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Gloriosa superba L.

1. NAME
   1.1 Scientific name
   1.2 Family
   1.3 Common name(s) of the plant and synonyms
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
   2.5 Poisonous parts
   2.6 Main toxins
3. CHARACTERISTICS
   3.1 Description of the plant
      3.1.1 Special identification features
      3.1.2 Habitat
      3.1.3 Distribution
   3.2 Poisonous parts of the plant
   3.3 The toxin(s)
      3.3.1 Name(s)
      3.3.2 Description, chemical structure, stability
      3.3.3 Other physico-chemical characteristics
   3.4 Other chemical contents of the plant
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances
   4.3 High risk geographical areas
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXINOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote/antitoxin treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventative measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    GLORIOSA SUPERBA

    International Programme on Chemical Safety
    Poisons Information Monograph 245
    Plant

    1.  NAME

        1.1  Scientific name

             Gloriosa superba L.

        1.2  Family

             Colchicaceae

        1.3  Common name(s) of the plant and synonyms

             Flame lily; glory lily

    2.  SUMMARY

        2.1  Main risks and target organs

             The toxins in G. superba have an inhibitory action on
             cellular division resulting in diarrhoea, depressant action
             on the bone marrow and alopecia.

        2.2  Summary of clinical effects

             Initial symptoms develop within two to six hours after
             ingestion of tubers of G. superba.  They are characterized
             by numbness and tingling around the mouth, burning and
             rawness of the throat, nausea, intense vomiting, abdominal
             pain and bloody diarrhoea leading to dehydration.  The other
             important complications that follow may include: respiratory
             depression, dyspnoea, shock, hypotension, marked leucopenia,
             thrombocytopenia, coagulation disorders, oliguria,
             haematuria, confusion, seizures, coma and  ascending
             polyneuropathy.  Alopecia and dermatitis are the late
             manifestations that develop about one to two weeks after
             poisoning.

        2.3  Diagnosis

             Bio-medical analysis: daily full blood counts,
             coagulation tests, serum electrolyte levels and urinalysis
             are the important investigations to assess the clinical
             condition.
    
             Blood collection for colchicine dosage has to be kept in the
             dark with anticoagulant.

        2.4  First-aid measures and management principles

             First aid measures:
    
             If the patient is conscious and alert, induce vomiting by
             tickling the back of the throat or by giving syrup of ipecac:
             6 to 18 months - 10 mL, 18 months to 12 years - 15 mL)
             followed by 1 to 2 glasses of water to induce vomiting. 
             Repeat after 15 minutes if no response.  If ipecac is not
             available or if the patient has not responded in 5 minutes
             after the second dose or in an adult, carry out a stomach
             wash out.
    
             The patient should be admitted to a hospital immediately
             with, if available, vomit and any remaining plant
             material.
    
             Management principles:
    
             Carefully monitor the respiration.  Ensure adequate airway. 
             Perform gastric lavage immediately.
    
             Anticipate and treat hypotension with adequate intravenous
             fluids and vasopressors.  Blood transfusion will also be
             helpful to support the circulation.  Continuous cardiac
             monitoring is useful.  Correct dehydration and electrolyte
             imbalance.  Monitor renal function.  Initial forced diuresis
             enhances elimination of colchicine and should be performed
             once dehydration and shock is corrected.  Keep the patient
             under observation.

        2.5  Poisonous parts

             All parts of the plant, especially the tubers, are
             extremely poisonous.

        2.6  Main toxins

             Colchicine, an alkaloid, is responsible for the toxic
             effect of G. superba.  The species also contains another
             alkaloid 'gloriosine'.

    3.  CHARACTERISTICS

        3.1  Description of the plant

             3.1.1  Special identification features

                    G. superba is a semi-woody herbaceous,
                    branching climber, reaching approximately 5 metres in
                    height.  1 to 4 stems arise from a single V-shaped
                    fleshy cylindrical tuber.  The leaves are stalkless,
                    lance-shaped, alternate or opposite or in whorls of up

                    to 3; leaf size: 5 to 15 cm long by 4 to 5 cm wide
                    with parallel veins and tips ending in spiral tendrils
                    which are used for climbing.  Large, showy, long-
                    stalked flowers are made up of 6 long reflexed petals
                    usually with wavy margins.  Flower size: 6 to 10 cm
                    long by 1 to 2.5 cm wide.  Flower colour:  usually
                    very bright ranging from red with yellow margins to
                    very pale yellow forms with a mauve or purple stripe;
                    pale white forms also occur.  Many additional colour
                    forms have arisen through cultivation.  The fruit is
                    oblong, 6 to 12 cm by 2 to 2.5 cm and contains about
                    20 globose red seeds in each valve (Huxley, 1992;
                    Neuwinger, 1994; Burkill, 1995).

             3.1.2  Habitat

                    The plant grows in sunny positions in free-
                    draining soil; it is very tolerant of nutrient-poor
                    soils.  In warm tropical countries it occurs in
                    thickets, bushland, forest edges and cultivated areas
                    up to a height of 2530 metres above sea level.  It is
                    widely grown as an ornamental in cool temperate
                    countries under glass or in conservatories (Neuwinger,
                    1994).

             3.1.3  Distribution

                    A native of tropical Africa and is now found
                    growing naturally throughout much of tropical Asia
                    including: India, Sri Lanka, Malaysia, Burma
                    (Jayaweera, 1982); G. superba is also planted
                    outdoors in the southern United States.  In cool
                    temperate countries it is treated as a greenhouse or
                    conservatory plant.

        3.2  Poisonous parts of the plant

             The entire plant, especially the tubers, are extremely
             poisonous.

        3.3  The toxin(s)

             3.3.1  Name(s)

                    The toxic properties of the plant are
                    essentially due to the highly active alkaloid
                    colchicine.
    
                    Colchicine:
                    CAS number:  64-86-8
    

                    Molecular formula:  C22H25NO6
                    Molecular weight:   399.44
                    Structural name:    colchicine
    
                    Another important alkaloid called gloriosine is also
                    found in tubers (Gooneratne, 1966).

             3.3.2  Description, chemical structure, stability

                    Colchicine occurs as pale yellow to greenish
                    yellow, odourless crystals or amorphous scales or
                    powder.  It darkens on exposure to light.

             3.3.3  Other physico-chemical characteristics

                    Melting point is 157C
    
                    Solubility in water is about 1/20.  It is freely soluble
                    in alcohol and chloroform (Windholz, 1983).

        3.4  Other chemical contents of the plant

             In addition to colchicine and gloriosine, G. superba
             also contains other compounds such as 3-desmethyl colchicine,
             beta-lumicolchicine, N-Formyldesacetyl-colchicine,
             2-desmethyl colchicine, chelidonic acid and salicylic acid
             (Duke, 1985).

    4.  USES/CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

                    Miscellaneous pharmaceutical product
                    Other therapeutic preparation

             4.1.2  Description

                    Different parts of the plant have a wide
                    variety of uses especially within traditional medicine
                    practised in tropical Africa and Asia.  The tuber is
                    used traditionally for the treatment of bruises and
                    sprains, colic, chronic ulcers, haemorrhoids, cancer,
                    impotence, nocturnal seminal emissions, leprosy and
                    also for inducing labour pains and abortion.  Because
                    of its similar pharmacological action, the plant is
                    sometimes used as an adulterant of aconite (Aconitum
                    sp.).  The juice of the leaves is used to kill head
                    lice and also as an ingredient in arrow poisons.  The
                    flowers are used in religious ceremonies. The tuber
                    has commonly been used as a suicidal agent among women
                    in rural areas and it has also been used for
                    homicide.
    

                    The tuber also claims antidotal properties to snake-
                    bite and in India it is commonly placed on window
                    sills to deter snakes.  Many cultures believe the
                    species to have various magical properties.  (Watt &
                    Breyer-Brandwijk, 1962; Neuwinger, 1994; Burkill,
                    1995).

        4.2  High risk circumstances

             In parts of tropical Africa and Asia the tubers of G.
             superba may be mistakenly eaten in place of Sweet Potatoes
             (Ipomoea batatas) since the former is a weed of farmland
             and the tubers resemble those of Sweet Potatoes.

        4.3  High risk geographical areas

             The highest risk areas are likely to be throughout the
             natural range of the species (i.e. tropical Africa and Asia,
             including Sri Lanka).  Accidental exposure to the plant may
             also occur in cool temperate countries of the West where it
             is grown as an ornamental.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Ingestion of tubers or other parts either intentionally
             or accidentally.

        5.2  Inhalation

             No data available.

        5.3  Dermal

             No data available.

        5.4  Eye

             No data available.

        5.5  Parenteral

             No data available.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Colchicine is readily absorbed from the gastrointestinal
             tract.  Absorption may be modified by pH, contents in the
             stomach and intestinal motility.

        6.2  Distribution by route of exposure

             Colchicine is actively taken up intracellularly. 
             Approximately 50% circulating  colchicine is bound to plasma
             proteins.  The apparent volume of distribution exceeds total
             body water (2.2  0.8 1/kg) (Ellenhorn et al., 1996).

        6.3  Biological half-life by route of exposure

             Colchicine has an extremely short plasma half life of
             about 20 minutes (Ellenhorn et al., 1996).

        6.4  Metabolism

             Colchicine is partially deacetylated in the liver
             although as much as 20% may be excreted unchanged by the
             kidneys.
    
             Large amounts of both colchicine and its metabolites are
             subjected to enterohepatic circulation (Ellenhorn et al.,
             1996).

        6.5  Elimination and excretion

             Colchicine and its metabolites are excreted in urine and
             faeces (Reynolds, 1982).

    7.  TOXINOLOGY

        7.1  Mode of action

             Colchicine affects cell membrane structure indirectly by
             inhibiting the synthesis of membrane constituents (Craker &
             Simson, 1986).  It binds to tubulin (the structural proteins
             of microtubules) preventing its polymerization into
             microtubules.  This antimiotic property disrupts the spindle
             apparatus that separates chromosomes during metaphase.  Cells
             with high metabolic rates (e.g. intestinal epithelium, hair
             follicles and bone marrow) are the most involved by the
             arrest of mitosis.  The variable effects of colchicine may
             depend on its binding to the protein subunit of microtubules
             with subsequent disruption of microtubule functions
             (Ellenhorn et al., 1996).  Colchicine also has an inhibitory

             effect on various phosphatases (Craker & Simson, 1986). 
             Gloriosine also has an antimitotic effect (Gooneratne,
             1966).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Nickolls (1965) has suggested that
                             the lethal dose of colchicine for man may be
                             about 60 mg although smaller amounts have
                             also caused death (Angunawela & Fernando,
                             1971).  Gooneratne (1966) has reported a
                             patient who survived after ingestion of 350
                             mg of colchicine tuber.

                    7.2.1.2  Children

                             No data available.

             7.2.2  Relevant animal data

                    LD50 of colchicine for rats was 5 mg/kg
                    (Dunuwille et al., 1968).

             7.2.3  Relevant in vitro data

                    No relevant data.

        7.3  Carcinogenicity

             No data available.

        7.4  Teratogenicity

             G. superba tubers are used for abortion (Duke, 1985).

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             No data available.

    8.  TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2 Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                             "Basic analyses"
                             "Dedicated analyses"
                             "Optional analyses"

                    8.3.1.2  Urine

                             "Basic analyses"
                             "Dedicated analyses"
                             "Optional analyses"

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

                    "Basic analyses"
                    "Dedicated analyses"
                    "Optional analyses"

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

             Sample collection
    
             Collection remaining plant material, vomit and gastric
             contents for identification purposes.
    

             Biomedical analysis
    
             Full blood counts with bleeding time, clotting time and serum
             electrolytes, blood urea and creatinine are essential
             investigations.
             Urine analysis could show haematuria, proteinuria or
             haemoglobin casts.

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Acute manifestations begin two to six hours
                    after ingestion and consist of burning pain in the
                    mouth and throat with thirst, followed by nausea,
                    intense vomiting, colicky abdominal pain and severe
                    diarrhoea with blood, leading to hypotension and
                    shock.
    
                    Delirium, loss of consciousness, convulsions,
                    respiratory distress, haematuria, oliguria, transient
                    leucocytosis followed by leucopenia, thrombocytopenia
                    with haemorrhages, anaemia, muscle weakness which may
                    progress to polyneuropathy are seen in the second or
                    third day.  Alopecia occurs 1 to 2 weeks after
                    intoxication as a late manifestation in
                    survivors.

             9.1.2  Inhalation

                    No data available.

             9.1.3  Skin exposure

                    No data available.

             9.1.4  Eye contact

                    No data available.

             9.1.5  Parenteral exposure

                    No data available.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No data available.

             9.2.2  Inhalation

                    No data available.

             9.2.3  Skin exposure

                    No data available.

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             The commonest clinical presentation of poisoning is
             severe gastroenteritis with nausea, vomiting, diarrhoea with
             blood leading to dehydration, hypovolaemic, shock and acute
             renal failure.  Muscle weakness, hypoventilation, ascending
             polyneuropathy, bone marrow depression and coagulation
             disorders are the other features of poisoning.
    
             Death in severe poisoning occurs due to shock or respiratory
             failure although haemorrhagic or infective complications may
             cause death after the first day.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Heart - there is no direct effect on the heart,
                    but fluid and electrolyte loss, often causes
                    hypovolaemic shock manifested by hypotension and
                    tachycardia.

             9.4.2  Respiratory

                    Respiratory failure is thought to be due to the
                    paralysis of intercostal muscles rather than the
                    direct depression of the respiratory centre by
                    colchicine (Angunawela & Fernando, 1971).
    
                    The patient may be dyspnoeic and cyanotic.

             9.4.3  Neurological

                    9.4.3.1  Central nervous system (CNS)

                             There is progressive paralysis of
                             the central nervous system and peripheral
                             nervous system (Wijesundere, 1986).
    
                             Confusion and delirium may develop either
                             secondary to poor cerebral perfusion or as a
                             result of direct cerebral toxicity (Ellenhorn
                             et al., 1996).  It may also cause
                             convulsions, restlessness and coma.

                    9.4.3.2  Peripheral nervous system

                             Ascending polyneuropathy, weakness,
                             loss of deep tendon reflexes may be
                             described.

                    9.4.3.3  Autonomic nervous system

                             No data available.

                    9.4.3.4  Skeletal and smooth muscle

                             Colchicine could have a direct toxic
                             effect on skeletal muscles causing muscular
                             weakness.  Rhabdomyolysis may occur with
                             significant increase in muscle enzymes and
                             myoglobinuria as a result of direct muscular
                             damage.
    
                             Muscle weakness that may persist for many
                             weeks may contribute to respiratory deficiency
                             (Ellenhorn et al., 1996).

             9.4.4  Gastrointestinal

                    Gastroenteritis including nausea, vomiting and
                    diarrhoea with blood accompanied by colic and
                    tenesmus.  Loss of fluids and electrolytes leads to
                    hypovolaemia.
    

                    Intestinal ileus may develop within the first few
                    several days and may persist up to a week (Ellenhorn
                    et al., 1996).

             9.4.5  Hepatic

                    Colchicine may exert direct hepatic toxicity
                    with moderate cytolysis.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Any direct toxic effect of the toxin
                             on kidney is not clear.  Renal failure is
                             probably secondary to excess fluid loss or
                             hypovolaemia and is preceded by oliguria and
                             haematuria.  Proteinuria could also occur
                             (Murray et al., 1983).

                    9.4.6.2  Other

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    Vaginal bleeding has been reported as a feature
                    of intoxication.  Tubers are used as an abortifacient
                    in some countries.

             9.4.8  Dermatological

                    Alopecia usually occurs one or two weeks after
                    the ingestion of G. superba.  A case of generalized
                    depilation has also been reported (Gooneratne, 1966). 
                    Desquamative dermatitis has been reported as another
                    dermatologic manifestation (Angunawela & Fernando,
                    1971).  Both these conditions can be attributed to the
                    antimitotic activity of the colchicine and gloriosine.

             9.4.9  Eye, ear, nose, throat:  local effects

                    Subconjunctival haemorrhages have been observed
                    (Gooneratne, 1966).
    
                    Burning and rawness of the throat may be early
                    symptoms of toxicity.

             9.4.10 Haematological

                    Colchicine has a depressant action on the bone
                    marrow which is characterized by a transient
                    leucocytosis followed by leucopenia.
    

                    It could also cause thrombocytopenia that may give
                    rise to various coagulation disorders resulting in
                    vaginal bleeding, conjunctival and gastrointestinal
                    haemorrhages.
    
                    Severe thrombocytopenia occurring within 6 hours of
                    poisoning has been documented (Saravanapavananthan,
                    1985).  Anaemia may occur, mostly secondary to
                    haemorrhages.

             9.4.11 Immunological

                    Patients are prone to infections as a result
                    of leucopenia.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Metabolic acidosis.

                    9.4.12.2 Fluid and electrolyte disturbances

                             There is an extensive fluid and
                             electrolyte loss due to intense vomiting and
                             diarrhoea or sometimes due to
                             haemorrhages.
    
                             Hypokalaemia, hypocalcaemia,
                             hypophosphataemia and hyponatraemia may
                             occur (Murray et al., 1983).

                    9.4.12.3 Others

                             Hypothermia could occur.

             9.4.13 Allergic reactions

                    No data available.

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    Pregnancy:  Data on effects of G. superba on
                    the foetus are not available.  However, colchicine is
                    contraindicated in pregnancy.  Down's syndrome and
                    spontaneous abortions have been reported.

        9.5  Other

             No data available.

    10. MANAGEMENT

        10.1 General principles

             Hospitalize the patient immediately.  Constant and
             prolonged monitoring is essential.  Ensure adequate
             ventilation.  Before instituting symptomatic and supportive
             therapy remove the plant material from gastrointestinal tract
             by emesis or gastric lavage without delay to minimize further
             absorption.  Give adequate intravenous fluids.  Correct any
             electrolyte imbalance.  Maintain a fluid balance chart.
    
             Specific measures should also be taken for the management of
             shock.  Cardiac monitoring is useful.
    
             Early forced diuresis may be of value.  Specific fragments
             a) b) have been experimented on animals.  No human data are
             available.

        10.2 Life supportive procedures and symptomatic/specific treatment

             Observation and monitoring:
    
             Monitor pulse, respiration and blood pressure.
    
             Fluid and electrolytes replacement:
    
             Give adequate oral fluids.  If the patient is unable to take
             oral fluids Ha 9 + 14.
    
             Hypotension and shock:
    
             Fluid loss may lead to hypovolaemic shock with hypotension: 
             Correct hypotension as required.
    
             Ensure a clear airway, improve ventilation and give oxygen
             (Ha 4 + 5 + 6).
    
             Early haemodynamic monitoring is very helpful (Murray et al.,
             1983).
    
             Respiratory:  If respiratory depression is present assisted
             ventilation and oxygen may be necessary.
    
             Renal failure:  Renal failure with oliguria is a common
             feature.  Maintain an adequate urine output with plenty of
             intravenous fluids.  Established renal failure may require
             peritoneal or haemodialysis.
    
             Leucopenia:  Fresh blood transfusions are necessary to
             correct leucopenia. 
    

             Prophylactic antibiotic therapy is advisable if leucopenia is
             present.
    
             Coagulation disorders:  If clotting time is abnormal, vitamin
             K and fresh frozen plasma should be given.  Haemorrhagic
             manifestations should be treated with fresh blood
             transfusions.
    
             Hypothermia:  This may be a poor prognostic sign.  Adopt
             measures to keep the patient warm.

        10.3 Decontamination

             If consciousness is not impaired AP4 + AP 5.7.8.

        10.4 Enhanced elimination

             Forced diuresis, if instituted early should be of
             benefit by eliminating colchicine.  Haemodialysis,
             haemoperfusion and other relevant measures are of no value
             because of large volume of distribution and limited renal
             excretion of colchicine (Ellenhorn et al., 1996).

        10.5 Antidote/antitoxin treatment

             10.5.1 Adults

                    There is no specific antidote available, but
                    immunotherapy (fragments fab) is available for
                    clinical trial on humans in some countries
                    (France).

             10.5.2 Children

                    There is no specific antidote available, but
                    immunotherapy (fragments fab) is available for
                    clinical trial on humans in some countries
                    (France).

        10.6 Management discussion

             No data available.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             A non-fatal case of poisoning following ingestion of
             boiled G. superba tubers has been described by Gooneratne
             (1966):
    
             A 21 year old married woman, who was said to have eaten about
             124 g of tuber (total amount of colchicine about 350 mg),
             developed gastrointestinal symptoms in 2 hours.
    

             On admission, about 24 hours after ingestion, she was
             unconscious and dehydrated.  Her blood pressure was 95/70 mm
             Hg, pulse rate was 122/minute and the respiratory rate was
             18/minute.  She developed acute renal failure, menorrhagia,
             subconjunctival haemorrhage in the left eye and after 11
             days, marked generalized alopecia. She eventually recovered
             and two months later her scalp hair showed regrowth.  Pubic
             and axillary hair also showed regrowth, though the latter
             remained very scanty.
    
             Angunawela and Fernando (1971) reported another non-fatal
             case of an 18 year old girl who had eaten raw tubers.  Six
             hours after ingestion she developed severe gastrointestinal
             symptoms, vaginal bleeding, acute renal failure, rapidly
             ascending polyneuropathy, respiratory distress, absence of
             tendon and plantar reflexes, leucopenia, alopecia and
             dermatitis.  She fully recovered in four weeks.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventative measures

             Public information.  Labelling cultivated plants for
             domestic use.

        12.2 Other

             See Poisons Information Monograph on Colchicine.

    13. REFERENCES

        Angunawela RM and Fernando HA (1971)  Acute ascending
        polyneuropathy & dermatitis following poisoning by tubers of G.
        Superba.  Ceylon Medical Journal, 16: 233-235.
    
        Burkill HM (1995)  The useful plants of West Tropical Africa, 2nd
        ed., vol. 3.  Royal Botanic Gardens, Kew.
    
        Craker LE and Simson JC (1986)  Recent advances in horticulture &
        pharmacology botany, vol I.  Arizona, Oryx Press.
    
        Duke JA (1985)  Handbook of medicinal herbs.  USA, CRC Press.
    
        Dunuwille R, Balasubramanium K and Bible SW (1968)  Toxic
        principles of Gloriosa superba. Ceylon Journal of Medical Science,
        17(2): 1-6.
    
        Ellenhorn MJ, Schonwald S, Ordog G and Wasserberger J (1996) 
        Ellenhorn's Medical toxicology: diagnosis & treatment of human
        poisoning, 2nd ed.  Williams & Wilkins, Baltimore.
    
        Gooneratne BWM (1966)  Massive generalized alopecia after
        poisoning by G. superba.  Br Med J, 1: 1023-1024.
    

        Huxley A ed-in-chief (1992)  The Royal Horticultural Society
        dictionary of gardening, vol 2. London, MacMillan Press.
    
        Jayaweera DMA (1982)  Medicinal plants used in Ceylon.  Colombo,
        National Science Council of Sri Lanka (part 3).
    
        Kimberly PR (1983)  Non steroidal anti-inflammatory agents and
        colchicine.  In:  Haddad LM and Winchester JF eds (1983)  Clinical
        management of poisoning and drug overdose.  Philadelphia.
    
        Murray SS, Kramlinger KG, McMichan JC and Mohr DN (1983)  Acute
        toxicity after excessive ingestion of colchicine.  Mayo Clin Proc,
        58: 528-532.
    
        Neuwinger HD (1994)  African ethnobotany. Poisons and drugs.
        Chemistry, pharmacology, toxicology.  English translation by A
        Porter.  Weinheim, Chapman & Hall.
    
        Reynolds JEF (1989)  Martindale: the extra pharmacopoeia, 29th ed. 
        London, The Pharmaceutical Press.
    
        Saravanapavananthan T (1985)  Plant poisoning in Sri Lanka. 
        Jaffna Medical Journal, 20(1): 17-21.
    
        Senanayake N and Karalliedde L (1986)  Acute poisoning in Sri
        Lanka; an overview.  Ceylon Medical Journal, 31(2): 61-71.
    
        Watt JM and Breyer-Brandwijk MG (1962)  The medicinal and
        poisonous plants of southern and eastern Africa.  Edinburgh, E. &
        S. Livingstone.
    
        Wijesundere A (1986)  Plant poisons.  Ceylon Medical Journal,
        31(2): 89-91.
    
        Windholz M ed. (1983)  The Merck Index: an encyclopedia of
        chemicals, drugs and biologicals, 10th ed. Rahway, New Jersey,
        Merck & Co., Inc.

    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
        ADDRESS(ES)

        Authors: Dr Ravindra Fernando and Miss Deepthi Widyaratna
        National Poisons Information Centre
        General Hospital
        Faculty of Medicine
        Kinsey Road
        Colombo 8
        Sri Lanka
    
        Tel: 94 1 694016/686143/691111 ext 306
        Fax: 94 1 699231
    

        Date: November 1989
    
        Peer Review: Adelaide, Australia, April 1991
    
        General edit and botanical review:
    
        Christine Leon
        Medical Toxicology Unit
        Guy's & St Thomas Hospital Trust
        c/o Royal Botanic Gardens, Kew
        Richmond
        Surrey
        TW9 3AB
        United Kingdom
    
        Tel: +44 (0) 181 332 5702
        Fax: +44 (0) 181 332 5768
        e-mail: c.leon@rbgkew.org.uk
    
        July 1997
    


    See Also:
       Toxicological Abbreviations