Chlordiazepoxide chemical structure
Find information on thousands of medical conditions and prescription drugs.

Librium

Chlordiazepoxide (marketed under the trade name LibriumĀ®) is a hypnotic drug which is a benzodiazepine derivative. It has sedative, anxiolytic and skeletal muscle relaxant properties. more...

Home
Diseases
Medicines
A
B
C
D
E
F
G
H
I
J
K
L
Labetalol
Lacrisert
Lactitol
Lactuca virosa
Lactulose
Lamictal
Lamisil
Lamivudine
Lamotrigine
Lanophyllin
Lansoprazole
Lantus
Lariam
Larotid
Lasix
Latanoprost
Lescol
Letrozole
Leucine
Leucovorin
Leukeran
Levaquin
Levetiracetam
Levitra
Levocabastine
Levocetirizine
Levodopa
Levofloxacin
Levomenol
Levomepromazine
Levonorgestrel
Levonorgestrel
Levophed
Levora
Levothyroxine sodium
Levoxyl
Levulan
Lexapro
Lexiva
Librium
Lidocaine
Lidopen
Linezolid
Liothyronine
Liothyronine Sodium
Lipidil
Lipitor
Lisinopril
Lithane
Lithobid
Lithonate
Lithostat
Lithotabs
Livostin
Lodine
Loestrin
Lomotil
Loperamide
Lopressor
Loracarbef
Loratadine
Loratadine
Lorazepam
Lortab
Losartan
Lotensin
Lotrel
Lotronex
Lotusate
Lovastatin
Lovenox
Loxapine
LSD
Ludiomil
Lufenuron
Lupron
Lutropin alfa
Luvox
Luxiq
Theophylline
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z

History

Chlordiazepoxide was the first benzodiazepine to be synthesized and made commercially available. It was an accidental discovery made by Leo Sternbach of Roche Pharmaceuticals in 1960. It has a medium to long half life.

Sternbach later went on to develop diazepam, better known as Valium, in 1963. The huge success of Valium made Roche the market leader in benzodiazepine products, and the company went on to develop and market nitrazepam in 1965 and later flurazepam and flunitrazepam in 1975.

Other drug companies soon jumped on board the benzodiazepine band wagon, with Wyeth's lorazepam and Upjohn (now Pfizer)'s alprazolam.

As prescriptions for benzodiazepines sky-rocketed through the late 1960s and 1970s, the problem of dependency began to emerge. However, chlordiazepoxide is still a useful treatment for patients suffering from acute anxiety. It is still manufactured and prescribed today, along with a wide variety of other benzodiazepines, all of which have similar properties.

Pharmacology

Chlordiazepoxide is believed to act on the GABAA receptor, thereby producing inhibitory effects similar to the other benzodiazepines.

Indications

Chlordiazepoxide is indicated for the treatment of insomnia, anxiety and panic attacks. It has also been used as a treatment for acute alcohol or opiate withdrawl.

Dosage

Chlordiazepoxide is available in dosages of 5mg, 10mg and 25mg.

Side Effects

Common side effects of chlordiazepoxide include:

  • Drowsiness
  • Depression
  • Impaired motor function
    • Impaired coordination
    • Impaired balance
    • Dizziness
  • Nervousness
  • Anterograde amnesia (especially pronounced in higher doses)

Contraindications

Use of chlordiazepoxide should be avoided in individuals with the following conditions:

  • Myasthenia gravis
  • Acute intoxication with alcohol, narcotics, or other psychoactive substances
  • Ataxia
  • Severe hypoventilation
  • Acute narrow-angle glaucoma
  • Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
  • Severe sleep apnea
  • Hypersensitivity or allergy to any drug in the benzodiazepine class

Overdose

An individual who has consumed too much chlordiazepoxide will display one or more of the following symptoms:

  • Somnolence (difficulty staying awake)
  • Mental confusion
  • Hypotension
  • Hypoventilation
  • Impaired motor functions
    • Impaired reflexes
    • Impaired coordination
    • Impaired balance
    • Dizziness
    • Muscle Weakness
  • Coma

In animal models, the oral LD50 of chlordiazepoxide is 537 mg/kg.

Read more at Wikipedia.org


[List your site here Free!]


Ambulatory detoxification of patients with alcohol dependence
From American Family Physician, 2/1/05 by Richard D. Blondell

The lifetime prevalence of alcohol problems is thought to be between 13.7 and 23.5 percent, indicating that these problems are common in ambulatory patients. (1) Family physicians play an important role in identifying these patients and intervening to the degree appropriate for the severity of disease and the patient's willingness to change.

Patients who have alcohol dependence may require detoxification to prevent alcohol withdrawal syndrome (AWS). When clinically appropriate, detoxification can be initiated in the ambulatory setting. (2) Most ambulatory patients wit h alcohol dependence can be detoxified quickly and safely without the use of psychoactive drugs.

Initial Evaluation

Screening to detect problem drinking is recommended in all adult and adolescent patients. (3) Direct questions about the quantity and frequency of alcohol consumption (to detect hazardous drinkers) and the four-item CAGE questionnaire (4) (to detect dependent drinkers)appear to be the most useful tools in primary care settings. (5,6) The CAGE questionnaire (feeling the need to Cut down, Annoyed by criticism, Guilty about drinking, and drinking in the morning to treat tremulousness or a hangover [Eye opener]) is the most popular tool to evaluate patterns of alcohol use.

At-risk drinking is defined as more than 14 drinks per week in men under age 65 and more than seven drinks per week in women and all adults aged 65 and older. One standard drink is equal to 12 oz of regular beer, 5 oz of wine, or 1.5 oz of distilled spirits. Heavy drinkers should receive a brief intervention designed to moderate their drinking. (7,8) These interventions are based on motivational interviewing techniques (Table 1). (9) Approximately 5 percent of the patients in a typical adult primary care practice would be expected to have alcohol dependence. (10) In patients without acute medical or surgical problems, about one third would be expected to develop mild to moderate AWS (e.g., tremulousness, tachycardia), and only a small minority would be expected to develop severe AWS if they abruptly stopped drinking. (1,11-13) In one study (11) of 1,024 ambulatory patients undergoing detoxification without psychoactive drugs, 3.7 percent experienced hallucinations, 1.2 percent had alcohol withdrawal seizures, and 1 percent developed delirium tremens.

Patients who are at risk for AWS may benefit from pharmacotherapy. Outpatient detoxification is an effective, safe, and low-cost treatment for patients with mild to moderate symptoms of AWS. (14) An appropriate candidate is a patient who meets the criteria for alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) (15) and is at low to moderate risk for AWS (Tables 2 (16-20) and 3 (15)). Patients with serious psychiatric involvement (e.g., suicidal ideation), concurrent acute illness, or severe AWS-related symptoms, or those who are at high risk for developing delirium tremens, are best detoxified in inpatient settings. (12,16-20) Because polysubstance abuse is common in patients with alcohol dependence, (21) physicians may wish to consider performing urine toxicology tests when the history or physical examination indicates that such screening may be helpful. Patients who are dependent on opioids or benzodiazepines may require detoxification from these substances as well.

Alcohol Withdrawal Syndrome

The goal of detoxification is to control the symptoms of AWS and to prevent alcohol withdrawal seizures, withdrawal delirium, and deaths from complications of AWS. Ultimately, the purpose of outpatient detoxification is to facilitate the patient's entry into an alcohol rehabilitation program.

AWS represents the unmasking of the adaptation that the brain makes to the chronic presence of alcohol. The symptoms and signs of AWS fall into three main categories: central nervous system (CNS) excitation (e.g., restlessness, agitation, seizures); excessive function of the autonomic nervous system (ANS) (e.g., nausea, vomiting, tachycardia, tremulousness, hypertension); and cognitive dysfunction.

STAGES OF WITHDRAWAL

AWS can be divided into three stages. Patients in stages 1 and 2 can be treated as outpatients unless contraindicated (Table 2). Those who progress to stage 3 should be transferred to an inpatient setting and evaluated for the cause of the delirium. (13)

Stage 1, "minor withdrawal," usually begins five to eight hours after the last drink and is characterized by anxiety, restlessness, agitation, mild nausea, decreased appetite, sleep disturbance, facial sweating, mild tremulousness, and fluctuating tachycardia and hypertension. Patients are coherent, but they may have mild cognitive impairment.

Stage 2, "major withdrawal," occurs 24 to 72 hours after the last drink and is characterized by marked restlessness and agitation, moderate tremulousness with constant eye movement, diaphoresis, nausea, vomiting, anorexia, and diarrhea. Patients often have marked tachycardia (i.e., greater than 120 bpm) and systolic blood pressure greater than 160 mm Hg. "Alcoholic hallucinosis," which consists of auditory or visual hallucinations, may be present. The patient may be disoriented and appear confused, but reorientation often is possible. Seizures--typically grand mal--may occur but are not always preceded by other symptoms. They usually are single seizures that last less than five minutes, but some patients have seizures in salvos of two or three. Status epilepticus is not associated with alcohol withdrawal and indicates another problem.

Stage 3, "delirium tremens," can occur from 72 to 96 hours after the last drink. It is associated with fever, severe hypertension and tachycardia, delirium, drenching sweats, and marked tremulousness. Causes of death during this stage include head trauma, cardiovascular complications, infections, aspiration pneumonia, and fluid and electrolyte abnormalities.

BASIC TREATMENT

Nonpharmacologic interventions are important in the management of AWS and include frequent reassurance, reality orientation, and nursing care. (22) Patients seem to do best when they are kept in an evenly lit, quiet room, and dark shadows, bright lights, loud noises, and other excessive stimuli are avoided. Liberal intake of noncaffeinated fluids can help prevent dehydration.

PHARMACOTHERAPY

Medications are used to prevent or treat the various clinical manifestations of AWS: sedatives for CNS excitation;sympatholytics for excessive ANS activity not controlled by sedatives alone; and neuroleptics as adjunctive therapy for cognitive dysfunction. (13)

Thiamine supplementation is essential in malnourished patients for the prevention of Wernicke's encephalopathy. Although most candidates for outpatient detoxification probably would not have a thiamine deficiency, the supplement can be given routinely because there are no adverse effects or contraindications to its use.

Long-acting benzodiazepines are t he agents of choice for monotherapy in patients with AWS. (23,24) The three most common treatment regimens for prevention of AWS are symptom triggered, (25) front loading, (26) and fixed schedule. (27) Dosages for these regimens are given in Table 4. (13,26,27) In clinical practice, the effective dosage can vary greatly from one patient to another. Long-acting benzodiazepines such as chlordiazepoxide (Librium) and diazepam (Valium) are preferred because they are the most effective in preventing alcohol withdrawal seizures and delirium. A short-acting benzodiazepine (such as oxazepam [Serax]) that does not have any active metabolites can be used in elderly patients, those in whom oversedation absolutely must be avoided, and those with significant liver disease that might impair their ability to metabolize a long-acting agent.

Some physicians use phenobarbital with great success in patients with AWS. However, barbiturates have not been evaluated clinically as thoroughly as benzodiazepines, have a narrow therapeutic window, may interact with many other medications, and have not been approved by the U. S. Food and Drug Administration for the treatment of patients with AWS.

Well-designed studies have found that clonidine (Catapres) and atenolol (Tenormin) are effective as adjuvant therapy in the treatment of AWS symptoms related to excessive ANS activity, but these studies have not been of adequate size to indicate what effect the agents have on the rate of delirium or seizures. (13)

There is some evidence to suggest that neuroleptics such as haloperidol (Haldol) are useful in the treatment of delirium in AWS. (22) However, because neuroleptics lower the seizure threshold, these agents should be used only after sedation has been achieved with adequate doses of a benzodiazepine.

Carbamazepine (Tegretol) is used extensively in Europe for treatment of AWS, but a recent systematic literature review (23) concluded that the evidence to support its use is less than the evidence to support the use of benzodiazepines. There is no evidence of efficacy for phenytoin (Dilantin) in the prevention and treatment of alcohol withdrawal seizures. Treatment with intravenous lorazepam (Ativan)is associated with a significant reduction in the risk of recurrent seizures in patients who develop an alcohol withdrawal seizure. (28)

Although magnesium may be administered to patients who are deficient, there is no evidence that routine administration of magnesium sulfate is of any benefit unless AWS is accompanied by cardiac arrhythmias. (29)

MONITORING RESPONSE TO THERAPY

A responsible person should monitor the patient undergoing detoxification and watch for signs and symptoms of worsening AWS. Figure 1 (30) presents an assessment scale that can be used by persons with little or no medical training to monitor the patient. Medical personnel should reevaluate patients on a daily basis if they score more than eight points on this scale despite treatment, experience a seizure, or develop delirium. (12) In patients without complications, detoxification usually is complete in four to five days.

Follow-up Care

Outpatient detoxification alone is not adequate treatment for alcohol dependence: it must be linked to involvement in a formal alcohol rehabilitation program. Many authorities believe that long-term involvement with self-help programs such as Alcoholics Anonymous also is an important part of a patient's long-term recovery.

After sobriety has been achieved, extreme caution should be used in prescribing mood-altering drugs and control led substances to recovering patients, if they are prescribed at all. Benzodiazepines, in particular, are contraindicated, as they frequently are abused. If there is a clear clinical indication, opioid agonists may be prescribed, but appropriate use should be closely monitored. Antidepressants, especially the sedating tricyclic anti-depressants, can be abused by patients with alcohol dependence. Most patients in the early stages of recovery will have depression; this generally responds to counseling without medication. However, some carefully selected patients may benefit from judicious use of antidepressants. Examples include patients who have a well-documented depressive disorder that predates alcohol dependence and responded to antidepressant treatment, and patients with depressive symptoms that persist despite ongoing psychotherapy for alcohol dependence.

The author indicates that he does not have any sources of conflict. Sources of funding: none reported.

Members of various family medicine departments develop articles for "Practical Therapeutics." This article is one in a series coordinated by the Department of Family and Geriatric Medicine at the University of Louisville School of Medicine, Louisville, Ky. Guest editor of the series is James G. O'Brien, M.D.

REFERENCES

(1.) O'Connor PG, Schottenfeld RS. Patients with alcohol problems. N Engl J Med 1998;338:592-602.

(2.) Lewis DC. The role of the generalist in the care of the substance-abusing patient. Med Clin North Am 1997;81:831-43.

(3.) U.S. Preventive Ser vices Task Force. Screening for alcohol misuse. Accessed online January 11, 2005, at: http://www.ahcpr.gov/clinic/uspstf/uspsdrin.htm.

(4.) National Institute on Alcohol Abuse and Alcoholism. Helping patients with alcohol problems: a health practitioner's guide. Bethesda, Md.: U.S. Dept. of Health and Human Ser vices, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 2003. NIH publication no. 03-3769.

(5.) Gordon AJ, Maisto SA, McNeil M, Kraemer KL, Conigliaro RL, Kelley ME, et al. Three questions can detect hazardous drinkers. J Fam Pract 2001;50:313-20.

(6.) Crowe RR, Kramer JR, Hesselbrock V, Manos G, Bucholz KK. The utility of the 'Brief MAST' and the 'CAGE' in identifying alcohol problems: results from national high-risk and community samples. Arch Fam Med 1997;6:477-83.

(7.) Ballesteros J, Duffy JC, Querejeta I, Arino J, Gonzalez-Pinto A. Efficacy of brief interventions for hazardous drinkers in primary care: systematic review and metaanalyses. Alcohol Clin Exp Res 2004;28:608-18.

(8.) Yarnall KS, Pollak KI, Ostbye T, Krause KM, Michener JL. Primary care: is there enough time for pevention? Am J Public Health 2003;93:635-41.

(9.) Miller WR, Rollnick S. Motivational interviewing: preparing people for change. 2d ed. New York: Guilford, 2002.

(10.) Manwell LB, Fleming MF, Johnson K, Barry KL. Tobacco, alcohol, and drug use in a primary care sample: 90-day prevalence and associated factors. J Addict Dis 1998;17:67-81.

(11.) Whitfield CL, Thompson G, Lamb A, Spencer V, Pfeifer M, Browning-Ferrando M. Detoxification of 1,024 alcoholic patients without psychoactive drugs. JAMA 1978;239:1409-10.

(12.) Mayo-Smith MF. Management of alcohol intoxication and withdrawal. In: Graham AW, Schultz TK, Wilford BB. Principles of addiction medicine. 2d ed. Chevy Chase, Md.: American Society of Addiction Medicine, 1998:431-40.

(13.) Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 1997;278:144-51.

(14.) Hayashida M, Alterman AI, McLellan AT, O'Brien CP, Purtill JJ, Volpicelli JR, et al. Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome. N Engl J Med 1989;320:358-65.

(15.) American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.: American Psychiatric Association, 1994.

(16.) Glickman L, Herbsman H. Delirium tremens in surgical patients. Surgery 1968;64:882-90.

(17.) Ferguson JA, Suelzer CJ, Eckert GJ, Zhou XH, Dittus RS. Risk factors for delirium tremens development. J Gen Intern Med 1996;11:410-4.

(18.) Wojnar M, Bizon Z, Wasilewski D. The role of somatic disorders and physical injury in the development and course of alcohol withdrawal delirium. Alcohol Clin Exp Res 1999;23:209-13.

(19.) Blondell RD, Looney SW, Hottman LM, Boaz PW. Characteristics of intoxicated trauma patients. J Addict Dis 2002;21:1-12.

(20.) Lukan JK, Reed DN Jr, Looney SW, Spain DA, Blondell RD. Risk factors for delirium tremens in trauma patients. J Trauma 2002;53:901-6.

(21.) Staines GL, Magura S, Foote J, Deluca A, Kosanke N. Polysubstance use among alcoholics. J Addict Dis 2001;20:53-69.

(22.) Naranjo CA, Sellers EM, Chater K, Iversen P, Roach C, Sykora K. Nonpharmacologic intervention in acute alcohol withdrawal. Clin Pharmacol Ther 1983;34:214-9.

(23.) Williams D, McBride AJ. The drug treatment of alcohol withdrawal symptoms: a systematic review. Alcohol Alcohol 1998;33:103-15.

(24.) Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal. CMAJ 1999;160:649-55.

(25.) Wartenberg AA, Nirenberg TD, Liepman MR, Silvia LY, Begin AM, Monti PM. Detoxification of alcoholics: improving care by symptom-triggered sedation. Alcohol Clin Exp Res 1990;14:71-5.

(26.) Sellers EM, Naranjo CA, Harrison M, Devenyi P, Roach C, Sykora K. Diazepam loading: simplified treatment of alcohol withdrawal. Clin Pharmcol Ther 1983;34:822-6.

(27.) Saitz R, Mayo-Smith MF, Roberts MS, Redmond HA, Bernard DR, Calkins DR. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA 1994;272:519-23.

(28.) D'Onofrio G, Rathlev NK, Ulrich AS, Fish SS, Freedland ES. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med 1999;340:915-9.

(29.) Wilson A, Vulcano B. A double-blind, placebo-controlled trial of magnesium sulfate in the ethanol withdrawal syndrome. Alcohol Clin Exp Res 1984;8:542-5.

(30.) Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CI WA-Ar). Br J Addict 1989;84:1353-7.

RICHARD D. BLONDELL, M.D., University of Louisville School of Medicine, Louisville, Kentucky

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

Return to Librium
Home Contact Resources Exchange Links ebay