Research J. Pharm. and Tech. 1(4): Oct.-Dec.

2008,
,

www.rjptonline.org

ISSN 0974-3618

REVIEW ARTICLE

Nocturia: Prevalence and Therapeutic Strategies

Ravindra Pandey1, Vishal Jain1, Amber Vyas1, SS Shukla1 and Tripti Jain2
1

Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur C.G

Rungata Institute of Pharmaceutical Sciences and Research, Bhilai C.G.
*Corresponding Author E-mail: ravindraiop@gmail.com

ABSTRACT:
Nocturia, is the most troublesome lower urinary tract symptoms Nocturia affects the patients by various ways with respect
to quality of life, sleep patterns and increased mortality. Overproduction of urine at night time is the main cause of
Nocturia because of the decreased secretion of anti-diuretic hormone (arginine vasopressin) also called (AVP).various
treatment available for the treatment of nocturia such as anticholinergics and vasopressin analogues. Desmopressin is a
synthetic replacement for anti-diuretic hormone, the hormone that reduces urine production during sleep. It may be taken
nasally, intravenously or as a pill.
KEY WORDS : Nocturia, Overproduction of urine at night

INTRODUCTION:
Nocturia, defined as awaking to void during the night1,
is the most troublesome lower urinary tract symptoms
(LUTS) 2, 3. The incidence increases with age.4 It has
been shown to rise from 30% to 60% in a population
with mean age of 49 years to 60% to 90% in a
population aged 60 to 80 years.5 In woman these
symptoms are often considered to result from aging,
childbirth or just being a woman6. Nocturia affects
the patients by various ways with respect to quality of
life, sleep patterns, and increased mortality 7.
Pathological categories
There are three categories for nocturia i.e. nocturnal
poly uria, low nocturnal bladder capacity or a
combination of nocturnal polyuria and low functional
bladder capacity. Overproduction of urine at night time
is the main cause of nocturia.because of the decreased
secretion
of
antidiuretic
hormone
(arginine
vasopressin) also called (AVP) 8,9.
Nocturia is not a trivial complaint and can affect
several aspects of a patients state of health. Even
rising once-nightly to void is bothersome for many
people. The standardization committee of the
international continence society (ICS) is currently
developing a world wide definition of nocturia and
comprehensive framework to improve the diagnosis
and treatment of this condition.

Received on 12.11.2008
Accepted on 15.12.2008

Modified on 10.12.2008
RJPT All right reserved

Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008;Page 324-327

Multifactorial Etiology of Nocturia-

The production of urine by the kidney follows a circadian

rhythm that changes with age in early childhood, when the
pattern is developing, diurnal urine production in 3 times the
nocturnal volume. This circadian rhythm is well established
by the age of 7 years and by adulthood, nighttime urine
production comprises just 25% of the total daily amount.
Pathological
condition
causing
nocturia
include
cardiovascular disease, diabetes mellitus and insipidus,
lower urinary tract obstruction to void for other reason, such
as anxiety or primary sleep disorders5.

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Behavioral and environmental factors contributing to

nocturia include consumption of diuretic medication,
caffeine, alcohol or excessive fluid shortly before
retiring for the night.10 prostatic diseases, and
neurogenic and unstable bladders have been reported to
lead to frequent nocturnal rising.10,12 in addition
,nocturia may result from stroke, congestive heart
failure peripheral edema ( for example due to
venousihsu
efficiency
or
nephrosis)
and
myeloneuropathy secondary to vertebral disk disease or
spondylosis11
Effects of sleep deprivation
Sleep is important for physical and mental well-being.
It is generally through that adults need about 7 to 8
hours sleep per night and that adequate sleep has a
restorative effect. the quality of sleep deteriorates with
increasing age and older adults have shallower and
more fragmented sleep patterns, possibly as a result of
the reduction in growth hormone secretion with age.13
Few physiology changes are seen with sleep loss and
mainly are noted with total asleep as opposed to partial
sleep deprivation, including changes in temperature
regulation, mood status (temporary euphoria in
depressed subjects) and central nervous system
function (paranoia, delusion).14 However, insufficient
or disrupted sleep has commonly been linked with
physical and mental disorders, particularly depression
and mood alteration,15,16 as well excessive daytime
sleepiness leading to poor motivation and job
performance.17

diurnal production of urine. This increased nocturnal

diuresis results in nocturnal urine volume in excess of
bladder capacity, creating the need for night time voiding in
the form of nocturnal enuresis or nocturia.20 Several
definition of nocturnal polyuria have been used, such as
nocturnal urine volume in excess of 6.4 ml/kg.14 or
exceeding a third of the total daily urine output 13 and
nocturnal diuresis 0.9 ml or greater per minute21,22 but none
has achieved widespread acceptance .The preferred
definition is when nocturnal urine volume is more than 35%
of the total 24-hour urine production and we defined the
nocturnal polyuria index as nocturnal urine volume (NUV)
per 24-hour urine greater than 0.35.23 Another precise
definition characterizes nocturnal polyuria according to the
exact number of hours asleep and the fraction of urine
output that would be expected during this time.
Diminished nocturnal bladder capacity
Problems with low nocturnal bladder capacity exist when
nocturnal voiding occurs at bladder volume less than
functional bladder capacity.24 Nocturia index is nocturnal
urine volume /functional bladder capacity, with the first
morning void included in the nocturnal urine volume.
Nocturia index minus 1 equals the predicted number of
nightly voids. The nocturnal bladder capacity index is
defined as the difference between the predicted numbers of
nightly voids (ANV). The significance of this difference is
that the greater the nocturnal bladder capacity index, the
more nocturia may be attributed to diminished nocturnal
bladder capacity and sensory urge disorders.
Th era pe ut ic St rat eg ies
Nocturnal polyuria remediable medical causes of nocturnal
polyuria should be identified and treated but in some cases
nocturia persists and in most clearly identifiable remediable
conditions are not evident. Empirical treatment options
include evening fluid restriction (a form of behavior
modification), timed diuretics, symptomatic treatment
agents.25, 26

M echanis m of Nocturia
Although in many cases nocturia may be caused by
bladder dysfunction (for example inflammation or
prostatic obstruction) or sleep apnea,18 simple
overproduction of urine during the night is another
common etiology.6 There are three broad categories of
pathophysiology which account for nocturia, which
refer to as noctural polyuria, low noctural bladder
capacity and mixed nocturia (a combination of noctural
polyuria and noctural bladder capacity). These
categories are generated through interpretation of a
single 24- hour voiding diary in which each voided
volume is tabulated with corresponding time as to
whether voiding was within hours awake or asleep.
Polyuria defined as 24-hour urine output greater than
2,500 ml19 may cause nocturia through generally
increased urine production when noctural urine output
exceeds functional bladder capacity as it is does with
noctural polyuria. However, polyuria and nocturnal
polyuria are not mutually inclusive.

Elderly patients with nocturia due to bladder instability have

been treated with anti-cholinergic therapy, such as
propantheline, oxybutynin and scopolamine.27,28 These
agents reduce but do not eliminate the number of nocturnal
voids. Side effects include dry mouth, drowsiness, facial
flushing and confusion. Patient diagnosed with sleep
disorders causing or due to nocturia are commonly treated
with hypnotics. Traditionally barbiturates have been used
but due to problems of dependence and tolerance,
benzodiazepines now are more commonly prescribed and
occasionally effective to help some patient resume sleep
after awaking.2 9

Nocturnal polyuria
The nocturnal polyuria syndrome was defined by
asplund as increased urine output during the night.
However, in contrast to diabetes insipidus (when intake
and output are increased), 24-hour urine production
remains normal ,indicating a variation in normal

Anti-cholinergics
Drugs in this category act by blocking the parasympathetic
nerves that control voiding or by exerting a direct
spasmolytic effect on the detrucer muscle of the bladder.
Thus, they target bladder dysfunction rather than imbalance
between nocturnal urine production and bladder capacity.

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Oxybutynin
Oxybutynin is used for the treatment of urinary
frequency, urgency and incontinence, characteristics
features of overactive or irritable bladder. It is
associated with a high incidence of unpleasant side
effects and the dosage needs to be carefully assessed,
particularly in the elderly. Tolterodine- tolterodine is a
bladder- selective agent with similar activity to
oxybutynin. It is equally effective, but better tolerated,
thanoxybutynin in the treatment of overactive bladder.
Tricyclic antidepressants
The mode of action of TCAS in the treatment of
nocturia is unclear due to narrow therapeutic window
and their toxicity following overdose.
Flavoxate hydrochloride
It is a smooth muscle relaxant with antimuscarinic
effects. It is used for symptomatic relief of pain and
urinary frequency associated with inflammatory
disorders of the urinary tract.
Desmopressin
It is a synthetic replacement for anti-diuretic hormone,
the hormone that reduces urine production during
sleep. It may be taken nasally, intravenously, or as a
pill. Doctors prescribe Desmopressin30 most frequently
for treatment of diabetes insipidus or bedwetting.
formula C46H64 N14O12S2, mol.mass 1069.22g/mol.
Desmopressin has also been shown to cause a
significant decrease in nocturnal urinary volumes.31

Vasopressin receptor type 1 (v1)

Vasopressin receptor type 2 (v2)
The v1 receptor mediates the unwanted mediate vasopressin
effects of the hormone and the v2 receptors are responsible
for its anti diuretic properties. Desmopressin is a pure v2
receptor agonist and, therefore does not have the unwanted
pressure activities of vasopressin, but retains the anti
diuretic properties of the natural hormone.
When bound to the v2 receptors in the kidney distal
nephrons, desmopressin increases the permeability of the
collecting ducts and tubules there by enhancing water reabsorption. As a consequence, the extra cellular fluid
becomes more dilute while the urine becomes more
concentrated thereby reducing the volume of urine
produced. Desmopressin provides efficacy and safety in the
Nocturia in women.32

CONCLUSION:
Impact of nocturia on quality of life produces the miserable
incidences. Nocturia is not only detrimental to the quality of
sleep and well being but is also related to increased
mortality and risk of falling at night particularly in the
elderly. Desmopressin significantly prolonged the duration
of sleep until the first nocturnal void, which is an important
indicator of quality of life. There are the various treatments
available for nocturia but safest and proper treatment
according to dug profile is Desmopressin. Because of
mechanism of action related to AVP levels. Other drug
shows its usefulness on other problems like nocturia due to
bladder disorders.

REFERENCES:
Chemistry of Desmopressin
Two structural changes, which increase the stability
and action of desmopressin, distinguish it from
vasopressin deamination p of l-arginin at the molecule
and substitution of L-arginin at position 8 with the
enantiomer d-arginine. The desmopressin molecule is,
therefore polarized with a basic amino acid at position
8 and alipophilic n-terminal31.

Mechanism of Action
Vasopressin receptors found in the kidney, liver, brain,
pituitary gland, aortic smooth muscle and platelets.
These receptor are divided into sub types:

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