Psychopharm Quiz 5 - Nicotine

two families of cholinergic receptors

nicotinic and muscarinic receptors

nicotinic receptors

respond to the agonist nicotine, an alkaloid found in the tobacco plan

Muscarinic Receptors

respond to muscarine, an alkaloid first isolated from fly agaric mushrooms

nicotinic receptors are what kinds of receptors?

ionotropic

When Ach binds to nicotinic receptors

the channel opens and Na+ and Ca2+ enter the neuron or muscle cell, which depolarizes the cell membrane

Nicotinic receptors mediate fast excitatory responses in both

CNS and PNS

ionotropic receptors can exist in three states

closed, open, desensitized

desensitized receptor

pore is closed and cannot be opened while in the desensitized state

prolonged exposure to agonist enhances

rate of conversion to desensitized state

Only after a desensitized nicotinic receptor spontaneously undergoes re-sensitization

is it capable of responding to an agonist

depolarization block

The resting potential of the membrane is lost, and the cell cannot be excited until the agonist is removed and the membrane repolarized

nicotinic receptor distribution in PNS

neuromuscular junctions and ganglia of ANS

nicotinic receptor distribution in CNS

Hippocampus, cerebral cortex, VTA, NAcc, basal ganglia

nicotine is an akaloid

found in tobacco leaves

large-leaf tobacco

originated in South America, where it was domesticated more than 5000 years ago

small-leaf tobacco

is native to eastern North America and the West Indies

Tobacco was first encountered by Europeans when Columbus reached the West Indies

tobacco was quickly taken up by Europeans and in the 1600s, England commercialized tobacco growing in Virginia

Cigarettes began to be used in Europe in the

mid 19th century, with popularity in US exploding over the next 30 years

nicotine popularity was spurred on by

new methods of curing tobacco leaves that improved flavor and by invention of the cigarette machine, which increased production dramatically

e-cig was patented in 2003

A solution of nicotine is heated and vaporized; the resulting aerosol is inhaled by the user

nicotine vaporization step is common to all

ENDS (electronic nicotine delivery systems), with popularity growing in younger people

smoking is a major cause of illness and premature death

WHO estimates over 5 million people worldwide die each year from the direct consequences of tobacco use, and an estimated 600,000 nonsmokers die from exposure to secondhand smoke

tobacco use accounts for 1/3 of all

cancers (stomach, cervix, throat, etc.) and causes 90% of lung cancers

secondhand smoke increases the risk of disease

causes 3,000 lung cancer deaths/year among nonsmokers and contributes to as many as 40,000 deaths related to cardiovascular disease

Exposure to tobacco smoke in the home increases the severity of

asthma for children and is a risk factor for new cases of childhood asthma

ETS exposure has been linked to

SIDS

routes of nicotine administration

- Buccal- Transdermal- Intranasal- Oral Inhalation- Lozenge- Transdermal patch- Nasal spray- Inhaler

A typical cigarette contains 6 to 11 mg of nicotine

though no more than 1 to 3 mg actually reaches the smoker's bloodstream

the amount of nicotine available depends on

smoker's behavior (e.g., number of puffs and length of each puff)

Nicotine enters the smoker's lungs on tiny particles called

tar, a complex mixture of hydrocarbons, some of which are known to be carcinogenic

Tar contributes to the taste and smell of cigarette smoke, and along with nicotine

these sensory qualities contribute to the reinforcing effects of smoking

Nicotine readily passes through the absorbent surface of

the lungs to the bloodstream; in addition to the mouth and nostrils when tobacco is chewed or snorted as snuff

Typical smokers take 10 to 15 puffs per cigarette

each puff delivers nicotine in 7-20 seconds to the brain

PET imaging suggests that nicotine rapidly accumulates

in the brain with each puff

Nicotine content of e-cigarettes varies across a wide range

Only a portion of the nicotine is inhaled; peak plasma nicotine levels vary substantially with nicotine concentration in the cartridge, rate of puffing, and puff duration.

most nicotine is metabolized to

cotinine by liver enzyme P450 2A6

Some people have low CYP2A6 activity and thus

low metabolism; less likely to become smokers and can quit easier

half life of nicotine is

2 hours; with smoking repeatedly throughout the day preventing withdrawal symptoms.

Frequent smoking leads to ever-increasing peak levels of nicotine during the day

since each dose builds on the residual nicotine from the previous one, but tolerance also builds

Nicotine works by activating

nicotinic cholinergic receptors (nAChRs)

nicotine is a direct

agonist

nicotinic cholinergic receptors (nAChRs) are ionotropic receptors

made up of five subunits that conduct Na+ ions across the cell membrane and produce a rapid excitatory response by the postsynaptic cell

High doses of nicotine lead to persistent activation of nAChRs and

continuous depolarization of the cell; cell can't fire until nicotine is removed

if nicotine can't be removed, it results in a biphasic effect that

begins with stimulation of nicotinic cholinergic functions but then turns to a nicotinic receptor block

High-affinity nicotinic receptors in the VTA

stimulates burst firing of DA neurons, increasing DA release in the NAcc