Does COKEII=NewCOKE? I live in an...

[Ripper2860]

yea right -- sure ...

nicotine is one bad assed poison, one of the deadliest ..

even the cbc tested random coffee to put this rumor to bed ..

Nicotine is only deadly in mega doses.

Cancer doesn't run in my family so I know at least 10 people over 60 who have smoked a pack a day since their teens.

There are other chemcials in the tabacco that make it worsde also.

The nicotine gun won't give throat cancer in the studies that have been done.

Also Krispy Kreme has the best donuts, but I have never tried their coffee. I am from Seattle so I am quite a coffe snob. If it isn't freshly roasted and ground it probably sucks.

I have never actually had Starbucks it costs too much and there are so many other places to get good coffee here.

another wacky statement -- No one has claimed Nicotine causes cancer - its all the other stuff ..

Further-
Nicotine is one of the most toxic of all poisons and has a rapid onset of action. Apart from local caustic actions, the target organs are the peripheral and central nervous systems.


I will copy the complete abstract from IPCS INCHEM (International Programme on Chemical Safety, a cooperative programme of the World Health Organization (WHO), the International Labour Organisation (ILO), and the United Nations Environment Programme (UNEP). The authoritative source on the risk assessment of chemicals.)

Nicotine
1. NAME
1.1 Substance
1.2 Group
1.3 Synonyms
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Brand names, Trade names
1.6 Manufacturers, 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
3.4 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.2 High risk circumstance of poisoning
4.3 Occupationally exposed populations
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
7.1 Mode of Action
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Relevant animal data
7.2.3 Relevant in vitro data
7.2.4 Workplace standards
7.2.5 Acceptable daily intake (ADI) and other guideline levels
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
8. TOXICOLOGICAL 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 analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
10.4 Decontamination
10.5 Elimination
10.6 Antidote 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
12.2 Specific preventive measures
12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES

CHEMICAL SUBSTANCES
1. NAME
1.1 Substance
Nicotine
1.2 Group
Alkaloid of Nicotiana Tabacum
1.3 Synonyms
(S)-3-(1-Methylpyrrolidin-2-yl)pyridine
1.4 Identification numbers
1.4.1 CAS number
54-11-5
1.4.2 Other numbers
1.5 Brand names, Trade names
Nicabate
Nicobrevin
Nicotinell TTS
Nicorette
Nicoret
Cigarette tobacco
Black leaf
Nicocide
Nico-fume


Transdermal patches deliver 5 to 30 mg nicotine over 24 hours;
used patch has significant nicotine content

Cigarette tobacco varies in its nicotine content but common
blends contain 15 to 25 mg per cigarette with a current trend
towards lower levels.

Nicotine insecticides: 40% solution of the sulfate.

Chewing gum - nicotine polacrilex: 2 and 4 mg nicotine bound
to an ion exchange resin in a sugar-free flavoured chewing gum
base.
1.6 Manufacturers, Importers
Ciba Geigy
Glaxo-Lake Pharmaceuticals
Lundbeck Ltd
Merrell
2. SUMMARY
2.1 Main risks and target organs
Nicotine is one of the most toxic of all poisons and has a
rapid onset of action. Apart from local caustic actions, the
target organs are the peripheral and central nervous systems.
Nicotine is also a powerfully addictive drug.
2.2 Summary of clinical effects
Burning sensation in the mouth and throat, salivation,
nausea, abdominal pain, vomiting and diarrhoea.
Gastrointestinal reactions are less severe but can occur even
after cutaneous and respiratory exposure.

Systemic
effects include: agitation, headache, sweating, dizziness,
auditory and visual disturbances, confusion, weakness and lack

of coordination.

A transient increase in blood
pressure, followed by hypertension, bradycardia, paroxysmal
atrial fibrillation, or cardiac standstill may be observed.


In severe poisoning, tremor, convulsions and coma occur.
Faintness, prostration, cyanosis and dyspnoea progress to
collapse. Death may occur from paralysis of respiratory muscles
and/or central respiratory failure.
2.3 Diagnosis
Burning sensation in the mouth and throat, salivation,
nausea, abdominal pain, vomiting and diarrhoea
Agitation, headache, sweating, dizziness, auditory and visual
disturbances, confusion, weakness and lack of coordination.

In severe poisoning, tremor, convulsions and coma occur.
Faintness, prostration, cyanosis and dyspnoea progress to
collapse.

Plasma nicotine level: nicotine concentrations in the urine
are not useful in the management of overdose since these vary
according to changes in pH and urine flow.

White cell count: polymorphonuclear leucocytosis

Urinalysis: glycosuria.
2.4 First-aid measures and management principles
There are no known antidotes.

Immediate establishment of an airway, monitoring of breathing
patterns, and maintenance of circulation are essential in
cases of serious overdose. Preparations for possible seizures
or rapid progression to coma and artificial ventilation
procedures should be kept ready, oxygen may be required.

If vomiting has not occurred following nicotine ingestion,
remove stomach contents by gastric lavage. Induction of
emesis is less preferable to lavage since convulsions or coma
may intervene.

Single or multiple doses of activated charcoal may be used.
Children who ingest more than one cigarette should receive
activated charcoal and medical observation for at least
several hours.

If nicotine is spilled on the skin, immediately wash
thoroughly with running water (avoid warm water).

Seizure activity and agitation can be controlled with diazepam
or barbiturates.

Cholinergic symptoms may be ameliorated with atropine.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance

Nicotine is a natural alkaloid obtained from the dried
leaves and stems of the Nicotiana tabacum and Nicotiana rustica,
where it occurs in concentrations of 0.5-8%. Cigarette tobacco
varies in its nicotine content, but common blends contain 15-25
mg per cigarette, with a current trend towards lower
levels.
3.2 Chemical structure
3.3 Physical properties
Molecular weight: 162.26

Nicotine is a liquid alkaloid. It is water soluble and
has a pKa of 8.5. It is a bitter-tasting liquid which is
strongly alkaline in reaction and forms salts with acids.
3.4 Other characteristics
Store at room temperature, below 86 F (30°C). Protect from
light and air.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
Nicotine is most frequently encountered in tobacco
products for smoking, chewing, sniffing and tobacco
"without smoking".

As an insecticide (now rare), and as an adjunct to
smoking cessation programmes (gums, patches). It is a substance
of abuse.
4.2 High risk circumstance of poisoning
Nicotine is most frequently encountered in tobacco products
for smoking, chewing, sniffing and tobacco "without smoking".

As an insecticide (now rare), and as an adjunct to smoking
cessation programmes (gums, patches). It is a substance of
abuse.
4.3 Occupationally exposed populations
People who are involved in the processing and extracting
tobacco (green tobacco sickness), as well as mixing, storing
and applying certain insecticides.
5. ROUTES OF ENTRY
5.1 Oral
Poisoning occurs in children who ingest cigarettes or
cigars or 2nicotine gum. In adults chewing tobacco or nicotine
gum, and people who ingest liquid nicotine in the form of
insecticide preparations.
5.2 Inhalation
Inhalation is the most frequent route of entry because of
worldwide tobacco smoking.
5.3 Dermal
Dermal exposure to nicotine can lead to intoxication. Such
exposure has been reported after spilling or applying nicotine-
containing insecticides on the skin or clothes (Loockhart,
1933; Benowitz, 1987), and as a consequence of occupational
contact with tobacco leaves (green tobacco sickness)
(Weizenecker, 1970; Gehlbach, 1974).
5.4 Eye
No data available.
5.5 Parenteral
No data available.

5.6 Others
Tobacco has been used in enemas and poultices (Gosselin,
1988).
6. KINETICS
6.1 Absorption by route of exposure
Nicotine is a water and lipid soluble drug which, in the
free base form, is readily absorbed via respiratory tissues,
skin, and the gastrointestinal tract. Nicotine may pass
through skin or mucous membranes when in alkaline solution (in
which nicotine is largely unionized).

When tobacco smoke reaches the small airways and alveoli of
the lung, the nicotine is rapidly absorbed. The rapid
absorption of nicotine from cigarette smoke through the lungs
occurs because of the huge surface area of the alveoli and
small airways, and because of dissolution of nicotine at
physiological pH (approximately 7.4) which facilitates
transfer across cell membranes.

Chewing tobacco, snuff, and nicotine polacrilex gum are of
alkaline pH as a result of the selection of appropriate
tobacco and/or buffering with additives by the manufacturers.
The alkaline pH facilitates absorption of nicotine through
mucous membranes.
6.2 Distribution by route of exposure
After absorption, nicotine enters the blood where, at pH
7.4, it is about 70% ionized. Binding to plasma proteins is less
than 5%. Studies showed that, after intravenous administration,
the distribution of C14-labeled nicotine is immediate, reaching
the brain of mice within 1 min. after injection. Similar
findings based on positron emission tomography of the brain,
were seen after injection of 11C-nicotine in monkeys. (US
Department of Health Report of Surgeon General 1988).

Nicotine inhaled in tobacco smoke enters the blood almost as
rapidly as after rapid I.V. injections. Because of delivery
into the lung, peak nicotine levels may be higher and lag time
between smoking and entry into the brain shorter than after IV
injection.

After smoking, the action of nicotine on the brain is expected
to occur quickly. Rapid onset of effects after a puff is
believed to provide optimal reinforcement for the development
of drug dependence. The effect of nicotine declines as it is
distributed to other tissues. The distribution half-life,
which describes the movement of nicotine from the blood and
other rapidly perfused tissues, such as the brain, to other
body tissues, is about 9 min. (Feyerabend, 1985). Distribution
kinetics, rather than elimination kinetics (half-life about 2
hr) determine the time course of the CNS actions of nicotine
after smoking a single cigarette.

The apparent volume of distribution in animals is
approximately 1.0 L/kg whereas in one clinical study it was
2.0 L/kg in smokers and 3.0 L/kg in nonsmokers (Ellenhorn,
1988).

6.3 Biological half-life by route of exposure
The elimination half-life of nicotine averages 2 hours
(Benowitz, 1982 Feyerabend, 1985). The half-life of a drug
is useful in predicting the rate of accumulation of that drug
in the body with repetitive dosing and the time course of
decline after cessation of dosing. Consistent with a half-life
of 2 hours, accumulation of nicotine over 6 to 8 hours during
regular smoking and persistence of significant levels of
nicotine in the blood for 6 to 8 hours after cessation of
smoking, i.e. overnight, has been observed (Benowitz, 1982b).
Thus, cigarette smoking represents a situation where the
smoker is exposed to significant concentrations and possibly
pharmacological effects of nicotine for 24 hours a day.

Apparent acute tolerance to nicotine, determined on the basis
of observations of the relationship between venous blood
levels and effects, may be due to distribution disequilibrium
between venous and arterial blood; venous blood levels
substantially underestimate concentrations of nicotine in
arterial blood and at potential sites of action. True
tolerance does, however, develop rapidly, with a half-life of
development and regression of about 35 minutes. The kinetics
of tolerance may be another determinant of cigarette smoking
particularly when the smoker smokes his next cigarette.
6.4 Metabolism
Nicotine is a tertiary amine which is composed of a
pyridine and a pyrrolidine ring. Nicotine undergoes a large
first pass effect during which the liver metabolizes 80% to 90%;
to a smaller extent, the lung also is able to metabolize
nicotine.

The major metabolite of nicotine is cotinine; nicotine-1'-N-
oxide is a minor metabolite. Cotinine is also extensively
metabolized and trans-3'-hydroxycotinine is its a major
metabolite. The most abundant metabolite in the mice is trans-
3'-hydroxy-cotinine, accounting for almost 40%, whereas
cotinine itself accounts for only about 15% of the dose of
nicotine.

Cotinine levels in various biological fluids are widely used
to estimate intake of nicotine in tobacco users. The
usefulness of cotinine as a quantitative marker of nicotine
intake, is limited by individual variability in percentage
conversion of nicotine to cotinine and in rate of elimination
of cotinine itself. Since it accounts for a much greater
percentage of nicotine, trans-3'-hydroxycotinine measurement,
either alone or in combination with measurement of other
metabolites, may be a superior quantitative marker of nicotine
intake.
6.5 Elimination by route of exposure
Nicotine and its metabolites (cotinine and nicotine 1-N-oxide)
are excreted in the urine. At a pH of 5.5 or less, 23% is
excreted unchanged. At a pH of 8, only 2% is excreted in the
urine. The effect of urinary pH on total clearance is due
entirely to changes in renal clearance. (Ellenhorn, 1988).


Nicotine is secreted into saliva. Passage of saliva containing
nicotine into the stomach, combined with the trapping of
nicotine in the acidic gastric fluid and reabsorption from the
small bowel, provides a potential route for enteric nicotine
recirculation. This recirculation may account for some of the
oscillations in the terminal decline phase of nicotine blood
levels after I.V. nicotine infusion or cessation of smoking.

Nicotine freely crosses the placenta and has been found in
amniotic fluid and the umbilical cord blood of neonates.
Nicotine is found in breast milk and the breast fluid of non-
lactating women and in cervical mucous secretions (US
Department of Health and Human Services, a report of the
Surgeon General 1988).
7. TOXICOLOGY
7.1 Mode of Action
Nicotine is an agonist at nicotinic receptors in the
peripheral and central nervous system. In man, as in animals,
nicotine has been shown to produce both behavioral stimulation
and depression. Pharmacodynamic studies indicate a complex
dose response relationship, due both to complexity of
intrinsic pharmacological actions and to rapid development of
tolerance.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The mean lethal dose has been estimated to be 30
to 60 mg (0.5-1.0 mg/kg) (Gosselin, 1988).
7.2.1.2 Children
The lethal dose is considered to be about 10 mg
of nicotine (Arena, 1974).
7.2.2 Relevant animal data
Dog: oral LD50: 9.2 mg/kg
mouse: oral LD50: 3.3 mg/kg (RTECS, 1985-86)
rat: oral LD50: 50 mg/kg
7.2.3 Relevant in vitro data
No data available.
7.2.4 Workplace standards
MSHA standard air : TWA = 0.5 mg/m3 (skin)
OSHA standard air : TWA = 0.5 mg/m3 (skin)
(RTECS, 1985-86)
7.2.5 Acceptable daily intake (ADI) and other guideline levels
Not relevant.
7.3 Carcinogenicity
Literature reports indicate that nicotine is neither an
initiator nor a promoter of tumours in mice. There is
inconclusive evidence to suggest that cotinine, an oxidized
metabolite of nicotine, may be carcinogenic in the rat. (PDR,
1987).
7.4 Teratogenicity
Nicotine rapidly crosses the placenta and enters the fetus.
Some investigations have reported teratogenic effects of high
doses of nicotine, which interfered with osteogenesis in mice
and chick embryos. Chronic nicotine treatments of pregnant
rats throughout gestation produced subtle neurological changes
which manifested themselves as behavioral or

electrophysiological alterations in the offspring. Thus,
several studies suggest that nicotine, at least in high doses,
may have toxic effects on the fetus. Smoking is associated
with impaired growth and development of the fetus. 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 offspring of smoking mothers, but other
reports positive associations. One study has reported an
association between paternal smoking and the incidence of
congenital malformations (US Department of Health and Human
Services (1988)).
7.5 Mutagenicity
In the Ames Salmonella typhimurium mutagenesis and mammalian
cell cytogenic assays, nicotine did not posses any genotoxic
activity, although it induced separable DNA damage in the
Escherichia coli pol A+/A-system (US Department of Health and
Human Services, 1988)
7.6 Interactions
Smoking increases the metabolism of certain compounds and
lowers blood levels of drug such as phenacetin, caffeine,
theophylline, imipramine and pentazocine through enzyme
induction. Other reported effects of smoking, which do not
involve enzyme induction, include reduced diuretic effects of
furosemide and decreased cardiac output, and antagonism of the
hypotensive effects of propranolol, which may also relate to
the normal effects of nicotine. Both smoking and nicotine can
increase the level of circulating cortisol and catecholamines.
Therapy with adrenergic agonists or with adrenergic blockers
may need to be adjusted according to changes in smoking
status.
8. TOXICOLOGICAL 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
Not relevant
8.3.1.2 Urine
To detect glycosuria
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
Not relevant.
8.3.3 Haematological analyses
White cell count or full blood count.
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
Symptoms of nicotine poisoning may develop within 15
minutes. The onset of symptoms is much more rapid after
the ingestion of liquid nicotine (e.g. insecticide
preparations) Death may occur within 5 minutes of
ingestion of concentrated nicotine insecticides. Four to
eight milligrams orally may produce serious symptoms in
individuals not habituated to nicotine. Gastrointestinal
signs and symptoms occur first and include mouth and
throat burning followed by profuse salivation, nausea,
vomiting, abdominal pain and occasionally diarrhoea.

More severe intoxication results in dizziness, weakness
and confusion, progressing to convulsions, hypertension
and coma. Intense vagal stimulation may cause transient
cardiac standstill or paroxysmal atrial fibrillation.
Death is usually due to paralysis of respiratory muscles
and/or central respiratory failure.
9.1.2 Inhalation
In humans, acute exposure to nicotine even in low doses
(similar to the amounts consumed by tobacco users)
elicits autonomic and somatic reflex effects. Dizziness,
nausea and/or vomiting are commonly experienced by
nonsmokers after low doses of nicotine, such as when
people try their first cigarette. However cigarette
smokers rapidly become tolerant to these effects.
9.1.3 Skin exposure
Dermal exposure to nicotine can also lead to
intoxication. Such exposures have been reported after

spilling or applying nicotine containing insecticides on
the skin or clothes and as consequence of occupational
contact with tobacco leaves.

A self-limiting illness known as "green-tobacco
sickness" has been described in young man handling
uncured tobacco leaves in the field; it consists of
pallor, vomiting and prostration and is probably due to
the percutaneous absorption of nicotine from wet leaves.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
Serious poisoning has occurred from the use of aqueous
infusions of tobacco as enemas (Gosselin, 1988).
Nicotine 2 mg administered intranasally as a 2% aqueous
thickened solution was better absorbed than the same
dose given as a chewing gum (Russell, 1983)
9.2 Chronic poisoning
9.2.1 Ingestion
Chronic poisoning by nicotine is possible by chewing
tobacco or nicotine gums.
9.2.2 Inhalation
Smoking causes coronary and peripheral vascular disease,
cancer, chronic obstructive lung disease, peptic ulcer
and reproductive disturbances, including prematurity.
Nicotine may contribute to tobacco related disease, but
direct causation has not been determined because
nicotine is taken up simultaneously with a multitude of
other potentially harmful substances that occur in
tobacco smoke and smokeless tobacco.
9.2.3 Skin exposure
Through transdermal nicotine
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
Not relevant
9.3 Course, prognosis, cause of death
In fatal cases of nicotine poisoning, death is usually rapid;
it occurs nearly always within 1 hour and occasionally within
5 minutes. According to the traditional view, death is due to
paralysis of the respiratory muscles; paralysis of medullary
centres controlling respiration requires a larger dose.
Circulatory failure is not necessarily permanent; if heart
action can be initiated by external cardiac massage or
intracardiac epinephrine while respiration is maintained,
death may be prevented (Franke, 1936). If the patient survives
the initial period, the prognosis is good (Gosselin 1988)
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
The overall effect on the cardiovascular system leads to
tachycardia, peripheral vasoconstriction and elevations
of blood pressure with an attendant increase in the work

of the heart. Nicotine may induce vasospasm and cardiac
arrythmias. Tolerance does not develop to the
catecholamine-releasing effects of nicotine.

Acute effects

A transient increase in blood pressure followed by
bradycardia, paroxysmal atrial fibrillation, or cardiac
standstill is observed.

Chronic effects

Nicotine could contribute both to the atherosclerotic
process and to acute coronary events by several
mechanisms. Nicotine could promote atherosclerotic
disease by its actions on lipid metabolism and
coagulation by hemodynamic effects and/or by causing
endothelial injury.

Nicotine may act by releasing free fatty acids,
enhancing the conversion of VLDL (very low density
lipoproteins) to LDL (low density lipoproteins),
impairing the clearance of LDL and/or by accelerating
the metabolism of HDL (Brischetto, 1983; Gluette Brown,
1986; Grasso, 1986; Hojnacki, 1986.)

Nicotine could affect platelets by increasing the
release of epinephrine, which is known to enhance
platelet reactivity by inhibiting prostacyclin, an
antiaggregatory hormone secreted by endothelial cells,
or perhaps directly (Sonnenfeld, 1980). Alternatively,
by increasing heart rate and cardiac output and thereby
increasing blood turbulence or by a direct action,
nicotine may promote endothelial injury. Cigarette
smoking, most likely mediated by nicotine, facilitates
AV nodal conduction which could result in an increased
ventricular response during atrial fibrillation (Peters,
1987). Nicotine could aggravate peripheral vascular
disease by constricting small collateral arteries and/or
by inducing local thrombosis. Patients with coronary or
peripheral vascular disease are likely to suffer some
increase in risk when taken nicotine. Nicotine could
contribute to the progression of chronic hypertension by
aggravating vasoconstriction either in sympathetic activation
or inhibition of prostaglandin synthesis.

Based on its pharmacological actions, it is likely that
nicotine plays a role in causing or aggravating acute
coronary events. Myocardial infarction can be due to one
or more of these precipitating factors: excessive demand
for oxygen and substrates; thrombosis; and coronary
spasm. Nicotine increases heart rate and blood pressure and,
therefore, myocardial oxygen consumption.

Nicotine consumed in the form of nicotine gum has been
studied in patients with coronary artery disease.

Nicotine gum (4mg) increased myocardial contractility in
healthy people, but in patients with coronary artery
disease, nicotine gum decreased contractility in the
ischaemic regions of the myocardium, consistent with
aggravation of ischaemia (Bayer, 1985). In the most
severe cases of coronary artery disease, overall
contractility decreased after nicotine gum. This study
supports the idea that nicotine contributes to the
induction of myocardial ischaema in susceptible smokers.


In addition to creating an imbalance between myocardial
oxygen supply and demand, nicotine may promote
thrombosis. Nicotine may also induce coronary spasm by
sympathetic activation or inhibition of prostacyclin.
Coronary spasm has been observed during cigarette
smoking (Maouad, 1984).

Sudden cardiac death in smokers might result from
ischaemia, combined with the arrhythmogenic effects of
increased amounts of circulating catecholamines released
by nicotine.
9.4.2 Respiratory
Acute effects

Initial tachypnoea, but later dyspnoea, decreased
respiratory rate, and cyanosis may be seen. Respiratory
arrest may occur within minutes, and resultant death
within 1 hour.

Chronic effects

Nicotine may directly or indirectly influence the
development of emphysema in smokers, but further
research is needed to define the magnitude of the
contribution of nicotine to the pathogenesis of smoking
including chronic lung disease. Nicotine can also worsen
pulmonary function in smokers who already have lung
disease. Acute exposure to nicotine induces constriction
of both central and peripheral airways (Yamatake, 1978).
The increase in airways resistance by nicotine involves
vagal reflexes and stimulation or parasympathetic
ganglia in the bronchial wall (Nakamme, 1986). The
magnitude of bronchoconstriction
observed in experimental animals and humans following
acute inhalation of cigarette smoke is correlated with
the level of nicotine in the smoke (Beck, 1986)
suggesting that nicotine may be an important factor in
the increased airways resistance of smokers.
9.4.3 Neurological
9.4.3.1 CNS
The effects of nicotine are generally dose-
dependent and extremely high doses can produce
toxic symptoms such as delirium. These effects
also occur in nicotine tolerant individuals.
Nicotine first stimulates and later depresses

the CNS. Headache, confusion, dizziness,
agitation, restlessness and incoordination develop
initially after serious nicotine overdose; 30 minutes
later, convulsions and coma occur.
9.4.3.2 Peripheral nervous system
Neuromuscular symptoms include hypotonia,
decreased deep tendon reflexes, weakness,
fasciculations and paralysis of muscles
(including respiratory muscles).
9.4.3.3 Autonomic nervous system
Cholinergic symptoms often observed initially
include diaphoresis, salivation, lacrimation,
increased bronchial secretions, miosis and later
mydriasis.

Nicotine has actions at the sympathetic ganglia
and on the chemoreceptors of the aorta and
carotid bodies. Nicotine also affects the
adrenal medulla, releasing catecholamines.
9.4.3.4 Skeletal and smooth muscle
Weakness, fasciculations and paralysis of
muscles (including respiratory muscles)
9.4.4 Gastrointestinal
Acute effects

Gastrointestinal symptoms occur first and include
burning of the mouth and throat followed by profuse
salivation, nausea, vomiting, abdominal pain and
occasionally diarrhoea.

Chronic effects

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
(Kikendall, 1984). In animals, nicotine potentiates
peptic ulcer formation induced by histamine or
pentagastrin (Konturek, 1971).
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Others
9.4.7 Endocrine and reproductive systems
The action of nicotine on the adrenal medulla (release
of catecholamines) does not appear to be affected by
tolerance, and may aggravate patients with
hyperthyroidism, phaeochromocytoma or insulin-dependent
diabetes.
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
Not relevant.
9.4.12.2 Fluid and electrolyte disturbances
Not relevant.
9.4.12.3 Others
Action on lipids.

Nicotine may act by releasing free fatty acids,
enhancing the conversion of VLDL (very low
density lipoproteins) to LDL (low density
lipoproteins), impairing the clearance of LDL
and/or by accelerating the metabolism of HDL.
(Brischetto, 1983; Gluette Brown, 1986; Grasso,
1986; Hojnacki, 1986).
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
Pregnancy

Nicotine in any form may be harmful to the fetus.
Exposure to nicotine during the last trimester has been
associated with a decrease in breathing movements.
These effects may be the result of decreased placental
perfusion caused by nicotine. One miscarriage during
nicotine therapy has been reported. Studies of pregnant
rhesus monkeys have shown that maternal nicotine
administration produced acidosis, hypoxia and hypercarbia
in the fetus. Nicotine has been shown to be teratogenic in
mice treated cutaneously with 25 mg/kg, which is
approximately 300 times the human oral dose. Studies in
rats and monkeys have not demonstrated a teratogenic effect
of nicotine in newborn which occur during cigarette smoking.
Cigarette smoking is associated with impaired fetal growth
and development.

Breast feeding

Nicotine passes freely into the breast milk in small
quantities, which are not clinically significant,
averaging 91ppb in one study. Heavy smoking (20-30
cigarettes per day) may alter the supply of milk and
cause nausea and vomiting in the infant.
9.5 Others
Withdrawal Syndrome. Need for oral gratification and other
psychological problems may result in the production of
symptoms of withdrawal including anxiety, impaired
concentration and memory, depression, hostility, sleep
disturbances, and increased appetite (Ellenhorn 1988).
9.6 Summary
10. MANAGEMENT
10.1 General principles
There is no known antidote. Immediate establishment of an

airway, monitoring of breathing patterns, and maintenance of
circulation are essential in serious overdose cases.
Preparations for possible seizures of rapid progressing to
coma must be initiated in serious overdose cases by
establishment of an intravenous line, supplemental oxygen,
cardiac monitoring, and direct observation.

Artificial ventilation procedures should be kept ready;
oxygen
may be required.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Plasma
10.2.2 Biomedical analysis
Full blood count
Urinalysis (glycosuria)
10.2.3 Toxicological analysis
Plasma nicotine levels and metabolites in urine.
10.2.4 Other investigations
No data available.
10.3 Life supportive procedures and symptomatic treatment
Artificial ventilation and oxygen therapy until spontaneous
breathing is adequate. Keeps the airways clear.

Profuse salivation may require continuous oral suction.
Bronchial secretions, excess salivation, and diarrhoea may
be
ameliorated by atropine. If severe or persistent convulsions
occur, they may be controlled with small intravenous doses
of
barbiturates or diazepam.
10.4 Decontamination
If contact was with the skin, remove contaminated clothing
and wash the skin thoroughly with water without rubbing (avoid
warm water). If the patient has swallowed nicotine, induce
emesis if there are no convulsions and respiration is
normal. Wash out the stomach. Activated charcoal may be left
in the stomach.

Children who ingest more than one cigarette should receive
activated charcoal and medical observation for at least
several hours.
10.5 Elimination
Haemodialysis and haemoperfusion have not been evaluated in
acute nicotine poisoning. Acidification of urine may
increase excretion of nicotine but although pharmacologically
sound, its clinical value remains to be established and could be
harmful.
10.6 Antidote treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Malizia (1983) described four children who ingested two
cigarettes each and developed salivation, vomiting,

diarrhoea, tachypnoea, tachycardia, and hypotension within 30
minutes and depressed respiration and cardiac arrhythmias within
40 minutes. Convulsions occurred within 60 minutes of
ingestion. All recovered after gastric lavage, activated
charcoal, intermittent positive pressure ventilation, and 5
mg diazepam intravenously for convulsions.

A 23 year old woman who had smoked two packs per day for
several years chewed a single piece of nicotine gum (2 mg
nicotine) after which she developed nausea, tremor, flushing,

palpitations, paresthesias, pruritus, vomiting, diarrhoea,
confusion and abdominal pain. She recovered after treatment
and with prochlorperazine, morphine and atropine (Mensch,
1984).
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
No data available.
12.2 Specific preventive measures
Preventative measures for occupational exposure to nicotine
include adequate ventilation, chemical goggles, mechanical
filter respirator, rubber gloves, aprons and boots.
12.3 Other
No data available.
13. REFERENCES
eutical BArena J (1974). Poisoning IV Ed. New York Charles
Thomas Ed.

Bayer F et al (1985). The compartment of the contraction behavior
of he left ventricle under nicotine exposition. Therapiewoche
35:1968-74.

Beck ER et al (1986). Bronchoconstriction and apnea induced by
cigarette smoke: Nicotine dose dependence. Lung 164:293-301.

Benowitz NL et al (1987). Prolonged absorption with development
of tolerance to toxic effects after continuous exposure to nicotine.
Clinical Pharmacology and Therapeutics 42(1):119-220

Benowitz NL et al (1982a). Interindividual variability in the
metabolism and cardiovascular effects of nicotine in man. J
Pharmacol Exp Ther 221:368-372.

Benowitz NL et al (1982b). Circadian blood nicotine
concentrations during cigarette smoking. Clin Pharmacol Ther 32:758-764.

Brischetto CS et al (1983). Plasma lipid and lipoprotein profiles
of cigarette smokers from randomly selected families: Enhancement of
hyperlipidemia and depression of high-density lipoprotein. Am J
Cardiology 52(7):675-80.

Cluette-Brown J et al (1986). Oral nicotine induces an
atherogemic lipoprotein profile. Proceedings of the Society for Experimental
Biology and Medicine 182(3):409-413.


Ellenhorn MJ et al (1988). Medical Toxicology. Diagnostics and
Treatment of Human Poisoning , 1 Ed. Elsevier Science Publishers,
New York: 912-920.

Feyerabend C et al (1985). Nicotine pharmacokinetics and its
application to intake from smoking. Br J Clin Pharmacol 19:239-247

Franke FE, Thomas JF (1936). The treatment of acute nicotine
poisoning J Am Med Assoc 106:507.512

Gehlbach SH et al (1974). Green-tobacco sickness. An illness of
tobacco harvesters. J Am Med Assoc 229(14):1880-83.

Gnasso A et al (1986). Acute influence of smoking on plasma
lipoproteins. Proceedings of the Society for Experimental Biology
and Medicine 182:414-418.

Gosselin RE (1988). Clinical toxicology of Commercial Products.
VI.ed Baltimore, Williams & Wilkins: 311-313.

Hojnacki et al (1986). Oral nicotine impairs clearance of plasma
low density lipoprotein. Proceeding of the Society for Experimental
Biology and Medicine 1823):414-418.

Kikendall JW et al (1984). Effect of cigarette smoking on
gastrointestinal physiology and non-neoplasic digestive disease.
J Clin Gastroenterology 61:65-79.

Kontureck SJ et al (1971). Effects of nicotine on gastric
secretion and ulcer formation in cats. Proceedings of the Society for
Experimental Biology and Medicine 138, 2:674-677.

Lockhart LP (1933). Nicotine poisoning (letter). Br Med J 1:246-247

Malizia E et al (1983). Acute intoxication with nicotine
alkaloids and cannabinoids in children from ingestion of cigarettes. Hum
Toxicol 2:315-316.

Maonad J et al (1984). Diffuse or segmental narrowing (spasm) of
the coronary arteries during smoking demonstrated on angiography. Am
J Cardiology 53:354-355.

Mensch AR, Hoden M (1984). Nicotine overdose after a single piece
of nicotine gum. Chest 85:801-802

PDR (1987) Physician's desk reference. 41st ed. Barnhart E. 1070-72

Peters et al (1987). Electrophysiologic effects of cigarette
smoking in patients with and without chronic beta-blocker therapy. Am J
Cardiol 60:1078-1082.

RTECS (1986) Registry of Toxic Effects of Chemical Substances
NIOSH (vol 3A):3060-424.

Russell MAH et al (1983). Br Med J 286:683.


Sonnenfeld & Wennmalm (1980). Inhibition by nicotine of the
formation of prostacyclin - like activity in rabbit and human vascular
tissue. Br J Pharm (71):609-613.

US Department of Health and Human Services (1988). A Report of
the Surgeon General, The Health consequences of smoking. Nicotine
addiction. US Department of Health and Human Services, Public
Healtch Service. Office of the Assistant Secretary for Health, Office
on Smoking and Health 32-33: 601-602.

Weizenecker & Deal WB (1970). Tobacco croppers sickness. J
Florida Med Assoc, 57(12): 13-14.

Yamatake Y et al (1978). Drug responses of canine, bronchus and
bronchiole. Chemical and Pharmaculletin 26:318-320
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESSES
Author: Julia Higa de Landoni
Section of Toxicology
Hospital de Clinicas San Martin
Cordoba 2351
Capital Federal
Buenos Aires
Argentina

Date: March 1991

Peer Review: Adelaide, April 1991

Congrats to BJ_M for holding what I am sure is the record for the longest OT post !!

[ViRaL1]

If that was it, you just took the crown by quoting it.

[Shadowmistress]

Watch Indolikaa try and top that tomorrow.

[ViRaL1]

How YOU doin?

[Doramius]

ANyone else ever hear of TEEM soda. I think it's what later became 7*UP, if I remember correctly. Maybe not, but I remember the soda.

[ViRaL1]

http://www.ambev.com.br/english/produtos/refrigerantes/limoes/0005

[offline]

Nicotine was the active ingredient in Rat Poison during the early part of the 20th century. It is famous for its use as an assassination drug amongst the so called "80 percent men" during the 40ies in Germany. So called, as they demanded 80% interest on black market loans.

The Oil of Tobacco Poison was often mixed with beer or as an additive
to benzine hypo's (a common injection peddled during the time)