class presentation on the Absorption, distribution, metabolism and excretion of nicotine

1. NICOTINEA D M E O F N I C O T I N E
B Y
G L O R I A A S A N T E W A A

2. OUTLINE
• Introduction
• Dosage forms
• Absorption
• Distribution
• Toxicity
• Pharmacological effects
• Metabolism
• Excretion
• References
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3. INTRODUCTION - NICOTINE
• Chemical Formula - C10H14N2
• Chemical name - 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
• Source- naturally found in tobacco plant (Nicotiana tabacum),
tomatoes, potatoes, eggplant and green peppers
• tobacco leaves contain up to 10% nicotine
Nicotine is also derived from nicotinic acid, a B-vitamin also known as
niacin
Class of phytochemical- pyridine-piperidine alkaloid
• 2nd most widely used psychoactive drug
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Figure 1

4. DOSAGE FORMS
• Smokeable - Cigarette
- Pipe
- Cigar
• Leaf (Chewing)
• Leaf (Dip)
• Snuff (powdered)
• Tablet
• Lozenge
• gum
• Nasal spray
• Transdermal Patch (extended release)
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Figure 1 Figure 2
Figure 3
Figure 4

5. USES
• pharmacotherapy for smoking cessation
• a potential medication for several diseases such as Alzheimer's Disease
• a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6)
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6. ABSORPTION OF NICOTINE
Membrane of absorption effectiveness
Lung (smoking) very rapid
Oral and nasal mucosa (cigar, tobacco chewing,
nasal spray)
More slowly but longer lasting
Skin (patch) slower absorption, more constant blood levels
stomach (tablet) (uncommon) poor (nicotine is strong base – stomach is
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7. CIGARETTE SMOKING
• Nicotine in a cigarette – about 7 mg
• Smoking – delivers about 1-3 mg to the smoker about 0.7 ug/puff
• Smoking is quickest and most efficient way to get nicotine to the brain
• Reinforcing effects are strongest
• As nicotine blood levels fall, another puff is taken
• Smokers may typically take about 20 puffs/cigg
• Delivering in total about 13ug/kg
• Technique of smoker can increase nicotine (time smoke is in lungs, rapid
puffing)
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8. DISTRIBUTION OF NICOTINE IN THE
BODY
• Nicotine is quickly and thoroughly distributed in the body, to brain,
placenta and all body fluids (including breast milk).
• When taken in by cigarette or cigar smoking, it takes about 7 seconds
to cross the blood-brain barrier but has a direct effect on the body for
only about 30 minutes
•
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9. TOXICITY
• Symptoms of overdose include nausea, abdominal pain,
vomiting, diarrhea, diaphoresis, flushing, dizziness, disturbed
and vision, confusion, weakness, palpitations, altered respiration
hypotension.
• LD50= 60 mg
• Chronic effects include- Emphysema
-Chronic bronchitis
-Stroke
-Vascular disease
- cancer
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10. PHARMACODYNAMICS
• Dose-dependent action- nicotinic acetylcholine receptors
• Agonist – low doses – Stimulation Nicotine binds to the presynaptic nicotinic
receptors exciting the neuron to fire more action potentials causing an
increase in dopamine release.
• Nicotine also affects neurons by increasing the number of synaptic vesicles
released
• When bound, it opens a Na+ channel and depolarizes the cell membrane
• Antagonist – high doses– Blocks receptors-brief stimulation followed by
blockade of transmission
• Itranvenous administration of nicotine causes release of acetylcholine,
norepinephrine, dopamine, serotonine, vasopressin, beta-endorphin and
ACTH. Nicotine is a highly addictive substance.
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11. PHARMACOLOGICAL EFFECTS
• Stimulates hypothalamus to produce antidiuretic hormone, causing
fluid retention.
• Reduces activity coming in from muscles, producing relaxation.
• stimulates release of catecholamines, stress hormones, adrenaline,
epinephrine
• Inhibits stomach secretions, stimulates bowel (laxative in nontolerant
person).
• increases metabolism of fat; dull taste buds.
• Slows stomach contractions; increases blood sugar.
• improves attention/memory; although high doses may increase
nervousness, tremors, seizures, panic attack.
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12. METABOLISM
• Liver metabolizes 80–90% before excretion by kidneys by enzymes in the
liver moslty Enzymes in the CYP 450 family (CYP2A6, CYP 2B6)
• Phase 1 metabolism is carried out mostly by the CYP2A6, CYP 2B6 and FMO
(flavin-containing monooxygenase)
• Phase 2 metabolism is done by UGT (UDP-glucuronosyltransfease)
• Some amount of nicotine directly enters the phase 2
• Nicotine has a half-life of about 2 hours.
• The major metabolite of nicotine is cotinine, which is the basis for tests.
• Nicotine is also metabolized in the lungs to cotinine and nicotine-N-oxide
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13. METABOLISM CONTD
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14. EXCRETION
• Urine
• Feaces
• Sweat
• Breast milk-
heavy smoker
0.5 mg per liter
of milk
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15. REFERENCES
• Armitage AK, Dollery CT, George CF, Houseman TH, Lewis PJ, and Turner DM (1975)
Absorption and metabolism of nicotine from cigarettes. Br Med J 4: 313-316.
• Armstrong DW, Wang X, and Ercal N (1998) Enantiomeric composition of nicotine in
smokeless tobacco, medicinal products and commercial reagents. Chirality 10: 587-591.
• Kyerematen GA, Morgan ML, Chattopadhyay B, deBethizy JD, and Vesell ES (1990b)
Disposition of nicotine and eight metabolites in smokers and nonsmokers: identification in
smokers of two metabolites that are longer lived than cotinine. Clin Pharmacol Ther 48:
641-651.
• Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Fackenthal JD, Rogan PK, Ring
B, Wrighton SA, et al. (2003) Hepatic CYP2B6 expression: gender and ethnic differences and
relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J
Pharmacol Exp Ther 307: 906-922.
• World Health Organization (WHO). Online.
<http://www.who.int/health_topics/tobacco/en/> (accessed: 2 April 2003).
• Covers tobacco and international efforts to track and reduce use of tobacco
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THANK
YOU !!!