okay welcome to neuro and psych pharmacology 2
going over sedative hypnotics anti-anxiety and ADHD medications
we're going to go over set of hypnotic and anti-anxiety agents first and then
ADHD agents second so let's get started with uh just an overview of the difference between
a sedative is and a hypnotic so a sedative and a synonym for a sedative is an anxiolytic so
to lyse something is to break it in half you might have heard of autolysis where some cell
destroys itself anxiolytic means to lyse or break up anxiety so a sedative is just
meant to reduce anxiety calm the patient as opposed to an hypnotic a hypnotic
helps the patient fall asleep and it may also help the patient stay asleep though some
medications only work to help the patient fall asleep and the reason for that is we want medicine
working for as little time as necessary so if you have something that works late into the night
it may be artificial and the patient may not get good sleep so hypnotic though is something
that's going to help a patient fall asleep and in some cases stay asleep some of the medications
are a sedative some are a hypnotic and others are both so let's look at a specific class of
sedative hypnotics the benzodiazepine and a normal neuron with gamma aminobutyric acid which we call
gaba receptor and the action potential firing normally so we have this receptor we have the
neuron and then that action potential okay so that's what works normally
benzodiazepines bind and activate gaba receptors on neurons the chloride ions enter and then
you need more electrical impulses to fire the action potential and then the signal stops so
what benzodiazepines are meant to do is meant to make it so that gaba can now
make it much harder for this to happen all right so the benzodiazepine comes in the chloride goes
in and then the electrical potential just kind of stays here or the action potential stays here
and doesn't fire down the axon sedative hypnotics so again the benzodiazepines one way to
remember a few of them is to use the calm mnemonic c-a-l-m c for clonazepam a for alprazolam l for
lorazepam and m for midazolam and those are klonopin xanax ativan and versed respectively
so the indications for benzodiazepines are much greater than just sedative-hypnotic just
for sleeping or insomnia they're good for anxiety panic disorder sedation anesthesia
premedication and seizures but in this part we're just talking about insomnia some
of the adverse drug reactions we have are you know certainly, when the person wakes up they may feel a
little bit drowsy or they may get a little even dizzy while they're taking something like this
they may find themselves confused and then cns depression is also a possibility as well
here's a note though benzodiazepine should not be combined with opioids it increases
the risk of cns or respiratory depression and it shouldn't be used long term due to abuse potential
if you are or have to combine them in some way we're going to need to make sure that
the patient has naloxone just in case there's some kind of overdose situation
benzodiazepines po onset time po meaning per o's or by mouth onset time so how long will these oral
tablets take to start working it's quite important to know that if you're going to have someone who's
having a seizure right now we wouldn't give them a tablet to hopefully stop the seizure
in an hour or something like that we would rather use these for maybe there's an event that they're
getting ramped up for maybe there's some kind of presentation it's important to know that it's
going to be almost an hour before the appraisalem or klondazepam work and lorazepam even maybe two
hours so if it's emergent we would use something like midazolam which is iv and works in minutes
but if it's something where we're going to have a situation where the patient's going to experience
anxiety to know that it's going to maybe take an hour or two before it really kicks in
now in terms of insomnia what we really are worried about is that it impairs the
person's daytime activity so some people are sleeping for five hours
and feel fine some people sleep for seven hours and feel fine some people need more
but the benchmark is is it affecting your day how are you feeling throughout the day and if you
can't do the things you normally need to do go to work and those types of things
then that's insomnia so the patient's symptoms are going to drive the individual treatment
if you're just anxious about things and and i don't want to say just but if there's an
anxiety component we would treat that and if it's a sleep component then we would treat that but
individual treatment based on the condition
benzodiazepine-like is actually not a benzodiazepine they're structurally different
but the same mechanism of action they produce only hypnotic effects so they're only going to be used
for sleep but how do we decide between two like s sopa clone which is lunesta or zolpidem which is
ambien so with eso baclone there's no real limit on the duration of use if someone needs it for
six months nine months something like that this is what we would probably turn to where zolpidem
we can only use for three to six months there is a metallic aftertaste and while
uncomfortable it's something that most patients can tolerate but certainly if we don't have to
have something like that it would be nice to use the zolpidem or we wouldn't have to deal with that
and then the adverse drug reactions are similar to benzodiazepines but the advantage
of these is that these are specifically for that sleep state and the hypnotic effects
another form of a sedative hypnotic is a melatonin agonist so again an agonist activates and
melatonin in the brain is a hormone that produces sleep remeltion or rosarem and you can see the rem
like rem cycle at the very end of that or rose rhymes with does that's another easy way to
remember what it's for instead of giving the patient melatonin we're just going to
activate the melatonin receptors as if there was melatonin in there and that will cause drowsiness
there's no abuse potential like the benzodiazepine and benzodiazepine likes this isn't uh scheduled
like the other one so that wouldn't be as big a deal and then there's no limit on the length
of use and the adverse drug reaction is very similar to placebo so if a patient can use
romelteon certainly a good choice patients may try to self-treat and go over the counter before
they ever go to a prescriber and the first generation antihistamine diphenhydramine
does produce drowsiness we usually find it in acetaminophen with diphenhydramine or tylenol pm
the tylenol is there for pain because a lot of times pain will keep someone up at night
but the combination takes care of the pain takes care of the insomnia or tries to at least so
with these though we're going to see adverse drug reactions that are cholinergic or anticholinergic
effects like dry mouth blurry vision constipation which can be quite troubling for the patient and
it only works for a week or two because the body will become tolerant to the drowsiness and you'll
still get the side effects so this is a very short-term solution not a long-term solution
next we'll do the anti-anxiety agents and talk first about what anxiety is
it's an emotional state from a real or perceived danger so
if someone is worried about something it's still going to activate that same fear center
that a real danger would even if it's not going to happen what are some of
the characteristics apprehension and dread and fear and unease deep discomfort deep worry about
what's going to happen in the future is a concern it impairs normal daily functioning so
if the anxiety is a discomfort like you don't want to go up and speak but you do and it's fine
then it's very different then you're not being able to make presentations to keep your job
or something like that possibly cause is serotonin and norepinephrine dysfunction
so when we're talking about how these drugs work if we see that there's serotonin norepinephrine
dysfunction then we know that maybe we could use something like ssris or snris to treat
because if that's the underlying cause and we can talk about it as acute or chronic so
an anxiety where certain instances or certain issues cause the anxiety is acute
versus something chronic where we have something that's a long standing issue they're continuous
continually dealing with anxiety issues maybe obsessive compulsive disorder things like that
so there are five classifications generalized anxiety disorder panic disorder obsessive
compulsive disorder social anxiety disorder and then ptsd or post traumatic stress disorder
something like generalized anxiety disorder we might start with an ssri or snri
it'll take two to three months to see the full benefits but we don't wait that long if in four to
six weeks we really see no response or maybe just a small response we might add a benzodiazepine
or we might add buspirone but this is how we would deal with generalized anxiety disorder
a bit about buspirone or brand Buspar we don't really know how it works it might affect serotonin
it can take up to two weeks to be effective but certainly much quicker than that two to
three months it has to be taken number of times a day which is somewhat difficult for some patients
and we want to be consistent if you take it with food continue to take it of food if you
take it without take it without but that will affect its ability to do its job panic disorder
versus panic attack so a panic attack is an episode of intense unprovoked fear so something
is just terrifying a person and it's very quick in its onset and it just kind of comes on the person
when we call it a panic disorder it's going to be multiple panic attacks that continue to happen
and how do these panic attacks present certainly palpitations or that pounding heartbeat chest pain
shortness of breath sweating chills fear of losing control or fear of death all of these things
can precipitate a panic attack and really really disable the patient to treat something like that
we would use an ssri with a benzodiazepine we would use the benzo for maybe two to four weeks
ssri should have kicked in by then or we can use an snri serotonin norepinephrine reuptake
inhibitor like venlafaxine xr and that might take about 12 weeks to be effective
we'll continue to treat for at least six months and we'll hopefully have fewer relapse rates
obsessive-compulsive disorder we want to watch out for obsession versus compulsion so an
obsession it's a recurring thought that reason cannot remove and so although logically you're
saying i shouldn't be thinking these things you continue to think about them
when you have an action like washing hands or something like that where you can't control that
repetitive act that would be a compulsion so drug treatment we would keep the patient on a selective
serotonin reuptake inhibitor for at least a year social anxiety disorder this is just a fear
of an intense recurrent fear of other scrutiny and a couple treatments we can use if it's
something chronic we could certainly use the SSRIs paroxetine or sertraline but if it's something for
a performance like I'm going to get up on stage in front of someone to speak a benzodiazepine
which might start working after an hour or two or a beta-blocker which can reduce
the heart rate now that can be used for performance only social anxiety disorder
ptsd the patients are continuing to re-experience a traumatic event in their past
and we want to actively avoid reminders of those i remember a student asking if i could remove
all mentions of firearms or guns from my exams because of that PTSD and it was very easy to
do for that student so again trying to avoid reminders and then it's a persistent hyper
arousal state always in that fight or flight-ready to attack mode or ready to defend mode treatments
that we have fluoxetine paroxetine and sertraline as SSRIs or maybe venlafaxine as an SNRI
the ADHD agents we'll first talk a little bit about
what adhd really gets in the way of and then we'll talk about some treatments so in the prefrontal
cortex we have centers for planning and problem solving and short-term memory and behavior there's
more activity in the non-ADHD brain than there is in the ADHD brain and what we want to do is
in some way see if we can't help improve focus and allow them to plan problem solve remember and
improve their behavior
so the animation is just basically saying
this is a lot more activity in the non-adhd brain regarding these four big caveats
with this decreased prefrontal cortex neuronal activity and I know that's a mouthful but we're
just saying that there's less activity with increased dopamine and norepinephrine reuptake
so what we're saying is that the drugs are there in the synapse but we are finishing
up with them too quickly so the medications will release or prevent the reuptake of that dopamine
and norepinephrine but the mechanism is a bit different than ssris and snris just to be clear
a couple of examples methylphenidate which you may know as Ritalin or Concerta
it's a 50 50 mix of Levo and Dextro isomers and then there's dexmethylphenidate which is
Focalin and you can see the word concentrate and Concerta for methylphenidate and focus in Focalin
Focalin is really just the dextro isomer or the right-handed isomer of the Levo and
dextro mix and so is it necessarily that much better maybe maybe not but that was the idea
we have availability as immediate release and extended release versions
because depending on when you are in the year for example if someone's using something like ritalin
for school we wouldn't really want it to last too long if they just need help during school
or for their school work which they do right after school so we might move to an immediate release if
we find that they're having some of these adverse drug reactions one that's not on here is insomnia
that can happen if we give it too late in the day and we'll talk about the next slide
but adverse drug reactions we can expect weight loss maybe gross suppression increased
heart rate and blood pressure psychosis which looks very much like schizophrenia
and then if stopped abruptly possibly withdrawal so the four that i'll just
put on this chart are methylphenidate which is ritalin dexmethylphenidate which is focal and xr
methylphenidate is Concerta or methylphenidate immediate released three times a day
and we see that these peaks happen somewhere around maybe 4 or 5 pm and then it gradually
tapers off but imagine if instead of taking at 7 am the patient took it at 11 am in that case
they would be wide awake for quite a long time and we would want to take some like
the immediate release and only maybe give two doses instead of three so that we avoid that
insomnia at the end of the night there is a non-stimulant atomoxetine which is stratera
it's a selective norepinephrine reuptake inhibitor with no dopamine activity and
it takes a couple of weeks to see the effects and almost up to three months for full benefits
and it is less effective than the stimulants like Ritalin but it doesn't have abuse potential so
it's kind of one or the other are you going to choose something that's a little more effective
with a stimulant or is there an issue with the abuse potential that we have to use this
and then adverse drug reactions similar to the stimulants
note there is an increased risk of suicidal thinking in children very rarely and it
appears during the first several months of use so certainly something to watch out for