Nicotine and Caffeine

Chapters 10 and 11

March 1, 2017
Tobacco Use Through History
Tobacco use originated among the original inhabitants of North and
South America

Its was introduced to Europe and the rest of the world from the first
voyage of Christopher Columbus.

1559: The year when historians mark tobacco to have been

officially introduced into Europe.
Snuffing and Chewing
Initially Europeans used tobacco in the form of pipe smoking.
Spanish explorers:
Ground a mixture of tobacco into a fine powder (snuff)
Placed or sniffed a pinch of it in the nose, and exhaled it with a sneeze
By the 1700s:
Snuffing overtook smoking as the dominant form of tobacco use.
 Forms of Tobacco
Form influences absorption

Orally - snuff, chewing tobacco, or gum

Smoke - cigarettes, cigars

Smokeless - vapour

Straight nicotine - e cigarets

Smokeless Tobacco
Smokeless tobacco is ingested by absorption through the membranes of the mouth
Rather than by inhalation of smoke into the lungs
 Forms of Tobacco:
Cigarettes: Flue-cured tobacco makes acidic
smoke that reduces absorption from
mouth, so nicotine must be inhaled to
lungs where pH has no effect on
absorption.

Nicotine is suspended in cigarette smoke

in form of minute particles (tars); and is
quickly absorbed into bloodstream from
lungs.

Pipe and cigar tobacco are air-cured; makes

alkaline smoke so nicotine is absorbed
from the mouth and does not need to be
inhaled.
 Whats in Tobacco?

The principal ingredients consumed during the smoking of tobacco are:

1. Nicotine
2. Tar
3. Carbon monoxide

The smoker inhales smoke in the form of:

a) Mainstream smoke (through the cigarette itself)
b) Sidestream smoke (released from the cigarette tip into the air)

otine
e primary psychoactive drug in tobacco products
otine is a toxic, dependence-producing psychoactive drug found exclusively in tobac
Nicotine - Pharmacokinetics

✤ Nicotine - 1 of ~ 4000 chemicals isolated from tobacco

smoke

✤ Typical cigarette contains 6 to 11mg of nicotine, no

more than 1 to 3 mg actually reaches the smokers
bloodstream

✤ Amount of nicotine absorbed also depends on the

smokers behaviour (number of puffs, length of each
puff)
 Cigarette smoking - Note:

tte; 30 cigarettes per day yields 300 “hits” of nicotine, whic

erally strongest when there is a short time interval betwee
Tobacco - Toxicity

Lethal dose = ~60 mg (40 mg has been deadly).

Symptoms: Abdominal pain, nausea, vomiting, diarrhea, headaches,
decrease in blood pressure, death from suppression of breathing.

Absorbed from every site on, or in, the body.

Nicotine: Mechanism
of Action

✤ Recall the neurotransmitter

Acetylcholine

✤ Receptor subtypes: each

subtype have additional Allow positive ions (Na+, Ca2+,)
variability (alpha, beta) to enter the cell

✤ 1. muscarinic Found on different kinds of neurons

DA, NE, Ach, GABA
✤ 2. nicotinic (ionotropic)
Acetylcholine

✤ Synthesized in the basal forebrain and projects to the basal ganglia

✤ hippocampus - memory

✤ amygdala - emotion

✤ cortex - executive function

Alzheimers - characterizes by
loss of cholinergic neurons

Suggests??
Nicotinic Acetylcholine Receptors

✤ Two general types:

✤ 1. Neuronal Type - allow Na+ Ca2+ entry into

neurons…..implications?

✤ 2. Neuromuscular junction Type - PNS interacts

with muscle tissues (which also fire action
potentials - muscle contracts)
 Nicotine Works at the Synapse
primary effect of nicotine is to stimulate CNS receptors that are sensitive to acetylch

Why differences between low and

high chronic doses?

- desensitization of receptors

Leads to cellular adaptive

tolerance - chronic smokers have
higher numbers of nAchRs
Cellular Adaptive
Tolerance

✤ Upregulation of nAChrs in
prefrontal cortex via In situ
hybridization

✤ a) non smoker

✤ b) smoker

✤ c) non specific binding

(smoker)
 Tobacco
High comorbidity of cigarette use in depression and
schizophrenia. In the US 70% of all cigarettes smoked are
by people with a diagnosis of a psychiatric illness
(Grant et al 2004)

Tobacco contains harmala alkaloids that function to

(antagonize) block MAO - direct antidepressant effect

The increased release of DA also functions to decrease

unwanted side effects of typical antipsychotics used in
schizophrenia
Nicotine - Various Pharmacological
Effects (primarily a periphery list)
Vomiting - initially (area postrema in brainstem) this becomes tolerant
Fluid retention - stimulates hypothalamus to produce antidiuretic hormone
Relaxation - decreases input from muscles
Cardiovascular - increases HR, BP, and contractility; but CO2 decreases oxygen
carrying capacity to cells
Faster Aging - increases contractility of blood vessels in skin - decreasing O2
Laxative - Inhibits Stomach secretions, stimulates bowel (laxative)
May increase metabolism of fat
Dulls taste buds
Increases blood sugar
May improve attention/memory but high doses elicit anxiety, nervousness, panic
attack, seizures
May have antidepressant effect - self medication?
Second-hand smoke:
Tobacco smoke that is inhaled by nonsmokers from the burning cigarettes of nearby
smokers
Also referred to as environmental tobacco smoke or sidestream smoke
 Health Consequences of Tobacco Use

onic obstructive pulmonary disease (COPD):

A group of diseases characterized by impaired breathing due to an abnormality in the air passages.
onic bronchitis:
A respiratory disease involving inflammation of bronchial tissue following a build-up of excess mucus in air passages

Emphysema:
An enlargement of air sacs in the lungs and abnormalities in the air sac walls, causing great
difficulty in breathing
Health Consequences of Tobacco Use

Ischemic stroke:
A disease in which there is an interruption of or reduction in blood flow to the brain.

Causes paralysis, sensory loss, cognitive deficits, OR

Causes a combination of neuropsychological effects

Arteriosclerosis:
A disease in which blood flow is restricted because the walls of the arteries harden and
lose elasticity.

Atherosclerosis
A disease in which blood flow is restricted because of build-up of fatty deposits inside
arteries
 Health Consequences of Tobacco Use

Lung Cancer
Carcinomas:
Cancerous tumours or growths
Other Cancers

Leukoplakia:
Small white spots inside the mouth and nasal cavity, indicating precancerous tissue

Erythroplakia:
Small red spots inside the mouth and nasal cavity, indicating precancerous tissue.

Nitrosamines:
A group of carcinogenic compounds found in tobacco
 Health Consequences of Tobacco Use

Special Health Concerns for

Women
Tobacco use presents specific
health risks for women

Women who smoke:

Have a more than 3 times greater risk

of dying from stroke due to brain
hemorrhaging

Have an almost 2 times greater risk of

dying from a heart attack
 Quitting Smoking: The Good News and
the Bad

Good News: Undoing the Damage

arch has clearly shown that when people quit smoking, many health risks diminish ra

fortunately, nicotine dependence is very strong, and it is difficult to quit smoking.

wide range of smoking cessation treatments are available.

bout 50 percent of smokers eventually succeed in quitting on a permanent basis.

Quitting Smoking: The Good News and
the Bad
Treatment of Nicotine Dependence

Behavioural Smoking Cessation Programs

Acupuncture
Hypnosis

Low Nicotine Content Cigarettes - not useful

Nicotine Replacement (gum, patches, nasal sprays, and inhalers
Efforts to Reduce Craving - SSRI’s buproprion, nicotine agonists chantix
 Treatment Methods to Stop Substance
Abuse
ychological Methods for Stopping Substance Abuse
Cognitive Behavioural Methods
Success often depends on the persons willingness to change

es of Change Model - moving from contemplation to action is a critical step in ceasing

Recall the concept of self efficacy - does the person believe they have the ability to quit
Multi-Stage Models

✤ Step by step explanation for how someone develops intention and then carries the intention
through to behaviour

✤ Stages of Change Model

✤ 6 linear stages to help understand change

✤ 1. precontemplation - not thought of changing

✤ 2. contemplation - symptom or feel a need to change

✤ 3. action - visit a physician or take steps to change

✤ 4. maintenance - working to maintain change

✤ 5. termination - 3+ years of changed behaviour classifies as termination

✤ 6. relapse - engaging in changed behaviour

Stages of Change
Model
Stage of Change Description

not thought of change or

Precontemption perceive the need to do so
✤ People who are in a symptom or thought has
different stages Contempation them coinsidering change
show different engage in change behaviour,
psychosocial Action see a Dr
characteristics continue engaging in change
from people in Maintenance behaviour
other stages
if maintenance maintained for 3+ yrs
Termination then in termination
sometimes this happens - not a failure
Relapse can return back to the maintenance
stage
 Treatment Methods to Stop Substance
Abuse
ychological Methods for Stopping Substance Abuse

ognitive Behavioural Methods - Four other techniques

ter personality / risk factors that increase risk of use - reduce social anxiety, impulsivit

negative reinforcement for use - improve coping; stress management (PMR); treat de

3. Increase positive reinforcement for abstinence - monetary or intrinsic

4. Cue exposure - exposure to cues that encourage use, without

engaging in using behaviour (reverse conditioning ‘unlearning’)
 Treatment Methods to Stop Substance
Abuse
ehavioural Methods for Treating Substance Abuse

1. Self monitoring - record personal using behaviour

ts of behaviour; identify and remove cues associated with use ; remove alcohol or ciga

ting Response - performing a behaviour that is incompatible with use; running instead

4. Scheduled Reduction - Can use only at specified intervals that become further apart

avioural Contracting - identifying and stating consequences of use in a contract (publi

 Treatment of Nicotine Dependence -
Nicotine Replacement Therapies
be used as first line of treatment

pproved NRT’s
atch, gum, lozenge, nasal spray, inhaler
be used in combination or with therapy or other pharmacological approaches

Patch - dose can be decreased over time

side effects, skin irritation, nausea, vivid dreams
 Treatment of Nicotine Dependence -
Reduce Cravings
n (Zyban) - for depression (wellbutrin)
sed as 1st line treatment.
se = 300 mg/day.
150 mg/day, 7 days prior to quit date; after 3 to 4 days increase dose to 300 mg (15
cts:
eriness, insomnia and GI symptoms
s
e in those with eating disorders.
 Treatment of Nicotine Dependence -
Reduce Cravings
Varenicline (Chantix)

Approved: May 2006

Unique MOA: Partial agonist at nicotinic ACh receptors

Blocks ability of nicotine to stimulate ACh receptors, thus blocking

activation of DA system (reward system).

Elimination half-life = 24 hours.

Renal route

Possible side effects - reports of increased depression rates and suicidal

ideation clinical trials in progress
Treatment of Nicotine Dependence -
Reduce Cravings
 Treatment of Nicotine Dependence -
Vaccine Therapy Investigational

Qbeta, NicVAX)
r injections

nicotine in blood and bind it to larger molecule, preventing entry to brain a

ficient antibody to bind all nicotine and reduce amount entering brain to subpharma
ot smoke enough to overwhelm amount of antibodies in blood.
s withdrawal symptoms or craving.
repeatedly administered.
 Caffeine - Introduction

psychoactive substance in the world; used daily by ~80 percent of adult U

0 mg) increase alertness, energy, and ability to concentrate.

es, increases gastric secretions and urine output.

ption rarely a health risk.

duce anxiety, restlessness, insomnia and tachycardia in some people

 Caffeine - Active Substances

Caffeine belongs to a family of stimulant compounds called xanthines.

Caffeine is found in:

Coffee, tea, chocolate, many soft drinks, and some medications

Xanthines also include:

Theophylline (found in tea)
Theobromine (in chocolate)

Ferdinand Runge, who called it Kaffeebase (because it was alkaloid, i.e. basic). The
Caffeine - Sources of Coffee
Major Sources of Coffee
The global coffee market is represented by two species of coffee
beans

1. Coffea arabica:
A type of coffee bean native to the Middle East, but now grown
principally in South America.
It is typically referred to simply as arabica.

2. Coffea robusta:

A type of coffee bean grown principally in

Indonesia, Brazil, and Africa.
 Caffeine - Tea

Tea is the world’s oldest caffeine-containing beverage.

Tea drinking originated in China.

Was introduced to Europe by Dutch traders in the early 17 th

century

It became most popular in Britain and Russia.

Tea is a brew of leaves from the Camellia sinensis (tea plant).

Tea contains caffeine and theophylline.
 Caffeine - Chocolate

from cocoa bean pods, which grow directly on the trunk and thick main branches of

According to popular legend:

Chocolate was a gift from the Aztec god Quetzalcoatl to give humans a taste of paradise.

Chocolate originated in pre-Columbian Central America and was introduced into

Europe by the return of Cortés to Spain in 1528.

Its popularity spread across Europe in the 17 th century.
Caffeine - Chocolate

The Xanthine Content in Chocolate

The amounts of xanthines in chocolate are much smaller than in coffee or tea:
A typical 1-ounce (28-gram) piece of milk chocolate
Contains about 6–8 mg of caffeine
Contains about 40 mg of theobromine
 Caffeine - Soft Drinks

ld in per capita consumption of soft-drink products, about 170 litres annually (a bit le

sumed by the average Canadian.

 Caffeine - Over the Counter
Medications
Caffeine is sold purely as a stimulant in over-the-counter (OTC) drugs, such as:

Wake-Ups, NoDoz, Vivarin tablets

Pain relievers, cold remedies, diuretics, and weight-control aids

, in particular, has a strong bronchodilating effect and is useful for treating asthmatic
Caffeine - Mechanism of Action
 Caffeine - Mechanism of
Action
Effects of Caffeine on the Synapse
How caffeine works on adenosine receptors:

Normally adenosine binds to metabotropic adenosine

receptors in the brain.
Causes downstream effects within the cell (neuron) that lead to
sedation and drowsiness, and inhibits dopamine release in the
midbrain.

Caffeine acts as an antagonist on these receptors.

Results in
Decreased sedation and drowsiness (stimulation)
Increased dopamine release (reward)
Caffeine - Pharmacokinetics
Caffeine - Dependence
Caffeine - Tolerance
Caffeine - Toxicity
 Caffeine - Behavioural Effects

feine on Behaviour
eduction in fatigue and boredom, as well as a delay in the onset of sleep.
ence that caffeine intake may reduce the risk of the cognitive decline in women, and to a lesser ex

ses: Produce anxiety, restlessness, insomnia and tachycardia in some sensitive peo
 Caffeine - Health Risks?

from moderate consumption of caffeine are not clinically significant, except in certai
cular effects
sis and bone fractures
pment of bone loss among the elderly