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Health

Effects of
JOY ANNE C. NICODEMUS, MD

SMOKING
Adapted from the
lecture of
Smoking
KILLS
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TABLE of TOXIC and
TUMORIGENIC AGENTS of
CIGARETTE
GAS PHASE SMOKE
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
Toluene108 ug
Phenol 20-150 ug
Catechol 40-2880 ug
Stigmasterol 53 ug
Total phytosterols 130 ug
Naphthalene2.8 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
Methyquinoline6.7 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
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SMOKER’S LUNG
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SMOKER’S LUNG
Increase in lung
Congestion
temperature to 98.6  F
Irritation
Spasm
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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
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)
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LUNG CANCER
LUNG CANCER
LUNG CANCER
LUNG CANCER
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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
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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)
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
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OTHER EFFECTS of
SMOKING
Penile arteries
constrict  slower
time for erection
Impotence
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CHRONIC BRONCHITIS
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EMPHYSEMA
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THE FEMALE SMOKER
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Reach Second level
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menopause 2-3 ● Fourth level

years earlier ● Fifth level

than non-
smokers
Lower levels of
Estrogen and
are more
susceptible to
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
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
Loss of performance
Concentration level
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THANK YOU
FOR YOUR
ATTENTION