okay welcome to neuropsych 4 we're going to go over three topics local anesthetics in a little
more detail than when we first talked about axonal conduction versus synaptic transmission
substances of abuse including alcohol and nicotine
so the two different steps to neuron signal transmission are the targets for medications
the axonal conduction like the local anesthetics the drugs aren't selective
all axons work basically the same there's many adverse effects relative to synaptic transmission
although they can certainly have some and then there are very few medications that
inhibit this transmission in this way on the other side the synaptic transmission drugs like the
selective serotonin reuptake inhibitors that affect serotonin or that serotonin
norepinephrine reuptake inhibitors that affect serotonin and norepinephrine they can be really
selective working on different synapses specific neurotransmitters and most medications work
this way because we want something selective rather than something that is not selective
again the mechanism of action for a local anesthetic is to inhibit sodium
channels it stops the action potential and the neurotransmitter release benzocaine is one example
you can use it over the counter to take care of a toothache and it's an ester type so it would be
more allergenic and a little bit more of a concern if you were going to inject it whereas lidocaine
which you can find over the counter as well a solarcaine is an amide-type that causes less
allergic reactions this is one we prefer we'll talk about lidocaine in a very different use
an injectable use in a minute but in this case when everything's topical there's not really
much of a difference it's just that you wouldn't really want to inject something like benzocaine
there's less of a risk of cns depression with something like this than an inhaled systemic
anesthetic just as a caveat so local anesthetics work on the fast firing neurons and the sensory
neurons are the ones that fire most frequently it eventually inhibits the motor neurons but on
a graph of time to loss sensation we begin with getting rid of the pain then cold
then warmth touch pressure then the motor function a local anesthetic like an epidural
we would inject into the epidural space that surrounds the spinal cord lidocaine bupivacaine
these are often used for this and the spinal injections go even closer to the spinal cord
you can get severe hypotension that's hypo meaning less tension blood pressure so a severe reduction
in blood pressure headaches can occur and then the headaches can be resolved by lying down
so another use for local anesthetics is going to be when we're talking about uh
lidocaine and you're going to the dentist so the local anesthetic can cause a bit of vasodilation
where the vessels open up and that creates really fast absorption in a short duration of action
and when you're going to have a procedure you don't want a short duration of action you want the
dentist to have all the time they need to work on whatever's going on with your teeth
in as long a time as they need so what they can do is is add a vasoconstrictor to counter
these effects it slows absorption lengthens the duration of action up to 100 percent and also
reduces some risk of toxicities epinephrine is commonly added with local anesthetics
the first substance of abuse we'll look at is alcohol
it's been consumed for thousands and thousands of years it's used to be there's a
book that talks about uh this great um kind of uh water really caused a real problem back in the day
in that getting clean drinking water was really tough and one well was affected by a diaper i
think it was that it was in someone's basement and i know this sounds gross but what happened was the
water went through the feces into the well and then there was this great cholera epidemic
but one of the area businesses had no problem with cholera and that business was a brewery and the
workers there would drink during their lunch break and it wasn't the beer that you're thinking of now
it was more like food back then sort of and that was a way to keep drinking water safe because the
alcohol would kill the bacteria but alcohol we're talking about now it's one of the most
commonly abused substances in the us and world 75 percent of US adults consume it regularly
eight percent have an alcohol abuse disorder and three percent of children or adolescents have an
alcohol abuse disorder so it's very widespread what happens with alcohol well if we're doing
it in moderation the effects on the body are a discrete decreased risk of ischemic stroke
coronary artery disease myocardial infarction and heart failure and you
may have heard this that a couple of drinks is protective for your cardiovascular system
however it's very tough because alcohol can be addicting so the misuse effects on the brain
generalize cns depression activates the reward pathway and kind of feeds into it
that you want it over and over again so what happens with certain blood alcohol levels
and I'm not sure anymore but I know that some states have even lowered the 0.08 to even a little
bit lower than that but legal intoxication is where you've got a slowed reaction and the idea is
that if you're drinking alcohol you're more likely to hurt someone else while you're driving a car
and as we go up and we usually hear like 0.08 is the legal legal limit in most states
but as you go up you not only impair motor function but you can go into a coma
and you can actually go into respiratory depression and death so very dangerous in
quantities that exceed that moderation we can have acute renal effects so anti-diuretic
hormone causes the kidneys to resorb water and decreases urinary formation and alcohol inhibits
ADH in the pituitary gland it acts as a diuretic and increases urine formation so when someone's
drinking alcohol sure they're drinking 12 ounces or 24 ounces of liquid but the alcohol itself
is a diuretic and acts as a diuretic and that's why they're urinating it's not necessarily that
they're just drinking all of this water so what are the chronic issues that are going to happen to
the liver first of all we get fatty liver swollen because of fat accumulation this is reversible
hepatitis or a fibrosis where scar tissue forms it's possible to recover but the scar
tissue remains and then cirrhosis is where the connective tissue destroys the liver
cells or the hepatic cells and this is irreversible there's a couple of different
issues that come along with this first of all there's Wernicke's encephalopathy where you have
these involuntary eye movements mental changes and ataxia this is an issue of thiamin deficiency
corsicoff psychosis is a chronic memory disorder brain lesions formed
because of the lack of thiamine
Wernicke's encephalopathy usually goes away with thiamin administration course to cost psychosis
occurs in 85 percent of warnicky patients that survive and that unfortunately is permanent
another issue is pregnancy so fetal alcohol syndrome alcohol is teratogenic it's a leading
cause of mental retardation and congenital malformation in the united states it can cause
certain abnormalities including craniofacial malformations growth restrictions
neurodevelopmental irregularities and withdrawal symptoms can be pretty severe as well so
the day since last drink on the bottom have it at 2 4 6 8 and then this very long
30 to 90 days but if you don't treat it it can cause
ultimately death if you have tachycardia hypertension fever tremor delirium agitation
seizures those things can be deadly hallucinations are possible around the second to sixth day
and then anxiety insomnia tremors nausea and anorexia and you can see that if
someone doesn't get alcohol and these are the things that are
in the future for them why they would just continue to drink continue to drink not only for
the pleasure of it but to avoid this withdrawal syndrome there are three primary medications that
you'll see with someone that has a diagnosis of alcoholism naltrexone vivitrol it inhibits the mu
and that little u or little cursive u is a mu in greek so the mu-opioid receptor
and the euphoria so the euphoria isn't there disulfiram or ant abuse literally anti-abuse
creates incomplete alcohol breakdown building up acetaldehyde and it causes flushing and headache
and severe nausea and vomiting but the thing with this is that it's patient can just say
well I'm not going to take these pills and then I won't feel this bad effect and then the last
one is acamprosate or Camprel this binds to the same sites and as alcohol and the CNS
and it prevents the uncomfortable feelings from abstinence so three different ways now
that we can attack this alcoholism but again it's a very very very difficult thing to get away from
the second substance of abuse we'll talk about is nicotine and as with alcohol it's prevalent
substance with the most people addicted to it around the world it's the greatest cause
of premature deaths and preventable illness in the US and it's delivered via cigarettes
so electronic cigarettes cigars chewing tobaccos many different ways that someone can get nicotine
and it only takes eight seconds for 90 to 98 of nicotine to be absorbed by the lungs and
bind to receptors in the CNS and I'm gonna if you're watching uh rather than listening
i'm gonna show you an animation that is in real time that is eight seconds worth so
that's it and then you know you could do the one one thousand two one thousand three one
thousand and so forth and see just how quickly it goes into the lungs and then into the brain
so nicotine is actually a mixed agonist antagonist and if you have a very low dose
it's very activating to the nicotine receptor and there are cardiovascular gi and central nervous
system effects if you have a very high dose it actually blocks the nicotinic receptor action
and that's an acute poisoning so nicotine is more complex than just something that
makes you feel good depending on the dose it can have very different effects so the gi effects we
begin by activating the nicotinic receptors in the parasympathetic rest and digest system this
activation causes increased acid secretion and GI motility and can promote vomiting so when
you see someone has an ulcer and you see that the person's not supposed to smoke this is why
the second part is it activates nicotinic receptors in the sympathetic system the
fight-or-flight response so norepinephrine epinephrine are released and we see this
increased heart rate constricted blood vessels and increased ventricular contraction force
so what do we do to stop smoking what are the options and there are a lot of them
so there are five FDA approved otc dosage forms over the counter dosage forms to help stop smoking
one a chewing gum two a lozenge three an inhaler four a nasal spray and five a transdermal patch
so for the gum, the gum must be chewed for nicotine release
and you chew and park in between the gum and cheeks for 30 minutes then repeat so some of the
drug reactions are throat and mouth soreness kind of aching jaw muscles get hiccups get belching
a little bit of an uncomfortable situation with those but I've heard success stories from
all five different forms it really is personal to the person and kind of deciding what it is
the best way and what would do the best job of replacing not only the nicotine itself but the
the action of smoking I used to have a teacher who would hold their chalk as if they had a cigarette
in their hand and you could just see that the the first thing that they were going to do after
you know they got out of class was replace that chalk with a cigarette so it was it is
there's mental components as well as on the physical components that go along with the actual
activation nicotine susception nicotine cessation so there are two FDA approved medications for
smoking cessation the story behind the first one which is propion sr bupropion has another name
called wellbutrin and it first came out as an atypical antidepressant and what people found
was that while they were getting treated for depression they just really didn't have much of
an urge to smoke and the manufacturer said that's great let's change the brand name from wellbutrin
which was for depression let's repackage it as something that's going to help someone with
smoking and they called it zyban to ban smoking now the issue with bupropion which
we'll talk about in a second is that there can be some risks with seizures on the other end
there's varenicline which is brand Chantix and has great results but there can certainly be some
side effects with that which i'll talk about in a second so these are the two choices that we have
bupropion sustained-release brand Zyban it's the only sr formulation approved for smoking
cessation it's again an atypical antidepressant we're not exactly sure how it works so it doesn't
fit neatly into ssri or snri and things like that it decreased the urge to smoke as these
depressants were taking the medication and it reduces withdrawal symptoms so
the anxiety the irritability all those things that people have as they try to stop smoking
adverse drug reactions that can come along with it you have some insomnia
seems counterintuitive but some agitation as well dry mouth and headache here's the big caveat
though it lowers seizure threshold don't use with a history of seizures what that means is so
there's a certain threshold that something has to happen in the brain for someone to have a seizure
this drug would make it easier for that seizure to happen in those with a history of seizures
the other drug is varenicline or chantix and this is a partial nicotinic receptor agonist
it prevents withdrawal symptoms and it blocks that nicotine reward pathway it's the
most effective medication for smoking cessation i personally have heard people that have stopped in
a few days and the issue that they had were some of the side effects so nausea insomnia
very abnormal dreams very vivid dreams headache and skin rash and the adverse drug reaction for
nausea is dose dependent so maybe almost a third maybe a little more two-fifths can experience
that nausea but the more that someone has to take the more that nausea would be prevalent