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