PHAR 300 Lecture Notes - Lecture 14: Mesolimbic Pathway, Bronchus, Trachea
7 Jun 2018
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PHAR300
Nicotine
Nicotine
-found in tobacco leaf and other plants -> easy source to extract the drug
-made by plants as an insecticide (still used like this in some countries, very effective but also
dangerous)
-frequent way of consumption : burning tobacco leaf, nicotine becomes volatile, carried in small
particles in the smoke, inhaled into the lungs and then absorbed
-cigarette : very effective and clever drug delivery system
-when smoke is inhaled -> very rapidly absorbed
through the blood stream, goes to the heart and to
other tissues (brain), nicotine is highly lipid soluble so
it rapidly gets to the brain (7sec from the puff to the
neurons => extremely rapid)
-IV -> same time as cigarette
-not just for nicotine, but for the 4-5 000 other drugs
present in cigarette smoke which are also very harmful
(any biomass that is burnt releases many chemical
compounds)
-harmful compounds are not removed by filters ->
filter removes large particles but nicotine…go strait to
the lungs
-nicotine
-many carcinogens : carbon monoxide impairs
blood ability to transport oxygen to tissue,
ciliotoxins impair ability of our lungs to clear the
various particles and dust we are inhaling
-very toxic on lungs and rest of the body
-dangerous effects
-deaths from cigarettes is extremely high, compared to alcohol (which is the second one),
car crashes… (about 60%)
-statistics : cigarette will kill 600 million people currently alive on planet earth (cancer,
chronic diseases such as cardiovascular diseases…)
-30% of all cancer deaths in Canada are due to smoking
-other side effects in smoking : ciliated cells in the airways die or are abnormal =>
mucocialiary function in the lungs is impaired (the more we smoke, the less the clearance
is in the lungs) -> we cannot get out the stuff we breathe under normal basis either ; normal
individual : most of the dust and smoke will be excreted and only a little will stay ; heavy
smoker : not removed
-lung cancer risk is 10 times greater if we are a smoker ; if asbestos worker + smoke =>
50-90 times greater
-not only lung cancer (which is the most common one) : bladder cancer…
-1/3 cardiovascular deaths (coronary heart diseases) are due to smoking (high blood
pressure, impairment in ability to bring oxygen because cigarette smoke contains CO,
endothelial injury (that line our blood vessels), atherosclerosis, platelet aggregation -> clots
can form in our brain), strokes are occurring to young people as well
-peripheral vascular disease -> people have trouble in walking…
1
-causes vasoconstriction (because of the nicotine) -> blood flow decreases in parts of the
body such as the skin, hair, eye (cataract) and gums
-smoking is one of the 2 causes of wrinkle (with UV)
-20% will die from chronic lung disease (bronchitis and emphysema)
-increased rate of infections (lung infections : influenza, pneumonia…), diabetes
-kills 1/2 of smokers (other ones will have chronic impairments)
-non-smokers (secondhand smoke) -> some smoke is breathed back by the smoker and side
stream smoke (from the other part of the cigarette, smoke goes to the room) contains a higher
concentration of some harmful ingredients because the temperature is different => causes
differential composition from the side stream to the main stream smoke
-heart diseases and cancers can be linked to second hand smoke, as well as problems for the
fetus and new born
-children are also very vulnerable because they have less control to escaping the smoke
-smoking is thus banned, and exposure to nicotine is banned as well in public places
-electronic cigarettes are dangerous as well
-nicotine is poison
Pharmacology of nicotine
-pharmacokinetics
-nicotine is highly lipid soluble -> able to slip to the blood, in the lungs
-other ways of absorbing it : when we inhale cigarette, the nicotine is absorbed from the nose
and mouth as well ; nicotine patches ; if we swallow nicotine : absorbed from the intestine
-weak base, absorption depends on the pH (remember : weak acid : non ionised form in
acidic environment is lipid soluble ; weak base : in basic environment the weak based is non
ionised and lipid soluble) -> if pH is more basic, nicotine will be more lipid soluble and
more readily absorbed
-cigarette production : lower acidity and increase alkalinity to have nicotine in a basic
environment -> non ionised and highly lipid soluble => increases the rate and total
absorption of the nicotine from the mouth, nose and lungs
-no first pass metabolism from the lungs -> goes to the brain right away from the heart
-smoke goes down the trachea, down into the bronchi and to the smaller airways to the
lungs ; surface area of the lungs is enormous for absorption and almost no barrier =>
absorption is very rapid
-nicotine concentration in the blood will depend
on the concentration in the smoke, rises
quickly and then slowly comes down
-smoker controls the drug delivery system ->
control bioavailability by altering the way
they smoke, automatically have to keep the
blood nicotine level as they are used to =>
they thus adjust how they smoke to the
amount of nicotine present in the cigarette
-different blood nicotine concentrations
depending on the way people absorb nicotine
(see graphs)
-absorption via the GI tract is very efficient :
small intestine (basic environment)
-distribution everywhere, quickly gets to the
brain and to all body organs (placenta, fetus,
breast milk)
-things that save a child from dying : lethal
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Document Summary
Found in tobacco leaf and other plants -> easy source to extract the drug. Made by plants as an insecticide (still used like this in some countries, very effective but also dangerous) Frequent way of consumption : burning tobacco leaf, nicotine becomes volatile, carried in small particles in the smoke, inhaled into the lungs and then absorbed. Cigarette : very effective and clever drug delivery system. Not just for nicotine, but for the 4-5 000 other drugs present in cigarette smoke which are also very harmful (any biomass that is burnt releases many chemical compounds) Harmful compounds are not removed by lters -> Lter removes large particles but nicotine go strait to the lungs. Many carcinogens : carbon monoxide impairs blood ability to transport oxygen to tissue, ciliotoxins impair ability of our lungs to clear the various particles and dust we are inhaling. Very toxic on lungs and rest of the body.
