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Strychnine

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS
      1.4.2 Other numbers
   1.5 Brand names/trade names
   1.6 Manufacturers and importers
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
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Other characteristics
4. USES/HIGH RISK CIRCUMSTANCES OF POISONING
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High-risk circumstances of poisoning
   4.3 Occupationally exposed population
5. ROUTES OF ENTRY
   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
7. TOXICOLOGY
   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 Animal data
      7.2.3 In vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
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 by:
      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 Systemic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system
         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 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eyes, ears, 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
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks, pregnancy, breast feeding, enzyme deficiencies
   9.5 Others
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses and other investigations
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
   10.3 Life-supportive procedures and symptomatic treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from the literature
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Prevention of poisoning
   12.3 Other
13. REFERENCES
14. AUTHORS, DATE
                           Strychnine

    1.  NAME

        1.1  Substance

             Strychnine

        1.2  Group

             Alkaloid, Stimulant of the central nervous system

        1.3  Synonyms

             Strychnidin-10-one
             Estricnina (Portuguese and Spanish)
             Stricnina (Italian)
             Strychnin(German)
             Strychnine (English and French)

        1.4  Identification numbers

             1.4.1  CAS

                    57-24-9

             1.4.2  Other numbers

                    NIOSH WL 2275000
                    SIC/CODES 2834; 2833
                    CEC 614-003-00-5.

        1.5  Brand names/trade names

             Certox
             Dog-Button
             Dolco Mouse Ceral
             Kwik-kill
             Mole Death
             Mouse Nots
             Mouse-Rid
             Mouse-Tox
             Pied Piper Mouse Seed
             Quaker Button
             Ro-Dex
             Sanaseed
             
             (Note:  In Portugal, rodenticides do not contain strychnine).

        1.6  Manufacturers and importers

             To be completed by each centre.
             
             (Note:  In Portugal, pesticides do not contain strychnine).

    2.  SUMMARY

        2.1  Main risks and target organs

             Strychnine is a potent convulsant.  It causes increased
             reflex excitability in the spinal cord that results in a loss
             of the normal inhibition of spread of motor cell stimulation,
             so that all muscles contract simultaneously.
             
             Strychnine is also dangerous when heated as it emits highly
             toxic fumes.

        2.2  Summary of clinical effects

             The symptoms usually appear within 15 to 30 min after
             exposure.
             
             The initial symptoms are tightness and twitching of the
             muscles, agitation, and hyperreflexia.
             
             Convulsions and hyperreactivity to stimuli are characteristic
             of strychnine poisoning.  The patient is conscious and has
             intense pain.
             
             The body arches backwards in hyperextension (opisthotonus). 
             The facial muscles contract producing a characteristic
             expression known as "risus sardonicus".
             
             Complications are lactic acidosis, rhabdomyolysis, and acute
             renal failure.
             
             The convulsions may recur repeatedly and each episode is
             followed by a period of relaxation.
             
             Death is caused by asphyxia or medullary paralysis.
             
             Cumulative toxicity from strychnine has not been
             reported.
             
             The prognosis for strychnine poisoning is good if the
             patient's condition can be maintained over the first 6 to 12
             hours.

        2.3  Diagnosis

             Diagnosis is based on a history of ingestion (or illicit
             intravenous drug abuse) and the development of muscular
             stiffness and generalised muscular contractions easily
             triggered by eternal stimuli, accompanied by hypothermia,
             lactic acidosis and rhabdomyolysis.
             

             Strychnine can be measured chemically but there is no time to
             perform this procedure before treatment.  Strychnine is found
             in the urine, the blood, and the gastric fluid.
             
             Serum glutamic oxaloacetic transaminase (SGOT) and creatine
             phosphokinase (CPK) are elevated in serum. Also lactate
             dehydrogenases (LDH) levels are raised.
             
             Measure acidosis and serum potassium.

        2.4  First-aid measures and management principles

             Therapy should be symptomatic and supportive.
             
             Prevent any secondary sensory input.
             
             Prevent or control convulsions with:--
             
                      -   diazepam
                      -   phenytoin
                      -   phenobarbital.
             
             Gastric aspirations and lavage may be done after the seizures
             are controlled.
             
             Give activated charcoal with a cathartic.
             Strychnine poisoning is rare.  It is caused by the accidental
             ingestion of tonic and cathartic pills.  Since they are
             brightly coloured and sugarcoated, they are attractive to
             children.
             
             The ingestion of strychnine bait causes accidental
             poisonings, particularly in children who are attracted by the
             similarity of the bait to peanuts.  Its use as a pesticide is
             a source of suicidal and homicidal poisonings, but these
             cases are rare.
             
             The ingestion of the whole plant, mainly the seeds of
             Strychnos nux vomica or Strychnos ignatii, can cause
             poisoning because these plants contain strychnine.
             
             Symptoms usually appear within 15 to 30 minutes after
             exposure.
             
             Convulsions and hyperreactivity to stimuli are characteristic
             of strychnine poisoning.  The patient is conscious throughout
             the episode and has intense pain.
             
             Death is caused by asphyxia.
             
             The prognosis for strychnine poisoning is good if the patient
             can be supported over the first 6 to 12 hours.
             

             First-aid measures:-
             
               -    Therapy should be symptomatic and supportive.
             
               -    Prevent any secondary sensory input.
             
               -    Prevent or control convulsions with:
             
                      -   diazepam
                      -   phenytoin
                      -   phenobarbital.
             
               -    Gastric aspiration and lavage may be used after the
                    seizures are controlled.
             
               -    Give activated charcoal with a cathartic.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Natural.
             
             Strychnine is an alkaloid obtained from the seeds of
             Strychnos or Loganiaceae:
             
                    Strychnos nux vomica Linnaeus
                    Strychnos ignatii.

        3.2  Chemical structure

             (Windholz, 1983; Sax, 1988).
             
             Molecular formula: C21H22N2O2
             
             Molecular weight: 334,40
             
                    C 75,42%
                    H  6,63%
                    N  8,38%
                    O  9,57%
             
             Structural formula:

        3.3  Physical properties

             3.3.1  Colour

                    Translucent or white

             3.3.2  State/form

                    Crystals or crystalline powder

             3.3.3  Description

                    Boiling point:  270C to 280C with decomposition
                    
                    Melting point:  268C to 290C depending on speed of
                                    heating
                    
                    Odour:  odourless
                    
                    Taste: a very bitter metallic taste
                    
                    pH of saturated solution: 9.5
                    
                    Specific gravity: 1.36 at 20 C referred to water at
                    4C
                    
                    Solubility:   1 g dissolves in:
                    
                             6400 mL water
                             3100 mL boiling water
                              150 mL  alcohol
                               35 mL chloroform
                              180 mL benzene
                              200 mL toluene
                              260 mL methanol
                              320 mL glycerol
                              220 mL  amyl alcohol
                    
                             very slightly soluble in ether.
                    
                    (Sax, 1988; Windholz, 1983)

        3.4  Other characteristics

             Products of combustion:  highly toxic
             
             Environmental risk, air pollution:  high
             
             Explosiveness: Stable
             
             (Sax, 1988; Hayes, 1982; Reynolds, 1982).

    4.  USES/HIGH RISK CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Pesticide:
                    
                    Strychnine and its salts are used for killing birds,
                    rodents, moles, and predatory animals, and for
                    trapping fur-bearing animals.
                    
                    Pharmaceutical:
                    
                    Strychnine is an unjustifiable component of
                    traditional tonics and cathartic pills.
                    
                    Properties have been attributed to the drug that it
                    does not possess or that it exhibits only when
                    administered in toxic doses.
                    
                    However, preliminary experiments suggest that
                    judicious treatment with strychnine may modify the
                    neurological deterioration that occurs in infants who
                    have "nonketotic hyperglycinemia" (Goodman & Gilman,
                    1985).  Improvement in severe forms of this condition
                    is limited and transient (Sankaran et al.,
                    1982).

        4.2  High-risk circumstances of poisoning

             Strychnine poisoning is rare.  It is caused by the
             accidental ingestion of tonic and cathartic pills which are
             brightly coloured and sugarcoated and thus attractive to
             children (Arena & Drew, 1986).
             
             The ingestion of strychnine bait causes accidental poisoning,
             particularly in children who are attracted by the similarity
             of the bait to peanuts.  Its use as a pesticide is a source
             of suicidal and homicidal poisonings, but these cases are
             rare.
             
             The ingestion of the whole plant, mainly the seeds of
             Strychnos nux vomica or Strychnos ignatii can cause poisoning
             because these plants contain strychnine.  Strychnol nux
             vomica contains 1.1 to 1.4% and Strychnos ignatii 2 to 3%
             (Poisindex, 1989a).
             

             The accidental ingestion or sniffing of strychnine when it is
             used to adulterate cocaine, heroin, LSD, and other street
             drugs, has caused poisoning (O'Callaghan et al., 1982).
             
             Strychnine emits toxic vapours when heated to
             decomposition.

        4.3  Occupationally exposed population

             The professions in which there may be exposure to
             strychnine are:
             
                    pharmaceuticals
                    agriculture
                    industry.
             
             Personal safety precautions: (protect skin with clothing to
             avoid contact and use) self-contained breathing apparatus
             (Sax, 1988).

    5.  ROUTES OF ENTRY

        5.1  Oral

             Ingestion of pills and pesticides with strychnine and
             also plants of Strychnos or Loganiaceae species.
             
             Strychnine is quickly absorbed from the gastrointestinal
             tract, mainly from the intestine.

        5.2  Inhalation

             When strychnine is sniffed or is smoked with adulterated
             marijuana, it is quickly absorbed from the mucous
             membranes.

        5.3  Dermal

             Skin allergen.

        5.4  Eye

             Unknown.

        5.5  Parenteral

             Strychnine is rapidly absorbed from parenteral sites of
             injection.  If subcutaneously injected, the site of the
             injection may affect the beginning of action (Sax,
             1988).

        5.6  Others

             Unknown.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Strychnine is rapidly absorbed from the gastrointestinal
             tract, nasal passages, or from parenteral injection sites. 
             Symptoms begin within 15 to 30 minutes, occasionally after a
             delay of 1 hour.  If it is taken by mouth, the time of action
             depends on whether the stomach is empty or full, and on the
             type of food that is eaten.

        6.2  Distribution by route of exposure

             Strychnine travels in both plasma and erythrocytes, and
             rapidly leaves the bloodstream.  Approximately 50% can enter
             the tissues in 5 minutes (Reynolds, 1982).
             
             In a fatal poisoning, there were concentrations in the bile,
             the liver, and stomach wall (Perper, 1985).

        6.3  Biological half-life by route of exposure

             Half-life=10 hours.
             
             Strychnine concentrations were measured in a patient who
             attempted suicide.  The half-life of 10 hours suggested that
             normal hepatic function can efficiently degrade strychnine
             even when the quantity ingested is high enough to cause
             severe poisoning.  The elimination constant (Kel=0.07 h-1)
             indicates that 7% of the strychnine in the serum at any one
             moment would be eliminated in 1 hour (Edmunds et al.,
             1986).

        6.4  Metabolism

             Strychnine is readily metabolized, mainly by enzymes of
             hepatic microsomes.  The rate of destruction is such that
             approximately two lethal doses can be given over 24 hours
             without cumulative effects (Goodman & Gilman, 1985).

        6.5  Elimination

             A few minutes after ingestion, strychnine is excreted
             unchanged in the urine, and accounts for about 5% of a
             sublethal dose given over 6 hours (Boyd et al., 1983).
             

             Approximately 10 to 20% of the dose will be excreted
             unchanged in the urine 24 hours later.  The percentage
             excreted decreases with the increasing dose.  Of the amount
             excreted by the kidneys, about 70% is excreted in the first 6
             hours, and almost 90% in the first 24 hours (Weiss & Hatcher,
             1922).  Excretion is almost complete in 48 to  72 hours
             (Cooper, 1974).

    7.  TOXICOLOGY

        7.1  Mode of action

             Strychnine causes excitation of all parts of the central
             nervous system,  It increases the level of neuronal
             excitability by interfering with inhibitory influences on the
             motor neurons.  The site of action of strychnine is the
             postsynaptic membrane.  The convulsant action of the
             substance is due to interference with the postsynaptic
             inhibition that is mediated by glycine.  Glycine is an 
             inhibitory transmitter to motor neurons and interneurons in
             the spinal cord.  Strychnine acts as a selective competitive
             antagonist to block the inhibitory effects of glycine at the
             glycine receptors.  Studies indicate that strychnine and
             glycine interact with the same receptor complex, although
             probably at different sites (Goodman & Gilman, 1985).

        7.2  Toxicity

             7.2.1  Human data

                    The maximum exposure limit is approximately
                    0.15 mg/m3.
                    
                    There is one report of one case on ingestion of 3.75 g
                    that was not fatal (Poisindex, 1989b).

                    7.2.1.1  Adults

                             The lethal dose for adults varies. 
                             The minimal oral human lethal dose ranges
                             from 30 to 120 mg.  When given intravenously
                             or subcutaneously, the lethal dose is
                             significantly lower.

                    7.2.1.2  Children

                             The lethal dose in children may be
                             as low as 15 mg (Goodman & Gilman,
                             1985).

             7.2.2  Animal data

                    oral-rat LD50:               16 mg/kg
                    intraperitoneal-rat LD50:    2500 g/kg
                    subcutaneous-rat LD50:       1200 g/kg
                    intravenous-rat LD50:        960 g/kg
                    oral-mouse LD50:             2 mg/kg
                    intraperitoneal-mouse LD50:  980 g/kg
                    subcutaneous-mouse LD50:     474 g/kg
                    intravenous-mouse LD50:      410 g/kg
                    oral-dog LDLo:               1100 g/kg
                    subcutaneous-dog LdLo:       350 g/kg
                    intravenous-dog LDLo:        250  g/kg
                    oral-cat LDLo:               750 g/kg
                    subcutaneous-cat LDLo:       750 g/kg
                    intravenous-cat LDLo:        330 g/kg
                    oral-rabbit LDLo:            600 g/kg
                    subcutaneous-rabbit LDLo:    700 g/kg
                    intravenous-rabbit LDLo:     350 g/kg
                    oral-pigeon LD50:            21 mg/kg
                    subcutaneous-pigeon LDLo:    1 mg/kg
                    subcutaneous-chicken LDLo:   3 mg/kg
                    oral-duck LD50:              3 mg/kg
                    subcutaneous-duck LDLo:      1 mg/kg
                    subcutaneous-frog LDLo:      35 g/kg
                    
                    (NIOSH, 1983-84 Supplement)

             7.2.3  In vitro data

                    Strychnine has been studied extensively.  The
                    convulsions caused by strychnine have a characteristic
                    motor pattern which is determined by the most powerful
                    muscles acting as a given joint.  In most laboratory
                    animals, convulsions are characterized by tonic
                    extension of the body and limbs.  Typical strychnine
                    convulsions also occur in spinal animals.  Thus, the
                    effects of strychnine are often attributed to a spinal
                    locus of action, although other parts of the CNS are
                    also excited by doses that produce the characteristic
                    motor manifestations in a spinal animal (Goodman &
                    Gilman, 1985).

             7.2.4  Workplace standards

                    Occupational exposure limits:
                    TLV: ppm; 0.15 mg/m3 (as TWA)
                    (IIPCS & CEC, 1990)

             7.2.5  Acceptable daily intake (ADI)

                    The maximum permissible atmospheric
                    concentration of strychnine is 150 g per m3
                    (Reynolds, 1982).

        7.3  Carcinogenicity

             No data available.

        7.4  Teratogenicity

             Ims-rat TDLo: 500 g/kg /5D preg (Sax, 1988).

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             No data available.

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Symptoms appear in 15 minutes to 1 hour after
                    ingestion causing violent generalized
                    convulsions.

             9.1.2  Inhalation

                    After sniffing, toxic symptoms of poisoning
                    appear in 30 minutes and are the same as the symptoms
                    that appear after ingestion.

             9.1.3  Skin exposure

                    Strychnine may be an allergen that is caused by
                    direct skin exposure (Sax, 1988).

             9.1.4  Eye contact

                    Not described.

             9.1.5  Parenteral exposure

                    Symptoms are the same as after ingestion (see
                    Section 9.1.1).

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning by:

             Chronic poisoning is not known (Cooper, 1974) and
             significant cumulative toxicity is not recognized (Gosselin
             et al., 1984).

             9.2.1  Ingestion

                    Not described.

             9.2.2  Inhalation

                    Not described.

             9.2.3  Skin exposure

                    Strychnine may be a chronic dermatological
                    allergen, but systemic effects are not known (Sax,
                    1988).

             9.2.4  Eye contact

                    Not described.

             9.2.5  Parenteral exposure

                    Not described.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Seizures are the major side effects of strychnine
             poisoning.
             
             Sometimes there are prodromal symptoms e.g., stiffness of
             facial and neck muscles and hyperreflexia.
             
             The patient is hyperexcited, and even a very small stimulus
             can precipitate violent convulsions.
             
             These convulsions are very painful because of the strong
             contractions of the muscles; the patient may even cry.  He is
             fully conscious and lucid until anoxia supervenes.
             

             Convulsions may occur frequently with intermittent periods of
             depression.  The frequency and severity of the convulsions
             are increased by sensory stimulation.
             
             If the patient survives 6 to 12 hours the prognosis is good
             (Boyd et al., 1983).
             
             If the convulsions are not treated, the patient may die with
             in 1 to 3 hours after a fatal dose.  Death is usually due to
             asphyxia from respiratory arrest during or between
             convulsions.

        9.4  Systemic description of clinical effects

             9.4.1  Cardiovascular

                    The pulse may be difficult to detect, and there
                    may be tachycardia and hypertension.

             9.4.2  Respiratory

                    The diaphragm, chest, and abdominal muscles are
                    in a sustained spasm and breathing becomes difficult. 
                    Hypoxia and cyanosis occur followed by death.

             9.4.3  Neurological

                    9.4.3.1  Central nervous system

                             Seizures are the major symptoms of
                             strychnine poisoning and are caused by
                             excitation of all parts of the CNS.
                             
                             The onset of symptoms may occur with a
                             prodromal syndrome that includes: tonic
                             twitching of the face and neck muscles,
                             muscular cramps in the legs, preceded by
                             restlessness, apprehension, and heightened
                             acuity of perception (hearing, vision,
                             feeling) and hyperreflexia.  However, the
                             initial symptoms may be only generalized
                             violent convulsions.  These convulsions can
                             begin suddenly after any minor sensory
                             stimulus and last from 50 seconds to 2
                             minutes.  Initially, the convulsions are
                             clonic but are soon followed by tonic
                             contractions similar to convulsions due to
                             tetanus.
                             
                             The patient remains conscious and has intense
                             pain.  After the convulsions, all the muscles
                             relax and sometimes the patient falls asleep
                             from exhaustion.  Hyperexcitability recurs
                             suddenly after 10 to 15 minutes.
                             

                             Repeated convulsions (1 to 10) are common
                             before recovery or death.  In severe
                             untreated poisoning, each convulsion lasts
                             longer than the previous one, and the
                             intervals between them are shorter.

                    9.4.3.2  Peripheral nervous system

                             No data available.

                    9.4.3.3  Autonomic nervous system

                             No data available.

                    9.4.3.4  Skeletal and smooth muscle

                             After strychnine poisoning, all
                             voluntary muscles contract simultaneously,
                             although there is no direct effect on
                             skeletal muscles.  The increase in muscle
                             tone is caused by the central action of the
                             drug (Goodman & Gilman, 1985).  The major
                             effects are caused by the action of the most
                             powerful muscle on the joint.
                             
                             During the convulsions, the patient shows
                             hypertonicity of the muscles beginning by
                             thrismus, risus sardonicus, and cramps of the
                             arms and legs, that are soon followed by
                             opisthotonus.
                             
                             Respiratory muscles - diaphragm, thoracic,
                             and abdominal, also contract.  Respiration
                             ceases, and the patient may die.
                             
                             Repeated convulsions with muscular spasms are
                             very painful.  They are succeeded by the
                             relaxation of all muscles.
                             
                             Rhabdomyolysis associated with myoglobinuria,
                             and also elevation of serum glutamic
                             oxaloacetic transaminase (SGOT), lactate
                             dehydrogenases (LDH), and creatine
                             phosphokinase (CPK), may occur after the
                             intense muscular contractions.

             9.4.4  Gastrointestinal

                    Vomiting may occur (Gosselin et al., 1984). 
                    Small quantities of strychnine have an extremely
                    bitter taste and cause reflex gastric secretion
                    (Gossel & Bricker, 1984).

             9.4.5  Hepatic

                    No data available.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Rhabdomyolysis and myoglobinuria
                             have been reported and renal damage may occur
                             from precipitation of myoglobin in the renal
                             tubules (Conn, 1988).

                    9.4.6.2  Others

                             The urine may have a green colour
                             because commercial preparations of strychnine
                             that are used as rodenticides contain
                             methylene-blue (Bismuth et al.,
                             1987).

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Strychnine may be a skin allergen if there is
                    direct or chronic skin exposure.

             9.4.9  Eyes, ears, nose, throat: local effects

                    The eyes protrude and the pupils dilate.  One
                    case of mystagmus was reported: bilateral horizontal
                    pendular nystagmus that was not responsive to diazepam
                    ceased spontaneously (Blain et al., 1982).
                    
                    The throat may be dry (Hayes, 1982).

             9.4.10 Haematological

                    Leukocytosis may also occur (Poisindex, 1989b)

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Lactic acidosis: seizures and
                             muscular spasms may cause hyperthermia and
                             lactic acidosis.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Hyperkalaemia and dehydration can
                             occur after several convulsions (Gosselin et
                             al., 1984).

             9.4.13 Allergic reactions

                    Strychnine may be an allergen if there is
                    direct or chronic contact with the skin (Sax,
                    1988).

             9.4.14 Other clinical effects

                    During the remissions, cold perspiration
                    covers the skin (Gosselin et al., 1984), and the
                    patient may be thirsty.

             9.4.15 Special risks, pregnancy, breast feeding, enzyme
                    deficiencies

                    There may be elevations of serum glutamic
                    oxaloacetic transaminase (SGOT), lactate
                    dehydrogenases (LDH), and creatine phosphokinase (CPK)
                    (Poisindex, 1989b).

        9.5  Others

             No data available.

    10. MANAGEMENT

        10.1 General principles

             Treatment of strychnine poisoning is symptomatic and
             supportive.
             
             Since strychnine is rapidly absorbed from the
             gastrointestinal tract and may cause convulsions with 15 to
             60 minutes, the main object of therapy is to prevent or
             control convulsions and asphyxia.
             
             Emesis is not contraindicated.

        10.2 Relevant laboratory analyses and other investigations

             10.2.1 Sample collection

                    Take samples of blood, urine, and gastric
                    fluid for biomedical analysis, and a sample of the
                    product for identification.

             10.2.2 Biomedical analysis

                    The drug can be detected in the urine, blood,
                    gastric aspirate, and other organs by colorimetry or
                    ultraviolet spectrophotometry, but gas-liquid
                    chromatograph with a flame ionization detector is more
                    accurate.
                    
                    Blood levels do not indicate the need for therapy or
                    the extent of the treatment.
                    
                    The following biomedical investigations should be
                    carried out
                    
                             -  lactic acidosis
                             -  hyperkalaemia
                             -  elevation of creatine phosphokinase, serum
                                glutamic oxaloacetic transaminase, lactate
                                dehydrogenases, and leukocytosis.

             10.2.3 Toxicological analysis

                    No data available.

        10.3 Life-supportive procedures and symptomatic treatment

             Reduce all sensory stimulation to a minimum by keeping
             the intoxicated patient in a warm, quiet, and darkened
             room.
             Protect the patient from self-inflicted injury.
             
             Support respiratory and cardiovascular functions and
             administer:
             
             Diazepam IV     Adult:  5 to 10 mg initially over one minute.
                             If convulsions continue give further 10 mg
                             over one minute.
             
                             Children:  the dose is 0.5 mg/kg..
             
             If an intravenous line is not available, diazepam may be
             given rectally.
             

             If convulsions cannot be controlled with diazepam or if they
             recur, administer phenobarbitone or phenytoin.
             
             Phenobarbitone  Adult: 10 to 15 mg/kg slowly administered
                             intravenously upto a total dose of 30
                             mg/kg.
             
                             Child:  10 to 15 mg/kg at a rate of 25 to 50
                             mg/min.
             
             Phenytoin IV    Adult:  15 to 20 mg/kg (in 0.9% normal
                             saline) not to exceed 50 mg/kg.
             
                             Child:  15 mg/kg at a rate of 0.5 to 1.5
                             mg/kg per min is recommended.
             
             For seizures that do not respond to previous treatments,
             general anaesthesia including neuromuscular blocking agents,
             such as tubocurarine or suxamethonium chloride should be
             used, with assisted respiration using oxygen.
             
             Tubocurarine chloride is usually administered by intravenous
             injection over 1 to 1.5 minutes.  For infants or other
             patients in whom a suitable vein is not accessible, the drug
             may be administered intramuscularly in the same dosage as the
             intravenous drug. The usual initial dose is 75 to 150 g/kg
             body weight, with subsequent doses as required.
             
             Suxamethonium chloride is usually administered
             intravernously, but may also be given intramuscularly. The
             usual single dose of suxamethonium chloride for an adult is
             20 to 100 mg intravenously.  Doses may be repeated if
             necessary with little danger of cumulative effect.
             
             The recommended dose for children is 1 to 2 mg/kg
             intravenously.
             
             When administered intramuscularly, the dose for adults and
             children is up to 2.5 mg/kg body weight to a maximum total of
             150 mg (Reynolds, 1982).

        10.4 Decontamination

             Administer activated charcoal alone or with cathartic. 
             Emesis or gastric lavage is not recommended because they may
             cause convulsions.
             
             When convulsions and hyperactivity are completely controlled,
             gastric lavage can be performed safely.
             

             Activated charcoal:            Administer aqueous charcoal
                                            alone or mixed with saline
                                            cathartic or sorbitol.
             
                                            Adult:  60 to 100 g
                                            Child:  30 to 60 g  (Borges,
                                            1986)
             
             Cathartics:
             
             Saline cathartics:
             
             Magnesium or sodium sulfate:
             
                             Adult:  30 g per dose
                             Child:  250 mg/kg per dose
             
             Sorbitol:       Adult:  1 to 2 g/kg per dose to a maximum of
                             150 g per dose
                             Child:  (over 1 yr old): 1 to 1.5 g/kg per
                             dose as a 35% solution to a maximum of 50 g
                             per dose.  Monitor fluid and electrolyte
                             status, especially in children  (Abrantes &
                             Marques Penha, 1986).

        10.5 Elimination

             Forced acid diuresis seems to enhance urinary excretion
             but should be avoided if rhabdomyolysis and associated
             myoglobinuria are present since an acidic urine may
             precipitate myoglobin in the renal tubules and cause renal
             insufficiency.
             
             There are not enough data available to assess the efficacy of
             peritoneal dialysis after strychnine intoxication.

        10.6 Antidote

             There is no antidote.

        10.7 Management discussion

             There are no major controversies or alternatives
             regarding patient management.  Treatment is designed to
             prevent convulsions and to protect medullary asters from
             excessive stimulation and from anoxia (Gosselin et al.,
             1984).

    11. ILLUSTRATIVE CASES

        11.1 Case reports from the literature

             A 1-year-old child swallowed Easton's syrup tablets
             prescribed for her mother and became distressed within 30
             minutes.  She convulsed 30 minutes later and was sent to
             hospital where her stomach was washed out.  Convulsions
             became continuous and the infant was given intramuscular
             paraldehyde for opisthotonos.  Cardiac arrest was reversed
             and she was given desferrioxamine and intravenous sodium
             bicarbonate and noradrenaline.  Despite external cardiac
             massage and intermittent positive-pressure respiration, she
             died approximately 3 to 3.5 hours after the accident.  From
             examination of the viscera, it was estimated that she had
             swallowed iron 2.94 g and strychnine 16 mg, with 0.79 g of
             quinine (Stannard, 1969).
             
             A 13-month old child ate Easton's syrup tablet and cried and
             became rigid 15 minutes later.  In hospital, he had a
             convulsion and respiratory arrest that required mouth-to-
             mouth assisted respiration and external cardiac massage.  He
             continued to have repeated fits and intermittent respiratory
             arrest and was given endotracheal intubation and oxygen
             therapy.  Facial grimacing and opisthotonos persisted. 
             Muscular relaxation occurred immediately after an intravenous
             injection of 2.5 mg diazepam.  Gastric lavage was performed
             with sodium bicarbonate solution 45 minutes after the
             accident, and desferrioxamine mesylate was given to
             counteract possible iron intoxication from the Easton's
             formula.  Convulsions were completely controlled with
             diazepam and the endotrachael tube was removed 6 hours later
             (Jackson et al., 1971).

             A 50-year-old man took an unknown quantity of strychnine that
             he used to control skunks on his bee farm.  He was admitted
             to hospital with generalized convulsions and in extreme pain. 
             When he was given diazepam 10 mg intravenously the seizures
             stopped in less than 1 minutes and gastric lavage was
             performed.  Diazepam 10 mg every 6 hours intramuscularly
             stopped the spasms (Harden & Griggs, 1971).
             
             A 42-year-old man ingested an unknown quantity of strychnine
             in a suicide attempt.  On arrival at hospital, he complained
             of severe muscle cramps and within 5 minutes developed
             convulsions and respiratory arrest.  He was immediately given
             succinyl choline intravenously, and was then intubated and
             ventilated mechanically.  He had a cardiac arrest, and
             although external cardiac massage was successful, he remained
             unconscious for 72 hours.  He was given bicarbonate but
             developed a mixed respiratory and metabolic acidosis; with
             mechanical ventilation, the acidosis improved considerably. 
             During this period, he was sedated and was given muscle

             relaxants.  He developed a severe chest infection and from
             days 8 to 18 required a further period on the ventilator. 
             Two hours after the poisoning, gastric lavage was performed
             with 10 g activated charcoal and 2 litres water. Forty-eight
             hours after admission, there was biochemical evidence of
             rhabdomyolysis, and renal failure occurred. Peritoneal
             dialysis was begun, but due to technical problems, the
             treatment was changed to intermittent haemodialysis.  Renal
             function was fully recovered.  After discharge at 8 weeks, he
             returned to work, but serial psychometric testing showed
             residual impairment of short- and medium-term memory
             (Edmunds, 1986).

    12. ADDITIONAL INFORMATION

        12.1 Availability of antidotes

             There is no specific antidote.

        12.2 Prevention of poisoning

             There is no justification for use of strychnine as
             bitter and analeptic.
             
             Do not use strychnine as a pesticide.
             
             Strychnine should be kept out of the reach of children and
             irresponsible people.
             
             For safe use of the pesticides, follow instructions
             carefully.
             
             Wear skin protection (rubber gloves and synthetic clothing)
             and self-contained breathing apparatus wherever the product
             is manufactured, packaged, or stored.

        12.3 Other

             No data available.

    13. REFERENCES

        Abrantes J & Marques Penha J (1986).  Therapeutic arsenal in
        clinical toxicology.  Emergncia Mdica, II(6): 9-17 (in
        Portuguese).
        
        Arena JM & Drew RH (1986).  Poisoning, toxicology, symptoms,
        treatments.  Springfield, Illinois, USA, CC Thomas, 228-229
        (1128).
        
        Bismuth C, Baud FJ, Conso F, Frejaville JP & Garnier R (1987). 
        Toxicologie Clinique, Paris, Flammarion, 427 (956 pp).
        

        Blain PG, Nightingale S & Stoddart JC (1982). Strychnine
        poisoning: abnormal eye movements.  Journal of Toxicology -
        Clinical Toxicology, 19(2): 215-217.
        
        Borges A (1986).  The use of ipecac syrup and activated charcoal
        in toxicology.  Emergncia Mdica, II(6): 4-7 (in Portuguese).
        
        Boyd RE, Brennan PT, Deng JF, Rochester DF & Spyker DA (1983). 
        Strychnine poisoning.  Am. J. Med., 74: 507-512.
        
        Conn HJ (1988). Current therapy.  Philadelphia, WB Saunders &
        Company, 1038 (1092 pp).
        
        Cooper P (1974).  Poisoning by drugs and chemicals.  London,
        Alchemist Publications, 193-194 (218 pp).
        
        Edmunds M, Sheehan TMT & Van't Hoff W (1986). Strychnine
        poisoning: clinical and toxicological observations on a non-fatal
        case.  Journal of Toxicology - Clinical Toxicology, 24(3): 245-
        255.
        
        Goodman LS, Gilman AG & Gilman A (1985).  The pharmacological
        basis of therapeutics, New York, Macmillan Publishing Co., Inc.,
        582-584 (1839 pp).
        
        Gossel TA & Bricker JD (1984).  Principles of clinical toxicology,
        New York, Raven Press, 295-296 (357 pp).
        
        Gosselin RE. Smith RP & Hodge HC (1984).  Clinical toxicology of
        commercial products, Baltimore/London, The Williams & Wilkins Co.,
        III, 375-379.
        
        Harden JA & Griggs RC (1971)  Diazepam treatment in a case of
        strychnine poisoning.  Lancet, 2: 372-373.
        
        Hayes WJ (1982).  Pesticides studied in man.  Baltimore/  London,
        Williams & Wilkins, 96-101 (672 pp).
        
        IPCS/CEC (1990) International Chemical Safety Card Strychnine.
        Series 3 No. 0197.
        
        Jackson G, Ng SH, Diggle GE & Bourke IG (1971).  Strychnine
        poisoning treated successfully with diazepam.  Br. Med. J. 3: 519-
        520.
        
        NIOSH - Registry of Toxic Effects of Chemical Substances , 1983-
        84.  Cumulative supplement to the 1981-82 edition, Maryland,
        Advanced Engineering & Planning Corp., Inc., 1738-1739 (2050
        pp).
        

        O'Callaghan WG, Joyce N, Counihan HE, Ward M, Lavelle P & O'Brien
        E (1982).  Unusual strychnine poisoning and its treatment - report
        of eight cases.  Br. Med. J. 185: 478.
        
        Perper JA (1985).  Fatal strychnine poisoning - A case report and
        review of literature.  J. Forensic. Sci., 30: 1248-1255, in
        Poisindex (1989) Strychnine.
        
        Poisindex System (1989a).  Strychnos ignatii and strychnos nux-
        vomica.  Denver, Colorado, Rocky Mountain Poison Center.
        
        Poisindex System (1989b).  Strychnine.  Denver, Colorado, Rocky
        Mountain Poison Center.
        
        Reynolds JEF(1982) Martindale The extra pharmacopoeia.  London,
        The Pharmaceutical Press, 319-320, 995-1000 (2025 pp).
        
        Sankaran K, Casey RE, Zaleski WA & Mendelson IM (1982).  Glycine
        encephalopathy in a neonate: treatment with intravenous strychnine
        and sodium benzoate.  Clin. Pediat. (Phila). 21: 636-663.
        
        Sax NI (1988).  Strychnine.  Dangerous properties of industrial
        material.  Report, 8(1): 78-83.
        
        Stannard NW (1969).  Child death due to Easton's tablets. 
        Practitioner, 203: 668-669. In Gosselin 1984.
        
        Weiss S & Hatcher RA (1922)  Studies on strychnine.  J. Pharmac.
        Exp. Ther., 19: 419-482.  In Gosselin 1984.
        
        Windholz  (1983)  The Merck Index Rahway, New Jersey, USA, Merck &
        Co. Inc., 1268.

    14. AUTHORS, DATE

        A. Borges, J. Abrantes, MT. Teixeira, P. Parada
        Centro de Informmacao Antivenenos
        Instituto Nacional de Emergnca Mdica
        Rua Infante D. Pedro 8
        1700 Lisbon
        Portugal
        
        Tel:        73 05 03
        Telex:      13 304 SNALP P
        Telefax:    77 34 74
        
        March 1989
        

        Reviewer:   A.F. Rahde
                    Poison Control Centre
                    Rua Riachuelo 677
                    Apartado 201
                    90010 Porto Alegre
                    Brazil
        
                    Tel:     55-512-275419
                    Telex:   051-2077 FUOC BR
                    Telefax: 55-512-391564
        
                    May 1989.
        
        Peer Review:         Hamilton, May 1989
                             London, March 1990
        
        Editor:              M.Ruse
        
        Finalised:           IPCS, April 1997.

    



    See Also:
       Toxicological Abbreviations
       Strychnine (ICSC)