Nicotiana tabacum L
| 1. NAME |
| 1.1 Scientific name |
| 1.2 Family |
| 1.3 Common name(s) |
| 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 |
| 4.2 High risk circumstances |
| 4.3 High risk geographical areas |
| 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 by route of exposure |
| 7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY |
| 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 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 |
| 8.6 References |
| 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 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 Others |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, 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 |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 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/toxinological analysis |
| 10.2.4 Other investigations |
| 10.3 Life supportive procedures and symptomatic treatment |
| 10.4 Decontamination |
| 10.5 Elimination |
| 10.6 Antidote/antitoxin treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases |
| 11.3 Internal cases |
| 12. ADDITIONAL INFORMATION |
| 12.1 Availability of antidotes/antitoxins |
| 12.2 Specific preventive measures |
| 12.3 Other |
| 13. REFERENCES |
| 13.1 Clinical and toxicological |
| 13.2 Botanical |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
POISONOUS PLANTS
1. NAME
1.1 Scientific name
Nicotiana Tabacum L
1.2 Family
Solanaceae
1.3 Common name(s)
Fumo
Petume
Petina
Pitura
etum
Tabaco (Brazil)
Tabaco (Argentina)
Tobacco (USA).
2. SUMMARY
2.1 Main risks and target organs
Nicotianas are highly toxic plants due to their nicotine
alkaloid content. The effects of nicotine alkaloid are a
result of the summation of actions at ganglionic sites, motor
end plates and smooth muscle. The central nervous system is
affected, initially by stimulation, resulting in tremors and
convulsions, progressing to depression. Death occurs from
respiratory failure. Vomiting is a result of stimulation of
the emetic chemoreceptor trigger zone.
The cardiovascular responses are generally due to stimulation
of sympathetic ganglia and adrenal medulla combined with
discharge of catecholamines. The target organs are nervous
system and heart.
2.2 Summary of clinical effects
The onset of symptoms in acute nicotine alkaloid poisoning is
usually rapid. In the case of ingestion of leaves and other
parts of the plant there is a delay in the onset of the
symptoms due to slower gastric absorption of the alkaloid.
Symptoms following a relatively small dose are transient and
consist of salivation, nausea, vomiting, diarrhoea,
bradycardia and dizziness.
In severe poisoning with pure alkaloid, the patient may
collapse and die within minutes from overwhelming paralysis.
Where death is delayed, abdominal pain is marked with severe
diarrhoea and a cold sweat. Mental confusion, giddiness,
restlessness, muscular weakness and disturbed vision and
hearing are followed by a loss of coordination, and
unconsciousness. Blood pressure may initially be raised and
respiration stimulated, but is soon followed by a fall in
blood pressure, a rapid irregular pulse and laboured
breathing. Clonic convulsions are followed by collapse and
complete muscle relaxation. Reflexes disappear and
respiration becomes slow and weak, followed by respiratory
arrest.
2.3 Diagnosis
At low doses, symptoms are transient and consist of salivation,
nausea, vomiting, diarrhoea, bradycardia and dizziness.
At higher doses, abdominal pain is marked with severe
diarrhoea and a cold sweat. Mental confusion, giddiness,
restlessness, muscular weakness and disturbed vision and
hearing are followed by a loss of coordination, and
unconsciousness. Respiration is stimulated, he pulse is rapid
and irregular and breathing is laboured. Clonic convulsions
are followed by collapse and complete muscle relaxation.
Reflexes disappear and respiration becomes slow and weak,
followed by respiratory arrest.
In severe poisoning with pure alkaloid, collapse and death may
be rapid.
Standard biomedical tests as indicated.
Sample collection: Collect remnants of plant and vomitus in
clean bottles.
2.4 First-aid measures and management principles
If the plant has been swallowed, the stomach should be emptied
and a purgative administered.
There is no specific antidote. Convulsions should be
controlled with diazepam, and airway ensured and respiration
maintained.
2.5 Poisonous parts
Leaves, stems, roots and flowers.
2.6 Main toxins
Nicotine.
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
Annual herb, shrub or small tree; from 0.90 to 1.50 m
tall according to the variety. The leaves are elliptic
or oblanceolate; flowers clustered at the end of the
branches; have a cylindrical calyx and are greenish or
reddish in the upper part. Fruit has different forms
with globular seeds.
3.1.2 Habitat
N. tabacum is sensitive to temperature, air, ground
humidity and the type of land. Temperatures of 20 to 30
°C are best for adequate growth; an atmospheric humidity
of 80 to 85% and soil without a high level of nitrogen
are also necessary.
3.1.3 Distribution
N. tabacum is a native of tropical and subtropical
America but it is now commercially cultivated worldwide.
Other varieties are cultivated as ornamental plants or
grow as a weed.
3.2 Poisonous parts of the plant
Every part of the plant except the seed contains nicotine, but
the concentration is related to different factors such as
species, type of land, culture or weather conditions.
The concentration of nicotine increases with the age of the
plant. Tobacco leaves contain 2 to 8% of nicotine combined as
malate or citrate. The distribution of the nicotine in the
mature plant is widely variable: 64% of the total nicotine
exists in the leaves; 18% in the stem, 13% in the root, and 5%
in the flowers.
3.3 The toxin(s)
3.3.1 Name(s)
Nicotine
3.3.2 Description, chemical structure, stability
Nicotine is a tertiary amine composed of a pyridine and
pyrrolidine ring.
Chemical name: 3-(1-methyl-2-pyrrolidyl) pyridine.
Chemical structure:
CAS No: 54-11-5
Molecular weight: 162.2
3.3.3 Other physico-chemical characteristics
Nicotine is a colourless to pale yellow, very
hygroscopic, oily liquid with an unpleasant pungent
odour and sharp burning persistent taste. It gradually
becomes brown on exposure to air or light.
Soluble in water, alcohol, chloroform, ether, kerosene,
light petroleum and fixed oils. Store in airtight
containers. Protect from light.
3.4 Other chemical contents of the plant
Anabasine: alkaloid similar to the nicotine but less active.
Glucosides: tabacinine, tabacine.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
The nicotine of tobacco is used as an insecticide.
Instillation of tobacco enemas for treatment of
intestinal worms or constipation.
Dried tobacco leaves for chewing, snuffing or smoking.
4.2 High risk circumstances
Poisoning has been reported from percutaneous absorption in
tobacco harvesters, during manufacture and the workers in the
tobacco industry.
Death has followed the use of tobacco infusions as enemas in
the treatment of intestinal parasites in children.
Fatal cases have been reported after ingestion of tobacco's
infusions in attempted suicide or mistaking wild tobacco for
and edible plant.
4.3 High risk geographical areas
Cultivated areas of N. tabacum or in places where different
varieties of nicotianas are cultivated as an ornamental or
grown as a weed.
In Argentina, the cultivated area of tobacco is in the north-
west or the country (Salta, Jujuy).
Rio Grande do Sul is the most important area for tobacco
cultivation in Brazil.
5. ROUTES OF ENTRY
5.1 Oral
Chewing tobacco leaves, sucking the flowers, eating as cooked
greens, or ingesting infusion of tobacco leaves.
5.2 Inhalation
Smoking or snuffing dried tobacco leaves.
5.3 Dermal
Acute nicotine poisonings have been reported from percutaneous
absorption in tobacco harvesters (green tobacco sickness).
5.4 Eye
No data available.
5.5 Parenteral
No data available.
5.6 Others
Instillation of tobacco enemas for treatment of worms or
constipation.
6. KINETICS
6.1 Absorption by route of exposure
Nicotine is readily absorbed from the respiratory tract,
buccal, vaginal and rectal mucosae and skin. Severe poisoning
has resulted from percutaneous absorption. Being a relatively
strong base, its absorption from the stomach is minimal unless
intragastric pH is raised. Intestinal absorption is far more
efficient.
Nicotine is not readily absorbed in the stomach from ingested
tobacco, as when children swallow cigarettes, and the initial
stimulus to vomiting usually removes most of it before much
harm is done by an otherwise serious dose.
Chewed or sniffed tobacco is buffered to an alkaline pH to
facilitate the absorption of nicotine through mucous
membranes.
When the smoke of burning tobacco reaches the small airways
and alveoli of the lung the nicotine is absorbed rapidly,
regardless of the pH of the smoke. Presumably the rapid
absorption of nicotine from tobacco smoke through the lung is
the result of the huge surface area of the alveoli and small
airways, and the dissolution of nicotine into fluid or
physiologic pH, which facilitates transfer across cell
membranes.
6.2 Distribution by route of exposure
Smoking is a unique form of systemic drug administration, in
that nicotine enters the circulation through the pulmonary
rather than the portal or system venous circulation. The lag
time between smoking and the entry of nicotine into the brain
is shorter than that observed when nicotine is injected
intravenously.
Nicotine enters the brain quickly, but levels decline rapidly.
Nicotine crosses the placenta freely and has been found in
amniotic fluid and the umbilical-cord blood of neonates.
It is found in breast milk and in the breast fluid of
nonlactating women.
Its concentration in breast milk is so low that the dose of
nicotine consumed by an infant is small and unlikely to be of
physiologic consequence. The milk of lactating women who are
heavy smokers would contain 0.5 mg/litre of nicotine. The
volume of distribution is 2.6 l/kg and the percentage of serum
binding of nicotine is 4.9%.
6.3 Biological half-life by route of exposure
The half-life of nicotine averages 2 h, although there is
considerable variability among people (range: 1 to 4 h).
6.4 Metabolism
Nicotine is rapidly and extensively metabolized (80 to 90%),
primarily in the liver, but also to a small extent in the
lungs and kidneys.
Nicotine's primary metabolites are cotinine and nicotine-N-
oxide, neither of which appears to be pharmacologically
active. Their formation involves oxidation, demethylation and
pyridine N-methylation.
Cotinine, because of its long half-life (16 to 20 h), is
commonly used in surveys and treatment studies as a marker of
nicotine intake. The most abundant metabolite in the urine is
3'-hydroxycotinine, which could also prove to be a useful
indicator of nicotine exposure.
6.5 Elimination by route of exposure
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
Nicotine binds stereospecifically to acetylcholine receptors
at autonomic ganglia, the adrenal medulla, neuromuscular
junction and the brain.
As a consequence of the stimulation of nicotinic receptors,
possibly located on presynaptic sites, short-term exposure to
nicotine results in the activation of several central nervous
system neurohumoral pathways, leading to the release of
acetylcholine, norepinephrine, dopamine, serotonin,
vasopressin, growth hormone, and ACTH.
Most of the effects of nicotine on the central nervous system
are due to the direct action on brain receptors, although
activation of the brain through afferent nerves of
chemoreceptors in the carotid bodies or the lung may also
contribute.
Nicotine excites nicotinic receptors in the spinal cord,
autonomic ganglia, and adrenal medulla, the last of which
causes the release of epinephrine. Nicotine evokes the
release of catecholamines and facilitates the release of
electrical stimulation-evoked neurotransmitters from
sympathetic nerves in blood vessels.
In experimental preparations, nicotine in low doses causes
ganglionic stimulation but in high doses it causes ganglionic
blockade after brief stimulation. This biphasic response
pattern is observed in the intact organism as well, although
the mechanism is far more complex:
At very low doses, similar to those seen during cigarette
smoking, the cardiovascular effects appear to be mediated by
the central nervous system, either through the activation of
chemoreceptor afferent pathways or by direct effects on the
brain stem. The net result is sympathetic neural discharge,
with an increase in blood pressure and heart rate.
At higher doses, nicotine may act directly on the peripheral
nervous system, producing ganglionic stimulation and the
release of adrenal catecholamines.
At extremely high doses, nicotine produces hypotension and
slowing of the heart rate, mediated by either peripheral
ganglionic blockade, vagal afferent nerve stimulation, or
direct depressor effects mediated by action on the brain.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Lethal doses of nicotine may be estimated in 0.5
mg to 1 mg/kg body weight (about 40 to 60 mg).
Two to four drops pure nicotine can prove lethal
(each drop: 23-33 mg). There was death with the
ingestion of 30 g of tobacco or infusion of 15 to
20 g of tobacco or with administration of enemas to
8 g or inhalation of 0.8 g of tobacco as snuff.
7.2.1.2 Children
The lethal dose is considered to be about 10 mg
of nicotine. (Arena, 1974)
7.2.2 Animal data
LD50 dog: 1 mg/kg
LD50 horse: 200 to 300 mg
LD50 rat p.o.: 55 mg/kg
LD50 rat IV: 1 mg/kg. (RTECS, 1986)
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
Smoking of cigarettes is causally related to cancer of the
respiratory tract, the upper digestive tract, pancreas, renal
pelvis and bladder; cigarette smokers also face an increased
risk for cancer of the cervix (USDHHS 1982; IARC 1986). Many
carcinogenic agents have been identified in cigarette smoke
but no single component nor chemical group(s) of component is
solely responsible for the carcinogenic activity of cigarette
smoke in the various organs. Laboratory bioassay suggest that
polynuclear aromatic hydrocarbons and N-nitrosamines play
significant roles in the induction of cancer in smokers
(USDHHS 1989, IARC 1986).
7.4 Teratogenicity
Whether cigarette smoking is associated with increased rates
of congenital malformations in humans is controversial.
Several studies show no association or a lower incidence of
malformations in the offspring of smoking mothers, but others
report positive associations. Smoking is associated with
impaired fetal growth and development.
7.5 Mutagenicity
In the Ames Salmonella typhimurium mutagenesis and mammalian
cell cytogenic essays nicotine did not posses any genotoxicity
although it induced reparable DNA damage in the Escherichia
coli. prl. A +/A-system (USDHH, 1988).
7.6 Interactions
Several pharmacodynamic interactions arise from hemodynamic
effects of nicotine in cigarette smoke. For example, by
reducing the blood flow to the skin and subcutaneous tissue,
cigarette smoking may slow the absorption of insulin from
subcutaneous sites. Smoking may impair the efficacy of beta-
blockers and calcium antagonists in patients with hypertension
or angina pectoris.
Cigarette smoking and oral contraceptives may interact
synergistically to increase the risk of stroke and premature
myocardial infarction in women. Cigarette smoking appears to
enhance the procoagulant effects of oestrogens. For this
reason, oral contraceptives should be used only with care in
women who smoke cigarettes.
Cigarette smokers experience less sedation than nonsmokers
from several drugs that act on the central nervous system,
including diazepam, chlordiazepoxide, and chlorpromazine.
Smoking probably acts by producing arousal of the central
nervous system rather than by accelerating metabolism and
reducing the brain levels of these drugs.
The efficacy of analgesics such as propoxyphene, may be
reduced in cigarette smokers, even in the absence of
pharmacokinetics interaction. Cigarette smoking is a major
risk factor for the recurrence of peptic ulcer disease and the
failure of treatment with antacids or H2 blockers. Sucralfate,
which acts on the gastric mucous barrier, seems to be equally
effective in smokers and nonsmokers and may be the drug of
choice for peptic ulcer disease in cigarette smokers (Laurence,
1980).
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
The plant or tobacco can be identified in
specimens of vomitus or gastric lavage.
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
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Tobacco leaves have caused severe poisoning when eaten
as cooked greens. The plant has been the cause of
illness in children sucking the flowers.
Gastric absorption of nicotine from tobacco taken by
mouth is delayed because of slowed gastric emptying;
vomiting caused by the central effect of the fraction
initially absorbed may therefore remove much of the
tobacco remaining in the stomach.
The onset of symptoms of acute nicotine poisoning is
rapid; they include nausea, salivation, abdominal pain,
vomiting, diarrhoea, cold sweat, headache, dizziness,
disturbed hearing and vision, mental confusion, and
marked weakness. Faintness and prostration ensue; the
blood pressure falls;
breathing is difficult; the pulse is weak, rapid and
irregular - and collapse may be followed by terminal
convulsions. Death may result within a few minutes from
respiratory failure caused by paralysis of the muscles
of respiration.
9.1.2 Inhalation
Poisoning by inhalation occurs through smoking tobacco
or inhaled snuff.
In naive subjects, cigarette smoking commonly produces
dizziness, nausea, vomiting and pallor as a result of
mild intoxication.
9.1.3 Skin exposure
Green-tobacco sickness, in which tobacco harvesters are
exposed to dew containing nicotine, results in nausea,
vomiting, pallor, weakness, dizziness, light-headedness,
headache and sweating. Less common symptoms are
abdominal pain, chills and excessive salivation.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
Acute poisoning has been reported when tobacco was used
as a parasiticide and when administered by enema as an
anthelmintic in children (Arena, 1974).
9.2 Chronic poisoning
9.2.1 Ingestion
Chewing leaves of tobacco (see monograph on nicotine).
9.2.2 Inhalation
Smoking tobacco (see monograph on nicotine)
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
Nicotine is a highly toxic substance and death may occur
within a few minutes in acute poisoning due to respiratory
failure arising from paralysis of the muscles of respiration.
If supportive care can be instituted early, the prognosis is
good. Tobacco is much less toxic than is anticipated from its
nicotine content. Apparently, the intestinal absorption of
nicotine from tobacco is so slow that metabolic inactivation
sometimes keeps pace with absorption. Spontaneous vomiting may
also remove many unabsorbed alkaloids. On the other hand,
serious poisonings and deaths have occurred following
contamination of infant formula feeds with tobacco. (Gosselin,
1988).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
The ultimate response of any one structure or system
represents the summation of the several different and
opposing effects of nicotine. For example, the drug can
increase the heart rate by excitation of sympathetic or
paralysis of parasympathetic cardiac ganglia, and it can
slow the heart rate by paralysis of sympathetic or
simulation of parasympathetic cardiac ganglia. In
addition, the effects of the drug of the chemoreceptors
of the carotid and aortic bodies and on medullary
centres influence heart rate, as do the cardiovascular
compensatory reflexes resulting from changes in blood
pressure caused by nicotine.
Finally, nicotine causes a discharge of epinephrine from
the adrenal medulla, and this hormone accelerates the
cardiac rate and raises blood pressure.
On the cardiovascular system the effects are those of
sympathetic stimulation. There is vasoconstriction in
the skin and vasodilatation in the muscles, tachycardia
and a rise in blood pressure of about 15 mm Hg systolic
and 10 mm Hg diastolic. Ventricular extrasystole may
occur. Cardiac output, work and oxygen consumption
increase. Coronary vascular resistance decreases and
blood flow increases in men aged 20 to 50 years. However,
if the resistance is fixed by atherosclerosis, flow does
not increase, though work and oxygen consumption do. This
may be the mechanism of tobacco-induced angina pectoris.
It is possible that nicotine stimulates the myocardium by
releasing noradrenaline stored in it, but at present it
seems likely that this effect only occurs with higher
doses.
9.4.2 Respiratory
Cigarette smoking is the major cause of chronic
obstructive lung disease. Nicotine may directly or
indirectly influence the development of emphysema in
smokers. It rapidly accumulates in the pulmonary
epithelial cells and some of its metabolites are
retained in the lung for a long period (USDHHS, 1988).
9.4.3 Neurological
9.4.3.1 CNS
Nicotine markedly stimulates the central nervous
system (CNS). Moderate doses produce tremors in
both man and laboratory animals, with somewhat
larger doses, the tremor is followed by
convulsions. The excitation of respiration is a
particularly prominent action of nicotine. Although
large doses act directly on the medulla oblongata,
smaller doses augment respiration reflexly by
excitation of the chemoreceptors of the carotid and
aortic bodies. Stimulation of the CNS is followed by
depression, and death results from failure of
respiration due to both central paralysis and
peripheral blockade of muscles of respiration.
Nicotine causes vomiting by a complex of central
and peripheral actions. The central component
of the vomiting response is due to stimulation
of the emetic chemoreceptor trigger zone in the
area postrema of the medulla oblongata.
In addition, nicotine activates a number of
vagal and spinal afferent nerves that form the
sensory input of the reflex pathways involved in
the act of vomiting.
Nicotine exerts an antidiuretic action as the
result of stimulation of the hypothalamic -
neurohypophyseal system with the consequent
release of antidiuretic hormone (ADH).
9.4.3.2 Peripheral nervous system
The effects of nicotine on the neuromuscular
junction are similar to those on ganglia.
However, with the exception of avian and
denervated mammalian muscle, the stimulant phase
is largely obscured by the rapidly developing
paralysis. In the latter stage, nicotine also
produces neuromuscular blockade due to receptor
desensitization. In contrast to autonomic ganglia,
where lobeline causes depolarization and acts like
nicotine, the end-plate of skeletal muscle fibres is
blocked but not depolarized by lobeline.
Nicotine, like acetylcholine, is known to
stimulate a number of sensory receptors. These
include mechanoreceptors that respond to
stretch or pressure of the skin, mesentery,
tongue, lung, and stomach; chemoreceptors of the
carotid body; thermal receptors of the skin and
tongue; and pain receptors. Prior administration
of hexamethonium prevents the stimulation of the
sensory receptors by nicotine, but has little effect
on physiological stimuli. The explanation of these
observations is controversial.
9.4.3.3 Autonomic nervous system
The major action of nicotine consists initially
in transient stimulation and subsequently a more
persistent depression of all autonomic ganglia.
Small doses of nicotine stimulate the ganglion
cells directly and facilitate neuronal transmission.
At larger doses of the drug, the initial
stimulation is followed very quickly by a
blockade of transmission, whereas stimulation of
the ganglion cells coincides with their
depolarization. Depression of transmission
by adequate doses of nicotine occurs both during
the depolarization and after it has subsided.
Nicotine also possesses a biphasic action on the
adrenal medulla; small doses evoke the discharge
of catecholamines, and larger doses prevent
their release in response to splanchnic nerve
stimulation.
Nicotine also causes the release of techolamines
in a number of isolated organs. This action
results in a sympathomimetic response to
nicotine that is blocked by drugs known to
prevent the effects of catecholamines.
9.4.3.4 Skeletal and smooth muscle
Nicotine stimulates the discharge of Renshaw
cells, which inhibit the motor activity of
anterior horn cells. Nicotine may also
stimulate the pulmonary afferent nerves, which
in turn inhibit alpha motor neurons that act on
skeletal muscle.
As a result, phasic stretch-reflex responses,
such as the patellar reflex, are reduced and
certain muscles are relaxed.
However, increased electromyographic activity
and tonicity of the trapezius muscle have been
observed after smoking (Laurence, 1980).
9.4.4 Gastrointestinal
In contrast to the cardiovascular actions of nicotine,
the effects of the drug on the gastrointestinal tract
are due largely to parasympathetic stimulation. The
combined activation of parasympathetic ganglia and
cholinergic nerve endings results in increased tone and
motor activity of the bowel.
Nausea, vomiting and occasional diarrhoea are observed
following systemic absorption of nicotine.
Cigarette smoking is a risk factor for peptic ulcer
disease and an even stronger risk factor for delayed
healing, failure to respond to therapy and relapse
(Kikundal, 1984)
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
Cigarette smoking has been reported to increase the
circulating levels of catecholamines, vasopressin,
growth hormone, ACTH, cortisol, prolactin, neurophysin 1,
and beta-endorphin; these effects are believed to be
mediated by nicotine.
Many studies of the effects of smoking on endocrine
function have been performed in smokers who have smoked
to the point of toxicity (that is, nausea) but the
pattern of hormone release observed with nausea may not
be representative of nicotine's action at levels more
relevant to human smoking.
In studies of more moderate smoking, small increases in
vasopressin, beta-endorphin, and cortisol have been
found.
However, when cortisol concentrations were measured
throughout the day, there were no differences whether
subjects were smoking or not. It appears that in humans
some endocrine responses result from the stress of the
experimental situation or from rapid smoking procedures
and differ from those that result from smoking at normal
rates. In addition, the development of tolerance to the
effects of nicotine may result in hormonal effects being
seen after single cigarettes but not with repetitive
smoking. It has been speculated that the release of
vasopressin may mediate improvement in memory and the
release of beta-endorphin may mediate the nicotine-related
relief of anxiety and decrease in pain perception.
In women, cigarette smoking is associated with earlier
menopause and an increased risk of osteoporosis,
believed to be associated with lower levels of
oestrogens in smokers than in nonsmokers. In
postmenopausal women receiving oestrogens, lower serum
oestrogen levels are seen in smokers than in nonsmokers.
It has been suspected that smoking acts primarily by
accelerating the hydroxylation of oestradiol. Recent
evidence also suggested that nicotine and other alkaloids
in tobacco inhibit the formation of oestrogen by inhibiting
an enzyme in granulosa cells or placental tissue. This
enzyme is responsible for the conversion of androstenedione
or testosterone to oestrogens.
9.4.8 Dermatological
No data available.
9.4.9 Eye, ears, nose, throat: local effects
No data available.
9.4.10 Haematological
No data available.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
The body weight of smokers is on average 2.7
to 4.5 kg lower than that of nonsmokers. When
a smoker stops, he or she typically gains
weight in the subsequent year (to proximately
the level of those who have never smoked).
Weight control or the fear of gaining weight
after stopping smoking may be a motive for
continuing to smoke, particularly among women.
Certain cigarette advertisements conspicuously
use slender women to reinforce this
association. Studies in animals indicate that
weight loss is an effect of nicotine.
The mechanism of this effect has not been
fully elucidated, but current evidence
suggests that smoking is associated both with
reduced consumption of food, particularly
sweet foods, and with increased energy use.
The magnitude of weight gain after the
discontinuation of smoking has been associated
with lipoprotein-lipase activity in adipose
tissue before the smoker stops smoking
suggesting a direct effect on lipid
metabolism. Studies of the action of nicotine
on carbohydrate metabolism have had
conflictive results. Smoking may increase the
levels of insulin and glucose in the short-
term, probably as a result of the stress
reaction. However, habitual smokers have not
been shown to have abnormal carbohydrate
metabolism.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
Studies in animals show the rapid development to
tolerance to many effects of nicotine, although
tolerance may not be complete. Smokers know that
tolerance develops to some of the effects of smoking.
In naive subjects, the first cigarette commonly
produces dizziness, nausea and vomiting, effects to
which the smoker rapidly becomes tolerant.
Tolerance to subjective effects and acceleration of the
heart rate develop within a day in regular smokers.
Tolerance may develop to toxic effects, such as nausea
and vomiting, even during the 8 h course of an
accidental nicotine poisoning, despite the persistence
of nicotine in the blood in extremely high
concentration.
9.4.15 Special risks
Nicotine crosses the placenta freely and has been found
in amniotic fluid and the umbilical cord blood of
neonates. It is found in breast milk and in breast
fluid of nonlactating women. Its concentration in
breast milk is so low that the dose of nicotine
consumed by an infant is small and unlikely to be of
physiologic consequence. Cigarette smoking during
pregnancy increases the risk of low birth weight,
prematurity, spontaneous abortions, and perinatal
mortality in humans, which has also been referred to as
the fetal tobacco syndrome. (Nieburg, 1985).
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
The treatment of acute nicotine poisoning needs to begin
quickly. The stomach should be emptied by induced emesis
with ipecac syrup or gastric lavage. Activated charcoal and
a cathartic should be administered to prevent further
absorption. Supportive therapy should be directed towards
maintaining respiration and blood pressure and control
convulsions.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Arterial blood for gases.
Blood for routine test.
Urine for routine test.
10.2.2 Biomedical analysis
Routine blood and urine tests.
10.2.3 Toxicological/toxinological analysis
Investigation of cotinine in urine and/or nicotine in
plasma.
10.2.4 Other investigations
No data available.
10.3 Life supportive procedures and symptomatic treatment
Supportive therapy should be directed toward maintaining
respiration and blood pressure and continued for as long as
necessary.
Diazepam should be given cautiously to control convulsions.
10.4 Decontamination
Prompt treatment of poisoning is essential. If contact was
with the skin, remove contaminated clothing and wash the
skin thoroughly with cold water without rubbing.
If the patient has swallowed tobacco, induce emesis with
ipecac syrup. Wash out the stomach with water. Alkaline
solutions should be avoided. A slurry of activated charcoal
should be passed through the tube and left in the stomach.
In a case of use of tobacco enemas, give a cleaning enema
with water.
10.5 Elimination
Excretion of nicotine decreases when the urine is alkaline.
10.6 Antidote/antitoxin treatment
10.6.1 Adults
No antidote is available.
10.6.2 Children
No antidote is available.
10.7 Management discussion
No data available.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
a. Green tobacco sickness is a self-limiting
occupational illness of tobacco harvesters. Symptoms
characteristically begin with a headache and dizziness
during the afternoon of the harvest, and progress to
abdominal pain, protracted vomiting and prostration by
evening. The illness lasts only 12 to 24 h but recurs
frequently in susceptible workers after repeated harvest
exposure. As many as 12 recurrences have been reported in 8
weeks by some workers. Mortality and long-term sequelae from
the illness have not been documented (Gehlbach, 1974).
b. Early on the day of admission a 76-year-old man
had picked a wild green plant that was growing in a vacant
lot in south-east San Diego. He thought the plant was
pokeweed (Phytolacca americana) which he had eaten as a
child in Arkansas. Approximately 5 h prior to admission he
consumed the plant with dinner. About 1.5 h later his wife
noted him to be ataxic and complaining of feeling "sick and
weak". He then became diaphoretic and semi-responsive and
an ambulance was summoned. Ipecac syrup was administered by
the paramedics and vomiting occurred. Upon arrival in the
emergency department, the patient was awake and alert with
severe nausea and vomiting. Shortly after admission he
became unresponsive except to deep pain. Vital signs
included BP 210/140, respiration 16/min and shallow, and
pulse of 90 min. There was profuse diaphoresis and muscle
twitching. Because of decreasing depth of respiration, an
endotracheal tube was inserted and mechanical ventilatory
assistance was begun. The patient was admitted to the
intensive care unit. The patient was treated with IV fluids
and respiratory support. His mental status 24 h after
ingestion recovered and he was extubated. He was discharged
3 days after admission (Manoguerra, 1982-1983).
c. An eight month old child swallowed two cigarette
butts from an ash-tray. Rapidly, he developed a states of
coma with dyspnoea that needed intubation, ventilation and
gastric lavage. No other causes were found. He also
received atropine for hypersalivation. This case stresses
the higher toxicity of cigarette butts, in which nicotine is
concentrated (Borys, 1988).
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins
No antidote is available.
12.2 Specific preventive measures
Precautions should be taken when collecting tobacco leaves
to avoid their contact with the skin.
12.3 Other
No data available.
13. REFERENCES
13.1 Clinical and toxicological
Arena J (1974). Poisoning 4th Ed. New York. Charles Thomas.
Benowitz NL (1987) In: The Pharmacology of Nicotine -
Proceedings, Satellite Symposium of the Tenth International
Congress of Pharmacology. Gold Coast, Queensland,
Australia. September 4-6, Edited by Raul M. and Thurau K;
IRL Press, Washington D.C. 11-14.
Benowitz NL (1988). Pharmacologic aspects of cigarette
smoking and nicotine addiction. N Eng J Med 319: 1318-28.
Benowitz NL et al (1982). Interindividual variability in the
metabolism and cardiovascular effects of nicotine in man. J
Pharmacol Exp Ther 221:368-372.
Borys DJ, Setzer SC, Ling LJ (1988). CNS depression in an
infant after the ingestion of tobacco. Vet Hum Toxicol 30:20-22.
Gehlbach SH et al (1974). Green tobacco sickness. An illness
of tobacco harvesters. J Am Med Assoc 229:1880-83.
Goodman & Gilman (1986). Las Bases Farmacologicas de la
Terapéutica. d. Médica Panamericana S.A. 220.
Gosselin RE (1988). Clinical Toxicology of Commercial
Products. 6th ed. Baltimore, Williams & Wilkins, 311-313.
Hardin JW, Arena JM (1974). Human poisoning from native and
cultivated plants. Durham, North Carolina, Duke University
Press: 140.
IARC (1986). International Agency for Research on Cancer.
Tobacco Smoking. IARC monographs on the evaluation of the
carcinogenic risk of chemicals to humans. Volume 38,
WHO/IARC.
Jouglard J (1977). Intoxications d'origine végétale in
Encyclopédie Médico-Chirurgicale, Paris. Editions
Techniques - 16.065 A 20.
Kikendall JW et al (1984). Effect of cigarette smoking on
gastrointestinal physiology and non-neoplastic digestive
disease. Journal of Clinical Gastroenterology 6:65-79.
Laurence DR, Benett ON (1980). Clinical pharmacology.
London, Churchill Livingstone. 465-72.
Nieburg P et al (1985). The fetal tobacco syndrome. J Am
Med Assoc 253:2998-99.
Reynolds JEF (1982). Martindale, The Extra Pharmacopoeia
28th ed. London, UK. The Pharmaceutical Press.
RTECS (1986). Registry of Toxic effects of Chemical
Substances. NIOSH (vol 3A). 3060-424.
Schvartsman S (1979). Plantas venenosas. Sao Paulo.
Sarvier Ed. 143-46.
USDHHS (1982). US Department of Health and Human Services.
The Health consequences of smoking: Cancer. A Report of
the Surgeon General US Department of Health and Human
Services. Public Health Service. Office on Smoking and
Health. DHHS Publications N°(PHS). 82-50179.
USDHHS (1988). US Department of Health and Human Services.
Nicotine addiction. The health consequences of smoking. A
report of the Surgeon
General. 32-33: 601-602.
13.2 Botanical
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Dr Julia Higa de Landoni
Seccion Toxicologia
Hospital de Clinicas "José de San Martin"
Cordoba 2351
1120 Capital Federal
Argentina
Date: March 1990.
Peer Review: Adelaide, Australia, April 1991