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PLANTS-CATHA EDULIS (KHAT)

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The stimulating and sympathomimetic effects of khat are due to the phenylpropylamines cathinone and, to a much lesser extent, cathine (norpseudoephedrine).
    B) Khat is the predominant trivial name for the plant Catha edulis and its leaves, which contain sympathomimetic alkaloids.

Specific Substances

    A) SYNONYMS
    1) Cat
    2) Gat (Yemen)
    3) Kaht
    4) Khat
    5) Kat
    6) Miraa (Kenya)
    7) Muhulo (Tanzania)
    8) Mulka
    9) Musitate (Uganda)
    10) Q'at
    11) Qat (Yemen)
    12) Quat
    13) Tchai
    14) Tschat (Ethiopia)
    15) Tshaad

Available Forms Sources

    A) FORMS
    1) GATHERING: The sprouting ends of branches and young shoots are harvested and sold in bundles which are usually tightly wrapped in plastic, damp paper or false banana leaves. The wrapping is meant to avoid wilting and drying; unprotected leaves lose much of their potency within one day of harvest.
    2) Cathinone has been included in schedule I, and cathine in schedule III, of the UN Convention on Psychotropic Substances following a recommendation of the World Health Organization (Elme et al, 1987). Thus, cathinone is only available for scientific use.
    3) HAGIGAT: An illicit capsule containing 200 mg cathinone and sold in Israel as a substitute for Khat. It can be purchased at convenience stores as a natural stimulant and aphrodisiac for men and women. In Hebrew, the translation of Hagigat is "Gat/Khat" party. Of note, chewing Khat leaves is a tradition followed by many immigrants to Israel, and has been adopted by many others; its use is considered legal (Bentur et al, 2008).
    B) USES
    1) Khat has a slightly aromatic odor and sweet astringent taste. Usually, the leaves are chewed and the juice is swallowed while the residues are kept in the cheek (as a quid of tobacco) for up to 2 hours and are then expectorated. Sometimes, the chewed leaves are also swallowed. Infrequently, khat is brewed as a tea, or it is crushed and mixed with honey to make a paste.
    2) Khat is often used as a social drug. In some regions, especially in Yemen, it is chewed in the setting of gatherings that may be quite formal.
    3) A 1995 Ethiopian study found that Khat consumption, traditionally confined to certain segments of the population, had become popular among all segments, with adolescents and young adults the most affected groups (Selassie & Gebre, 1996).
    4) A study of 207 Somalis living in London found that 78% had used Khat and that a majority (76%) used more after relocation to London, playing a role in supporting the cultural identity of the Somalian community (Griffiths, 1997).
    5) Historically, khat has been used for the treatment of fatigue and depression, as well as for obesity and gastric ulcers (Al-Meshal, 1988).
    6) Cathine (d-norpseudoephedrine) is widely used in certain countries as the active principle of pharmaceutical preparations inducing anorexia (Eisenberg et al, 1987).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Khat has a slightly aromatic odor and sweet astringent taste. Usually, the leaves are chewed and the juice is swallowed while the residues are kept in the cheek (as a quid of tobacco) for up to 2 hours and are then expectorated. Sometimes, the chewed leaves are also swallowed. Infrequently, khat is brewed as a tea, or it is crushed and mixed with honey to make a paste. It has traditionally been used in parts of Africa (ie, Somalia and Ethiopia) and the Middle East.
    B) PLANT: Catha edulis is an evergreen bush or tree of the family Celastraceae. Khat grows in southwestern Arabia and in East Africa between Sudan and Madagascar, and it is cultivated in these regions. There is also a sporadic khat cultivation in Israel.
    C) TOXICOKINETICS: Khat is the predominant trivial name for the plant Catha edulis and its leaves, which contain sympathomimetic alkaloids. The primary active ingredient is cathinone a sympathomimetic alkaloids; the other minor alkaloid is cathine ((+)- or d-norpseudoephedrine), and (-)-norephedrine. The stimulating and sympathomimetic effects of khat are due to the phenylpropylamines cathinone and, to a much lesser extent, cathine (norpseudoephedrine).
    D) WITH POISONING/EXPOSURE
    1) SUMMARY: The acute effects of chewing khat are due to the phenylpropylamine content of the leaves. SYMPTOMS: Central stimulation and activation of the sympathetic nervous system, which is usually mild and rarely life-threatening except in the elderly and those with underlying cardiovascular disease. ONSET: Usually occurs within 20 minutes. DURATION: Several hours.
    2) MILD TO MODERATE TOXICITY: COMMON: Anorexia with malnutrition and constipation, headache, hyperactivity, insomnia, and tremors are common effects. Dilated pupils can occur. OTHER EVENTS: CARDIOVASCULAR: Mild hypertension and tachycardia with palpitations can occur. GASTROINTESTINAL: Gastritis, ulcers, and severe nausea are possible. OTHER: Urinary retention may develop.
    3) SEVERE TOXICITY: Cathinone can be very addictive. Dysrhythmias and myocardial ischemia are rare effects.
    4) NEURO: Behavioral changes in users may include euphoria, garrulous speech, or aggressive verbal outbursts. Rarely, schizophrenic behavior or manic-like psychosis may develop.
    5) HEENT: Dilated pupils, chemosis, pseudoexophthalmus, dry mouth, and stomatitis have been reported.
    6) VITAL SIGNS: Increased heart rate, blood pressure, respirations, and temperature may be seen.
    0.2.3) VITAL SIGNS
    A) Increased heart rate, blood pressure, respirations, and temperature may be seen.
    0.2.20) REPRODUCTIVE
    A) Low infant birth weight has been reported.

Laboratory Monitoring

    A) Khat contains phenylalkylamines which may cross-react with related compounds such as amphetamine or phenylpropanolamine.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Khat abusers usually chew the plant material, but usually do not swallow. Following oral exposure inducing emesis is not recommended because of the potential for cardiovascular instability.
    B) 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.
    C) Behavioral changes, increased motor activity, and hyperventilation generally require only supportive therapy and ECG monitoring.
    D) SEIZURES: Although not yet reported with khat, seizures are possible.
    1) 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).
    a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    E) TACHYARRHYTHMIAS: Sedate with benzodiazepines, if agitated. Esmolol may be useful if tachycardia with hemodynamic compromise develops.
    F) VENTRICULAR DYSRHYTHMIAS/SUMMARY: Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    G) HYPERTENSION: Monitor vital signs regularly. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary. Sedation with benzodiazepines may be helpful in agitated patients with hypertension and tachycardia. For severe hypertension sodium nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. See main treatment section for doses.

Range Of Toxicity

    A) Toxic effects may occur with normal use.

Clinical Effects

Summary Of Exposure

    A) USES: Khat has a slightly aromatic odor and sweet astringent taste. Usually, the leaves are chewed and the juice is swallowed while the residues are kept in the cheek (as a quid of tobacco) for up to 2 hours and are then expectorated. Sometimes, the chewed leaves are also swallowed. Infrequently, khat is brewed as a tea, or it is crushed and mixed with honey to make a paste. It has traditionally been used in parts of Africa (ie, Somalia and Ethiopia) and the Middle East.
    B) PLANT: Catha edulis is an evergreen bush or tree of the family Celastraceae. Khat grows in southwestern Arabia and in East Africa between Sudan and Madagascar, and it is cultivated in these regions. There is also a sporadic khat cultivation in Israel.
    C) TOXICOKINETICS: Khat is the predominant trivial name for the plant Catha edulis and its leaves, which contain sympathomimetic alkaloids. The primary active ingredient is cathinone a sympathomimetic alkaloids; the other minor alkaloid is cathine ((+)- or d-norpseudoephedrine), and (-)-norephedrine. The stimulating and sympathomimetic effects of khat are due to the phenylpropylamines cathinone and, to a much lesser extent, cathine (norpseudoephedrine).
    D) WITH POISONING/EXPOSURE
    1) SUMMARY: The acute effects of chewing khat are due to the phenylpropylamine content of the leaves. SYMPTOMS: Central stimulation and activation of the sympathetic nervous system, which is usually mild and rarely life-threatening except in the elderly and those with underlying cardiovascular disease. ONSET: Usually occurs within 20 minutes. DURATION: Several hours.
    2) MILD TO MODERATE TOXICITY: COMMON: Anorexia with malnutrition and constipation, headache, hyperactivity, insomnia, and tremors are common effects. Dilated pupils can occur. OTHER EVENTS: CARDIOVASCULAR: Mild hypertension and tachycardia with palpitations can occur. GASTROINTESTINAL: Gastritis, ulcers, and severe nausea are possible. OTHER: Urinary retention may develop.
    3) SEVERE TOXICITY: Cathinone can be very addictive. Dysrhythmias and myocardial ischemia are rare effects.
    4) NEURO: Behavioral changes in users may include euphoria, garrulous speech, or aggressive verbal outbursts. Rarely, schizophrenic behavior or manic-like psychosis may develop.
    5) HEENT: Dilated pupils, chemosis, pseudoexophthalmus, dry mouth, and stomatitis have been reported.
    6) VITAL SIGNS: Increased heart rate, blood pressure, respirations, and temperature may be seen.

Vital Signs

    3.3.1) SUMMARY
    A) Increased heart rate, blood pressure, respirations, and temperature may be seen.
    3.3.2) RESPIRATIONS
    A) The respiration rate commonly increases (Nencini et al, 1984a).
    3.3.3) TEMPERATURE
    A) Hyperthermia and sweating are common (Halbach, 1972). A slight increase in body temperature occurs (Nencini et al, 1984a).
    3.3.4) BLOOD PRESSURE
    A) Mild increases in blood pressure are common (Nencini et al, 1984a; Widler et al, 1994).
    3.3.5) PULSE
    A) Tachycardia and palpitations may occur (Halbach, 1972).

Heent

    3.4.2) HEAD
    A) Temporomandibular joint dysfunction has been associated with khat chewing (Hill & Gibson, 1987).
    3.4.3) EYES
    A) CHEMOSIS: Conjunctival edema may be seen with khat users (Luqman & Danowski, 1976).
    B) MYDRIASIS may be seen with khat users (Halbach, 1972).
    C) OPTIC ATROPHY: Bilateral optic atrophy with central scotomas has been reported in two high-dose users of khat (Roper, 1986).
    D) PSEUDOEXOPHTHALMUS may be seen with khat users (Luqman & Danowski, 1976; Roper, 1986).
    3.4.6) THROAT
    A) FRICTIONAL KERATOSIS: Stomatitis, periodontal disease, and frictional keratosis of the buccal mucosa have been reported (Halbach, 1972; Hill & Gibson, 1987).
    B) XEROSTOMIA: Mouth dryness is frequently reported (Soufi et al, 1991).
    C) TEETH DISCOLORATION: Regular Khat use causes brownish staining of the teeth.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) VASCULAR DISORDER
    1) WITH POISONING/EXPOSURE
    a) Exaggerated cardiovascular response to physical effort may be noted (Galkin V & Mironychev, 1964) (LeBelle et al, 1965).
    B) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Palpitations and tachycardia have occurred (Bentur et al, 2008; Halbach, 1972).
    b) ONSET: Effects may be seen in 15 to 20 minutes after chewing/ingestion (Lawrence Review, 1984).
    C) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Mild increases in blood pressure are common (Nencini et al, 1984b; Widler et al, 1994).
    b) Mean arterial pressure increases by 20 to 30% during khat use (Nencini & Ahmed, 1989).
    c) In a 10 month, prospective, observational study from Israel of 34 Hagigat users (illicit capsules containing 200 mg cathinone), hypertension (140/90 to 190/110 mmHg) was reported in 9 (26.5%) patients. The median age of users in this study was 25 years. The capsules were analyzed and contained a high dose of cathinone (ie, each capsule was the equivalent of 555.5 g Khat leaves as compared to an average chewing session that is equivalent to being exposed to 100-200 g of Khat leaves) (Bentur et al, 2008).
    D) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) Arrhythmias and myocardial insufficiency and infarct have been described, particularly in the elderly and predisposed (Halbach, 1972).
    E) MYOCARDIAL ISCHEMIA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a 10 month, prospective, observational study from Israel of 34 Hagigat users (illicit capsules containing 200 mg cathinone), myocardial ischemia was reported in 3 young adults (ranging in age from 16 to 35 years). Two patients developed myocardial ischemia and pulmonary edema. One patient, a 16-year-old male, required mechanical ventilation for several days. All patients fully recovered (Bentur et al, 2008).
    F) PERIPHERAL ISCHEMIA
    1) WITH POISONING/EXPOSURE
    a) Users complain of cold extremities possibly due to peripheral vasoconstriction (Luqman & Danowski, 1976).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IN-VITRO STUDIES
    a) CHRONOTROPIC EFFECT: Khat extracts have a positive chronotropic effect on in vitro heart preparations when exposure is acute, but have a negative chronotropic effect following prolonged exposure (Nabil et al, 1986).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) Shortness of breath may occur (Giannini et al, 1992).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Pulmonary edema has been described, particularly in older and predisposed individuals (Halbach, 1972).
    C) HYPERVENTILATION
    1) WITH POISONING/EXPOSURE
    a) A mild increase in respiratory rate is common (Nencini et al, 1984a).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a 10 month, prospective, observational study from Israel of 34 Hagigat users (illicit capsules containing 200 mg cathinone), headache (n=17 {50%}), restlessness (n=4 {11.8%}), paresthesias (n=4 {11.8%}), and dizziness (n=4 {11.8%}) were commonly reported neurotoxic effects. In 11 patients, prolonged headache was reported for up to 7 days after exposure. Other symptoms that were reported less frequently included: anxiety, nervousness, mood changes, hallucinations, and difficulty concentrating (Bentur et al, 2008).
    B) CEREBROVASCULAR ACCIDENT
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A previously healthy 41-year-old man experienced a major stroke after chewing khat. He had chewed khat regularly for 11 years and had a familial history of severe arterial hypertension and neurological deficit in family members who also regularly chewed khat. On admission, his blood pressure was 190/95 mm Hg. Several hours after the first stroke episode, CT scan revealed a right-sided middle cerebral artery infarction. Following treatment with aspirin and amlodipine, he recovered completely. He did not take his medications regularly, and experienced another stroke episode after chewing khat. MRI of the brain 11 days after the second stroke episode revealed a larger middle cerebral artery infarction and diffuse white matter abnormalities. The patient recovered completely after discontinuing khat use (Vanwalleghem et al, 2006).
    C) CEREBRAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 28-year-old woman developed an intracerebral hemorrhage following cathinone abuse (ie, "Hagigat" - illicit capsules containing 200 mg cathinone) and required surgical intervention. She developed permanent spasticity of the left hand and paresis of the left leg (Bentur et al, 2008).
    D) HYPERESTHESIA
    1) WITH POISONING/EXPOSURE
    a) Hyperesthesia has been reported infrequently (Kalix, 1988).
    E) INSOMNIA
    1) WITH POISONING/EXPOSURE
    a) Insomnia is a commonly reported (Halbach, 1972).
    F) PARKINSONISM
    1) WITH POISONING/EXPOSURE
    a) METHCATHINONE (EPHEDRONE) ABUSE: Four cases of manganism, presented as impaired postural control, hypophonic dysarthria, hypokinesia and dystonia have been reported in persons using repeated intravenous injections of methcathinone solution, prepared by combining pseudoephedrine and potassium permanganate. Manganese content of the final mixture was 0.6 g/L with ephedrone yield of approximately 44% (Sikk et al, 2007). One man developed manganese-induced levodopa-resistant parkinsonism with profound hypophonia after intravenously injecting himself once or twice daily for several months with a methcathinone solution, prepared by combining 12 tablets containing 60 mg of pseudoephedrine hydrochloride with 0.3 g of potassium permanganate (deBie et al, 2007).
    G) CENTRAL STIMULANT ADVERSE REACTION
    1) WITH POISONING/EXPOSURE
    a) Tremors, hyperactivity, increased alertness, and irritability may develop (Kalix, 1988; Pantelis et al, 1989; Giannini et al, 1992).
    b) Amphetamine-like excitation and euphoria have occurred (Widler et al, 1994).
    H) CEREBRAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Cerebral hemorrhage has been reported (Halbach, 1972).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PERSONALITY DISORDER
    a) Hypermotility and stereotyped behavior of animals induced by cathinone have been reported (Zelger et al, 1980). These are due to enhanced transmitter release from catecholaminergic nerve terminals in the CNS (Kalix, 1984a).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a 10 month, prospective, observational study from Israel of 34 Hagigat users (illicit capsules containing 200 mg cathinone), vomiting (n=11 {32.4%}), nausea (n=8 {23.5%}), and abdominal pain (n=7 {20.6%}) were commonly reported toxic effects (Bentur et al, 2008).
    B) LOSS OF APPETITE
    1) WITH POISONING/EXPOSURE
    a) Anorexia is can develop in khat users (Halbach, 1972; Bentur et al, 2008).
    C) CONSTIPATION
    1) WITH POISONING/EXPOSURE
    a) Constipation is common in khat users (Halbach, 1972; Nencini & Ahmed, 1989).
    D) ESOPHAGITIS
    1) WITH POISONING/EXPOSURE
    a) Esophagitis and meteorism have also been observed (Halbach, 1972).
    E) DRUG-INDUCED ILEUS
    1) WITH POISONING/EXPOSURE
    a) Paralytic ileus has also been attributed to habitual khat use (Halbach, 1972).
    F) GASTRIC ULCER
    1) WITH POISONING/EXPOSURE
    a) Ulcers, predominantly gastric vs duodenal, are reported in habitual users. These effects may be due to the high tannin content of the material (Luqman & Danowski, 1976).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GASTRIC ULCER
    a) A daily oral dose of 200 mg/kg of the flavonoid fraction of Catha edulis, given to rats for 2 days prior to pylorus ligation and phenylbutazone administration, had significant gastric anti-ulcer activity (Tariq et al, 1984).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL EJACULATION
    1) WITH POISONING/EXPOSURE
    a) Delayed ejaculation has been reported (Luqman & Danowski, 1976).
    B) IMPOTENCE
    1) WITH POISONING/EXPOSURE
    a) Spermatorrhea with testicular pain and impotence have been associated with chronic khat consumption (Halbach, 1972).
    C) SEMEN EXAM: ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Khat may inhibit spermatogenesis and decrease sperm counts (Drake, 1988).
    D) RETENTION OF URINE
    1) WITH POISONING/EXPOSURE
    a) Urinary retention has been reported (Luqman & Danowski, 1976; Giannini et al, 1986).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Diaphoresis may occur (Halbach, 1972).
    B) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) Flushing can develop (Halbach, 1972).

Reproductive

    3.20.1) SUMMARY
    A) Low infant birth weight has been reported.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) HUMANS - Teratogenic effects have not been described.
    2) ANIMALS - Khat has been reported to induce teratogenic and congenital defects in chicks (Hammonda, 1972).
    3.20.3) EFFECTS IN PREGNANCY
    A) HUMANS
    1) Khat may contribute to hypertensive disease of pregnancy (Drake, 1988).
    2) Low infant birth weight has been reported in khat-chewing mothers (Ghani et al, 1987).
    3) Khat has been shown to decrease uteroplacental blood flow (Jansson et al, 1988).
    B) ANIMAL STUDIES
    1) Khat, administered to rats, in doses of 250 and 500 mg, had a significant and dose dependent anti-implantation activity (Tariq et al, 1987).
    2) Rats receiving the above dose at days 8 to 12 of pregnancy had a significant increase in abortions (Tariq et al, 1987).
    3) In experimental animals, anti-estrogenic activity and decreased estradiol have been noted (Al-Meshal et al, 1984; Tariq et al, 1987).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Poor lactation has been reported (Luqman & Danowski, 1976).
    a) MOTHERS - Although the dopaminergic effects of khat may inhibit prolactin secretion and decrease breast milk production, no alteration in plasma prolactin levels has been observed (Nencini & Ahmed, 1989).
    2) CHILD - The khat alkaloid cathine (d-norpseudoephedrine) is excreted in the breast milk of women who chew khat and has been found in the urine of a breast-fed infant (Kristiansson et al, 1987).
    a) Anticipated effects in the infant include anorexia, constipation, and GI upset (Kristiansson et al, 1987).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) ESOPHAGEAL CARCINOMA
    1) Incidence of esophageal cancer may be increased by khat chewing, but this has not been confirmed (Kalix, 1990).
    B) MOUTH CARCINOMA
    1) One case series suggested a relationship between long term khat chewing and oral cancer (Soufi et al, 1991).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Khat contains phenylalkylamines which may cross-react with related compounds such as amphetamine or phenylpropanolamine.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Plasma concentrations of cathinone correlate with its stimulant and sympathomimetic effects (Brenneisen et al, 1990; Widler et al, 1994)
    2) Peak plasma concentrations - The chewing of a portion of khat containing per kg body weight 0.80 mg cathinone, 0.67 mg cathine, and 0.37 mg norephedrine resulted in peak plasma concentrations of 127 ng/ml after 127 min, 89 ng/ml after 183 min, and 110 ng/ml after 200 min, respectively (Widler et al, 1994). Part of the latter two compounds originates from the metabolism of cathinone.
    a) The ingestion of 0.5 mg cathinone/ kg body weight resulted in a peak plasma concentration of 107ng/ml after 72 min (Brenneisen et al, 1990). The ingestion of 60 mg cathine (d-norpseudoephedrine) resulted in a peak plasma concentration of 200mg/ml at 1.3 hours (Frosch, 1977).
    4.1.3) URINE
    A) URINARY LEVELS
    1) Cathinone, norephedrine, and norpseudoephedrine can be detected in urine by HPLC and GC/MS (Brenneisen et al, 1986). With common screening tests, these phenylalkylamines may be misidentified by cross-reacting as amphetamine or phenylpropanolamine (d,1-norephedrine).

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) For the identification of khat samples by forensic or law enforcement authorities, a rapid TLC test has been developed (Lehmann et al, 1990).
    2) A GC-MS method for the identification of the khat alkaloids and their isomers in plant material has been described by LeBelle et al (1993).
    3) Ultraviolet spectrophotometry, GLC, and GC-MS methods are discussed by Dal Cason (1992).
    4) Cathinone, its synthetic congener methcathinone, and the isomers of norephedrine and ephedrine can readily be distinguished in drug samples by infrared spectroscopy (Dal Cason, 1992).
    5) Cathinone can also be identified by thin layer chromatograpy, vapor phase infrared detection, and mass spectrometry (Lee, 1995).
    a) A quantitative spectrophotometric analytical technique has been developed that is linear in the range of 0.08 to 24 mcg/mL with a detection limit of 0.08 mcg/mL (al-Obaid, 1998). This technique may be applied to analysis of cathinone in Khat leaves.
    6) In plant material that has been dried and stored, cathinone is largely converted to cathine and therefore, difficult to detect. On the other hand, cathinone is readily detected in material tthat has been kept refrigerated for 10 days or frozen up to one month (Lee, 1995).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with persistent vital sign abnormalities, psychiatric symptoms, or evidence of organ ischemia or injury should be admitted for observation and treatment.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Most patients will become asymptomatic after a 4 to 6 hour observation period and can then be discharged.

Monitoring

    A) Khat contains phenylalkylamines which may cross-react with related compounds such as amphetamine or phenylpropanolamine.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Khat abusers usually chew the plant material, but usually do not swallow the plant. Following oral exposure inducing emesis is not recommended because of the potential for cardiovascular instability.
    B) 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) SUPPORT
    1) The CNS stimulation may require sedation with benzodiazepines or droperidol.
    a) CAUTION: DROPERIDOL: Based on cases of QT prolongation and/or torsades de pointes in patients receiving droperidol at doses at or below recommended dosing, it should be reserved for use in patients who fail to show an acceptable response to other agents (Anon , 2001).
    b) A baseline ECG (repeat as indicated) and continuous cardiac monitoring for 3 hours are recommended for all patients receiving droperidol.
    2) Tachycardia may respond to sedation with benzodiazepines. Ventricular dysrhythmias may respond to lidocaine.
    3) Hypertension seldom requires treatment. Severe hypertension may be treated with nitroprusside, labetalol, nifedipine, or hydralazine.
    4) Hyperthermia may be controlled with cooling blanket or similar measures.
    B) MONITORING OF PATIENT
    1) Monitor ECG and vital signs of symptomatic patients.
    C) PSYCHOMOTOR AGITATION
    1) MILD CNS SYMPTOMS
    a) Agitation, disorientation, increased motor activity, euphoria, hyperventilation and tachypnea generally require only conservative support therapy. In severe cases diazepam may be necessary (Kalix, 1988).
    b) INDICATION
    1) If patient is severely agitated, sedate with IV benzodiazepines.
    c) DIAZEPAM DOSE
    1) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    2) 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 (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    d) LORAZEPAM DOSE
    1) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
    2) 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 (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    e) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation.
    f) Extreme agitation and hallucinations may respond to intravenous droperidol (up to 0.1 mg/kg).
    2) PSYCHOSIS
    a) Treat with neuroleptics such as phenothiazine or butyrophenone. Chlorpromazine, haloperidol, and thioridazine have all been used with success (Kalix, 1988).
    b) HALOPERIDOL: 5 to 10 mg orally or IV (adult), 0.05 to 0.1 mg/kg orally or IV (child); repeat as necessary in 10 to 60 minutes up to 10 to 30 mg in an adult.
    c) CHLORPROMAZINE: No more than 0.5 mg/kg IM, repeated after 30 minutes if necessary.
    D) TACHYARRHYTHMIA
    1) Tachycardia usually responds to mild sedation with benzodiazepines.
    2) DIAZEPAM: 5 to 10 mg orally or IV (adult), 0.05 to 0.1 mg/kg orally or IV up to 10 mg/dose (child); repeat as necessary in 10 to 60 minutes up to 30 mg in an adult.
    3) TACHYCARDIA SUMMARY
    a) Evaluate patient to be sure that tachycardia is not a physiologic response to dehydration, anemia, hypotension, fever, sepsis, or hypoxia. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops.
    b) If therapy is required, a short acting, cardioselective agent such as esmolol is generally preferred (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
    c) ESMOLOL/ADULT LOADING DOSE
    1) Infuse 500 micrograms/kilogram (0.5 mg/kg) IV over 1 minute (Neumar et al, 2010).
    d) ESMOLOL/ADULT MAINTENANCE DOSE
    1) Follow loading dose with infusion of 50 mcg/kg per minute (0.05 mg/kg per minute) (Neumar et al, 2010).
    2) EVALUATION OF RESPONSE: If response is inadequate, infuse second loading bolus of 0.5 mg/kg over 1 minute and increase the maintenance infusion to 100 mcg/kg (0.1 mg/kg) per minute. Reevaluate therapeutic effect, increase in the same manner if required to a maximum infusion rate of 300 mcg/kg (0.3 mg/kg) per minute (Neumar et al, 2010).
    3) The manufacturer recommends that a maximum of 3 loading doses be used (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
    4) END POINT OF THERAPY: As the desired heart rate or blood pressure is approached, omit loading dose and adjust maintenance infusion as required (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
    e) CAUTION
    1) Esmolol is a short acting beta-adrenergic blocking agent with negative inotropic effects. Esmolol should be avoided in patients with asthma, obstructive airway disease, decompensated heart failure and pre-excited atrial fibrillation (wide complex irregular tachycardia) or atrial flutter (Neumar et al, 2010).
    E) VENTRICULAR ARRHYTHMIA
    1) VENTRICULAR DYSRHYTHMIAS SUMMARY
    a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    2) LIDOCAINE
    a) LIDOCAINE/INDICATIONS
    1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).
    b) LIDOCAINE/DOSE
    1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
    a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
    2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    c) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).
    d) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    3) PROCAINAMIDE
    a) PROCAINAMIDE/INDICATIONS
    1) An alternative drug in the treatment of PVCs or recurrent ventricular tachycardia when lidocaine is contraindicated or not effective. It should be avoided when the ingestion involves agents with quinidine-like effects (e.g. tricyclic antidepressants, phenothiazines, chloroquine, antidysrhythmics) and when the ECG reveals QRS widening or QT prolongation suspected to be secondary to overdose(Neumar et al, 2010; Vanden Hoek,TL,et al).
    b) PROCAINAMIDE/ADULT LOADING DOSE
    1) 20 to 50 milligrams/minute IV until dysrhythmia is suppressed or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%), or a total dose of 17 milligrams/kilogram is given (1.2 grams for a 70 kilogram person) (Neumar et al, 2010).
    2) ALTERNATIVE DOSING: 100 mg every 5 minutes until dysrhythmia is controlled, or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%) or 17 mg/kg have been given (Neumar et al, 2010).
    3) MAXIMUM DOSE: 17 milligrams/kilogram (Neumar et al, 2010).
    c) PROCAINAMIDE/CONTROLLED INFUSION
    1) In conscious patients, procainamide should be administered as a controlled infusion (20 milligrams/minute) because of the risk of QT prolongation and its hypotensive effects (Link et al, 2015)
    d) PROCAINAMIDE/ADULT MAINTENANCE DOSE
    1) 1 to 4 milligrams/minute via an intravenous infusion (Neumar et al, 2010).
    e) PROCAINAMIDE/PEDIATRIC LOADING DOSE
    1) 15 milligrams/kilogram IV/Intraosseously over 30 to 60 minutes; discontinue if hypotension develops or the QRS widens by 50% (Kleinman et al, 2010).
    f) PROCAINAMIDE/PEDIATRIC MAINTENANCE DOSE
    1) Initiate at 20 mcg/kg/minute and increase in 10 mcg/kg/minute increments every 15 to 30 minutes until desired effect is achieved; up to 80 mcg/kg/minute (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    g) PROCAINAMIDE/PEDIATRIC MAXIMUM DOSE
    1) 2 grams/day (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    h) MONITORING PARAMETERS
    1) ECG, blood pressure, and blood concentrations (Prod Info procainamide HCl IV, IM injection solution, 2011). Procainamide can produce hypotension and QT prolongation (Link et al, 2015).
    i) AVOID
    1) Avoid in patients with QT prolongation and CHF (Neumar et al, 2010).
    F) HYPERTENSIVE EPISODE
    1) Hypertension usually responds to sedation with benzodiazepines.
    2) DIAZEPAM: 5 to 10 mg orally or IV (adult), 0.05 to 0.1 mg/kg orally or IV up to 10 mg/dose (child); repeat as necessary in 10 to 60 minutes up to 30 mg in an adult.
    G) MALIGNANT HYPERTENSION
    1) SODIUM NITROPRUSSIDE/INDICATIONS
    a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.
    2) SODIUM NITROPRUSSIDE/DOSE
    a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).
    3) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION
    a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    4) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS
    a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    5) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS
    a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    6) NITROGLYCERIN/INDICATIONS
    a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).
    7) NITROGLYCERIN/ADULT DOSE
    a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).
    8) NITROGLYCERIN/PEDIATRIC DOSE
    a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).
    H) BODY TEMPERATURE ABOVE REFERENCE RANGE
    1) Employ cooling measures such as cooling blanket, sponging, IV fluids, bladder and gastric lavage with cool fluid.
    2) Sedation and/or paralyzing agents may be necessary to control neuromuscular hyperactivity.
    I) DRUG WITHDRAWAL
    1) SUMMARY: A case of khat addiction has been successfully managed by Giannini et al (1992). After the failure of hydroxyzine (50 mg IM) to alleviate khat-induced symptoms, the patient was successfully treated for withdrawal with bromocriptine (0.625 mg 4 times a day, gradually tapered over 5 days).

Enhanced Elimination

    A) URINARY ACIDIFICATION/NOT RECOMMENDED
    1) Would be expected to enhance the excretion of khat alkaloids, but it is potentially dangerous in the setting of sympathomimetic poisoning and is therefore not recommended.

Range Of Toxicity

Summary

    A) Toxic effects may occur with normal use.

Therapeutic Dose

    7.2.1) ADULT
    A) FRESH LEAVES
    1) Fresh leaves: Approximately 100 to 200 grams of fresh leaves are chewed, one at a time and acts as a stimulant. The juice is swallowed while the residue is retained in the cheek and later ejected (Kalix, 1996).
    2) CANTHINONE "HAGIGAT" CAPSULES
    a) Hagigat is an illicit capsule containing an estimated 200 mg of canthinone. It was estimated that a 200 mg capsule is equivalent to 555.5 g of Khat leaves (ie, a 2.8 to 5.6 sessions of chewing based on a session being equal to 100-200 g of leaves)(Bentur et al, 2008). Therefore, the authors suggest that the higher content and availability of canthinone in Hagigat as compared to chewing Khat leaves may increase the potential risk of toxicity. Possible adulterants found in the capsules may also play a role.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The rather slow release of alkaloids during the chewing and the ready inactivation of cathinone tend to limit the effects of khat. Nevertheless, the usual doses may cause cardiovascular problems in the elderly, in predisposed persons, and during exercise. Toxic effects are usually due to large single doses during chronic (multiple dose) use.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) KHAT PHENYLALKALAMINES -
    1) The phenylalkylamines of khat are structurally similar to sympathomimetic amines of the ephedrine and amphetamine type, and to catecholamine neurotransmitters such as norepinephrine and dopamine. They act like the amphetamines by stimulating the release of these transmitters from presynaptic nerve endings, which leads to indirect activation of central and peripheral catecholaminergic pathways (Kalix, 1984a).
    2) Cathinone is the main active constituent of fresh khat. Other compounds are less potent (Kalix & Braenden, 1985; Geisshusler & Brenneisen, 1987; Nencini & Ahmed, 1989).
    3) There is some evidence that inhibition of monoamine oxidase (Nencini et al, 1984b) and interaction with serotonin pathways (Kalix, 1984b) contributes to the activity of the khat alkaloids.
    B) ORAL AND GASTROINTESTINAL SYMPTOMS - are probably due to the high tannin content of khat.
    C) CATHINONE and cathine (norpseudoephedrine) have been shown to have, in vitro, neuromuscular blocking and local anesthetic activity (Guantai et al, 1987).
    D) TOLERANCE - may develop to the sympathomimetic effects of khat in habitual users (Nencini et al, 1984a).
    E) The alkaloid content of 22 different samples of freshly frozen khat, expressed as percent of dry weight, was 0.009% to 0.322% cathinone, 0.005% to 0.753% cathine (norpseudoephedrine), and 0.0007% to 0.084% norephedrine. Further, certain samples contained up to 0.056% phenylpentenylamines (Geisshusler & Brenneisen, 1987).

Toxicologic Mechanism

    A) Toxic symptoms due to khat consumption are manifestations of excessive pharmacological effects.

References

General Bibliography

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