Exam 2: Nicotine and Caffeine Flashcards
Nicotine Administration Route etc.
Plant Alkaloid
Base with pKa 8.5
Inhalation
Buccal
Nasal
Transdermal
Biotransformation of Nicotine
Nicotine (2 hr. 1/2 life)
CytoP450
Cotinine (16 hr. 1/2) life
Oxidation
Risk factors for nicotine addiction
Fast metabolism
Caucasians
females
Is nicotine itself what cause health problems?
No
What creates acetylcholine from acetyl CoA and Choline?
ChAT
Choline
Acetyltransferase
What breaks down acetylcholine from acetyl CoA and Choline?
AChE
Acetylcholinesterase
Cholinergic pathways
Hippocampus: LDT/PPT; lateral dorsal tegmentum/peripeduncular tegmentum
Axon terminals: VTA, ventral tegmental area
Goes back ground to VTA to terminate in cortex/hippocampus
Cholinergic cellbodies in front part project to cortex and hippocampus, but they ___
die in alzheimers
Nicotine acts like
acetylcholine
agonist
Types of nicotine receptors
ionotrophic and metabotrophic
Nicotinic ionotrophic receptors
2x acetylcholine or nicotine molecules binds
Na+ enters
binds betwen alpha4/beta2
Is nicotine an agonist or antagonist? (Tricky)
Both. At first, agonist. But then, antagonist. When clear system, receptor back to desensitized state, then wants nicotine again. Causes dependency
Cholinergic nicotinic receptors
Skeletal muscles, brain neurons, ANS, Adrenal medullary cells
What acetylcholine receptor leads to tremor?
Nicotinic
What predominates in nicotine activation?
Parasym.
has M and N receptors
Nicotine effects on mood (acute)
arousal, alertness, attentive, relaxed
Sympathetic effects of nicotine
respiration, hear rate and bp go up
suppressed appetite
decreased diuresis
Parasympathetic effects of nicotine
increased GI activity
Acute toxic effects of nicotine
dizziness, nausea, vomiting
Other toxic effects of nicotine:
Area postrema Twitches/tremors- high doses Seizures- stimulant Respiratory suppression: blocks contraction of respiratory muscles AND inhibits medullary respiratory centers. Even death
Will nicotine stimulate or inhibit respiration?
Small = stimulate High = repress
Nicotine at Nm (muscles) at high dose
twitch
tremor
paralysis
What is amount for nicotine poisoning?
500 mg (60 mg?) 1 cigarette = 15mg
How does repiratory suppression work at high doses?
1) blocks contraction of respiratory muscles
2) inhibiting medullary respiratory centers
Therapeutic Uses
current: smoking cessation, other diseases under study.
Chronic smoking: Physical withdrawal
Tolerance and withdrawal syndrome.
Irritability, anxiety, distraction, restlessness, insomnia, hunger, weight gain
A4-beta2
(nACh nicotinic receptors) + radio tracers, what happens?
Nicotine displaces radio labelled tracers.
3 puffs = 75% displacement.
When smoking stops and receptors later exposed, hypersensitive and start to experience withdrawal symptoms.
Microdialysis
technique used to measure release of NT from certain brain areas in rodent, insert into rat brain, pump fluid, CSF flushes araea and draw back up, get the NT release in certain region.
Microdialysis of dopamine release
NA pump fluid out, draw it out, look at release in NA.
high Dose = higher dopamine release in NA
Where is the dopamine released?
NA
When tobacco is burned?
1) Carcinogens (benzene, formaldehyde, vinyl chloride)
2) Toxic metals
3) Poisons (ammonia, CO)
Smoking on cardiovascular system
1) Increases demand (heart rate/bp)
2) Reduces oxygen supply to heart (atherosclerosis, CO reduces affinity of hemoglobin for oxygen, impairs pulmonary function (chronic obstructive pulmonary disease)
Emphysema
damage to alveoli, not reversible
Chronic Bronchitis
inflammation of bronchial tubes
Only ___ that try to quit smoking actually quit.
1/5 (20%)
Pharmacotherapy for smoking addiction
Buproprion antidepressant blocks dopamine reuptake
Varenicline partial nicotinic receptor agaonist
Nicrotine replacement to occupy receptors
Caffeine is just
Xanthine with a whole lotta methyl (-CH3)
Caffeine (kinetics):
1) Administration
2) Acid/base?
3) 1/2 life?
Oral
Base
4 hr
Cross BBB
metabolized to paraxanthine, (84%) theobromine, (12%)
theophylline (4%)
Normal doses of caffeine block
adenosine receptors
(A2a), mild dis inhibition. when blocked by methylxanthine
Very high doses of caffeine will do what 3 things?
1) inhibit phosphodiesterase
2) Block GABA-A receptors
3) Increase calcium release
Acute cognitive effects of methylxanthines
arousal, alterness, wakeful, energy
concentration, reaction, dexterity
Acute physiological effects of methylxanthines
decrease blood flow to brain
increased/decreased risk of migraines?
increase respiration
dilated airways
increased gastric secretions
diuresis
Toxic effects of caffeine (500-1000 mg)
Anxiety, irritability, insomnia, fever, flushed
Toxic effects of caffeine >1500 mg
paranoia, delusions, hallucinations, stereotypies
Therapeutic uses of methylxanthines (caffine)
Headache, asthma, sleep apnea, narcolepsy
Caffeine tolerance
increased adenosine receptors
Caffeine dependence
physical: headache, fatigue, craving
Positive reinforcement: weak, increase dopamine in cortex
Why is caffeine associated with lower risks of certain disease?
anti oxidants which are anti inflammatory
