Tobacco . Its definition, available forms , fatal dose , contents , pathophysiology , pharmacokinetics and toxicology. Diagnosis and treatment of toxicity.

1. TOBACCO TOXICOLOGY
By R. Vishali
18GT1T0023
Pharm.D 4th Year
SRI VENKATESWARA COLLEGE OF PHARMACY
RVS NAGAR, CHITTOOR

2. CONTENTS
1. TOBACCO
2. SMOKED FORM OFTOBACCO
3. SMOKELESS FORM OFTOBACCO
4. EPIDEMILOGY
5. A CIGARETTE CONTAINS
6. NICOTINE
7. NICOTINE FATAL DOSE
8. TOBACCO DOSES
9. TOXICOKINETICS
10. CLINICAL FEATURES
11. COMPLICATIONS
12. PATHOPHYSIOLOGY
13. DIAGNOSIS
14. TREATMENT

3. 1.TOBACCO
• Tobacco is a plant originally indigenous to the Americas which is now grown across the world. Its
leaves contain high levels of the addictive chemical nicotine and many cancer-causing chemicals,
especially polyaromatic hydrocarbons (PAHs).
• The leaves may be smoked (in cigarettes, cigars, and pipes), applied to the gums (as dipping and
chewing tobacco), or inhaled (as snuff).
• Nicotine is now being extracted from the leaf to produce novel nicotine products, such as e-
cigarettes, but also for Nicotine Replacement Therapies, which are used to treat tobacco
addiction.

4. 2.SMOKED FORM OF TOBACCO:
• Bidis
• Cigarettes
• Cigars
• Cheroots
• Chuttas
• Dumti
• Pipes
• Hooklis
• Chillum
• Hookahs

5. 3. SMOKELESS FORMS OF TOBACCO:
• Spit , chew , snuff and dip is the form of smokeless tobacco.
• Pan with tobacco, pan masala with tobacco.
• Tobacco , areca nut and slaked lime preparation, Manipuri tobacco, mawa, khaini , chewing
tobacco , snus , gutkha.

6. 4. EPIDEMILOGY:
• 130 crore people smoke tobacco worldwide.
• Tobacco kills up to half of its users.
• Tobacco is the second most cause of death in the world.
• Children who are engaged in tobacco related works are especially vulnerable to “GREEN
TOBACCO SICKNESS” which is caused by the continuous absorption of nicotine through the
skin from the handling of wet tobacco leaves.

7. 5. A CIGARETTE CONTAINS:

8. 6. NICOTINE:
• Nicotine is the chemical in the tobacco that makes it hard to quit.
• Nicotine produces pleasing effect in brain, but these effects are temporary, so one reach for
another tobacco based substance.
• When an addict person tries to avoid or stop it they experience unpleasant mental and physical
changes. These are symptoms of nicotine withdrawal.
7. NICOTINE FATAL DOSE:
• Nicotine is highly toxic; 2 to 5 mg can cause nausea, and 40 to 60 can cause death. However,
survival has occurred with ingestion of 1- 4 grams.

9. 8.TOBACCO DOSES:
• CIGARETTE TOBACCO: contains about 10-15mg of nicotine per cigarette. Average
cigarette delivers 1-3 mg nicotine to brain.
• NICOTINE GUM : contains 2-4 mg per piece. Slow absorption and high degree of pre
systemic metabolism.
• NICOTINE LOZENGES: contain 2-4 mg of nicotine and ingestion can cause serious toxicity
in a child.
• TRANSDERMAL PATCHES: May produce intoxication in light smokers or in non-smokers,
particularly children( deliver an average of about 5-22mg of nicotine over the 16-24 hours of
intended applications).

10. Other major ingredient are:
• Tar – it’s important not to mix cigarette tar with natural occurring tar such as wood tar. Wood
tar has microbicidal properties that cannot be claimed for cigarette tar. Tar is an umbrella
name for a number of particulates that smokers ingest when smoking– basically, tar is
everything a smoker inhales and contains every single poisonous particle that can be found in
cigarettes.
• Tar coats the lungs, causing cilia cells to die out. Without that barrier, tar gets immediate
access to the alveoli where it infects the organ with carcinogenic ingredients and causes
cancer and other pulmonary diseases.

11. • Carbon monoxide – carbon monoxide is a highly poisonous gas that is a byproduct of
burning cigarettes. It is also found in car emissions and interferes with breathing and
circulatory system. Carbon monoxide enters the bloodstream via the lungs, taking up the
space reserved for oxygen. As a result, the cells in the body get less oxygen and the heart has
to pump faster in order to deliver that limited supply. Blood pressure also shoots up and this
puts smokers at a higher risk of suffering a heart attack.

12. • Acetic acid – acetic acid can be found in household products such as cleaning wipes,
disinfectants, and degreasers. It’s also used for industrial and manufacturing purposes.
• Toluene – found in gasoline and used in the manufacturing of explosives.
• Naphthalene – a poisonous compound used in production of mothballs.
• Hydrogen cyanide – a poison that was used in prison executions.
• Acetanisole – a fragrance used in perfume industry.
• Methanol – an ingredient regularly found in antifreeze used in car industry.
• Methane – gas found in excrement.
• Urea – a compound found in sweat and urine.

13. 9. TOXICOKINETICS
• ABSORPTION – Through oral mucosa , lungs, intestinal mucosa ,skin
• VOLUME OF DISTRIBUTION: Approximately 1L/kg
• METABOLISM : 80 – 90% metabolized in liver. Remaining in lung and kidney
• ELIMINATION: 2-35 % excreted unchanged in urine
• HALF-LIFE: 1 – 4 hours

14. 10. CLINICAL FEATURES:
1. Acute poisoning:
• Agitation, drowsiness, dizziness, headache
• Excessive salivation, pallor, sweating
• Abdominal pain, nausea , vomiting
• Lack of coordination, twitching, tremor
2. Chronic poisoning:
• Lung cancer
• Non-pulmonary cancer: Mouth, larynx, esophagus, stomach, liver, pancreas, bladder, uterine
cervix, breast, brain.
• Respiratory disease: emphysema, bronchitis, asthma, pneumonia.

15. • Cardiovascular disease: coronary heart disease, hypertension, arterial thrombosis, stroke.
• Nicotine withdrawal: Manifestation of nicotine withdrawal can occurs within 4-8 hors of the
last cigarette. Manifestation include change in mood, insomnia, difficulty concentrating,
restlessness, decreased heart rate and weight gain. Craving is common, increased coughing,
poor performances in vigilance tasks can occur.

16. 11. COMPLICATIONS:
• Smoking decreases the blood supply to brain, constrict the blood vessels and causes
atherosclerosis.
• Cancers of the tongue, salivary gland, mouth pharynx and for brown teeth.
• Lung cancer and emphysema.
• Nicotine causes the blood clots and development of plaque which leads to the risk of heart attack.
• Esophageal cancer, stomach cancer, kidney cancer.
• Poor blood circulation damages the blood vessels lead to death of body tissue which increases risk
of gangrene.
• More fracture due to higher rate of osteoporosis.
• Eye exposure: Irritation, abrasion, pain, redness, blurred vision, headache

17. 12.PATHOPHYSIOLOGY:
Frequent exposure to a substance of abuse
Leads to alteration of neurons at cellular and molecular level
Results in physiological alteration and associated behaviors related to addiction
Results in tolerance, sensitization, dependance, withdrawal, craving and stress-induced relapse

18. - How carbon monoxide effect our body?
• When carbon monoxide enters the lungs through breathing, it binds with
hemoglobin in red blood cells to make carboxyhemoglobin (COHb), which is
then transported into the bloodstream. Once this happens, oxygen cannot
bind with receptors on the same cell.
• Carbon monoxide is much faster at binding with hemoglobin than oxygen
(about 200 times faster). So when CO is present in the lungs, it wins the
spot on the red blood cells. This process diminishes the oxygen-carrying
capacity in the bloodstream
• The normal level of COHb in the bloodstream from environmental exposure to carbon
monoxide is less than 1%. For smokers, COHb saturation in the blood is much higher. Factors
including brand, number of cigarettes smoked and the amount of time affect saturation levels.

19. - How tar effects on our body?
• Tar starts its damaging work in the mouth by rotting and blackening teeth, damaging gums,
and desensitizing taste buds. It forms a tacky brown or yellow residue on the inside of the
lungs. It damages the cilia (which help to keep our airways clean) allowing all toxins to travel
freely into the lungs causing many problems (lung cancer, emphysema, or other lung
diseases).

20. 13. DIAGNOSIS:
• Acute poisoning can be confirmed by estimating plasma nicotine level; but the short half-life of
nicotine necessitates early withdrawal of blood. High pressure liquid chromatography is generally
utilized to assay nicotine levels. Plasma level greater than 40 to 50 ng/ml indicates serious toxicity.
• Polymorphonuclear leukocytosis and glycosuria are often encountered in nicotine overdose.
• Passive tobacco smoke exposure is usually determined by estimating cotinine levels in plasma,
urine, or saliva. Urine cotinine is also used as an index to nicotine exposure in tobacco workers
(especially harvesters).

21. 14. TREATMENT:
1. ACUTE POISONING:
Mild overdose requires only observation for 4-6 hours, after which patient can be discharged.
Serious overdose may be treated as follows:
• Decontamination by stomach wash. Emesis is contraindicated. Activated charcoal is effective
and must be administered in the usual manner.
• Since nicotine is weakly alkaline, excretion can be enhanced by acidification of urine (but it
can aggravate the condition of a convulsing patient in whom there is rhabdomyolysis).

22. • Symptomatic and supportive measures-
-Benzodiazepines for convulsions.
-Atropine for bradycardia.
-IV Fluids for vasopressors for hypertension
-Respiratory compromise is managed by oxygen, intubation and positive pressure ventilation.
2. CHRONIC POISONING (Addiction):
Nicotine withdrawal must be treated by a combination of therapies including psychological,
psychopharmacological, and nicotine replacement.
a) Nicotine replacement therapy- The rationale behind nicotine replacement is to prevent or
relieve nicotine withdrawal symptoms while stopping smoking behavior by replacing it with
another behavior.

23. -Nicotine gum (Polacrilex): The first nicotine preparation that was made available for use is the
nicotine gum. Approximately 50 to 70% of the nicotine is absorbed through the buccal mucosa, while
additional amounts are absorbed through swallowed saliva. Peak plasma concentration is reached 15
to 30 minutes after starting to chew the gum, as compared with 1 to 2 minutes after initiating
smoking. Chewing the gum too rapidly and vigorously can raise nicotine concentrations to
uncomfortable levels producing adverse effects (especially if the patient is also smoking at the same
time). If the gum is inadvertently swallowed, there is no cause for undue concern since the nicotine is
released and absorbed slowly producing only low blood concentrations. The actual efficacy of
nicotine gum, and the dose and duration of therapy are highly variable.

24. - Nicotine transdermal patch: The disadvantages of nicotine gum (frequent administrations,
unsightly chewing, bad taste, nausea, and dyspepsia) are mostly avoided by transdermal nicotine,
which is available as nicotine-releasing adhesive patches of varying sizes and delivery rates. The
nicotine is released either directly through the skin or through a membrane system in contact with
the skin. Side effects are mild and include dose related sleep disturbances, dyspepsia, myalgias,
and increased cough.
- Nicotine spray: It is available as a metered dose inhaler containing 100 mg of nicotine at 10
mg/ml, designed to deliver 200 equivalent puffs each releasing 0.5 mg of nicotine. Absorption
occurs through the nasal mucosa which may be affected to some extent in the presence of rhinitis.
The recommended dose is 2 sprays (one in each nostril) every ½ or 1 hour, subject to a maximum
of 40 doses (80 puffs) in any 24-hour period.

25. b) Other therapies:
-Clonidine: Clonidine is an alpha2 -adrenergic agonist that has been found useful in the treatment of
clonidine is effective for most withdrawal syndromes because it inhibits noradrenergic neurons. The
usual dose recommended is 150 to 200 mcg/day for 1 month.
-Antidepressants: Since it is well known that smokers who stop smoking have a high incidence of
depression, antidepressants such as doxepin and sertraline have been tried with varying degrees of
success in combating nicotine withdrawal.
-Nicotine agonists and antagonists: These drugs have the potential to block the effect of nicotine,
i.e. removing its reinforcing effect on smoking behavior.

26. REFERENCE
1. V.V Pillay modern medical toxicology- 4th edition
2. Tobacco and effects (slideshare.net)
3. PPT – Tobacco: The Harmful Effects PowerPoint presentation | free to view - id: 71d094-
NTI4M (powershow.com)