smoking Flashcards
what may some of the early stages of lung cancer be?
– persistent cough that gets worse over time
– coughing up blood or increased amounts of mucus
– constant chest pain
– shortness of breath, wheezing or hoarseness
– repeated bouts of pneumonia or bronchitis
– swelling of the neck and face
– appetite loss, weight loss and fatigue
how is smokers cough caused?
Smoke destroys important cleansing layer in the lungs, which in turn causes a build-up of mucus
– result is “smokers’ cough,” an alternative method that the lungs take in an attempt to cleanse themselves
what are the certain mechanisms for neoplasm formation?
mutation- loss, substitution, rearrangement
addition of new genetic material- result of infection viruses
changed gene expression- epigenetic change
what are the 3 main components of cigarette smoke?
benzo[a]pyrene
acrolein
n-nitrosodimethyl amine
what is benzo[a]pyrene?
it is a polycyclic aromatic hydrocarbon
what was the first isolated carcinogen?
benzo[a]pyrene
how are polycyclic aromatics formed?
formed by the incomplete combustion of fossil fuels
how does the CYP oxidation/ hydrolysis affect benzo[a]pyrene?
they produce epoxides
there is a strong electrophiles due to electronegative oxygen atom and strained 3-membered ring system; nucleophilic DNA can react
what effects does DNA adducts have on benzo[a]pyrene?
DNA adducts are bulky
cause local distortions
DNA replication is disrupted with errors caused by mis-reads, deletions,insertions
what do nitrosoamines do?
Nitrosoamines from tobacco smoke known to contribute to lung and bladder cancer
how is N-nitrosodimethyl amine activated?
Activated in vivo to potent alkylating agent
this is done by hydroxylation and activation by CYP enzymes
what adducts are formed from methyl diazonium ion reacting with DNA bases?
– N-7 Guanine adduct
– O-6 Guanine adduct
how is the methyldiazomium ion a carcinogen but also a chemotherapeutic agent?
depends on the amount you give
small amount= carcinogen
large amount= therapeutic agent eg temozolamide
what is the different between N-7 guanine adduct vs 0-6 guanine adduct?
N-7
- major adduct
easily repaired
O-6 adduct
minor adduct
not easily repaired
which is a major cause of mis-match
what is acrolein?
is one of the must abundant, reactive and mutagenic aldehydes in cigarette
smoke
* is found in cigarette smoke at levels up to 1000x higher than those of polycyclic aromatics
what can acrolein react directly with?
can react directly with guanine residues of DNA without being metabolically activated to produce DNA adducts
what is acrolein active towards?
is very reactive towards nucleophiles, including thiol-containing proteins
– cysteine residues
– a causative factor of haemorrhagic cystitis in cyclophosphamide and ifosamide administration
what are the signs and symptoms of exposure to acrolein? what harm could it do?
– material is extremely destructive to tissue of the mucous membranes and upper respiratory tract, eyes, and skin
– cough, shortness of breath, headache, nausea
what are the potential health effects of acrolin?
– inhalation: may be fatal if inhaled; material is extremely destructive to
the tissue of the mucous membranes and upper respiratory tract
– skin: toxic if absorbed through skin; causes skin burns
– eyes: causes eye burns
– ingestion: toxic if swallowed; causes burns
– target organs: liver, cardiovascular system, lungs, eyes, kidney
what would chronic acrolein toxicity look like?
– Genotoxicityin vitro -human : fibroblast and lymphocyte
– DNA damage
why do DNA adducts cause cancer?
During DNA replication the DNA helix is separated by DNA helicase
* A RNA primer can then be added to the separated DNA strand
* Another enzyme, DNA polymerase, adds nucleotides to the template strand
* If a DNA adduct has formed (e.g. N-7 guanine),
DNA polymerase can ‘mis-read’ the sequence
* This may result in a mutation (e.g.guanine
interacting with thymine)
* Accumulation of unrepaired errors can lead to
carcinogenic change
what are the consequences of DNA adducts?
Repair
* Apoptosis
* DNA damage
what DNA damage can smoking cause?
– altered DNA by replication -> mutation
– altered RNA by transcription
– altered protein synthesis by translation
– proliferation leads to carcinogenesi
what is bupropion?
origionally an antidepressant
but can be used to stop smoking
how should bupripion be given?
- Over 18 years old only
- Start 1-2 weeks before target stop date, initially 150 mg OD for 6 days then
150 mg BD. - Max period of treatment is 7-9 weeks
what is varenicline?
Vareniclineis a partial α4β2 nicotinic receptor partial agonist
can be used to stop smoking
how should varenicline be taken?
Start 1-2 weeks before target stop date, initially 0.5 mg OD for 3 days, then
increase to 0.5 mg BD for 4 days, then increase to 1 mg BD for 11 weeks
