nicotine, caffeine, kratom pt 1

vaping

originally developed to help smokers quiz

major difference in the way nictoine is delivered

burning cigarettes

reaches temp of 900 degrees C which causes combustion and could lead to carcinogenic chemicals

vaping does not involve

combustion- heats the ingredients into aerosol aka vapor

dramatically reduces the release of harmful chemicals (at least the thought)

nictoine pulmonary effects

cardio effects

vaping

bad because it results in the inhalation of heavy metal

zyn pouch

one zyn pouch generally has 3mg-6mg and it considered to have similar nictoine impact to roughly 0.5 to 2 cigarettes

cigarette contains 10 to 12 mg of nicotine but only 1 to 2 mg is usually inhaled

nicotine

alkaloid produced in the roots and concentrated in the leaves as a potent antiherbivore

stimulant effects are felt w/I 7-10 seconds

regular e-cigarette users

Average time course of plasma nicotine concentrations after smoking tobacco cigarettes or vaping JUULs or other brands of e-cigarette

• Peak plasma nicotine concentrations were related to nicotine concentration of e-liquid

nicotine is metabolized to

cotinine by cyp2a6 bases for biomarker for nicotine exposer

half life of nicotine

2 hours

half life of cotinine

20 hrs

• active metabolite and activates nACHrs at much lower potency compared to nicotine

cyp2a6 expressed is increased by

estrogen

faster nicotine metabolism in women than in men • Menthol inhibits CYP2A6 activity ▪ slower nicotine conversion to cotinine when smoking mentholated vs non-mentholated cigarettes

low cyp2a6 activity

educed nicotine metabolism • less likely to become smokers • Slow breakdown of nicotine is protective against smoking

nictoine activates

nicotinic cholinergic receptors (nAChRs)

nACHRs

a4b2 receptors. expressed in the DA neurons of the VTA

KO a4 or b2 neurons

do not self adminster nicotine

high doses of nicotine

persistent activation of nictonic receptors leading to continuous depolarization of the post synaptic cellc ausing depolarization block

depolarization block

cell cannot fire again until the nicotine is removed

bisphasic effects

begins with stimulation turns to blockade

effects of nicotine on smokers

produces a calm or relaxed state • partly as relief from nicotine withdrawal symptoms

nicotine withdrawal

Restlessness, irritability, increased appetite, insomnia, difficulty concentrating

effects on nonsmokers

heightened tension or arousal, light-headedness, dizziness, and nausea ▪ Tolerance develops with repeated use • Receptor desensitization

animal studies on nicotine

nicotine enhances working memory and attention

Rats given nicotine sow improvement on the 5CSRTT of attetion

improved performance with acute or chronic nicotine administration

poorer performance during withdrawal from chronic nicotine

non smokers given nicotine show enhanced performance over cognitive and motor tasks

nACHrs and attentional performance

MLA which is a alpha7antagonist blocks nictoine on omission of errors and there was an increase in errors

alpha 7 agonist

improve cognitive performance

nicotine enhancement of attention in low attention participants

increased stimulus of attention

nicotine enhancement of attention in high attention participants

no change

nicotine and VTA

doubles the firing rate of VTA DA neurons and enhanced DA release in NAcc

Tobacco smoke stimulates

DA neurons

mecamylamine

nACHR antagonist blocks the effects of tobacco smoke

tobacco smoke inhibits

MAO-A and MAOB in brain and other organs

MAOA and MAOB

important for the degradation of monoamines contributing the reinforcing effects of smoking.

nicotonic receptors

abundant in the adrenal medulla and on the autonomic ganglia

smoking activates both

sympathetic and parasympathetic systems and adrenal medulla

parasympathetic activation due to nicotine

most pronounced effects in stomach increases HCL and increases bowel contractility

overall increase in digestion

evident in weight loss

sympathetic activation of nicotine

tachycardia, elevated blood pressure

adrenal medulla

catecholamine secretion

accidental nicotine poisoning

swallowing

farmworkers in contact wit tobacco in field

insectides that contain nicotine

symptoms of nicotine poisoning

nausea, excessive salivation, vomiting, diarrhea, mental confusion, cold sweat ▪ Untreated fatal dose: respiratory failure due to depolarization block of diaphragm

aversive effects of nicotine is due to what receptor

a5nACH4 subunit

a5 nACHRs

α5-nAChRs are highly expressed in the interpeduncular nucleus, where they are activated by cholinergic input from the medial habenula

a5 nACHRs KO vs WT

•KO mice administer successively greater amounts of nicotine as the dose per infusion increases

•WT mice plateau at a relatively low level of intake because of the aversive effects of nicotine at higher doses

agonist of a5nACHR

effective treatment of nicotine use because it increase aversive effects

antagonist of a5nACR

reward of nicotine increases

acute tolerance to nicotine

•Cigarette smokers undergo acute tolerance over the course of the day

•related to desensitization of nicotinic receptors

• spikes induced by ACh application

• Desensitization of DA neurons to continuous exposure

• Absence of nicotine leads to resentization