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METHAQUALONE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Methaqualone, a quinazoline derivative, is a sedative and hypnotic agent.

Specific Substances

    1) Methaqualone
    2) Methachalonum
    3) Methaqualoni
    4) 2-Methyl-3-o-tolyquinazolin--4-(3H)-one
    5) Molecular Formula: C16-H14-N2-O
    6) CAS 72-44-6
    7) CAS 340-56-7 (hydrochloride)
    8) 2-METHYL-3-O-TOLYL-4(3H)-QUIN-AZOLINONE HYDROCHLORIDE

Available Forms Sources

    A) FORMS
    1) BASE VERSUS HCL SALT: Quaalude(R), Mequin(R), and Sopor(R) contain methaqualone base. Parest(R) contains methaqualone HCl. 200 mg of methaqualone HCl contains 175 mg of base. 400 mg of HCl contains 350 mg of base.
    2) TABLET STRENGTH/BRAND NAME:
    a) 150 mg tablets (Quaalude-150, Lemmon; Sopor, Arner-Stone); 200 mg capsules Parest-200, Parke-Davis); 300 mg tablets (Quaalude-300, Lemmon; Mequin, Lemmon; Sopor, Arner-Stone); 400 mg capsules (Parest-400, Parke-Davis)
    B) USES
    1) Methaqualone has been given orally in the short-term management of insomnia (S Sweetman , 2001). It has been made Class 1 and generally withdrawn from sales in 1982-83.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Withdrawal from methaqualone may cause nausea, vomiting, abdominal cramps, weakness, anxiety, restlessness, tachycardia and hyperreflexia progressing to seizures and delirium. Death may occur if severe withdrawal is not treated.
    B) WITH POISONING/EXPOSURE
    1) Methaqualone overdose results in ataxia, lethargy and coma. At lower doses, recreational users may report a euphoric effect. Ingestion of as little as 150 mg in a child will result in signs and symptoms of toxicity.
    2) Effects are those of progressive CNS depression, respiratory and cardiac failure, and may include coma, hypotension, absence of EEG activity, muscular hyperactivity, and respiratory depression.
    3) Fake (imitation) "Quaaludes" containing various amounts of benzodiazepines, methaqualone, barbiturates, ephedrine, meprobamate, meclizine, chlorpheniramine, diphenhydramine, sucrose, phencyclidine, and other unidentified chemicals have appeared in the US and other countries.
    0.2.5) CARDIOVASCULAR
    A) WITH POISONING/EXPOSURE
    1) Tachycardia, hypotension, and myocardial infarction have been reported in severe cases. Reversible ECG changes may occur.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Compared to barbiturates, marked respiratory depression is rare. Pulmonary edema and apnea may occur.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Ataxia, lethargy, limb hyperreflexia, seizures and coma may occur. Marked pyramidal signs such as hypertonicity, myoclonia and positive Babinsky responses may develop following severe poisoning.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Salivation, nausea, vomiting, and epigastric discomfort may occur.
    0.2.13) HEMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Blood clotting abnormalities, including thrombocytopenia and increased prothrombin and thromboplastin times, may be seen following acute overdoses.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Fixed drug eruptions and erythema multiforme have been associated with the use of methaqualone.
    0.2.20) REPRODUCTIVE
    A) Methaqualone is classified as US FDA Pregnancy Category D.
    0.2.22) OTHER
    A) WITH THERAPEUTIC USE
    1) Withdrawal from methaqualone may lead to serious adverse events, including seizures, delirium, and death if untreated.
    B) WITH POISONING/EXPOSURE
    1) Withdrawal from methaqualone may lead to serious adverse events, including seizures, delirium, and death if untreated.

Laboratory Monitoring

    A) Blood methaqualone levels are not clinically useful, however levels greater than 25 mg/L are consistent with significant intoxication in most patients.
    B) In severely intoxicated patients monitor CBC, liver and renal function tests, platelets, coagulation tests, electrolytes, arterial blood gases, and ECG.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Sedation generally occurs within 30 minutes, therefore induced vomiting is NOT recommended. Administer activated charcoal for recent ingestions. Patients with CNS depression require intubation prior to charcoal administration.
    B) Administer fluids with caution to avoid pulmonary edema. Thorough symptomatic and supportive therapy is essential.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    E) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    F) HEMODIALYSIS AND HEMOPERFUSION - Effective but should be reserved for those patients experiencing life-threatening symptoms unresponsive to conventional supportive, therapy.
    G) WITHDRAWAL - Withdrawal symptoms may be treated with phenobarbital 100 mg every 6 hours and increased as necessary to control withdrawal symptoms.
    H) Diazepam may be indicated if excessive muscle twitching, hyperactivity, or seizures occur.

Range Of Toxicity

    A) Hypnotic effects occur in oral doses of 150 to 400 mg in adults. Coma has occurred following ingestion of 2.4 grams. Death has occurred following ingestion of 8 grams.
    B) Acute ingestion of greater than 800 mg in an adult is usually considered toxic. Ingestion of as little as one tablet in a child is considered toxic.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Withdrawal from methaqualone may cause nausea, vomiting, abdominal cramps, weakness, anxiety, restlessness, tachycardia and hyperreflexia progressing to seizures and delirium. Death may occur if severe withdrawal is not treated.
    B) WITH POISONING/EXPOSURE
    1) Methaqualone overdose results in ataxia, lethargy and coma. At lower doses, recreational users may report a euphoric effect. Ingestion of as little as 150 mg in a child will result in signs and symptoms of toxicity.
    2) Effects are those of progressive CNS depression, respiratory and cardiac failure, and may include coma, hypotension, absence of EEG activity, muscular hyperactivity, and respiratory depression.
    3) Fake (imitation) "Quaaludes" containing various amounts of benzodiazepines, methaqualone, barbiturates, ephedrine, meprobamate, meclizine, chlorpheniramine, diphenhydramine, sucrose, phencyclidine, and other unidentified chemicals have appeared in the US and other countries.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Both hypothermia and mild hyperthermia may occur (Baggish et al, 1981).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) EYE MOVEMENTS - Alternating dysconjugate vertical skew deviation has been reported (Pan & Huang, 1984). Nystagmus may develop (Abboud et al, 1974)
    2) PUPILS - Pupils may be somewhat mydriatic and sluggishly responsive or may be miotic (Trese, 1981) Gitelson, 1967; Abbaud et al, 1974).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Tachycardia, hypotension, and myocardial infarction have been reported in severe cases. Reversible ECG changes may occur.
    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may develop, especially in severe poisonings (Abboud et al, 1974; Pascarelli, 1973).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension has been reported (Lawson & Brown, 1967; Burston, 1967) Gitelson, 1967). Hypotension is generally mild, but may be profound in severe overdose (Caridis et al, 1967).
    C) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) Myocardial infarction has been reported rarely (Lawson & Brown, 1967; Wason, 1982).
    D) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Reversible ECG changes occurred in 8 of 66 patients (consisting of RBBB and T-wave abnormalities) in a report of methaqualone and diphenhydramine intoxication (Matthew et al, 1968).

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Compared to barbiturates, marked respiratory depression is rare. Pulmonary edema and apnea may occur.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Noncardiogenic pulmonary edema developed in a 58 year old woman who developed profound hypotension (systolic BP 50 mm hg) after ingesting 20 to 30 tablets of methaqualone 250 mg and diphenhydramine 25 mg and was treated with forced diuresis (Caridis et al, 1967).
    B) HYPOVENTILATION
    1) WITH POISONING/EXPOSURE
    a) Respiratory depression and apnea occur in severe cases, especially if other CNS depressants are coingested (Gitelson, 1967; (Johnstone et al, 1971; Baggish et al, 1981).
    C) SUFFOCATING
    1) WITH POISONING/EXPOSURE
    a) Aspiration may occur in severe poisonings associated with CNS depression (Pascarelli, 1973; Coleman & Barone, 1981).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Ataxia, lethargy, limb hyperreflexia, seizures and coma may occur. Marked pyramidal signs such as hypertonicity, myoclonia and positive Babinsky responses may develop following severe poisoning.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) Dizziness, ataxia, slurred speech, and drowsiness may be seen with mild intoxication.
    b) Coma may develop and may persist for days (Brown & Goenechnea, 1973; (Coleman & Barone, 1981; Trese, 1981) Gitelson, 1967).
    B) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures or myoclonus may occur in severe overdoses (Lawson & Brown, 1967; Abboud et al, 1974).
    C) EXTRAPYRAMIDAL DISEASE
    1) WITH POISONING/EXPOSURE
    a) In severe poisoning, pyramidal signs such as hypertonicity, limb hyperreflexia, clonus, flailing limb motions, myoclonia and upgoing Babinski responses are common (Lawson & Brown, 1967; Pascarelli, 1973; Abboud et al, 1974).
    D) SPASMODIC MOVEMENT
    1) WITH POISONING/EXPOSURE
    a) Muscle fasciculation may occur (Gitelson, 1967; (Abboud et al, 1974)
    E) SYNCOPE
    1) WITH POISONING/EXPOSURE
    a) Syncope has been reported following the abuse of methaqualone smoked in combination with benzodiazepines and marijuana (Wilson et al, 1989).
    F) SECONDARY PERIPHERAL NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) There is one report of peripheral neuropathy secondary to a 7 gram overdose of methaqualone in a 73-year-old male (Constantinidis, 1975).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Salivation, nausea, vomiting, and epigastric discomfort may occur.
    3.8.2) CLINICAL EFFECTS
    A) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Increased salivation may occur and may increase the risk of aspiration (Abboud et al, 1974; Pascarelli, 1973).
    B) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting and abdominal pain have been reported (Pascarelli, 1973)
    C) DRUG-INDUCED ILEUS
    1) WITH POISONING/EXPOSURE
    a) Intestinal motility may become depressed for several days in severe cases (Gitelsen et al, 1967).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Elevations in serum aspartate aminotransferase developed in 8 of 72 patients in one series (Matthew et al, 1968).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) CYSTITIS
    1) WITH POISONING/EXPOSURE
    a) A severe necrotizing cystitis (dysuria, oliguria, frequency, suprapubic pain) has been reported after ingestion of byproducts of improper methaqualone synthesis (ie, ortho-toluidine) (Goldfarb & Finelli, 1974).

Hematologic

    3.13.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Blood clotting abnormalities, including thrombocytopenia and increased prothrombin and thromboplastin times, may be seen following acute overdoses.
    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION PATHWAY FINDING
    1) WITH POISONING/EXPOSURE
    a) In a series of patients with methaqualone and diphenhydramine intoxication (Mandrax), platelets dropped to 150,000 in 13/65 patients and the prothrombin ratio was greater than 1.3 in 9/72 (Matthew et al, 1968).
    b) A prolonged partial thromboplastin time has also been reported in 20% of cases (Lawson & Brown, 1967).
    B) RETINAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Trese (1981) reported a 23-year-old male who presented to the ED with retinal hemorrhage and thrombocytopenia (platelets 61,000 mm(3)) following an acute methaqualone overdose. Also notable were purpura across his back. Hemoglobin and hematocrit were also low.

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Fixed drug eruptions and erythema multiforme have been associated with the use of methaqualone.
    3.14.2) CLINICAL EFFECTS
    A) FIXED DRUG ERUPTION
    1) WITH THERAPEUTIC USE
    a) Cases of fixed drug eruption associated with the use of methaqualone have been reported (Slazinski & Knox, 1984; Parish et al, 1981; Heng, 1986).
    B) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - Parish et al (1981) report the case of a 23-year-old male presenting to the ED with a temperature of 103 degrees F (39.4 degrees C) and diffuse erythematous lesions over his entire body. The lesions appeared to be erythematous, macular-to-large and target-shaped. Vesicular bullae were seen on his shoulder, palms, soles, and penis. Treatment consisted of tapering doses of prednisone and resolution of the lesions occurred over several days.

Reproductive

    3.20.1) SUMMARY
    A) Methaqualone is classified as US FDA Pregnancy Category D.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Methaqualone is classified as US FDA Pregnancy Category D (Briggs et al, 1998).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Blood methaqualone levels are not clinically useful, however levels greater than 25 mg/L are consistent with significant intoxication in most patients.
    B) In severely intoxicated patients monitor CBC, liver and renal function tests, platelets, coagulation tests, electrolytes, arterial blood gases, and ECG.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) It is useful to MONITOR SGOT (AST), SGPT (ALT), electrolytes, glucose, and renal function tests in patients with severe intoxication.
    B) COAGULATION STUDIES
    1) Monitor prothrombin time or international normalized ratio (INR) in patients with severe intoxication.
    C) HEMATOLOGIC
    1) Monitor CBC in patients with severe intoxication.
    D) ACID/BASE
    1) Monitor arterial blood gases.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Monitor ECG in patients with severe intoxication.

Methods

    A) IMMUNOASSAY
    1) Semiquantitative and qualitative EMIT(R) homogeneous enzyme immunoassays are available for the measurement of methaqualone in urine. The detection limit (sensitivity) is 0.75 mcg/ml for methaqualone (Prod Info Emit (R), 1983; (Prod Info EMIT(R) - st- Urine methaqualone assay, 1983a).
    B) CHROMATOGRAPHY
    1) A GLC method for detecting methaqualone and metabolites in urine has been described (Kogan et al, 1978). Urine is the most suitable biofluid for drug detection analysis since levels are higher in urine than in serum.
    2) A TLC method for detecting methaqualone in urine has been described (Bailey & Jatlow, 1973).
    3) Maurer (1990) described a gas chromatography/mass spectrometry procedure to identify barbiturates and other sedative-hypnotics including methaqualone in urine.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Blood methaqualone levels are not clinically useful, however levels greater than 25 mg/L are consistent with significant intoxication in most patients.
    B) In severely intoxicated patients monitor CBC, liver and renal function tests, platelets, coagulation tests, electrolytes, arterial blood gases, and ECG.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    B) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    C) DRUG WITHDRAWAL
    1) ONSET occurs within 12 to 24 hours after the last drug dose and peaks in intensity at 48 to 72 hours (Kulberg, 1986).
    2) SYMPTOMS include disorientation, insomnia, hallucinations, and grand mal seizures, and may be treated with resubstitution of the drug and stepwise reduction of daily dose by 10 percent per day or with substitution of phenobarbital.
    3) PHENOBARBITAL may be started at 100 milligrams every 6 hours (3 to 6 milligrams/kilogram) and increased as necessary until withdrawal symptoms subside. After stabilization for 1 to 2 days, the phenobarbital may be tapered by 10 percent per day.

Enhanced Elimination

    A) EXTRACORPOREAL ELIMINATION
    1) Although hemodialysis and hemoperfusion are effective in removing methaqualone, they should be reserved for rare life-threatening situations. Many patients have been successfully treated without the aid of dialysis.
    B) HEMODIALYSIS
    1) Is effective in removing large amounts of drug in patients with severe intoxication.
    a) Using twin-coil dialysis, the blood level dropped from 10.5 milligrams/deciliter to 5.8 milligrams/deciliter after 2 hours in a patient who ingested 5 to 7.5 grams of methaqualone (Chardis et al, 1967).
    2) Experience with peritoneal and hemodialysis has revealed clearances of 7.5 and 23 milliliters/minute, respectively (Proudfoot et al, 1968).
    C) HEMOPERFUSION
    1) Clearances for methaqualone after ACAC hemoperfusion were high initially (275 milliliters/minute and 263 milliliters/minute) with a decrease to 150 milliliters/minute and 100 milliliters/minute at 2 hours (Chang et al, 1973).
    2) Resin hemoperfusion using an Amberlite XAD-4 resin cartridge at a plasma flow rate of 104 milliliters/minute was efficacious in removing methaqualone from a patient who had ingested 4.5 grams of drug. Mean plasma methaqualone clearance was 179 milliliters/minute (Baggish et al, 1981).
    3) Combined hemoperfusion hemodialysis in two overdose patients showed hemoperfusion clearance of 47 to 133 milliliters/minute and hemodialysis clearance of 102 to 131 milliliters/minute (Majelyne et al, 1979).
    4) ANIMALS - In an animal study at blood flow rates of 100 milliliters/minute, methaqualone clearance was 56 milliliters/minute during charcoal hemoperfusion and 100 milliliters/minute during resin hemoperfusion (Medd, 1974).
    a) Using XAD-4 resin hemoperfusion over 6 hours at blood flow rates of 200 milliliters/minute in dogs, methaqualone clearance ranged from 195 to 200 milliliters/minute (Rosenbaum, 1977).
    D) DIURESIS
    1) Forced diuresis is CONTRAINDICATED because of the possibility of pulmonary edema in patients intoxicated with the drug (Caridis et al, 1967). In addition, less than 2 percent of active methaqualone is eliminated via the kidney.

Range Of Toxicity

Summary

    A) Hypnotic effects occur in oral doses of 150 to 400 mg in adults. Coma has occurred following ingestion of 2.4 grams. Death has occurred following ingestion of 8 grams.
    B) Acute ingestion of greater than 800 mg in an adult is usually considered toxic. Ingestion of as little as one tablet in a child is considered toxic.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Doses of 150 milligrams to 400 milligrams in adults were used to produce hypnotic effects (Ellenhorn & Barceuloux, 1988).

Minimum Lethal Exposure

    A) ACUTE
    1) Fatalities have occurred in patients ingesting 8 grams (Ellenhorn & Barceuloux, 1988).

Maximum Tolerated Exposure

    A) GENERAL
    1) A patient's response to an overdose is variable because tolerance develops to the drug. Survival has been reported with the ingestion of 24 grams (300 milligrams/kilogram) (Ellenhorn & Barceleux, 1988).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) THERAPEUTIC SERUM CONCENTRATIONS - Have been reported up to 5 micrograms/milliliter (Ellenhorn & Barceleux, 1988).
    b) TOXIC LEVELS -
    1) Methaqualone blood levels between 20 and 80 milligrams/liter are consistent with significant intoxication in the majority of patients (Skoutakis & Acchiardo, 1983).
    2) CORRELATION - Of initial plasma level with grade of consciousness is not consistent because of varying tolerances to the drug.
    3) CHRONIC USERS and abusers of methaqualone may manifest less central nervous system depression in the presence of high levels than will non-abusers.
    4) In 6 fatal cases of methaqualone overdose, postmortem blood concentration of 5 to 42 milligrams/liter (mean 22 milligrams/liter) and 26 to 89 milligrams/liter (mean 55 milligrams/liter) were observed (Baselt & Cravey, 1977).
    5) In a fatal toquilone compositum (methaqualone plus diphenhydramine) overdose, biological fluid sampling revealed postmortem methaqualone concentrations of 800 mg/L, 30 mg/L, and 12 mg/L in blood, bile, and stomach, respectively (Fucci, 1996).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) In addition to sedative-hypnotic properties, methaqualone has anticonvulsant, antispasmodic, local anesthetic, and weak antihistaminic properties. It enhances codeine analgesia. Tolerance develops to the depressant, anticonvulsant, and behavioral effects.

Toxicologic Mechanism

    A) Methaqualone is a quinazoline derivative, lipid soluble non-barbiturate sedative-hypnotic. Some of the adverse effects may be related to impurities in street sources, such as ortho-toluidine. Pharmacological activity is primarily due to central nervous system depression. The anticonvulsant activity is mediated by serotonin pathways in the brain; drugs that increase brain serotonin act synergistically. Other activities include antispasmodic, local anesthetic, and antihistaminic effects (Prod Info Parest(R), methaqualone, 1981).

References

General Bibliography

    1) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    2) Abboud RT, Freedman MT, & Rogers RM: Methaqualone poisoning with muscular hyperactivity necessitating the use of curare. Chest 1974; 65:204.
    3) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    4) Alvan G, Lindgren JE, & Bogentoft C: Plasma kinetics of methaqualone in man after single oral doses. Eur J Clin Pharmacol 1973; 6:187-190.
    5) Alvan G: Plasma concentrations and effects of methaqualone after single and multiple oral doses in man. Eur J Clin Pharmacol 1974; 7:449-454.
    6) Baggish D, Gray S, & Jatlow P: Treatment of methaqualone overdose with resin hemoperfusion. Yale J Biol Med 1981; 54:147-150.
    7) Bailey DN & Jatlow PI: Methaqualone overdose: analytical methodology and the significance of serum drug concentrations. Clin Chem 1973; 19:615-620.
    8) Baselt RC & Cravey RH: A compendium of therapeutic and toxic concentrations of toxicologically significant drugs in human biofluids. J Anal Toxicol 1977.
    9) Baselt RC: Disposition of toxic drugs and chemicals in man. Vol 1. Centrally-acting drugs, Biomedical Publications, Canton, CT, 1978, pp 295-296.
    10) Briggs GG, Freeman RK, & Yaffe SJ: Drugs in Pregnancy and Lactation. 5th ed, Williams and Wilkins, Baltimore, MD, 1998.
    11) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    12) Brown SS: Assay of methaqualone in blood, In: Assay of Drugs and Other Trace Compounds in Biological Fluids, North-Holland, New York, NY, 1976, pp 179-194.
    13) Burston GR: Self-poisoning with Mandrax. Practitioner 1967; 199:340-344.
    14) Caridis DT, McAndrew GM, & Matheson NA: Hemodialysis in poisoning with methaqualone and diphenhydramine. Lancet 1967; 1:51-52.
    15) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    16) Chang TMS, Coffey JF, & Lister C: Methaqualone, methyprylon, and glutethimide clearance by the ACAC microcapsule artificial kidney: in vitro and in patients with acute intoxication. Trans Am Soc Artif Intern Organs 1973; 19:87.
    17) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    18) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    19) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    20) Coleman JB & Barone: Abuse potential of methaqualone-diphenhydramine combination (letter). Am J Hosp Pharm 1981; 38:160.
    21) Constantinidis K: Severe peripheral neuropathy after Mandrax(R) overdose. Br Med J 1975; 2:370.
    22) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    23) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    24) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    25) Fucci N: A case of lethal intoxication after ingestion of toquilone compositum. Am J Forensic Med & Pathol 1996; 17:231-232.
    26) Goldfarb M & Finelli R: Necrotizing cystitis secondary to bootleg methaqualone. Urology 1974; 3:54-55.
    27) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    28) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    29) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    30) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    31) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    32) Heng MC: Fixed drug eruption due to methaqualone. Aust J Dermatol 1986; 27:83-85.
    33) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    34) Johnstone RE, Manitsas GT, & Smith EJ: Apnea following methaqualone ingestion: report of a case. Ohio State Med J 1971; 67:1018.
    35) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    36) Kogan MJ, Jukofsky D, & Verebey K: Detection of methaqualone in human urine by radio immunoassay and gas-liquid chromatography after a therapeutic dose. Clin Chem 1978; 24:1425-1427.
    37) Kulberg A: Substance abuse: clinical identification and management. Pediatr Clin North Am 1986; 33:325-361.
    38) Lawson AHH & Brown SS: Acute methaqualone (Mandrax(R)) poisoning. Scot Med J 1967; 12:63-68.
    39) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    40) Majelyne W, De Clerck F, & Demeter J: Treatment evaluation of a severe methaqualone intoxication in man. Vet Human Toxicology 1979; 21(suppl):201-204.
    41) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    42) Matthew H, Proudfoot AT, & Brown SS: Mandrax poisoning: conservative management of 116 patients. Br Med J 1968; 2:101-102.
    43) Medd RK: Treatment of experimental drug intoxication in dogs by hemodialysis and hemoperfusion. Proc Int Soc Artif Organs 1974; 1:87.
    44) Morris RN: Plasma levels and absorption of methaqualone after oral administration to man. Clin Pharmacol Ther 1972; 13:719.
    45) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    46) Pan HY & Huang CY: Alternating skew deviations associated with Mandrax(R) overdosage. Aust NZ Med J 1984; 14:265-266.
    47) Parish LC, Cander L, & Witkowski JA: Erythema multiforme due to methaqualone. Acta Derm Venereol 1981; 61:88-89.
    48) Pascarelli EF: Methaqualone abuse, the quiet epidemic. JAMA 1973; 224:1512-1514.
    49) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    50) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    51) Product Information: EMIT(R) - st- Urine methaqualone assay. Syva Co, Palo Alto, CA, 1983a.
    52) Product Information: Parest(R), methaqualone. Parke-Davis, Detroit, MI, 1981.
    53) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    54) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    55) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    56) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    57) Proudfoot AT, Noble J, & Nimmo J: Peritoneal dialysis and hemodialysis in methaqualone (Mandrax(R)) poisoning. Scot Med J 1968; 13:232-236.
    58) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    59) Rosenbaum JL: Hemoperfusion in the treatment of acute poisoning, In: Artificial Organs (ed. RM Kenedi, JM Courtney, JDS Gaylor, & TT Gilchrist), Macmillan, London, UK, 1977.
    60) S Sweetman : Martindale: The Complete Drug Reference, (Electronic version). Pharmaceutical Press. London, UK (Internet Version). Edition expires 2001; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    61) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    62) Skoutakis VA & Acchiardo SR: Methaqualone poisoning: diagnosis and treatment. Clin Toxicol Consult 1983; 5:23-31.
    63) Slazinski L & Knox D: Fixed drug eruptions due to methaqualone. Arch Dermatol 1984; 120:1073-1075.
    64) Smyth RD, Lee JK, & Polk A: Bioavailability of methaqualone. J Clin Pharmacol 1973; 13:391-400.
    65) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    66) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    67) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    68) Trese M: Retinal hemorrhage caused by overdose of methaqualone (quaalude). Am J Ophthalmology 1981; 91:201-203.
    69) Wason S: Methaqualone. Clin Toxicol Rev 1982; 4:9.