Toxicology lec

1. Keep silence…!

2. “In the name of Allah the most
beneficent and merciful”.

3. References:
• Micheal Kosnett, Heavy metal intoxication and chelators;
Bertram G. Katzung, Basic and clinical
pharmacology:11:999-1011;2009
• Cutis D. Klassan,Heavy metals and heavy metal antagonists;
Goodman and Gilmans, Pharmacological basis of
therapeutics; 11;1753-66; 2005.
• Rang and Dale, Chelators, Pharmacology;6;668-75;2009
• Tripathi K.D.,Chelating agents; Essentials to medical
pharmacology; 6;865-68;2009
• R.S. Satoskar, Metal and their antagonists , Pharmacology
and Pharmacotherapeutics;21;1040-48;2009

4. Objectives
In this lecture we will learn about

5. Toxicology
All substances are poisons. There is none
which is not a poison. The right dose
differentiates a poison & a remedy.
- Paracelsus 1532
the father of modern toxicology”

6. History
 Socrates was forced to drink Hemlock (Conium
genus of one of the highly poisonous plant, F:
apiacae) for corrupting the youth of Athens
Cleopatra committed suicide through the bite of an
asp; a poisonous snake
 In 15th Century in Italy, Cesar and Lucrezia Borgia
assassinated many of their political rivals by
poisoning with arsenic, copper and phosphorus
 Lead caused poisoning in hundreds of thousands
from the time of Roman era till 17th and 18th century
as it was used in pottery, cosmetics, paints and in
automobile fuels

7. History
 Mustard Gas and other poisonous gases were used
in many wars started from WW-I in 1914 by
Germans
 Newer versions are Neurotoxins, Sarin (
organophosphorous compound)
Chemical toxicities has caused disasters too, like in
Bhopal, India in 1984 where release of methyl
isocyanate killed many thousands

8. Definitions
• Toxicology – is the science dealing with properties,
actions, toxicity, fatal dose, detection of,
interpretation of the result of toxicological analysis
and treatment of poisons
• Toxin – naturally derived, naturally exposed toxic
chemical
• Toxicant – manmade toxic chemical or of natural
origin but manipulated, concentrated, or dispersed
by humans
• Antidote – medicine given to counteract the
influence of poison or an attack of disease

9.  Forensic Toxicology is the study of the chemical
and physical properties of toxic substances and their
physiological effect on living organisms
 Forensic toxicology deals with the medico-legal
aspects of the harmful effects of chemicals on
human beings
 Clinical toxicology deals with diagnosis and
treatment of human poisoning
Poison is a substance (solid, liquid or gas), which if
introduced in the living body, or brought into contact
with any part thereof, will produce ill health or
death, by its constitutional or local effects or both

10.  Ideal Suicidal Poison:
 Should be cheap and easily available
 Should be tasteless or be of pleasant taste
 Capable of being administered with food materials
 Should be highly toxic and capable of sure shot
death
 Should be capable of producing painless death
 e.g. Opium and Barbiturates, but commonly used
are Organophosphorus compounds and Endrin

11. CLASSIFICATION OF POISONS
CORROSIVES:
Strong Acids:
Mineral / Organic Acids:
Sulphuric acid, Hydrochloric acid & Nitric acid
Organic Acids:
Carbolic acid, Oxalic acid, Acetic acid, etc.
Strong Alkalis:
Hydrates and Carbonates of Na, K, NH4
Metallic Salts:
ZnCl2, FeCl2, CuSO4, AgNO3, KCN, etc.

12. SYSTEMIC POISONS:
Cerebral:
CNS Depressants:
Alcohol, GA, Opioid
analgesics, Hypnotics and
Sedatives.
CNS Stimulants:
Cyclic Antidepressants,
Amphetamine, Caffeine.
Deliriant poisons:
Dhatura, Belladonna,
Hyoscyamus, Cannabis,
Cocaine, etc.
Spinal Poisons:
Nux vomica and Gelsemium
Peripheral poisons:
Conium and Curare.
Cardiovascular:
Aconite, Quinine, Oleander,
Tobacco, HCN.
 Asphyxiants:
An asphyxiant gas is a nontoxic or minimally
toxic gas which reduces or displaces the
normal oxygen concentration in breathing
air.
CO, CO2, H2S

13. Routes of Poison Administration:
 Inhalation:
 Benzene, Xylene, Acetone, Methyl Chloroform, CCl4, CO,
H2S, Methane, Lead, Mercury, Asbestos, etc.
 Injection into blood vessels
 Intradermal, Subcutaneous, Intramuscular Inj.
 Introduction into Stomach
 Introduction into natural orifices
 Rubbing into skin:
 Organic phosphates, Nicotine, Phenol, Mercury, and Hydro
cyanic acid

14. Factors Modifying Poison Actions:
 Quantity:
• Higher the quantity, more severe action
 Form of the Poisonous substance:
• Poison acts most rapidly in gaseous form
and least in liquid form
• When the combination of chemicals is
more soluble, then more is the action
• Alteration of action or efficacy when
mixed with inert substances
 Mode of Administration

15. Factors Modifying Poison Actions:
 Conditions of the body:
Age factor: Poisons have
greater effects at two
extremes of age
Idiosyncrasy: Which is
inherent personal
hypersensitivity
Habit: Effect of certain
poisons decreases with
habituation. It results from
a decreased reaction
between the chemical and
the biological effectors
 State of Health: A healthy
person tolerates better than a
diseased one
 Sleep and Intoxication: Action
of some poisons get delayed if
a person goes to sleep
 Cumulative Action: Those
poisons which are slowly
eliminated from the body, may
gradually accumulate and then
may produce poisonous
symptoms

16. The following group of symptoms are suggestive of
poisoning:
Sudden onset of abdominal pain, nausea, vomiting, diarrhea
and collapse (Arsenic)
Sudden onset of coma with constriction of pupils (Organo-
phosphates)
Sudden onset of convulsions
Sudden onset of delirium with dilated pupils. (Dhatura)
Paralysis of LMN (Lower Motor Neurons) type (Strychnine)
Jaundice and hepato-cellular failure (CCl4)
Oliguria with proteinuria and hematuria
Diagnosis of Poisoning
In these cases, collect:
 Stomach washings (entire)
 Urine (as much as possible)
 10ml of Blood

17. Diagnosis of Poisoning
First, collect all the relevant information from Inquest report and also from the
relative
Postmortem examination may show: External findings:
 STAINS on clothes, marks of vomit or poison
 COLOR CHANGES on affected skin and mucous membrane. (black
color in H2SO4 & HCl, brown in Nitric acid.
STAINING may be Dark brown/yellow in Phosphorus, Cherry red in
CO, Chocolate color in Nitrates, Nitrobenzene etc.
 ODOUR from nose and mouth may be GARLIC like (P, Arsine gas,
Arsenic), SWEETISH (Ethanol, Chloroform), ACRID (Paraldehyde,
Chloral hydrate), ROTTEN EGG (H2S, Mercaptans)
INJECTION MARKS may be detected which may suggest route of
administration.
SKIN may show HYPERKERATOSIS (Chr. Arsenic poisoning),
JAUNDICE (P, KClO4).
VIOLENCE MARKS such as bruise or other injuries if seen, suggests
mode of death from cause other than poisoning.

18. In the Dead [Cont…]
Internal Findings:
 SMELL: Peculiar smell seen in
Cyanide, Alcohol, Phenol,
Chloroform and Camphor
poisoning
 MOUTH & THROAT: To be
examined thoroughly for
evidence of corrosion and
inflammation or staining
 ESOPHAGUS: Marked softening
seen in Corrosive alkalis.
 UPPER RESPIRATORY
TRACT: May show evidence of
volatile poisons
 STOMACH: May show
hyperemia, color changes,
softening, ulcers, perforation, etc.
All the contents should be
emptied in a jar with NaCl and
the stomach preserved for
chemical analysis
 DUODENUM/INTESTINE: Ulceration
beyond pylorus points to natural disease.
Characteristic changes are seen in Hg
poisoning. Normal GI tract rules out
poisoning by Corrosives, Phenols, Hg and
Arsenic compounds
 LIVER: Phosphorus, Chloroform, TNT,
CCl4, etc leads to Necrosis of liver. Fatty
liver is seen in case of As, CCl4,
Mushroom poisoning, P4, etc.
 RESPIRATORY SYSTEM: Corrosive
poisons leads to glottic edema and
congestion
 KIDNEYS: Metallic poisons, Cantharidin
poison leads to degenerative changes. PCT
necrosis is seen with HgCl2, Phenols,
Lysol, CCl4 poisoning
 HEART: Subendocardial hemorrhages in
Left Ventricle are seen in Acute Arsenic
poisoning
 BLADDER / VAGINA / UTERUS: Should
be specially examined in cases of Criminal
abortion

19. General Lines of Treatment [ABCD…]
Airway/Antidote
Breathing
Circulation
Decontamination/Dextrose/Drugs
Removal of unabsorbed poisons:
Inhaled poisons: Fresh air
Injected poisons: Ligature application
Contact poisons: Immediate removal of clothing and washing
thoroughly
Ingested poisons: Gastric Lavage

20. Information resources
• Computerized database: Poisindex is a
computerized CD-ROM database that is
updated quaterly and is a primary source for
poison control centers
• Printed Publications: textbooks, manuals etc
• Internet
• Poison control center (A national poison and drug
information center with a toll-free telephone number (0800-77767)
set up at the Jinnah Postgraduate Medical Centre)

21. Gastrointestinal decontamination
Emesis:
 It is useful within 3 hrs of ingestion
 Done with ipecac syrup(30 ml)
Activated charcoal:
 It is useful within 1 hr of ingestion
 Works by adsorbing poisons
 Dose 50gm(adults), 1 gm/kg (children)
Gastric lavage:
It is useful within 3 hrs of ingestion
Tube used is Boas tube or Nasogastric tube

22. Gastric lavage is continued till the pumped out
washings are colorless. At this point a small amount
of the agent is left out inside the stomach
Contra-indications:
Absolute CI is Corrosive poisoning due to danger of
perforation of stomach. (Exception: Carbolic Acid
poisoning)
Can be used but by taking precautions in:
Convulsant poisons
Comatose patients
Volatile poisons
Hypothermia
Gastrointestinal decontamination

23. Catharsis
It is known to reduce the
transit time in GIT
Two types are
Ionic/saline and
Saccharide cathartics
Ionic/saline cathartics:
Magnesium citrate 4
ml/kg
Sodium sulphate 30 gm.
Saccharide cathartics:
Sorbitol (D - glucitol) 50
ml 0f 70% solution
Whole Bowel Irrigation
Involves the administration
of non-absorbable
polyethyleneglycol which is
instilled at the rate of 2L/hr.
in adults
Indications:
Large ingestion of iron,
lithium, sustained release or
enteric coated drugs
Gastrointestinal decontamination

24. ADMINISTRATION OF
ANTIDOTES
Physical antidotes: They
neutralize poisons by
mechanical action or prevent
their absorption.
Activated Charcoal:
This is a fine, black, odorless
powder
Produced by destructive
distillation of various organic
materials, usually from organic
pulp and then treating at high
temperatures. This process
increases the absorptive capacity
Particles are small but with high
absorptive capacity and it acts
mechanically by adsorbing and
retaining within its pores organic
and some mineral poisons
 Usually given mixed with
water
 Helpful in Barbiturates,
Atropine, Benzodiazipine,
Opiates, Quinine,
Strychnine,
Phenothiazines,
Pyrethrins, Aluminium
Phosphide, etc.
 Less useful in Corrosives,
Heavy metals, Cyanide,
Hydrocarbon and Alcohol
poisons
 Dose: 50 – 100 mg
(Adults) and 15 – 30 mg
(Children)

25. Demulcents:
These are substances which form a protective coating on the
gastric mucous membrane and thus do not permit the poison to
cause any damage
Examples include Milk, Starch, Egg white, Mineral oil, Milk of
Magnesia, etc.
Fats and oils should not be used for fat soluble poisons like,
Kerosene, Phosphorus, OP compounds, Phenol, Acetone, etc.
Bulky Foods:
They act as mechanical antidote to glass powder by
imprisoning the particles within its meshes and thus prevents
damage by the sharp glass particles

26. Physiological Antidotes:
 These are substances which produce exactly the
opposite actions to that of poison
 e.g. atropine in organophosphorus poisoning and
naloxone in morphine poisoning
Chelating agents:
 These agents act by forming stable and soluble
complexes by the inner ring structure which can
combine with the metallic poisons
 e.g. British Anti Lewisite (BAL) and Ethylene diamine
tetra-acetic acid (EDTA)

27. Methods for enhancing elimination of toxins
Urinary alkalization:
This is also known as alkaline diuresis
IV bicarbonate 1 lit. of 1.26% over 3 hrs is given
Potassium levels can fall, so add 20-40 mmol.
potassium to each lit. of IV fluids given
Aim for a Urinary pH of 7.5-8.5
 Indications: poisoning with chlorpropamide,
phenobarbitone, salicylates, phenoxy acetate
herbicides

28.  Extracorporeal
techniques:
Hemodialysis: can be
considered for poisoning with
salicylates,
ethylene glycol, methanol,
ethanol, theophylline &
lithium
Haemoperfusion: can be
considered for poisoning with
theophylline, phenobarbitone
& carbamazepine
 Multiple-dose activated
charcoal: This can increase
elimination of some drugs by
interrupting their enteroenteric
& enterohepatic circulation
 The dose given is 50 gm (1
gm/kg in children) of activated
charcoal every 4 hrs.
 Indications: poisoning with
carbamazepine, dapsone,
quinine, phenobarbitone,
theophylline
Methods for enhancing elimination of toxins
A medical procedure to
remove fluid and waste
products from the blood and
to correct electrolyte
imbalances
The passage of blood through columns
of adsorptive material, such as
activated charcoal, to remove toxic
substances from the blood.

29. Toxicity screening
• Acute toxicity
– administration of progressively larger single doses up to
the lethal dose
– “No-Effect” dose – largest dose at which a specific toxic
effect is NOT seen
– Minimum Lethal Dose – smallest amount of the drug
that can kill a study animal
– LD50 – dose that kills half of the experimental animal
population
• Subacute / chronic toxicity
– administration of multiple doses to detect any adverse
effects

30. Toxicity screening
• Mutagenicity –
– detection of possible ability to induce genetic
alteration (mutation)
• Carcinogenicity –
– detection of possible ability to induce abnormal
clonal uncontrolled proliferation of genetically
altered cells
• Teratogenicity –
– detection of possible deleterious effects on the
developing fetus

31. 1. Available dosage forms
include oral
immediate-release and
sustained-release preparations
as well as parenteral agents.
1. Toxicokinetics
Some agents have
prolonged elimination half-
lives (e.g., heroin,
methadone).

32. Clinical presentation
includes
Respiratory depression and
a Decrease level of
consciousness.
Rare effects include
Hypotension, Bradycardia,
and Pulmonary edema.
Seizures have been reported
in patients with renal
dysfunction in individuals
who are receiving
meperidine owing to the
accumulation of the
metabolite normeperidine.

33. 4. Laboratory data
includes baseline ABGs
and toxicology screens.
5. Treatment
a) Naloxone is given 0.4-2 mg every 5 min up to 10 mg and 0.03-
0.1 mg/kg in pediatric patients.
b) Naloxone has a very short half-life and resedation is a concern in
patients overdosing on long-acting opioids or sustained-release
dosage forms.
c) Nalmefene (Revex) has a half-life of 4-8 hr. Initial dosage s are
0.5 mg/70 kg. A follow-up dose 2-5 min later is 1 mg/70 kg.

34. Cocaine
Available forms:Includes alkaloid obtained from
Erythroxylyn coca.
Toxicokinetics: Cocaine is well absorbed after oral,
inhalational, intranasal, and IV administration. Cocaine is
metabolized in liver and excreted in the urine.
Clinical Presentation :Includes CNS and sympathetic
stimulation e.g hypertension, nausea, vomiting, seizure,
tachycardia). Death may result from respiratory failure,
myocardial infarction, or cardiac arrest.
Laboratory Data: Include cocaine and cocaine
metabolite urine screens.
Treatment: Benzodiazepine for sedation seizure
treatment, Labetalol for hypertension.

35. 1.There are variety of available forms
they are usually pesticides or
chemical warfare agents.
1.Toxicokinetics
Organophosphate are absorbed
through the lungs, skin, GIT, and
conjunctiva.

36. 1.Clinical presentation
includes excessive cholinergic
stimulation.
1.Laboratory data
include red blood cell acetyl
cholinesterase activity.
1.Treatment
a) Decontamination
b) Atropine is given 0.5-2 mg IV to reverse the
pheripheral muscarinic effects.
c) Pralidoxime (2-PAM; Protopam) is given 1g IV over 2
min and repeated in 20 min as needed.

37. 1. Available dosage forms
include liquid, sustained release tablets
and capsules as well as parenteral forms.
2. Toxicokinetics
Well absorbed orally with a Vd of
approx. 0.5 L/kg. Theophylline is hepatically
metabolized and has a half life of 4-8 hr.
Theophylline clearance depends highly on age,
concomitant disease states, and interacting
drugs.
3. Clinical presentation
includes nausea, vomiting, seizures,
and cardiac dysrhythmias. Chronic toxicity
carries a poor prognosis than acute toxicity.

38. Laboratory data
Therapeutic Theophylline
leaves are 5-20 µg/ml. Hyperglycemia
and Hypokalemia are seen with acute
ingestions. Other useful laboratory tests
include serum electrolytes, BUN,
creatinine, hepatic function, and ECG
monitoring.

39. 5.Treatment
includes maintaining an airway and treating seizures
and dysrhythmias as they occur.
Syrup of ipecac not recommended.
repetitive doses to enhance elimination. Whole-
bowel irrigation for massive ingestions (especially with sustained-
release products). Charcoal hemoperfusion is used in unstable
patients who are in status epilepticus. Hemodialysis is used when
hemoperfusion is unavailable.
(e.g., esmolol, brevibloc) are used to treat the
hypotension, tachycardia, and dysrhythmias caused by elevated
cyclic adenosine monophosphate levels.

40. 1.Available dosage forms
include a variety of OTC products:
oral, rectal, and topical.
2. Toxicokinetics
Salicylates are well absorbed after
oral administration. The half-life is 6-12 hr at lower
doses. In overdose situations, the half-life may be
prolonged to more than a 20 hr.

41. Clinical presentation
includes nausea, vomiting,
tinnitus, and malaise (mild toxicity). Lethargy,
convulsions, coma, and metabolic acidosis
appear in more severe overdoses. Potential
complications from therapeutic and toxic
doses include GI bleeding, increased PT,
hepatic toxicity, pancreatitis, and proteinuria.

42. 4.Laboratory data for the following 6-hr post ingestion
levels are;
a) 40-60 mg/dl : tinnitus.
b) 60-95 mg/dl : moderate toxicity.
c) More than p5 mg/dl : severe toxicity.
d) With the presence of acidemia and aciduria, evaluate
ABGs.
e) In addition, laboratory evaluation may show leukocytosis,
thrombocytopenia, increased or decreased serum glucose
and sodium, Hypokalemia, and increased serum BUN,
creatinine, and ketones.

43. 5. Treatment
Repetitive doses of activated charcoal every 6 hr,
with 1 dose of cathartic for patients who ingested > 150
mg/kg. Whole-bowel irrigation for large ingestions.
is given as noted in decontamination section to
enhance Salicylates excretion. This is indicated for levels >
40 mg/dl.
is used for severe intoxications when serum levels
are > 100 mg/dl. This method of decontamination is much
better than repetitive doses of activated charcoal.
replacement is administered as needed.
are used to correct any coagulopathy.

44. Barbiturates poisoning
• Large doses
Intentional (suicide )
Accidental

45. Acute poisoning
• Results in
• Marked respiratory
depression
• Tachycardia
• Decrease body temperature
• Oliguria (decrease urine
production)
• Circulatory collapse
• Renal faliure
• Coma (leads to death )
• Chronic poisoning
• Same signs as in acute
poisoning .
• But effects are more
pronounced when given
to empty stomach.

46. Treatment of barbiturate poisoning
• Maintenance of respiration and
circulation
• Alkalinization of urine
• Eg administration of osmotic diuretic
• In conscious patient – induce emesis
• Gastric lavage with activated charcoal
• Antidote – tacrine

47. Strychnine
• It is very bitter therefore produces increased salivary secretions
when taken orally
• It has been used in mixture meant to increase appetite
• It decreases inhibitory tone of spinal cord (inhibiting glycine)
• It decreases inhibitory effect of various fibers at synapses in spinal
cord
Strychnine poisoning :
Due to strychnine patient goes into convulsions
Convulsions are tetanic type and uncoordinated
Threshold of various stimuli is greatly reduced, therefore all external
stimuli will lead to convulsions such as excessive light, noise and by
touching patient
47

48. Strychnine poisoning :
• Due to simultaneous contraction of
both groups of muscles the body gets
a typical posture and this is called
OPISTHOTONUS
In lower limbs extensors are powerful
therefore
• Legs are stretched
• The muscles at the back of the neck
are also powerful therefore
• Necks goes backwards
• The muscles of trunk and limb region
are contracted and this part gets the
shape of an arch
In upper limbs flexors are more
powerful therefore
• they are flexed on chest
• Jaws are totally closed

49. Strychnine poisoning :
• These convulsions are repeated every 3-4 mins in
between convulsions are decreased
• Person may die due to stoppage of respiration
• These convulsions are very painful and unfortunately
person remains conscious during convulsions
Treatment :
• I/V thiopental Na
• I/V diazepam are used to control convulsions
• Muscle relaxants are also helpful
• The patient must be kept in very dark places, better in
sound proof room

50. Available forms Include gas line antifreeze, windshield washer
Toxicokinetics
Alcohol dehydrogenase converts methanol to formaldehyde, which is then
converted to formic acid
Clinical
Presentation
Stage 1: Euphoria, gregariousness, and muscle weakness for 6-36hr,
depending on the rate of formation of formic acid.
Stage 2: Vomiting, abdominal pain, diarrhoea, dizziness, headache, dyspnoea,
blurred vision, coma, cereberal edema, resp. And cardiac depression & death.
Laboratory
Data
Include severe metabolic acidosis, hyperglycaemia, and hyperamylasemia
Treatment
1. Gastric lavage
2. Folic acid administred at 1mg/kg IV every 4hr for 6 doses increase the
metabolism of formate.
3. Fomepizole
4. Na bicarbonate
5. Hemodialysis
Methanol

51. Available
forms
Include chlordiazepoxide. Diazepam, flurazepam, midazolam, lorazepam,
alprazolam, and triazolam.
Toxicokinetics These drugs are hepatically metabolized
Clinical
Presentation
Include drowsiness, ataxia, and confusion. Fatalities are rare.
Laboratory
Data
Drug level monitoring is not indicated
Treatment
1. Suppportive treatment includes gastric emptying , activated charcoal,
and a cthartic.
2. Flumazenil is given 0.2mg IV over 30 sec. Repeat doses of 0.5mg over
30sec. At 1min interval max. cumulative dose of 5mg.
Benzodiazepines

52. Available forms Include oral and parentral
Toxicokinetics
Digoxin is well absorbed, primarily renally eliminated, and has a half life of 36-
48hr. Its volume of distribution is 7-10L/kg. Equilibration b/w serum level and
myocardial binding requires 6-8hr.
Clinical
Presentation
Includes confusion, anorexia, nausea, and vomiting in mild cases, cardiac
dysrythmias are seen.
Laboratory
Data
Include serum digoxin levels, electrolytes, particularly serum potassium levels
and an ECG.
Treatment
1. Decontamination with activated charcoal is recommended.
2. Suportive therapy includes managing hyperkalemia, or hypokalemia, and
inotropic support is needed.
3. Digoxin specific FAB antibodies (Digibind)
Digoxin

54. Nicotine Forms
• Tobacco-Nicotiana tabacum
– (&Nicotiana rustica)
Smokeable :Cigarette, Pipe, Cigar
• Leaf (Chewing)
• Leaf (Dip)
• Snuff (powdered)
– Transdermal Patch…others

56. Acute Effects
• Classic stimulant effects of arousal (e.g. increased
heart rate and blood pressure, alertness, appetite
suppression)
• Carbon monoxide (in smoked form) reduces oxygen
transport to heart and other organs
• Vasoconstriction
• Can have calming (anxiolytic) effects in some
individuals
• Mild euphoria
• Cognitive enhancements
• Antidepressant effects

57. Chronic Effects: CANCER
• Tobacco use accounts for one-third of all
cancers
– Cancers relating to tobacco include:
• Mouth
• Pharynx
• Larynx
• Esophagus
• Stomach
• Lung
• Cigarette smoking has been linked to about 90
percent of all lung cancer cases
• 430,000 annual deaths are attributed to
cigarette smoking
• Cervix
• Kidney
• Bladder
• Throat
• Pancreas

58. More Chronic Effects
• Emphysema
• Chronic bronchitis
• Stroke
• Vascular disease
• Esophageal reflux
• Heart Disease
– It is estimated that nearly one-fifth
of deaths from heart disease are
attributable to smoking
* Many of these are actually caused by
other chemicals in cigarette smoke or in
smokeless tobacco products
• Secondary smoke also increases
the risk for many diseases
– Secondhand smoke is
estimated to cause
approximately 3,000 lung
cancer deaths per year among
nonsmokers and contributes
to as many as 40,000 deaths
related to cardiovascular
disease
– Exposure to tobacco smoke in
the home increases the
severity of asthma for children
and is a risk factor for new
cases of childhood asthma
– Environmental tobacco smoke
(ETS) exposure has been linked
also with sudden infant death
syndrome

59. Addiction
• Nicotine meets both the psychological and
physiological measures of addiction
– Psychological - People who are addicted to something
will use it compulsively, without regard for its negative
effects on their health or their life
– Physiological - anything that turns on the reward
pathway in the brain is addictive. Because stimulating
this neural circuitry makes you feel so good, you will
continue to do it again and again to get those feelings
back
Recent studies suggest those excitatory
amino acid systems and, in particular, N-
methyl-D-aspartate (NMDA) receptors,
may have an important role in this
phenomenon.

60. Tolerance & Withdrawal
• Mild tolerance to behavioral and cardiovascular effects
• Prolonged Desensitization of nicotinic acetylcholine
receptors (nAChRs), has been proposed as the mechanism of
chronic tolerance to nicotine
• Withdrawal may start after as little as one hour, may last for
as long as several months, can include:
– Craving
– Irritability
– Anxiety
– Dysphoria
– Anger
– Difficulty concentrating
– Restlessness
– Impatience
– Increased appetite, weight gain
– Insomnia

61. Treatment options
• Behavior modification
• Nicotine lozenges
• Nicotine gum
• Nicotine patches
• Nicotine inhaler
• Nicotine nasal spray
• Bupropion SR
• Self-help
• Pharmacotherapy
• Combined strategies

62. “That’s all……….!”