HEALTH EFFECTS OF
SMOKING
JOY ANNE C. NICODEMUS, MD
Adapted from the lecture of
Nestor F. Venida, M.D.
FPCCP, FPatacsi
TABLE OF TOXIC AND TUMORIGENIC
AGENTS OF CIGARETTE SMOKE
GAS PHASE AMOUNT/CIG.
Carbon dioxide 10-80 mg
Carbon monoxide 0.5-26 mg
Nitrogen oxides 16-600 ug
Ammonia 10-130 ug
Hydrogen cyanide 280-550 ug
Hydrazine 32 ug
Formaldehyde 20-90 ug
Acetone 100-940 ug
Acrolein 10-140 ug
CON’T TABLE OF TOXIC AND TUMORIGENIC
AGENTS OF CIGARETTE SMOKE
GAS PHASE AMOUNT/CIG.
Acetonitrile 60-160 ug
Pyridine 32 ug
3-Vinylpyridine 23 ug
N-Nitrosodimethylamine 4-180 ug
N-Nitrosoethylmethylamine 1-40 ug
N-Nitrosodiethylamine 0.1-28 ug
N-Nitrosopyrrolidine 0-110 ug
CON’T TABLE OF TOXIC AND TUMORIGENIC
AGENTS OF CIGARETTE SMOKE
PARTICULATE PHASE AMOUNT/CIG.
Total 0.1-40 mg
Nicotine 0.06-2.3 mg
Toluene 108 ug
Phenol 20-150 ug
Catechol 40-2880 ug
Stigmasterol 53 ug
Total phytosterols 130 ug
Naphthalene 2.8 ug
1-Methylnaphthalene 1.2 ug
2-Methylnaphthalene 1.0 ug
CON’T TABLE OF TOXIC AND TUMORIGENIC
AGENTS OF CIGARETTE SMOKE
PARTICULATE PHASE AMOUNT/CIG.
Phenantracene 2-80 ug
Benz(a)anthracene 10-70 ug
Pyrene 15-90 ug
Benzo(a)pyrene 8-40 ug
Quinoline 1.7 ug
Methyquinoline 6.7 ug
Harmane 1.1-3.1 ug
Norharmane 3.2-8.1 ug
Aniline 100-1200 ug
o-Toluidine 32 ug
CON’T TABLE OF TOXIC AND TUMORIGENIC
AGENTS OF CIGARETTE SMOKE
PARTICULATE PHASE AMOUNT/CIG.
1-Naphthylamine 1-22 ug
2-Naphthylamine 4.3-27 ug
4-Aminobiphenyl 2.4-4.6 ug
N’-Nitrosonornicotine 0.2-3.7 ug
NNK 0.12-0.44 ug
N’-Nitrosoanatabine 0.15-4.6 ug
N-Nitrosodiethanolamine 0-10 ug
SMOKER’S LUNG
SMOKER’S LUNG
Increase in lung
temperature to 98.6 F
CONGESTION
IRRITATION
SPASM
MUCO-CILIARY FUNCTIONS
Controlled by serotonin, ACH &
Kinins
Beat synch at 1000-1,300
strokes/min.
Pushes particulate substances
Out at 10-13 mm/min.
SMOKING INDUCES
CILIOSTASIS
Ciliary clearance to 3 mm/min.
Mucus secretion gland
hypertrophy narrowed airways
pathogenesis of chronic
bronchitis
CIGARETTE SMOKE
AND ALVEOLUS
Diffusion time of oxygen
Surfactant is denatured
alveolus hypoventilate and
collapse
lining cells disintegrate
SMOKE TARS
Slow rate of dissolution in
lung fluid which leads to:
Cumulative deposition in the
lungs, macrophages,
phagocytes, oral cavity, gums
and teeth
CELLULAR CHANGES
1. Cell mitochondria are destroyed
O2 delivery and utilization
2. Aryl hydrocarbon hydroxylase
level 6x more than normal
(converts polyaromatic
hydrocarbon to carcinogenic
metabolites)
CON’T CELLULAR CHANGES
3. Cancer surveillance vs. tumor
cells due to abnormal protein &
RNA synthesis
4. Oxidants can induce DNA
single strand breaks (Japan
Studies)
CONSISTENT EFFECTS OF
SMOKING
Peripheral vasoconstriction for 1 hr.
Release of adrenalin, N-A
catecholamines HR, BP, sugar
and fats
Platelet aggregation
CON’T CONSISTENT EFFECTS OF
SMOKING
lecithin cholesterol
deposition
Platelet CO hypoxia (200-
250x more affinity to HB)
GENETIC FACTORS
Chromosome 3 deletion of
short arm due to excess
radiation exposure loss
of cell growth control
CANCER
CIGARETTE ASH
Radioactive content of 0.09
pci from:
POLONIUM 210
THORIUM 228
RADON
MORTALITY FROM VARIOUS
DISEASES DUE TO CIGARETTE
SMOKING (434,200 DEATHS; U.S., 1998)
20% 2%
CVS DISEASES
43%
CA
COPD
INFANT DEATHS
35%
LUNG CANCER
LUNG CANCER
LUNG CANCER
LUNG CANCER
LUNG CANCER
CHIYEN, P.H. STUDY
8,005 smokers 22 yrs
Cancers in 1,389 (17.3%)
DR. MARGARET SPITZ
(M.D. ANDERSEN)
Identified a genetic background
among smokers who develop CA
in 30%
Gene is seen in 10% of general
population
OTHER CANCERS CAUSED BY
SMOKING:
Laryngeal CA
Oral CA
Nasopharyngeal CA
Bladder CA
Prostatic CA
Esophagus and Stomach CA
Pancreatic CA
Colorectal CA
Renal CA
Leukemia and Cervical CA
LUNG CANCER
ARTERIOSCLEROSIS:
LEADING CAUSE OF
HEART ATTACKS
CORONARY HEART DISEASE AND
SMOKING
Acute & chronic myocardial changes
Myocardial Ischemia due to coronary
spasm or platelet aggregation and
adhesiveness
Lowered threshold for Dysrhythmia
(esp. vent. fibrillation)
LDL cholesterol or HDL
cholesterol
OTHER SMOKING EFFECTS ON
THE HEART
Greater risk of MI, recurrent
heart attack and sudden death
2-4x increase, incidence of CHD
2-4x greater risk of sudden death
SMOKING AND PERIPHERAL
VASCULAR DISEASE
More than 90% of amputees have
smoked at least 20 cig./day
Continuing smoking have higher
complication rate
OTHER EFFECTS OF SMOKING
Penile arteries constrict
slower time for erection
Impotence
CHRONIC BRONCHITIS
EMPHYSEMA
EMPHYSEMA
THE FEMALE SMOKER
Reach menopause
2-3 years earlier
than non-smokers
Lower levels of
Estrogen and are
more susceptible to
Osteoporosis
CON’T THE FEMALE SMOKER
Inc. risk of Ischemic heart disease
Inc. risk of heart attack and stroke if they
are on pill
Inc. risk of Lung CA
Inc. risk of CA’s of the Pancreas, Bladder
and Larynx
Inc. risk of chronic bronchitis and
emphysema
SMOKING AND
CERVICAL CANCER
Female smokers are 3x more
likely to develop CERVICAL
CANCER
FERTILITY AND
SMOKING
Female smokers are 2-3x
more likely to be INFERTILE
PREGNANCY AND
SMOKING
Increased Risk of Complications:
Bleeding Tendencies
Spontaneous Abortions
Stillbirths
Placenta Previa
Abrupcio Placenta
Premature Rupture of Membranes
THE PASSIVE SMOKING CHILD
Inc. risk of sudden infant death syndrome or crib death
2x rate of serious respiratory infection
2x likelihood of developing asthma
5x increased frequency of developing allergic symptoms
Inc. susceptibility to deafness and other ear, nose &
throat problems
PATHOPHYSIOLOGY
OF NICOTINE
ADDICTION &
WITHDRAWAL
DEF’N: ADDICTION
State of being given up to a habit
A brain disease w/ permanent change in the brain’s chemistry
& physiology (Dr. Alen Leshner)
A disorder of the brain similar to other terms of mental illness
(Dr. Nora Volkow)
NICOTINE
A tertiary amine w/ pyridine &
pyrrolidine rings
The addictive major alkaloid
NICOTINE
6-8x more addictive than heroin
83% of cigarette smokers smoke
daily, only 10% of heroin users are
daily users
NICOTINE
A lethal poison w/c causes
intoxication to 1st-time users, to
some leaf harvesters & to children
NICOTINE ABSORPTION
Primarily in the lungs,
mucosa of the mouth, nose
& GIT
NICOTINE MOLECULE
0.32-0.40 micron – in particulate
phase of mainstream smoke
0.10-0.14 micron – vapor phase
of sidestream smoke, therefore,
easier to absorb
NICOTINE DELIVERY
3 mg – 8.4 mg per cigarette
4.5 – 133 mg per chewed
25% Brain
75% Body tissues
DRUG ADDICTION =
DRUG DEPENDENCE
Repetitive, compulsive use
driven by strong, irresistible
urges
NICOTINE blood stream
brain euphoric effects
reward maintained self-
administration
NICOTINE EFFECTS
THAT PROMOTE DEPENDENCY:
better performance on some
cognitive tasks
stress, depression
smokers weigh less (7 lbs)
NICOTINE EFFECTS
LOW DOSE – CV effects. CNS activating
chemoreceptors or direct effect on brain stem
sympathetic effect (BP, HR)
HIGH DOSE – acts on PNS w/ ganglionic
stimulation release of catecholamines
hypotension, HR, cold skin
NICOTINE BLOOD LEVEL
lasts 24 hours
8 am first smoke 3 mg/ml
NOON 35 mg/ml
NIGHT 2 mg/ml in AM
INHALED NICOTINE
PULMONARY CIRCULATION
Brain in 7-7.5 sec.
Systemic in 9 sec.
SMOKING ATTRIBUTABLE
DEATHS
CVS diseases – 43%
CA – 35%
COPD – 20%
Infant Deaths – 2%
HOW WE GET
ADDICTED
MODALITIES for BRAIN
STUDIES
(EEG, MRI-scans, POSITRON EMIS.TOM.SONO./PETS,
NEURO-BIO-PHARMACOLOGICAL ASSESS.)
Showed that NICOTINE induces
specific brain circuiting events
encoded in the brain ADDICTION
NICOTINE PLEASURE AREAS
posterior part of the brain
NICOTINE ADDICTION AREAS
inferior part of the frontal lobe
NICOTINE PATHWAY
SMOKES trillions of
NICOTINE molecules blood
stream lungs brain (7 mins.)
chem. & elec. Impulses
binds w/ specific nicotine
receptors
NICOTINE RECEPTORS
located in:
INTERPEDUNCULAR &
VESTIBULAR NUCLEI
in brain stem
BINDING takes place in the
SYNAPSES between neurons
w/ ACETYLCHOLINE
(CHOLINERGIC RECEPTORS)
NEUROTRANSMITTERS –
RELEASED CONSEQUENTLY
Beta-endorphins = calm/sedate smoker
Glutamate – w/ glucose generates nerve
cell energy activity
ACH – hastens neuron to neuron
transfer temporary sharpening of
intellectual performance
DOPAMINE fr. Ventral
tegmental areas n.
accumbens; amygdala; frontal
cortex
High euphoric phase
DOPAMINE RELEASE
triggers pleasurable events
and elation
MASTER MOLECULE OF
ADDICTION
FATE OF DOPAMINE
RELEASE
reabsorbed and passes to next
neuron
or
broken down by MAO
enzymes
OTHER SUBSTANCES RELEASED
1. B-endorphins – anxiety & tension
2. Serotonin – mood modulation, appetite
suppression
3. Vasopressin – temporary memory
improvement
4. ACH – arousal & cognitive enhancement
5. Noradrenalin – arousal, appetite
suppression
6. Dopamine – pleasure, appetite
suppression
NICOTINE LEVEL
brain activity with
withdrawal and craving
WITHDRAWAL SYNDROME
Craving Headache
Irritability Drowsiness
Restlessness GI dist.
Anxiety
Blunting of
Lossof performance
Concentration
level
THANK YOU FOR YOUR
ATTENTION
