Pharmacy Division Ramathibodi Hospital


News 28/05/2544

What's the latest in gamma-hydroxybutyrate (GHB) use and abuse, also known as the "date-rape drug"?

Montelukast may have advantages over salmeterol as supplementary treatment for patients whose asthma is not well controlled by inhaled corticosteroids alone.


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

O'Connell T, Kaye L, Plosay JJ 3rd
Am Fam Physician. 2000;62:2478-2483

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

Ferrara SD, Tedeschi L, Frison G, Rossi A
J Forensic Sci. 1995;40:501-504

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

Palatini P, Tedeschi L, Frison G, et al.
Eur J Clin Pharmacol. 1993;45:353-356

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

Ferrara SD, Zotti S, Tedeschi L, et al.
Br J Clin Pharmacol. 1992;34:231-235

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

Poldrugo F, Snead OC 3rd
Neuropharmacology. 1984;23:109-113

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."

Chest 2001;119:1021-1026.

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