GAMMA-HYDROXYBUTYRATE
What's the latest in gamma-hydroxybutyrate (GHB) use and abuse, also known as
the "date-rape drug"?
MONTELUKAST HELPFUL IN HARD-TO-CONTROL ASTHMA
Montelukast may have advantages over salmeterol as supplementary treatment for
patients whose asthma is not well controlled by inhaled corticosteroids alone.
Gamma-Hydroxybutyrate
GHB: A New and Novel Drug of Abuse
Nicholson KL, Balster RL Drug Alcohol Depend. 2001;63:1-22
There has been increasing attention in the United States to problems of abuse
of gamma-hydroxybutyrate (GHB), with some evidence for problems in other parts
of the world as well. In vitro and animal research show that, while GHB shares
some properties with abused central nervous system depressant drugs, it has unique
aspects of its pharmacology as well, including actions at a specific neural receptor
which probably mediates many of its effects. Abuse potential assessment of GHB
using standard animal models has not yielded a picture of a highly abusable substance,
but little human testing has yet been done. Very little systematic data exist
on tolerance and dependence with GHB, but both have been seen in human users.
Quantitative data on the prevalence of GHB abuse is incomplete, but various qualitative
measures indicate that a mini-epidemic of abuse began in the late 1980s and continues
to the present. GHB is often included with the group of 'club drugs', and can
be used as an intoxicant. It also has been used as a growth promoter and sleep
aid and has been implicated in cases of 'date rape', usually in combination with
alcohol. Undoubtedly the easy availability of GHB and some of its precursors has
contributed to its popularity. Recent changes in the control status of GHB in
the US may reduce its availability with as yet unknown consequences for the scope
of the public health problem. Drug abuse experts need to familiarize themselves
with GHB as possibly representing a new type of drug abuse problem with some unique
properties.
Gamma-Hydroxybutyrate (GHB): A Newer Drug of Abuse
Gamma-hydroxybutyrate (GHB) is an illicitly marketed substance that has recently
gained popularity among body builders and party attendees as a drug of abuse.
GHB is a depressant that acts on the central nervous system. It is purported as
a strength enhancer, euphoriant and aphrodisiac and is one of several agents reported
as being used as a "date rape" drug. Because of its central nervous system depressant
effects, GHB can be lethal when combined with alcohol or other depressants. Currently,
there is no accepted medical use for GHB, and the U.S. Food and Drug Administration
has prohibited its manufacture and sale. Clinicians should be familiar with the
typical clinical presentation of GHB and its adverse effects. In addition, patients
should be warned of its potential toxicity and be cautioned to avoid the use of
GHB.
Drugs Used in Acquaintance Rape
Smith KM J Am Pharm Assoc (Wash). 1999;39:519-525
Objective: To describe gamma-hydroxybutyrate (GHB), flunitrazepam,
and ketamine and their purported uses to facilitate acquaintance rape. Patient
presentation characteristics, treatment regimens, processes to detect the presence
of the medications by toxicology screening, and methods to avoid exposure are
discussed. Data sources: MEDLINE search from 1985 to 1998; additional references
found within the articles; information obtained from the Internet. Study selection: Clinical trials, reviews, and press releases
concerning the use of GHB, flunitrazepam, and ketamine to facilitate acquaintance
rape. Trials and reviews describing clinical effects, adverse effects, pharmacokinetics/pharmacodynamics,
and usage trends were evaluated. Literature judged to be pertinent by the author
was included in the discussion. Data extraction/data synthesis: Reports of the use of GHB, flunitrazepam,
and ketamine in acquaintance rape appear in the medical literature and lay press.
Many health care professionals may not be familiar with these medications, and
information about caring for patients under their influence is limited. Victims
lose their ability to ward off attackers, develop amnesia, and are unreliable
witnesses. Because symptoms caused by these agents mimic those of alcohol, not
all victims are screened for their presence. Legislative efforts to further limit
the use of or access to GHB, flunitrazepam, and ketamine have been initiated at
the state and federal levels. Pharmacists should know the symptoms of exposure
to the three agents; they should understand treatment regimens, methods to detect
the presence of these and other drugs that may have been used in a sexual assault,
and techniques individuals can use to avoid becoming victims of drug-assisted
acquaintance rape. Conclusion: Because of their extensive drug knowledge and frequent
access to patients, pharmacists are uniquely positioned to educate patients and
other health care professionals about the dangers of acquaintance rape drugs and
methods to reduce their risk of becoming victims.
Gamma-Hydroxybutyric Acid: An Emerging Recreational Drug
Kam PC, Yoong FF Anaesthesia. 1998;53:1195-1198
Gamma-hydroxybutyric acid (GHB) is no longer used as an anaesthetic induction
agent because of the high incidence of myoclonic seizures and vomiting. However,
it is used occasionally in Europe for the treatment of narcolepsy, alcohol dependence
and opiate dependence. Since the early 1990s, GHB has become a drug of abuse in
youths for its euphoric, sedative and anabolic effects. Common adverse effects
include a rapid onset of drowsiness, nausea, vomiting, myoclonic seizures and
coma of short duration. Clinicians should be alert for these adverse effects and
consider the possibility of GHB abuse in young adults with unusual clinical presentations
in the emergency department.
Gamma-Hydroxybutyrate: An Emerging Drug of Abuse That Causes Physical Dependence
Galloway GP, Frederick SL, Staggers FE Jr, Gonzales M, Stalcup SA, Smith
DE Addiction. 1997;92:89-96
Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets
many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing
absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy,
alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the
United States for euphoric, sedative and anabolic effects. Coma and seizures have
been reported following abuse of GHB, but dependence liability has received little
attention. The neuropharmacology, potential therapeutic uses and acute adverse
effects of GHB are reviewed, followed by a case series of eight people using GHB.
Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal
syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal
symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence
of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal
syndrome, which resolves without sequelae. Educational efforts should address
the narrow therapeutic index, possible physical dependence and dangers of combining
GHB with other drugs of abuse.
Fatality due to Gamma-Hydroxybutyric Acid (GHB) and Heroin Intoxication
The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric
acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known
to have been a heroin addict and to have taken other psychoactive substances,
who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic
examination showed generalized visceral congestion, edema and pulmonary anthracosis,
chronic bronchitis and chronic active hepatitis. Toxicological findings included
fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB
and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood),
84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine),
57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and
0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine
levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed
mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference
to its therapeutic use and to reports of non-fatal GHB intoxication.
Adverse Events Associated With Ingestion of Gamma-Butyrolactone -- Minnesota,
New Mexico, and Texas, 1998-1999
MMWR Morb Mortal Wkly Rep. 1999;48:137-140
Products containing gamma-butyrolactone (GBL) are marketed for many claimed purposes,
including to induce sleep, release growth hormone, enhance sexual activity and
athletic performance, relieve depression, and prolong life. GBL is converted by
the body into gamma-hydroxybutyrate (GHB), a drug banned outside of clinical trials
approved by the Food and Drug Administration (FDA). Recognized manifestations
of GHB toxicity include bradycardia, hypothermia, central nervous system depression,
and uncontrolled movements. This report describes seven cases of GBL toxicity
involving the product "Revivarant," which is labeled as containing 1.82 g of GBL
per fluid ounce, reported from two hospital emergency departments (EDs) in Minnesota
during October-December 1998 and summarizes an additional 34 cases of GBL toxicity
reported to poison centers in New Mexico and Texas during October 1998-January
1999.
Acute Poisoning From Gamma-Hydroxybutyrate in California
Chin MY, Kreutzer RA, Dyer JE West J Med. 1992;156:380-384
We report a series of 5 representative patients in California who experienced
adverse reactions from the illicitly marketed substance gamma-hydroxybutyrate
(GHB). The drug is a putative neurotransmitter marketed as a growth hormone releaser
for bodybuilders. The most commonly reported symptoms included abrupt drowsiness,
dizziness, and a "high." Other effects were headache, nausea, vomiting, myoclonic
jerking, and short-term coma. There have been no reported deaths. If product use
is discontinued, full recovery with no long-term side effects is universal. No
clear dose-response effect was observed; this may be attributable to differences
in susceptibility, wide variations in doses taken by the same person, or the coingestion
of other substances. Case interviews confirm that, despite being banned by the
US Food and Drug Administration, GHB is still widely available in the underground
drug market. Athletes and bodybuilders may take drugs for which there are claims
of improved performance or body image. Physicians should be alert for signs of
GHB poisoning in emergency department and clinic patients.
Pharmacokinetics of Gammahydroxybutyrate (GHB) in Narcoleptic Patients
Scharf MB, Lai AA, Branigan B, Stover R, Berkowitz DB Sleep. 1998;21:507-514
Sodium gammahydroxybutyrate (GHB) is an endogenous compound that has been under
investigation in the management of narcolepsy for about two decades. The data
confirm that GHB treatment decreases daytime sleepiness and episodes of cataplexy,
sleep paralysis, and hypnagogic hallucinations. The current study evaluated the
pharmacokinetics of GHB, given twice in one night to six narcoleptic patients
who had been chronically taking GHB nightly on a similar basis. Results confirmed
earlier reports and showed nonlinear pharmacokinetics. Maximum concentrations
were reached in 40 +/- 6.2 and 35.7 +/- 7 minutes after the first and second dose
respectively. Mean AUCinf was 17731.6 +/- 4867 mg/mL/m. Mean GHB T1/2 was 53 +/-
19 minutes. GHB elimination appears to be capacity-limited in some patients when
administered at a fixed dose of 3 g twice nightly at a 4-hour interval.
Gamma-Hydroxybutyrate Overdose and Physostigmine: Teaching New Tricks to an
Old Drug?
Caldicott DG, Kuhn M Ann Emerg Med. 2001;37:99-102
Gamma-hydroxybutyrate was introduced as an anesthetic agent in the 1960s and is
still used in some countries, despite recognized disadvantages. More recently,
it has emerged as a popular recreational drug. We report 3 cases of gamma-hydroxybutyrate
overdose, the effects of which were reversed by the administration of low-dose
intravenous physostigmine. The origins of this regimen and the case for physostigmine
as a potential antidote are described.
Dose-Dependent Absorption and Elimination of Gamma-Hydroxybutyric Acid in
Healthy Volunteers
Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate
withdrawal syndromes. Its absorption and disposition kinetics have been studied
in 8 healthy male volunteers following oral administration of single doses of
12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and
so the apparent oral clearance decreased significantly as the dose was increased,
whereas the terminal half-life and mean residence time increased. The peak plasma
concentrations normalised to the lowest dose fell significantly with increasing
doses, whilst the corresponding peak times increased. These findings suggest that
both the oral absorption and the elimination of GHB are capacity-limited processes.
GHB did not bind to significant extent to plasma proteins over the therapeutic
concentration range. The pharmacokinetic parameters in healthy volunteers were
not significantly different from those previously observed in alcohol-dependent
patients with compensated alcoholic liver disease.
Pharmacokinetics of Gamma-hydroxybutyric Acid in Alcohol Dependent Patients
After Single and Repeated Oral Doses
The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol
dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1
every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax
= 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB
was negligible (less than 1% of the dose). gamma-butyrolactone was not detected
in either plasma or urine, indicating that lactonization of GHB does not occur
in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB
nor in time-dependent modification of its pharmacokinetics. 4. In five subjects,
the data were consistent with nonlinear elimination kinetics of GHB. Administration
of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized
AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a
significant increase in tmax with little change in Cmax. 6. At the administered
doses, GHB did not accumulate in the plasma and caused no serious side effects.
Gamma-Hydroxybutyrate: A Health-Food Product Producing Coma and Seizurelike
Activity
Dyer JE Am J Emerg Med. 1991;9:321-324
Sixteen cases of adverse effects due to a new health-food product, gamma-hydroxybutyrate
(GHB), were reported to the San Francisco Bay Area Regional Poison Control Center
in the 5-month period from June to October 1990. Cases have also been reported
in eight other states. Adverse effects included coma (four patients) and tonic-clonic
seizurelike activity (two patients). Doses ranged from 1/4 teaspoon to 4 tablespoons.
Acute symptoms resolved within 7 hours. GHB was investigated as an anesthetic
agent during the 1960s until seizures and lack of analgesia precluded its use.
It was recently introduced in the health-food market as a food supplement for
body builders with claims of anabolic effects by stimulating growth hormone release.
GHB remains under investigational new drug status with the Food and Drug Administration
and is illegal for over the counter sale. The Food and Drug Branch of the California
Department of Health Services has prohibited further sale of this product in California
as have health departments in Florida and South Carolina; however, new cases continue
to be reported. Health professionals should be aware of the potential health hazards
of GHB.
1,4 Butanediol, Gamma-Hydroxybutyric Acid and Ethanol: Relationships and Interactions
We have investigated the interaction of 1,4 butanediol (1,4 BD) with ethanol and
the involvement of the major metabolite of 1,4 BD, gamma-hydroxybutyric acid (GHB)
in the ability of 1,4 BD to produce behavioral and EEG changes in rat as well
as the toxic side effects of 1,4 BD. Behavioral, electrical, and biochemical studies
in rats suggest that the effects of 1,4 BD are indeed mediated by GHB. Further,
ethanol appears to block conversion of 1,4 BD to GHB. 1,4 BD however potentiates
some of the behavioral effects of ethanol perhaps by a mechanism of action similar
to that of other alcohols. Thus 1,4 BD appears to have two types of pharmacologic
actions, one attributable to its conversion to GHB and the other an inherent property
of the diol itself.
Improved Pharmacological Activity via Pro-Drug Modification: Comparative Pharmacokinetics
of Sodium Gamma-Hydroxybutyrate and Gamma-Butyrolactone
Lettieri J, Fung HL Res Commun Chem Pathol Pharmacol. 1978;22:107-118.
Although gamma-butyrolactone (GBL) rapidly converts to gamma-hydroxybutyrate (GHB)
in vivo, the lactone gave significantly more prolonged hypnotic effects than GHB
when equimolar doses were compared both parenterally and orally in rats. Plasma
drug concentrations were higher after GBL administration through both routes,
consistent with the observed differences in the pharmacological activity of these
two compounds. Oral GBL was absorbed much faster than oral GHB, with the dual
effects of decreasing potential first-pass metabolism and elevating plasma drug
concentrations to the region where capacity-limited elimination is operative.
Parenteral GBL produced a slower initial drug plasma clearance than parenteral
GHB. In spite of the rapid metabolism of GBL to GHB, the apparent tissue distribution
of these two compounds may be different.
A Tale of Novel Intoxication: A Review of the Effects of Gamma-Hydroxybutyric
Acid With Recommendations for Management
Li J, Stokes SA, Woeckener A Ann Emerg Med. 1998;31:729-736
Gamma-Hydroxybutyric acid (GHB) is unfamiliar to many physicians in the United
States but enjoys clinical use elsewhere for applications in resuscitation, anesthesia,
and addiction therapy. Use within the United States is restricted to Food and
Drug Administration-approved clinical trials for treatment of narcolepsy. Recently
illicit use of GHB has emerged within the United States where it is distributed
for purported euphoric and "fat-burning" metabolic effects. Clinical effects can
be severe, progressing rapidly to respiratory arrest and death. We provide an
updated comprehensive review of the literature with particular emphasis on toxicology,
including GHB pharmacodynamics, clinical effects, and suggestions for overdose
management. Recommended management of acute GHB intoxication includes prevention
of aspiration, use of atropine for persistent symptomatic bradycardia, consideration
of neostigmine as a reversal agent, and treatment for coingested substances. Emergency
physicians are urged to become familiar with GHB because of its potential for
severe morbidity as well as its potential use as a future resuscitative agent.
A Tale of Novel Intoxication: Seven Cases of Gamma-Hydroxybutyric Acid Overdose
Li J, Stokes SA, Woeckener A. Ann Emerg Med. 1998;31:723-728
Study Objective: We describe seven patients presenting with combination
substance abuse involving gamma-hydroxybutyric acid (GHB). Methods: During a 3 month period, we identified consecutive patients
with GHB ingestion confirmed by urine mass spectrometry presenting to a high-volume
urban emergency department. Results: All patients presented with acute delirium and transient
but severe respiratory depression. With supportive care, including intubation
and mechanical ventilation in four cases, normal mentation and respiratory function
returned within 2 to 6 hours. None of these patients had documented seizures,
and none of the four patients who received naloxone had a reversal response. This
clinical observation supports previous experimental work in GHB-intoxicated human
subjects demonstrating neither epileptiform changes on electroencephalography
nor reversal with naloxone. Two findings are remarkable in this series. The first
is the observation of a peculiar state of violent aggression present on stimulation
of the GHB-intoxicated patient despite near or total apnea. The fact that patients
fully recovered from this state may be the result of a previously demonstrated
GHB hypoxia-sparing effect. The second is the observation of ECG abnormalities
in several cases, including U waves in five patients. Conclusion: Emergency physicians should be alerted to this agent,
its characteristic effects, and its potential for serious sequelae including respiratory
arrest and death.
Clinical Course of Gamma-Hydroxybutyrate Overdose
Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD Ann Emerg Med. 1998;31:716-722
Study Objective: To describe the clinical characteristics and
course of gamma-hydroxybutyrate (GHB) overdose. Methods: We assembled a retrospective series of all cases of
GHB ingestion see in an urban public-hospital emergency department and entered
in a computerized database January 1993 through December 1996. From these cases
we extracted demographic information, concurrent drug use, vital signs, Glasgow
Coma Scale (GCS) score, laboratory values, and clinical course. Results: Sixty-one (69%) of the 88 patients were male. The mean
age was 28 years. Thirty-four cases (39%) involved coingestion of ethanol, and
25 (28%) involved coingestion of another drug, most commonly amphetamines. Twenty-five
cases (28%) had a GCS score of 3, and 28 (33%) had scores ranging from 4 through
8. The mean time to regained consciousness from initial presentation among nonintubated
patients with an initial GCS of 13 or less was 146 minutes (range, 16-389). Twenty-two
patients (31%) had an initial temperature of 35 degrees C or less. Thirty-two
(36%) had asymptomatic bradycardia; in 29 of these cases, the initial GCS score
was 8 or less. Ten patients (11%) presented with hypotension (systolic blood pressure
< or = 90 mm Hg); 6 of these patients also demonstrated concurrent bradycardia.
Arterial blood gases were measured in 30 patients; 21 had a PCO2 of 45 or greater,
with pH ranging from 7.24 to 7.34, consistent with mild acute respiratory acidosis.
Twenty-six patients (30%) had an episode of emesis; in 22 of these cases, the
initial GCS was 8 or less. Conclusion: In our study population, patients who overdosed on
GHB presented with a markedly decreased level of consciousness. Coingestion of
ethanol or other drugs is common, as are bradycardia, hypothermia, respiratory
acidosis, and emesis. Hypotension occurs occasionally. Patients typically regain
consciousness spontaneously within 5 hours of the ingestion.
A Sudden Awakening From a Near Coma After Combined Intake of Gamma-Hydroxybutyric
Acid (GHB) and Ethanol
Louagie HK, Verstraete AG, De Soete CJ, Baetens DG, Calle PA J Toxicol Clin Toxicol. 1997;35:591-594
Objective: A case of a sudden awakening from a near coma after
combined intake or gamma-hydroxybutyric acid (GHB) (125 micrograms/mL), ethanol
(134 mg/dL), and cannabinoids is described. Methods: GHB was determined by gas chromatography-mass spectrometry
after acetonitrile precipitation and derivation with N-methyl-N-trimethylsilyltrifluoroacetamide,
using valproic acid as the internal standard. Conclusion: The described case illustrates the consequences of
GHB overdose. GHB overdose should be considered in every case of unexplained sudden
coma, i.e., without any evidence of head injury, intake of coma-inducing drugs,
or increasing intracranial pressure. GHB overdose will be missed by routine toxicological
screening.
Adverse Events, Including Death, Associated With the Use of 1,4-Butanediol
Zvosec DL, Smith SW, McCutcheon JR, Spillane J, Hall BJ, Peacock EA N Engl J Med. 2001;344:87-94
Background: 1,4-Butanediol is an industrial solvent that, when
ingested, is converted to gamma-hydroxybutyrate, a drug of abuse with depressant
effects, primarily on the central nervous system. After reports of toxic effects
of gamma-hydroxybutyrate and its resultant regulation by the federal government,
1,4-butanediol and gamma-butyrolactone, another precursor of gamma-hydroxybutyrate
and an industrial solvent, began to be marketed as dietary supplements. We investigated
reports of toxic effects due to the ingestion of 1,4-butanediol and reviewed the
related health risks. Methods: From June 1999 through December 1999, we identified
cases of toxic effects of 1,4-butanediol involving patients who presented to our
emergency departments with a clinical syndrome suggesting toxic effects of gamma-hydroxybutyrate
and a history of ingesting 1,4-butanediol and patients discovered through public
health officials and family members. We used gas chromatography-mass spectrometry
to measure 1,4-butanediol or its metabolite, gamma-hydroxybutyrate, in urine,
serum, or blood. Results: We identified nine episodes of toxic effects in eight
patients who had ingested 1,4-butanediol recreationally, to enhance bodybuilding,
or to treat depression or insomnia. One patient presented twice with toxic effects
and had withdrawal symptoms after her second presentation. Clinical findings and
adverse events included vomiting, urinary and fecal incontinence, agitation, combativeness,
a labile level of consciousness, respiratory depression, and death. No additional
intoxicants were identified in six patients, including the two who died. The doses
of 1,4-butanediol ingested ranged from 5.4 to 20 g in the patients who died and
ranged from 1 to 14 g in the nonfatal cases. Conclusions: The health risks of 1,4-butanediol are similar to
those of its counterparts, gamma-hydroxybutyrate and gamma-butyrolactone. These
include acute toxic effects, which may be fatal, and addiction and withdrawal.
The Treatment of Narcolepsy-Cataplexy With Nocturnal Gamma-Hydroxybutyrate
Broughton R, Mamelak M Can J Neurol Sci. 1979;6:1-6
Sixteen patients with narcolepsy and cataplexy were treated with gamma-hydroxybutyrate
(GHB) given at night and tailored to achieve as continuous a night's sleep as
possible. The dosage usually consisted of 1.5-2.25 gm orally at bedtime and then
one or two further 1.0-1.5 gm doses with awakenings during the night, and totaled
about 50 mg/kg. Apart from one patient who took only the bedtime dose, the subjective
quality of night sleep improved in all patients and the number of irresistible
daytime attacks of sleep and cataplexy substantially diminished. Some residual
daytime drowsiness remained and this usually responded well to low doses of methylphenidate.
Improvement has been maintained for up to 20 months without the development of
tolerance. Two patients experienced adverse side effects necessitating withdrawal
of GHB treatment, but no serious toxic effects have occurred.
Montelukast Helpful in Hard-to-Control Asthma
WESTPORT, CT (Reuters Health) May 18 - Montelukast may have advantages over salmeterol
as supplementary treatment for patients whose asthma is not well controlled by
inhaled corticosteroids alone, according to Scottish researchers.
Dr. Brian J. Lipworth and colleagues at the University of Dundee assessed the
relative efficacy of the leukotriene receptor antagonist montelukast and the long-acting
beta2-agonist salmeterol as additional treatment in patients still symptomatic
despite use of inhaled corticosteroids. In a placebo-controlled crossover study,
20 such subjects were given second-line treatment with montelukast once daily
for 2 weeks and salmeterol 50 mcg twice daily for 2 weeks.
As reported in the April issue of Chest, compared to placebo, there was a significant
difference in the concentration of adenosine monophosphate (AMP) required to cause
a 20% drop in lung function (FEV1) following both first and last doses of montelukast.
However, for salmeterol, a significant difference was seen only after the first
dose.
In addition, montelukast prompted a significant reduction in blood eosinophil
counts. No such response was seen with salmeterol. Nevertheless, both treatments
achieved a significant reduction in rescue bronchodilator use and a significant
improvement in morning peak expiratory flow. In fact, say the investigators, "there
were no significant differences between drugs for any end points except eosinophil
count."
The researchers call for further studies, but conclude that compared to use of
salmeterol in such patients, "the addition of montelukast may confer anti-inflammatory
effects."
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