  inhibit both COX-1 
(thereby accounting for their gastrointestinal toxicity) and 
COX-2  isoenzymes,  whereas  the  newer  NSAIDs  selec-
tively  inhibit COX-2  (found primarily  in  the CNS,  renal 
cortex, and vas deferens). 192  Limited PSG data are mixed 
and have shown both no effect 193  and decreased sleep efi-
ciency with acutely administered aspirin and ibuprofen in 
healthy  subjects. 190 , 194   In  one  placebo-controlled  study  of 
rheumatoid  arthritis  patients,  tenoxicam  (not  available  in 
the United States) improved clinical symptoms but did not 
affect  PSG  measures. 195   Subjective  reports  suggest  an 
improvement  in  sleep  quality  with  use  of  NSAIDs,  pre-
sumably because of a reduction in pain. Cognitive deficits 
are apparently rare with NSAIDs but may be a problem in 
older adults. 196
OTHER DRUGS
Corticosteroids
Corticosteroids  are  widely  believed  to  disrupt  sleep,  but 
the results of objective studies are inconsistent. Differences 
in  receptor  affinities  between  synthetic  and  endogenous 
corticosteroids,  dosage,  methodological  issues  associated 
with  the  study  of  patient  populations,  and  the  variety  of 
organ  systems  affected  by  corticosteroids  as  well  as  the 
variety  of  side  effects  reported 197   contribute  to  this 
confusion.
In  patient  populations,  corticosteroids  have  frequently 
been  associated  with  sleep  disturbance.  Approximately 
50% of patients treated with prednisone for optic neuritis 
reported  sleep disturbance compared with 20% receiving 
placebo. 198  Patients  taking  prednisone  for  oral  inflamma-
tory ulcerative disease reported a dose-related incidence of 
insomnia  ranging  from 12%  to 71%. 199  Parent  ratings of 
sleep  disturbance  increased when  steroids were  added  to 
the  chemotherapy  regimen  of  children  with  leukemia  or 
other  types of cancer. 200   Insomnia has also been  reported 
more frequently in patients with asthma receiving steroid 
medications. 201   In  addition, numerous  anecdotal  and  case 
reports implicate systemic corticosteroid use in insomnia. 
Behavioral observations of 12 healthy subjects given pred-
nisone  80  mg/day  for  5  days  showed  decreased  sleep  in 
25%  and mild  hypomania  in  67%. 202   Inhaled  glucocorti-
coids do not appear to have the same negative effects, but 
there  have  been  case  reports  of  hyperactivity,  insomnia, 
and psychosis with these drugs as well.
The most  consistent  effect  of  corticosteroids  on PSG-
recorded sleep in normal subjects is a marked decrease in 
REM sleep. 203  Although less consistent, there is good evi-
dence for increased waking during the night with cortisol, 
dexamethasone, and prednisone. Dexamethasone, admin-
istered before bedtime, resulted in increased daytime alert-
ness the next day as measured with MSLT. 204
In a single study evaluating performance in healthy sub-
jects,  prednisone  80  mg/day  given  for  5  days  produced 
increased  frequency  of  errors  of  commission  on  a  verbal 
memory task. 205  Prednisone was associated with decreased 
cognitive functioning  in a study of patients with systemic 
lupus erythematosus. 206
Pseudoephedrine and
Phenylpropanolamine
Pseudoephedrine  and  phenylpropanolamine  share  the 
pharmacologic properties of ephedrine but have less potent 
CNS-stimulating effects. These drugs are used extensively 
as  nasal  decongestants  and  are  available  in  a  variety  of 
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