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PLANTS-ARECA CATECHU

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Areca nut, the fruit of the areca or areca palm tree (Areca catechu), is used daily by about 15% of the world's total population. Areca nut is usually available as a chewable quid made up of different components: the seed from the palm Areca catechu, slaked lime, and a wrapping of a leaf from the vine Piper betle, with or without tobacco. The use of areca nut is more common in females than in males.

Specific Substances

    1) Areca catechu
    2) Areca nut palm
    3) Areca catechu L
    4) Areca catechu Linn, nut extract
    5) Areca nuts
    6) Areca semen
    7) Arekasame
    8) Arequier Nox d'arec (France)
    9) Betelnusse (Germany)
    10) Betel nut palm
    11) Betel nuts
    12) Binro (Japan)
    13) BN
    14) Catechu
    15) Fufal (Arabian)
    16) Gowe (Nepal)
    17) Kunsi (Burma)
    18) Noix D'arec
    19) Paan
    20) Paan masala
    21) Pan masal and Gutkha (India)
    22) Pan Parag
    23) Pansupari(TM) (India)
    24) Pinang (Malaysia)
    25) Pinang-wang (Taiwan)
    26) Poogiphalam, nut extract
    27) PW
    28) Pooga (Sanskrit, India)
    29) Popal (Persian)
    30) Puvak (Sinhalese)
    31) Sting (Tantric Corporation)
    32) Supari (Hindi, India)
    33) Superi (Bengal)

Available Forms Sources

    A) FORMS
    1) Areca nuts are available in the form of ghees, powders, bolmes, or enemas (Duke, 1985). In India, supari is available alone or as pan (Pansupari(TM)), a mixture of supari, lime, and other ingredients with or without tobacco in a areca leaf (Mangla, 1993; Anil & Beena, 1993).
    2) Pan masala and Gutkha (India) are perfumed, sweetened, chewable mixtures of tobacco and areca nut powder (Nelson & Heischober, 1999; Murlidhar & Upmanyu, 1996; Mangla, 1993). Tobacco or spices are added to areca nut for additional flavoring (Beecher et al, 1985).
    3) Prepared packets of arecal quid (paan masala) are available in the United Kingdom and other countries (Warnakulasuriya et al, 2002).
    4) In 1980, areca nut liqueur was developed in Guam (Beecher et al, 1985).
    5) In Taiwan, areca nuts are used with a special paste (ground oyster shell mixed with liquor, salt and sugar) for chewing (Wu et al, 1996). Areca nut may be wrapped in a leaf of Piper betle along with oyster shell powders (Nelson & Heischober, 1999) Wu et al, 1996).
    6) The dried areca nut ("incense chips" or "fragrant wood slice") is available in fresh and frozen forms (Nelson & Heischober, 1999).
    7) A herbal mixture "Sting" (Tantric Corporation) is available for sale on the Internet (Nelson & Heischober, 1999).
    8) "Inverted nuts" are grown upside down on the spadix. It is reported that these nuts are more potent than the normal areca nut (Deng et al, 2001).
    B) USES
    1) Areca nut has been used to treat local and systemic diseases such as dental caries, dysentery, fevers, intestinal complaints, malaria, bronchitis, diphtheria, laryngitis, glaucoma, ulcers, scurvy, bleeding gums, or to induce labor. In addition, it has been used as an antacid, an anthelmintic (to treat parasitic intestinal tapeworms and roundworms), and as a coagulant (Nelson & Heischober, 1999; Taufa, 1988; Beecher et al, 1985; Duke, 1985).
    2) Areca nut has been reported to possess sialogogue and masticatory properties. Areca alkaloids have powerful parasympathetic properties, producing euphoria, and counteract fatigue. It has been reported to reduce hunger and irritability ((Sweetman, 2000); Nelson & Heischober, 1999; Hung & Deng, 1998; Anil & Beena, 1993; Beecher et al, 1985).
    3) In veterinary medicine, arecoline has been used as a purgative and taeniafuge ((Sweetman, 2000); Taufa, 1988).
    4) A herbal mixture "Sting" (Tantric Corporation) is available on the World Wide Web, and is advertised to "increase respiration", to "decrease the workload of the heart", and to be used in "any physical activity such as dancing, sex, and hiking" (Nelson & Heischober, 1999).
    5) Areac nut is used during weddings, festivals, and parties to affirm partnerships or conclude peace negotiations (Nelson & Heischober, 1999). In addition, it has been used in the tanning industry, as black and red dyes, and to improve appetite and taste (Duke, 1985).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) DESCRIPTION: Areca catechu is a palm plant known for its seed, the areca nut. It is commonly, but erroneously referred to as " betel nut" because it is often chewed along with a betel leaf which originates from a different plant called the betel vine.
    B) DISTRIBUTION: The palm grows in the tropical Pacific, Asia and parts of east Africa.
    C) USES: The areca nut is chewed for its euphoric effect, as a digestive aid and as a cough/sore throat remedy. The areca leaf is used for its breath freshening properties; it contains phenolic volatile oil, which may cause sympathomimetic effects. Lime (calcium hydroxide) is often added to enhance extraction of the alkaloids from the areca nut.
    D) TOXICOLOGY: The nut contains several alkaloids, most significantly arecoline, which is a direct acting nicotinic agonist, which explains the muscarinic cholinergic effects that can be observed, including life-threatening bronchospasm.
    E) EPIDEMIOLOGY: Areca nut is the fourth most widely addictive substance in the world, after nicotine, alcohol and caffeine. It can be chewed alone, but is often combined with the areca leaf, tobacco, lime and flavorings to increase its appeal.
    F) WITH POISONING/EXPOSURE
    1) ACUTE TOXICITY: The cholinergic effects of arecoline may cause a familiar cholinergic toxidrome, including salivation, sweating, lacrimation, urinary incontinence, diarrhea, gastrointestinal upset, and emesis. Life threatening effects such as bronchoconstriction, bronchorrhea, and dysrhythmias (e.g., bradycardia) have been reported, but are rare. Several deaths have been attributed to areca nut exposure.
    2) CHRONIC TOXICITY: After years of chewing areca nut preparations, there are several devastating effects of using areca nut, some of which may be directly related to the compounds in the nut itself, and others attributable to the products it is often combined with such as tobacco. "Areca Nut Chewer's" syndrome encompasses several features common to chronic chewing of areca nut products. This syndrome includes: fibrosis of oral submucosal layers and muscles of mastication leading to trismus, white discoloration of oral mucosa, and increased oral temperature sensitivity. There is also a significant increase in leukoplakia and squamous cell carcinoma of the oral mucosa in chronic users. Areca nut chewing also appears to be an independent risk factor for the development of calcium urolithiasis (kidney stones). Hypercalcemia may occur, likely due to the large amounts of calcium absorbed from the lime (calcium hydroxide) used in areca nut products.
    0.2.5) CARDIOVASCULAR
    A) Mild tachycardia and hypertension are common. Myocardial infarction, chest pain, hypotension, or dysrhythmias rarely occur.
    0.2.6) RESPIRATORY
    A) Dyspnea, bronchoconstriction, and pulmonary edema have been reported rarely.
    0.2.7) NEUROLOGIC
    A) Extrapyramidal symptoms, dizziness, and vertigo have been reported in areca nut users. Hallucinations and acute reversible psychosis have been reported with large quantities.
    0.2.8) GASTROINTESTINAL
    A) Oral submucous fibrosis, periodontal disease, and oral leukoplakia have been reported after chronic use. Nausea and vomiting may occur.
    B) There is evidence that chronic use of "areca quid" with tobacco causes esophageal cancer.
    0.2.14) DERMATOLOGIC
    A) Areca chewer's perleche, flushing, and diaphoresis have been reported.
    0.2.20) REPRODUCTIVE
    A) The effects of areca nut in human offspring are unknown since there are no adequate and well-controlled clinical studies in pregnant women. There is some evidence to suggest that babies born to mothers who chew areca nut are at increased risk for low birth weight. Anomalies have been observed in mice.
    0.2.22) OTHER
    A) Mild cholinergic toxicity with SLUDGE syndrome may occur.

Laboratory Monitoring

    A) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    B) Monitor fluid and electrolytes in patients with prolonged vomiting or cardiac dysrhythmias.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Treat significant vomiting with IV fluids and electrolyte repletion. Monitor respiratory and cardiovascular function following a large ingestion. Obtain a baseline ECG and institute continuous cardiac monitoring as indicated. Atropine may be indicated to treat muscarinic effects: DOSE: ADULT: 2 to 4 mg IV, repeated every 3 to 60 min as needed to control symptoms, then as needed for 24 to 48 hr; CHILD: 0.04 to 0.08 mg/kg IV (up to 4 mg) repeated every 5 to 60 min as needed.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Life threatening events such as bronchoconstriction, bronchorrhea have been reported rarely. Treat bronchospasm with inhaled beta agonists. Treat bronchorrhea or other muscarinic effects with atropine. Cardiac dysrhythmias (bradycardia, ventricular fibrillation) are rare events. Institute continuous cardiac monitoring, pulse oximetry and oxygen therapy. Evaluate for acidosis, electrolyte disorders.
    C) DECONTAMINATION
    1) PREHOSPITAL: Spontaneous vomiting may occur after a significant exposure; prehospital decontamination is not indicated.
    2) HOSPITAL: Most exposures involve significant absorption across oral mucous membranes from chewing quid; the role of gastrointestinal decontamination is unclear. Spontaneous vomiting may occur after a significant exposure. Activated charcoal may be considered after a large ingestion (where the material is swallowed), if performed shortly after exposure and the patient is alert and the airway is protected.
    D) AIRWAY MANAGEMENT
    1) Airway management is not anticipated following a mild or moderate exposure, but may be indicated in patients with significant respiratory dysfunction (eg, dyspnea, bronchospasm), cardiac instability (eg, dysrhthymias) or CNS depression.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION PROCEDURE
    1) It is unknown if hemodialysis would be beneficial.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic child with a minor "taste ingestion" of an areca nut or areca quid (areca nut wrapped by lime-smeared Piper areca leaf) can likely be observed at home. An adult with minor symptoms (ie, nausea, vomiting) may remain at home. If persistent or worsening symptoms occur, the patient should be observed or admitted to a healthcare facility, as necessary.
    2) OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions who are symptomatic should be observed in a healthcare facility.
    3) ADMISSION CRITERIA: Patients with deliberate large ingestions or no previous exposure to areca nuts or chewing areca quid that demonstrate persistent cardiotoxicity, neurotoxicity or respiratory symptoms should be admitted.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, dysrhythmias, bronchospasm, coma), or in whom the diagnosis is not clear.
    H) TOXICOKINETICS
    1) The nut contains several alkaloids, most significantly arecoline, which is a direct acting nicotinic agonist, which can produce the muscarinic cholinergic effects that have been observed, including life-threatening bronchospasm.
    I) PITFALLS
    1) Inadequate doses of atropine to treat muscarinic symptoms. Other agents that may produce similar effects (ie, nicotine), if taken in large doses. Chronic users of quid may develop withdrawal.
    J) DIFFERENTIAL DIAGNOSIS
    1) Cholinergic effects due to other direct acting nicotinic agonists (eg, carbachol, coniine, cytisine, varenicline) or used in combination with other agents, such as nicotine.

Range Of Toxicity

    A) TOXICITY: A minimum toxic dose has not been established; toxicity is dependent on the alkaloid content of the nut.
    B) After the ingestion of 1 to 6 areca nuts, full recovery was reported in 14 of the 15 patients. One patient recovered following the use of an extract of 100 areca nuts. Another patient recovered after he chewed 66 areca nuts. One patients died of ventricular dysrhythmias and a myocardial infarction after use of a single areca quid.

Clinical Effects

Summary Of Exposure

    A) DESCRIPTION: Areca catechu is a palm plant known for its seed, the areca nut. It is commonly, but erroneously referred to as " betel nut" because it is often chewed along with a betel leaf which originates from a different plant called the betel vine.
    B) DISTRIBUTION: The palm grows in the tropical Pacific, Asia and parts of east Africa.
    C) USES: The areca nut is chewed for its euphoric effect, as a digestive aid and as a cough/sore throat remedy. The areca leaf is used for its breath freshening properties; it contains phenolic volatile oil, which may cause sympathomimetic effects. Lime (calcium hydroxide) is often added to enhance extraction of the alkaloids from the areca nut.
    D) TOXICOLOGY: The nut contains several alkaloids, most significantly arecoline, which is a direct acting nicotinic agonist, which explains the muscarinic cholinergic effects that can be observed, including life-threatening bronchospasm.
    E) EPIDEMIOLOGY: Areca nut is the fourth most widely addictive substance in the world, after nicotine, alcohol and caffeine. It can be chewed alone, but is often combined with the areca leaf, tobacco, lime and flavorings to increase its appeal.
    F) WITH POISONING/EXPOSURE
    1) ACUTE TOXICITY: The cholinergic effects of arecoline may cause a familiar cholinergic toxidrome, including salivation, sweating, lacrimation, urinary incontinence, diarrhea, gastrointestinal upset, and emesis. Life threatening effects such as bronchoconstriction, bronchorrhea, and dysrhythmias (e.g., bradycardia) have been reported, but are rare. Several deaths have been attributed to areca nut exposure.
    2) CHRONIC TOXICITY: After years of chewing areca nut preparations, there are several devastating effects of using areca nut, some of which may be directly related to the compounds in the nut itself, and others attributable to the products it is often combined with such as tobacco. "Areca Nut Chewer's" syndrome encompasses several features common to chronic chewing of areca nut products. This syndrome includes: fibrosis of oral submucosal layers and muscles of mastication leading to trismus, white discoloration of oral mucosa, and increased oral temperature sensitivity. There is also a significant increase in leukoplakia and squamous cell carcinoma of the oral mucosa in chronic users. Areca nut chewing also appears to be an independent risk factor for the development of calcium urolithiasis (kidney stones). Hypercalcemia may occur, likely due to the large amounts of calcium absorbed from the lime (calcium hydroxide) used in areca nut products.

Heent

    3.4.3) EYES
    A) MIOSIS
    1) Miosis, due to the action of arecoline on central cholinergic receptors, may occur with areca nut use. Blurred or darkened vision has been reported (Nelson & Heischober, 1999).
    B) MYDRIASIS
    1) Mydriasis, due to the action of arecoline on peripheral cholinergic receptors, may occur with areca nut use. Blurred or darkened vision has been reported (Nelson & Heischober, 1999).

Cardiovascular

    3.5.1) SUMMARY
    A) Mild tachycardia and hypertension are common. Myocardial infarction, chest pain, hypotension, or dysrhythmias rarely occur.
    3.5.2) CLINICAL EFFECTS
    A) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: After chewing one quid (areca nut wrapped by lime-smeared Piper areca leaf) of pinang-wang, a 47-year-old man with coronary artery disease suffered an acute myocardial infarction. It is suggested that the myocardial infarction was due to the parasympathetic effects of arecoline (the active alkaloid in areca nut) on abnormal coronary vascular endothelium leading to coronary vasospasm (Hung & Deng, 1998).
    b) CASE SERIES: In a retrospective study, 2 of 17 patients developed acute myocardial infarction after using 1 to 6 areca nuts. One patient smoked tobacco and had severe occlusion of both left anterior descending and right coronary arteries. Another patient, a 44-year-old man developed chest tightness, diaphoresis, and dyspnea after chewing one areca quid. He developed ventricular fibrillation and died; acute myocardial infarction and cardiac dysrhythmias were considered to be the cause of death. It is suggested that the muscarinic alkaloids of areca nut can induce coronary vasospasm. In addition, the concomitant ingestion of alcohol may aggravate vasospasm (Deng et al, 2001).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Arecoline, the cholinergic active alkaloid in areca nut, may cause hypotension (Hung & Deng, 1998).
    b) CASE SERIES: In a retrospective study, 5 of 17 patients developed hypotension after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    C) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Arecoline, the cholinergic active alkaloid in areca nut, may cause bradycardia (Hung & Deng, 1998).
    D) CHEST PAIN
    1) WITH POISONING/EXPOSURE
    a) Substernal chest pain has been reported in patients using unroasted areca nut (Deng et al, 2001; Chittivelu & Chittivelu, 1998; Chiang et al, 1998).
    b) CASE SERIES: In a retrospective study, 4 of 17 patients developed chest discomfort after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    E) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) In one study, a significant increase in heart rate lasting an average of 16.8 minutes was observed in 17 chronic areca nut chewers, 19 occasional chewers (2 to 4 times a week), and 11 new chewers (Chu, 1993).
    b) CASES REPORT: A 28-year-old man experienced palpitations, epigastralgia, and chest discomfort after chewing 4 areca quid. He developed paroxysmal supraventricular tachycardia which was treated with verapamil (Chiang et al, 1998).
    c) CASE SERIES: In a retrospective study, 7 of 17 patients developed tachycardia or palpitations after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    F) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) A couple of studies have revealed that new areca-nut chewers experienced a significant increase in systolic blood pressure. However, chronic and occasional areca-nut chewers did not experience any changes in blood pressure (Deng et al, 2001; Chu, 1993).
    G) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Two male patients developed serious cardiac dysrhythmias following alcohol drinking and areca nut chewing. One patient experienced chest tightness, dyspnea, diaphoresis, and palpitation after chewing 1 areca quid. He developed ventricular fibrillation and died despite immediate cardiopulmonary resuscitation. The other patient experienced palpitations, epigastralgia, and chest discomfort after chewing 4 areca quid. He developed paroxysmal supraventricular tachycardia which was terminated by repeated verapamil administration (Chiang et al, 1998).
    b) CASE REPORT: A 44-year-old man presented to the emergency department with chest tightness, diaphoresis, and dyspnea after chewing one areca quid. He developed ventricular fibrillation and died; acute myocardial infarction and cardiac dysrhythmia was considered to be the cause of death (Deng et al, 2001).

Respiratory

    3.6.1) SUMMARY
    A) Dyspnea, bronchoconstriction, and pulmonary edema have been reported rarely.
    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) Unroasted areca nut may produce dyspnea (Chittivelu & Chittivelu, 1998; Chiang et al, 1998; Choudhury, 1980).
    b) CASE SERIES: In a retrospective study, 6 of 17 patients developed tachypnea/dyspnea after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    B) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) An association between areca-nut chewing and bronchoconstriction in asthmatic patients has been reported ((Sweetman, 2000); Taylor et al, 1992; Kiyingi, 1992; Kiyingi, 1991).
    b) In-vitro studies with arecoline, a major alkaloid of areca nut, have shown dose-related contractions of human bronchial smooth-muscle. Another study has reported inhaled arecoline to cause bronchoconstriction in 6 of 7 asthma patients. In 1 of 4 asthmatic patients who regularly chewed the areca nut, a 30% drop in the forced expiratory volume in 1 s (FEV1) was noted in areca nut challenges (Kiyingi, 1992; Kiyingi, 1991).
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Acute lung injury and death have been reported in patients using large quantities of areca nuts (Deng et al, 2001; Nelson & Heischober, 1999).
    D) SUFFOCATING
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Five patients developed severe bronchospasm, dyspnea, cyanosis, and tachycardia following anesthesia. Fine particles of areca nut were found in throats of the patients. All patients recovered following symptomatic therapy. It is suggested that particles of areca nut remain in the mouth, cheek, gums, in the gaps of the teeth, and in the pharynx for a long time, even after gurgling and cleaning (Choudhury, 1980).

Neurologic

    3.7.1) SUMMARY
    A) Extrapyramidal symptoms, dizziness, and vertigo have been reported in areca nut users. Hallucinations and acute reversible psychosis have been reported with large quantities.
    3.7.2) CLINICAL EFFECTS
    A) EXTRAPYRAMIDAL DISEASE
    1) WITH POISONING/EXPOSURE
    a) One patient with chronic schizophrenia maintained on fluphenazine decanoate depot 50 milligrams every 3 weeks for 2 years, developed severe extrapyramidal symptoms (marked rigidity and bradykinesia) following heavy consumption of areca nut for almost 2 weeks. Another patient with a history of schizoaffective disorder, maintained on flupenthixol depot 60 milligrams every 2 weeks for one year, developed extrapyramidal symptoms (marked stiffness, tremor, and distressing akathisia) following heavy areca nut use for 2 weeks. In both cases, all symptoms resolved without intervention (Deng et al, 2001; Deahl, 1989).
    B) DYSTONIA
    1) WITH POISONING/EXPOSURE
    a) In a case-control study, areca nut and tobacco chewing was associated with increased risk of Meige's syndrome (blepharospasm and oromandibular-lingual dystonia) as well as development of spasmodic dysphonia, spasmodic dysphagia, tremor, and spasmodic torticollis (Behari et al, 2000).
    C) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) Dizziness and vertigo have been reported in the novice areca nut users (Nelson & Heischober, 1999).
    b) CASE SERIES: In a retrospective study, 4 of 17 patients developed dizziness after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    D) HALLUCINATIONS
    1) WITH POISONING/EXPOSURE
    a) Auditory hallucinations, grandiose and persecutory delusions have been reported in heavy areca-nut users (Nelson & Heischober, 1999).
    E) COMA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a retrospective study, 3 of 17 patients developed coma after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    F) NUMBNESS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a retrospective study, 3 of 17 patients developed numbness after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).

Gastrointestinal

    3.8.1) SUMMARY
    A) Oral submucous fibrosis, periodontal disease, and oral leukoplakia have been reported after chronic use. Nausea and vomiting may occur.
    B) There is evidence that chronic use of "areca quid" with tobacco causes esophageal cancer.
    3.8.2) CLINICAL EFFECTS
    A) ORAL SUBMUCOSAL FIBROSIS
    1) WITH POISONING/EXPOSURE
    a) In several studies, the chronic consumption of areca nut has been shown to cause oral cancer and its precursors leukoplakia and submucous fibrosis (Warnakulasuriya et al, 2002; Nelson & Heischober, 1999; Trivedy et al, 1999; Thomas & MacLennan, 1992).
    1) "Areca Nut Chewer's" syndrome encompasses several features common to chronic chewing of areca nut products. The syndrome includes: fibrosis of oral submucosal layers and muscles of mastication leading to trismus, white discoloration of oral mucosa, increased oral temperature sensitivity (Chaturvedi, 2009).
    b) CASE REPORT: A 12-year-old girl from India developed oral submucous fibrosis after chewing Pansupari(TM) (roasted areca nut dusted with a powder containing slaked lime and flavoring agents) a minimum of once daily for almost 5 years. She was treated with intralesional injections of aqueous extract of healthy human placenta (Placentrex, 2 mL) for two months, repeated at an interval of three days. A remarkable improvement in the burning sensation of the mouth and moderate improvement in mouth opening were observed. The authors suggest that there might be an HLA-linked genetic susceptibility for areca nut alkaloids and tannins in individuals with oral submucous fibrosis (Anil & Beena, 1993).
    c) One study reports that an adult chewing areca daily will consume more than 5 milligrams of copper daily (copper concentrations in areca range 205 to 535 nmol/g). The absorbed copper induces lysyl oxidase activity upregulating collagen synthesis by fibroblasts, leading to an excessive crosslinking (Trivedy et al, 1997).
    d) CASE REPORT: An 18-year-old man from India developed oral submucous fibrosis after chewing a mixture of tobacco and areca nut (Pan masala and Gutkha) for 2 years. Physical examination revealed a restricted mouth opening of less than 2 cm, partial trismus, and generalized whitish hue (marble-like appearance) of the buccal mucosa and oral cavity (Murlidhar & Upmanyu, 1996).
    B) LEUKOPLAKIA
    1) In several studies, the chronic consumption of areca nut has been shown to cause oral cancer and its precursors leukoplakia and submucous fibrosis (Warnakulasuriya et al, 2002; Nelson & Heischober, 1999; Trivedy et al, 1999; Thomas & MacLennan, 1992).
    2) CASE REPORT: A 59-year-old Cambodian woman with a 30-year history of daily use of areca nut quid, developed generalized severe leukoplakia which involved the buccal mucosa, the floor of the mouth, the tongue and the attached gingiva (Heidelman & Graham, 1985).
    C) PERIODONTITIS
    1) WITH POISONING/EXPOSURE
    a) Chronic areca nut use increases the prevalence of periodontal disease. It is suggested that areca quid produces hypersalivation due to the cholinergic effect and leads to pooling of saliva adjacent to the quid. The calcium salts in the saliva cause a heavy deposition of calculus around the crowns of the teeth (Beecher et al, 1985).
    D) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting have been reported in the novice areca nut users (Nelson & Heischober, 1999).
    b) CASE SERIES: In a retrospective study, 4 of 17 patients developed vomiting and 5 developed nausea after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).
    E) ABDOMINAL COLIC
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a retrospective study, 3 of 17 patients developed abdominal colic after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) METABOLIC ALKALOSIS
    1) Milk-alkali syndrome (hypercalcemia, renal insufficiency, and metabolic alkalosis) occurred in two patients who had chewed a large quantity of areca-nut paste containing calcium carbonate from oyster shells. Both patients chewed a large amount of areca nuts (an average of 30 and 50 per day) for more than 30 years. It was estimated that the patients had ingested 6 to 9 grams of calcium carbonate per day. Symptoms resolved after discontinuation of areca nuts and administration of saline solution (Wu et al, 1996).

Dermatologic

    3.14.1) SUMMARY
    A) Areca chewer's perleche, flushing, and diaphoresis have been reported.
    3.14.2) CLINICAL EFFECTS
    A) CHEILITIS
    1) WITH POISONING/EXPOSURE
    a) Areca chewer's perleche, which is known as an angular cheilitis, is an inflammatory condition that occurs at the corner of the mouth and appears at cracks or splits. Areca nuts also stain the oral mucosa to a deep red color. These conditions are caused by constant moistness and maceration (Nelson & Heischober, 1999; Beecher et al, 1985).
    B) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) Flushing has been reported in the novice areca nut users (Deng et al, 2001; Nelson & Heischober, 1999).
    C) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Diaphoresis has been reported in the novice areca nut users. (Nelson & Heischober, 1999).
    b) CASE SERIES: In a retrospective study, 5 of 17 patients developed increased sweating after using 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts) (Deng et al, 2001).

Reproductive

    3.20.1) SUMMARY
    A) The effects of areca nut in human offspring are unknown since there are no adequate and well-controlled clinical studies in pregnant women. There is some evidence to suggest that babies born to mothers who chew areca nut are at increased risk for low birth weight. Anomalies have been observed in mice.
    3.20.2) TERATOGENICITY
    A) HUMANS
    1) The effects of areca nut in human offspring are unknown since there are no adequate and well-controlled clinical studies in pregnant women. A case-controlled study of 453 pregnant women showed no significant differences between areca chewers and controls with regard to antenatal infections, birth weights, or congenital abnormalities (Taufa, 1988).
    B) LOW BIRTH WEIGHT
    1) Babies born to mothers who chew areca nut, with or without tobacco, appear to be at increased risk for low birth weight (Senn et al, 2009).
    C) ANIMAL STUDIES
    1) A dose-related decrease in the number of fetuses with ossified coccygeal vertebrae, an increase in the number of fetuses with unossified 5th metacarpals, indicating a delay in skeletal maturity, increased resorptions, and reduced fetal weights were reported in the offspring of animals (Swiss albino mice) treated with aqueous extracts of ripe areca nuts of unprocessed and processed varieties at dose levels of 1, 3, and 5 mg/day/mouse (27 +/- 1 gram body weight) through days 6 to 15 of gestation (Sinha & Rao, 1985).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) ORAL CARCINOMA
    1) BETEL QUID CHEWING: Use of betel quid in Indian culture is very common and may be part of many religious practices. It is typically made of areca nut, catechu, slaked lime and often contains tobacco and is placed in the oral cavity for many hours. Chewing on the quid or "paan" releases carcinogenic nitrosamines from the areca nut. Chronic exposure can result in pre-neoplastic changes. Overall, it has been suggested that half of all oral cancers reported In India could be prevented if betel quid chewing could be halted (Travasso, 2013).
    2) In several studies, the chronic consumption of areca nut has been shown to cause malignant disorders of the oral cavity. In addition, the use of tobacco with areca nut may produce oral cancer. The International Agency for Research on Cancer has listed areca nut as a group A carcinogen (Warnakulasuriya et al, 2002; Nelson & Heischober, 1999; Trivedy et al, 1999; Thomas & MacLennan, 1992).
    3) Thomas & MacLennan (1992) believed that the slaked lime added to the areca nut, causes the mean pH of the corner of the mouth to rise to 10; thereby allowing reactive oxygen species to be released from the areca quid ingredients to induce cell proliferation (Thomas & MacLennan, 1992).
    B) ESOPHAGEAL CANCER
    1) CHRONIC EXPOSURE: There is sufficient evidence that "areca quid" with tobacco causes esophageal cancer (Secretan et al, 2009).
    C) HEPATIC CANCER
    1) CHRONIC EXPOSURE: There is some evidence to suggest "areca quid" without tobacco may cause hepatic cancer (Secretan et al, 2009).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    B) Monitor fluid and electrolytes in patients with prolonged vomiting or cardiac dysrhythmias.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor serum electrolyte concentrations, particularly in symptomatic patients with prolonged vomiting and/or cardiac dysrhythmias.
    2) Monitor urine output and fluid status.
    3) Pulmonary function testing and chest x-ray may be indicated in patients with dyspnea or bronchospasm.
    B) VITAL SIGNS
    1) Monitor temperature, heart rate, and blood pressure as indicated.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.

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 deliberate large ingestions or no previous exposure to areca nuts or chewing areca quid that demonstrate persistent cardiotoxicity, neurotoxicity or respiratory symptoms should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic child with a minor "taste ingestion" of an areca nut or areca quid (areca nut wrapped by lime-smeared Piper areca leaf) can likely be observed at home. An adult with minor symptoms (ie, nausea, vomiting) may remain at home. If persistent or worsening symptoms occur, the patient should be observed or admitted to a healthcare facility, as necessary.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, dysrhythmias, bronchospasm, coma), or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions who are symptomatic should be observed in a healthcare facility.

Monitoring

    A) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    B) Monitor fluid and electrolytes in patients with prolonged vomiting or cardiac dysrhythmias.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) Spontaneous vomiting may occur after a significant exposure. Most exposures involve significant absorption across oral mucous membranes from chewing quid; the role of gastrointestinal decontamination is unclear.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Most exposures involve significant absorption across oral mucous membranes from chewing quid; the role of gastrointestinal decontamination is unclear. Activated charcoal should be considered after large ingestions.
    B) 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) Treatment is symptomatic and supportive.
    2) Monitor fluid and electrolytes in patients with prolonged vomiting or cardiac dysrhythmias.
    3) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Vomiting may be prolonged with large ingestions, resulting in fluid and electrolyte loss. Monitor and replace as necessary.
    C) ATROPINE
    1) ATROPINE sulfate is the drug of choice to reverse actions at muscarinic receptors.
    2) DOSE: ADULT: INITIAL DOSE: 2 to 4 mg IV repeated every 3 to 60 minutes as needed to control muscarinic symptoms, then as needed for 24 to 48 hours. CHILD: INITIAL DOSE: 0.04 to 0.08 mg/kg up to 4 mg (usual dose 1 mg IV), repeated every 5 minutes as necessary.
    D) BRONCHOSPASM
    1) Inhaled beta-agonist bronchodilators, steroids, and ipratropium may reverse bronchoconstriction (Nelson & Heischober, 1999).
    2) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    3) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    5) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    6) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    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) AMIODARONE
    a) AMIODARONE/INDICATIONS
    1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).
    b) AMIODARONE/ADULT DOSE
    1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).
    c) AMIODARONE/PEDIATRIC DOSE
    1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).
    d) ADVERSE EFFECTS
    1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).
    F) PRALIDOXIME
    1) Cholinesterase regenerators such as pralidoxime (2-PAM) are not needed.
    G) EXPERIMENTAL THERAPY
    1) ORAL SUBMUCOUS FIBROSIS: Intralesional injection of aqueous human placental extract (Placentrex(R)), 2 mL every 3 days for 2 months, was shown to be effective, lasting, and safe for treatment of oral submucous fibrosis in a 12-year-old girl following chronic areca nut chewing (Anil & Beena, 1993). Placentrex(R) is an aqueous extract of human placenta that contains nucleotides, enzymes, vitamins, amino acids, and steroids, and has an action of "biogenic stimulation". It has been suggested that Placentrex(R) stimulates the pituitary and adrenal cortex, regulates the metabolism of tissues, and increases the vascularity of tissues.

Enhanced Elimination

    A) SUMMARY
    1) It is unknown if hemodialysis would be beneficial.

Range Of Toxicity

Summary

    A) TOXICITY: A minimum toxic dose has not been established; toxicity is dependent on the alkaloid content of the nut.
    B) After the ingestion of 1 to 6 areca nuts, full recovery was reported in 14 of the 15 patients. One patient recovered following the use of an extract of 100 areca nuts. Another patient recovered after he chewed 66 areca nuts. One patients died of ventricular dysrhythmias and a myocardial infarction after use of a single areca quid.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) The quid is usually chewed 2 to 12 times daily for up to an hour (Taylor et al, 1992).
    2) The following doses have been reported: Powder 1 to 2 grams; fruit extract 1 to 2 milliliters; tincture 5 to 10 milliliters (Kapoor, 1990).

Minimum Lethal Exposure

    A) SUMMARY
    1) A minimum toxic dose has not been established; toxicity is dependent on the alkaloid content of the nut.
    B) CASE REPORT
    1) A 44-year-old man developed chest tightness, diaphoresis, and dyspnea after chewing one areca quid. He developed ventricular fibrillation and died; acute myocardial infarction and cardiac dysrhythmia was considered to be the cause of death (Deng et al, 2001).

Maximum Tolerated Exposure

    A) SUMMARY
    1) One source believes that 30 g is practically nontoxic. However, another study reports that large doses (8 to 10 g seed) may be fatal (Duke, 1985).
    B) CASE SERIES
    1) In a review of 17 cases, Deng et al (2001) reported the following adverse clinical manifestations after the use of 1 to 6 areca nuts (one patient chewed 66 areca nuts; another patient used an extract of 100 areca nuts): tachycardia, palpitations, dyspnea, hypotension, sweating, nausea and vomiting, dizziness, abdominal colic, numbness, coma, and myocardial infarction. Full recovery was reported in 16 of the 17 patients (Deng et al, 2001).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 681 mg/kg (RTECS, 2000)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Arecoline, a volatile cholinergic lipoid soluble alkaloid, is the active ingredient of Areca catechu. Areca nut has various sympathetic and parasympathetic effects. One study suggests that areca-nut chewing is dose-dependent. Low-dose areca-nut chewing increases sympathetic activity, causing a cardioacceleratory response and alterations in sympathetic skin response. However, larger doses (3 to 4 areca nuts) may increase the parasympathetic activity (Chu, 1995).
    B) Arecoline has the properties of acetylcholine at central ganglionic and peripheral nicotinic and muscarinic receptors (more muscarinic than nicotinic). Arecoline has more nicotinic activity than pilocarpine and methacoline. It stimulates mucous membranes and the central nervous system, speeds up the breathing rate, decreases the efficiency of the heart, stimulates peristalsis, increases exocrine secretion, produces marked bronchial constriction by peripheral action, and causes bradycardia and hypotension in the cardiovascular system. In addition, it has psychotropic and antihelminthic activity (Nelson & Heischober, 1999; Hung & Deng, 1998; Chiang et al, 1998; Beecher et al, 1985; Duke, 1985).
    C) Arecaidine, a hydrolyzed product of arecoline and lime, lacks the typical parasympathomimetic effects of arecoline. However, it may produce the psychological changes associated with areca chewing (Chu, 1993). Arecaidine and guvacine inhibit the uptake of gamma-aminobutyric acid and produce CNS depression (Chiang et al, 1998).
    1) In-vitro cell-transformation assay (used to detect animal carcinogenicity) yielded a positive result for both arecaidine and arecoline. These results suggest that arecaidine may have some human carcinogenic effects (Ashby et al, 1979).
    D) The areca nut contains 15% tannins which produce an astringent effect on oral mucous membranes. An ether oil, a component of the Piper areca leaf, is responsible for the aroma and taste of the quid and the anesthetic-like effect on the oral mucosa. Piper areca leaf also contains fluoride ion. Lime promotes the release of aromatic oil from Piper areca leaf and the arecoline and red coloring from the areca nut. It is reported that lime is the major cause of the severe abrasion found on the occlusal surfaces on the teeth of areca nut chewers (Beecher et al, 1985).

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