Speaker 1: Welcome back today. We're gonna be doing psychopharmacology fundamentals. So
SSRIs block serotonin reuptake first line for depression and anxiety.
If you remember serotonin, we talked about that neurotransmitter. It's
associated with depression anxiety. We'll talk about typical antipsychotics. The
block dopamine D two receptors caused motor side effects, though
we'll talk a little bit more about that later. Atypical antipsychotics,
lithium which is mostly used with bipolar mood by stabilizes mood,
but also what they call it narrow therapeutic index. We'll
talk a little bit more. Benzo diazepines they activate GABA activity,
fast acting but addictive. And pharma Codkinetics and pharmacode dynamics
are the two things we're going to be talking about
as well.
Speaker 2: Pharmicintics.
Speaker 1: Pharmakinetics is how the body handles drugs. Pharma codynamics is
what drugs do to the body. So one is pharmakinetics
is what the drugs do to what the body does
to the drugs, and pharmacodynamics is what the drugs due
to the body. So you can think of dynamics thinking
of drugs doing to the body. Kinetics is what the
body does to the drugs. So let's go ahead and
get started here. So pharmacokinetics, we'll start there. This is
how again, how the drug moves through the body, but
how the body influences it. So absorption is number one.
You got four stages, absorption, distribution, metabolism, and excretion. How
the drug enters the bloodstream. Of absorption, most psychotropics are
taken orally and absorbed in the gastrointestinal tract. The bioavailability,
which is the percentage that actually reaches systemic circulation. It's
an important understanding what you need to understand this for
psychopharmacology because every drug is different in bioavailability and one
of the reasons it's reduced by a first pass what
they call first pass tabolism in the liver or the
hepatic portal. Hepatic portal means the liver portal, and this
is where it breaks down quite a bit. This is
where it metabolizes. Member we're using enzymes to break it down.
Distribution is how the drug spreads through the body. Lipophilic
fat loving drugs, like most psychiatric medications. Why because that
lipophilic component allows us to cross.
Speaker 2: The blood brain barrier more easily.
Speaker 1: For instance, when you give individuals dopamine who have Parkinson's right,
you want to give them dopamine because they're low on dopamine.
It won't cross the blood brain barrier that way. You
have to give them levodopa, which converts and then crosses
the blood brain barrier because it's got a LiPo philic component.
Speaker 2: Attached to it.
Speaker 1: So again, absorption is how the drug enters the bloodstream.
Distribution is how the drug spreads through the body. Metabolism
is how the body breaks it down. We talked about
that minute ago, mostly in the liver using see why
P four fifty cytochrome P four fifty enzymes. The variations
in these enzymes affect how fast people metabolize medications, which
it helps explain individual sensitivity, something we see here with
ethnic differences. Certain Asian cultures. African American cultures may have
issues with these enzymes. Not enough of these enzymes, so
it can increase the toxicity of certain medications or alcohol. Last,
but not lease is excretion, how the drug leaves the body,
usually through urine, which can lead eventually with too many
drugs to impaired kidney or liver function, which can slow
the process as well, I can impair it. But if
you already have impaired kidney or liver function, this is
also something that the psychiatrist is going to be aware
of to determine what he can prescribe to you or
she can prescribe to you. Increasing drug levels and toxicity
risk are associated with impaired kidney or liver function. Also,
as you get older, as senior sixty five and older,
your kidney and liver are not functioning anymore the same
or if you pre pubescent ten or nine years old,
it's not strong enough yet either to.
Speaker 2: Process these drugs.
Speaker 1: So one last time, the four stages of pharmacokinetics which
your body does to the drugs is absorption, distribution, metabolism,
and excretion.
Speaker 2: I put it adme.
Speaker 1: Pharmacodynamics how drugs affect the brain. So let's look at
how the receptor binding in the drug mechanism of action works. First,
one is agonist, and what this does is activate the
receptor and it increases whatever neurotransmitter you want. Antagonists block
the receptor, preventing activation. Reuptake inhibitors block the transporters, keeping
transmitters on the syneptic cleft longer, basically increasing the amount
as well. Enzyme inhibitors prevent neurotransmitter breakdown like MAOIs, and
if you prevent the breakdown, you have a build up again,
so you're trying to increase the amount.
Speaker 2: Every psychiatric drug works.
Speaker 1: By changing neurotransmitter act civity, and that changes and that
change ripples too, circuits involved in emotion, motivation, and cognition. Remember,
the drugs either increase or decrease. That's pretty much it. Antidepressants,
let's look at those ssrise. The mechanism is it blocks
the reuptake of serotonin also known as five HT.
Speaker 2: So increase its availability.
Speaker 1: Some examples are zoloft sirtulene or prozac, fluoxetine, selexa, cetyla,
pram lexapro acetyloprim, peroxetine which is paxel. The uses are
depression anxiety OCD PTSD. Side effects could be gastrointestinal upset,
sexual dysfunction that's the big one for most people, sleep disturbance,
and rare serotonin syndrome, which is really serious and dangerous
causes agitation, tremor, and fever or fever. One of the
key things you have to pay attention to is it's
the first line of treatment for depression, and exacs take
two to six weeks for full effect. S n our
eyes SO s n R eyes. Serotonin oropeneferine reuptake inhibitors
mechanisms that block the reuptake of serotonin and orapenephrine. Examples
are vin lexaphene which is effects or deloxetine which is symbalta.
Uses a gainer depression, anxiety, and neuropathic pain side effects
similar to SSRISE, but you have to add one extra component,
which is the increased blood pressure due to the neuropenefferent effects.
Speaker 2: Now we go to TCA's.
Speaker 1: These are not very often used anymore due to the
side effects sedation, dry mouth, weight gain, constipation, cardiac arrythmias.
Speaker 2: And overdose.
Speaker 1: They usually hit a lot of the different neurotransmitter receptors.
This is why they tend to have a pretty good
effective rate, but just a lot of side effects. They
block serotonin and norapenefferent reuptake, also block histamine and acetocholine.
Some of the examples of the medications are amatriptylene, nor
tryptylene and emipamine. Key point is it's lethal and overdose,
so be really careful with people who are suicidal patients
who are suicidal. Finally, as MAOIs, again, these are not
used ver any very often, in examples finelzene or transhycoprene.
They inhibit monamine oxidase. Remember as is always an enzyme,
so monomine oxidase is that enzyme, and this is the
enzyme that breaks down serotonin dopamine oora preneferent.
Speaker 2: So it's a blot.
Speaker 1: It's inhibiting that which increases serotonin dopamine oiora prenefferent. You
can see why it's so powerful, but unfortunately a lot
of side effects and a lot of restrictions. Will get
to that in a minute. Usually used for atypical depression
and treatment resistant depression. Hypertensive crisis is usually the issue
with this drug. These drugs, this class and MAOIs the
side effects hypertensive crisis. With tyramine containing foods, you can't
eat these, wine, delimeats or chocolate. Also side effect could
be serotonin syndrome. Again very deadly, so most of the
time if they use these at all, it's usually the
last resort. Again for treatment resistant or atypical depression. Antipsychotic
so we got two categories, typical and atypical. Typical is
first generation, atypical is second generation. So the first generation
strong D two dopamine receptor antagonists right reducing the amount
of dopamine. Examples of haliparadol and chlochromazine. Chlochromazine, I believe
was the first one ever used, and it was not
used originally for psychosis.
Speaker 2: It was used for something else.
Speaker 1: The uses are schizophrenia for their positive symptoms, does not
work well for negative acute agitation and delirium. Side effects
are extra paramidal symptoms or dystonia, acathesia, parkinsonism, tart of
dyskinesia also causes sedation and anticholinergic effects, So again extra
paramidal symptoms. So let me get back to some of
these symptoms in case you're not familiar with them.
Speaker 2: So, Dystonia is.
Speaker 1: The sustained or intermittent muscle contractions that cause abnormal, often
repetitive movements or postures. Usually it starts within hours to
days of starting or increasing dopamine blocking agents. In this case,
again we're looking at antipsychotics. Symptoms include muscle spasms, neck twisting,
also known as torticolis or eye rolling, ocular GYRC crisis,
or jaw clenching.
Speaker 2: It can have.
Speaker 1: It can be treated with anticolinergics like benz tropene or benzodiazepines.
Acathesia is a subjective feeling of inner restlessness with the
need to be in constant motion so pacing, shifting weight,
inability to sit still, likely related again to dopamine oia.
Per different imbalance. Treatment is benn zodiazepines and beta blockers.
Tart of dyskinesia is involuntary repetitive movements, especially of the face, mouth,
and tongue. I would recommend you look at some YouTube
videos to see these, then you won't forget them. Symptoms
are lipsmacking, tongue protrusion, grimacing, and limb jerking. Treatment is
discontinuation of switch to anti or switch to atypical antipsychotics.
But back to these, we go back to the typical
first generation key idea for these or the main focus
is really effective for delusions and hallucini hallucinations, but prone
to movement related side effects. Atypicals now are weaker D
two antagonists compared to the typical, and they're also a
serotonin five H two A antagonist. Examples are respiradomes, respradol,
e lonza, pene quatiapine, and closepine. Closeipine has been making
quite a bit of a comeback lately. The uses are schizophrenia,
bipolar disorder. Side effects are metabolic syndrome so weight gain again,
diabetes and lipid changes can be problematic. Sedation closet pine
is dangerous too. Right now it can lead to a granullysotosis,
which requires blood monitoring.
Speaker 2: Is it could the blood cells could be killing or
dying off.
Speaker 1: Atypicals are better tolerated, but not side effect free. Next
we move to angiolytics or anti anxiety medication benzodiazepines. They're
usually the go to initially lorazepam, aprasilam, diazepam so those
xanix things of that nature. They bind to GABBA A receptors,
increasing gabba's inhibitory effects. Right, so gabba slows things.
Speaker 2: Down, it's inhibitory.
Speaker 1: They would be used for anxiety, panic, insomnia, alcohol withdrawal,
social anxiety side effects, sedation, memory, and parent but the
most dangerous is dependents also withdraw seizures.
Speaker 2: These are not.
Speaker 1: Typically recommended due to addiction risk. This is the key thing,
exceptually especially.
Speaker 2: For the exam.
Speaker 1: Remember high addiction risk here, and they're not recommended for
long term. A lot of psychiatrists usually will start off
with combining an SSRI because it takes so long, three
to two to six weeks, usually four weeks, and they'll
combine it with the benzos and start relaxing them and
having some kind of effect. Once about two or three
weeks are kicked in, then they pull them off or
wean them off the benzodiazepine and leave them on the
SSRI and hopefully that'll help the client. But usually if
it's really necessary. The other one you can use for
anti anxiety is abuse perone. That's b U S p
I O n E, usually used for general anxiety disorder.
But it's non sedating, so side effects are dizzyness, nausea
and that's it. There's no dependence or sedation issues there
save for long term use.
Speaker 2: But takes several weeks to work.
Speaker 1: This is why you can see you can't really combine
it with an SSRI if you're trying to get a
meeting effect. We're heading over to what they're usually known
as the bipolar drugs, right, so we got lithium, which
is one of the more popular ones. They don't know
exactly how it operates, so the mechanism is unclear. It
likely affects second messengers what they call IP three or
CAMP as well. Modinating modulating neuronal excitability typically used for
manic episodes and suicide prevention. Tremor, hypothyroidism, right gain are.
Speaker 2: Usually the side effects.
Speaker 1: One thing to remember for the exam is renal toxicity.
So kidneys narrow therapeutic window, which means you can have
you can.
Speaker 2: Over you have high toxicity.
Speaker 1: You have a really small window of how much you
can take before you can also get high toxicity issues,
so it requires blood monitoring every week or two red
flag we're a toxic at high levels, like I've mentioned,
so monitor kidney function.
Speaker 2: And drug levels regularly. So renal toxicity.
Speaker 1: Membor renal is kidney anti convulsants valparate or dipicoat us.
It's known as increases GABBA used for mania and seizures.
Side effects for them as weight gain, tremor liver toxicity.
Another one is for the anti convulsants is carba mazepine,
which blocks sodium channels, so dipicote increases gappa carbonymy sepene
blocks sodium channels, and it's used for bipolar or trigeminal
neurolgia or pain in the net one of the cranial
nerves or three risk though of granulocytosis, so similar to
what we talked about earlier, that risk that you had
a granulocytosis as well with another medication that we talked
about earlier, closeipine for antipsychotics or closepine. And last but
not lease is lemetro gene also known as lamictyl and
modulates glutamate. Best for bipolar risk of Stevens Johnson syndrome,
so you have to ty trate slowly, which means increase
slowly or come off slowly.
Speaker 2: Another one is stimulants.
Speaker 1: Now for our last group stimulants, methyl fenodate which is
riddlin and amphetamines is adderall.
Speaker 2: Another popular one is motoxinitine.
Speaker 1: A motoxetine, amoxetine jesus can't say it, or stratterra amoxetine
or straterra. They're used for ADHD or narcolepsy. Side effects
are insomnia, appetite suppression, increased heart rate, and irritability. An
important tip for you to remember is a screen for
cardiac risk. That's what they need to do before they
take these medications. Screen for cardiac risk and substance misuse
before prescribing. Always make sure to match in your head
the medications with the disorders major depression SSRISE, SNRIES, increased
serotonin oripenephrone anxiety disorders SSRISE again, use proone short term benzodiazepines.
Remember they work on GABA and serotonin, schizophrenia, atypical anti
psychotics now, so those are gonna be resperadol or respiradome, elonzapene,
closetpine and quatiapene, bipolar disorders, lithium and volprate or depoicode also,
so that's what it's known as. Stabilized mood through second
messengers ADHD, stimulants, increased dopamine oripenephrine, and OCD high doses,
high doses of s SSRIs for OCD. Remember, if it
enhances your GABA, your brain slows. That's one of the
effects of benzodiazepines. So for now that's gonna be it.
We covered a lot of drugs, uh so the pharmacological
component again, you don't have to get deep into the weeds,
into the mechanisms. Just know the newer transmitters that have
the medications are working for and what disorders. So hopefully
when we cover the neuro transmitters and now they're recovering
the pharmacology side, you'll have a better understanding