YouTube Transcript:
Pharmacodynamics

Skip watching entire videos - get the full transcript, search for keywords, and copy with one click.

AutoDub

Understand YouTube Foreign Videos

Immersive YouTube Voice Translation

Break language barriers, embrace global quality content

Solve Foreign Video Barriers Instantly

Video Transcript

what's up ninja nerds in this video

today we are going to be talking about pharmacodynamics

pharmacodynamics

if you guys really want to understand

this i truly strongly urge you guys go

down in the description box below we

have a link to our website on our

website we'll have some awesome notes

but even better some illustrations that

you guys can follow along with me as we

go through this lecture so go check that

out also please if you guys like this

video if you benefit from it it makes

sense it helps you please support us in

the best way you can do this by hitting

that like button commenting down the

comment section and please also

subscribe now let's talk about pharmacodynamics

pharmacodynamics

when we talk about pharmacodynamics it's

basically a very interesting concept

that we're going to pick up from

pharmacokinetics so if you guys remember

from pharmacokinetics really basic

the adme the absorption of the drug the

distribution of the drug the metabolism

of the drug and the excretion of the

drug were all a part of the

pharmacokinetics where you take a drug

and we said in a perfect world let's say

that we take it orally po moves through

the gastrointestinal tract has to be

absorbed so it has to cross cell

membranes when it crosses cell membranes

to get into the blood

it goes into the hepatic portal system

the hepatic portal system will then take

this medication to the liver the liver

will always if it goes via the oral

route will get some piece of that drug

where it can activate or you know break

down some of the actual drugs so it'll

have what's called first pass effect or

first pass metabolism

so then what it'll do is some of that

drug it may metabolize and then the

other remaining portions it'll put into

the systemic circulation from there we

know once the drug goes it'll actually

distribute throughout the actual

vasculature and into the tissues where

it can go and exert its effect

this here is where we're going to see

the pharmacodynamic effect but if you

guys remember finishing off the pharmacokinetics

pharmacokinetics

after a drug is done performing its

particular function or it's moving

through the circulation it can be taken

to the kidneys where it can be excreted

or it can be taken to the liver where it

can be metabolized and also excreted and

these are the primary organs of

clearance of the drug

now whenever the drug gets to the actual

tissues what we can see is what the drug

does to the actual body whereas

pharmacokinetics is like

you know what the body is actually doing

to the drug if you will so now we have

to see what does this drug actually do

to the body particularly the cellular

component of our tissues or organs

subsequently so if we take and we

actually look and zoom in at this drug

interaction here we're going to look at

one of these particular cells so here's

our drug in order for a drug to be able

to bind to a cell and produce a

particular cellular response

it needs to be able to act on a receptor

right so there needs to be a receptor

that the drug can actually bind to once

it binds to that receptor it'll then

produce a particular cascade of events

intracellularly that activate the cell

or inhibit the cell and cause it to

produce the appropriate cellular

response so some drugs are working to

inhibit the cells some drugs are working

to stimulate the cell either way that is

the cellular response in order for the

drug to do that it has to bind either 2a

extracellular receptor we'll put ec

receptor and then via second messenger

systems work to be able to stimulate

second messages to produce the cellular response

response

or the drug has to be able to move into

the cell and bind onto a intracellular receptor

receptor

where it will then again produce a

cellular response via a specific cascade

of events what we have to understand now

is if we take this drug and have it bind

onto extracellular receptors what are

the different types of extracellular

receptors and why are they different

what are some examples of drugs that act

with different types of receptors and

then we talk about the intracellular

receptors and what kind of drugs

particularly interact that way we're not

going to go down the crazy rabbit hole

of signal transduction and intracellular

receptor pathways we talk about that in

cellular biology but it's just enough

for us to understand the basic concept

here and the last thing we'll do is

we'll talk about something called

desensitization also known as

tachyphylaxis intolerance with respect

to drug receptor interactions all right

so let's come and now talk about when we

have a drug interacting with a receptor

let's say an extracellular receptor what happens

happens

all right so we have different types of

extracellular receptors

first one that i want you guys to

remember is drugs can actually bind onto

extracellular receptors that are poor

what's called a ligand ligand-gated

ion channel it's actually pretty

straightforward let's say here i have a

neuron on this neuron i have these

particular channels if you will that are

supposed to allow for maybe particular

ions maybe positive ions to flow in

maybe negative ions to flow in maybe

positive ions to flow either way it's

some kind of concept like that there's a

little gate if you will

that's basically

controlling the entry of drugs so

there's these ions are not going to be

able to allow for these this gate is

blocking these ions from moving into the

actual cell

but if i give a particular drug

that wants to bind into this little

pocket here that's a part of the

ligand-gated ion channel and once it

binds onto that pocket it lifts the gate open

open

and now this gate that was completely closed

closed

is open and there's an opportunity for

the particular ions to easily flow in or

out of this neuron

and now this is actually a really cool

concept for example let me tell you an

example of a particular drug here let's

say i have

a drug

such as

lorazepam so lorazepam

is really interesting because lorazepam

acts on what's called gaba a receptors

so it'll work on what's called gaba a

receptors now gaba a receptors are

ligand-gated ion channels so let's

pretend this black dot here is gaba

gaba

when gaba binds on to these channels

these channels are generally closed

we don't want them to be open but when

gaba binds to it what it'll do is it'll

open up the channel and allow for

negatively charged chloride ions

to easily flow

flow

into the actual neuron

and as these chloride ions inflow into

the neuron it makes the cell super

negative and it basically hyper

polarizes it and decreases action

potentials you want to know why this is

interesting we can give lorazepam in

situations where you want to decrease

the activity of neurons you know where

that would be a very important situation

seizures so it may be able to work to

inhibit or decrease seizure activity so

that's kind of one example

of how drugs can work at the receptor

and produce a cellular response is they

bind onto a ligand-gated ion channel

either open that channel close that

channel and then depending upon what

kind of channel they bind onto will

determine which kind of ion flows in or

out and then the associated cellular

response so you get you see how that

happens there

all right so the next situation here

that we have to talk about where a drug

can bind to an extracellular receptor

and produce the cellular response

is not the ally and data but it can be

via what's called g-protein-coupled

receptors this is also pretty cool

so g-protein-coupled receptors are

what's called seven pass receptors

or serpentine receptors and basically it

has a little receptor domain where the

drug combines so this is the receptor

domain so where a drug would actually

bind into that pocket and then there's

these like you see how it actually moves

through the actual membrane seven times

one two three four five six seven that's

why they call it a seven pass

transmembrane receptor

what happens is

drugs can actually bind onto

these particular receptor domain when it

binds on to the receptor domain of each

one of these little pockets here of this

g protein coupled receptor what it does

is it changes the shape of the actual

receptor it changes the shape of this

intracellular domain if you will now

this intracellular domain is connected

to something called a g protein so it's

connected to something called a g

protein and there's different types of g

proteins if you will

so here i'm going to have a g protein

for each one

one of the g proteins

may be what's called gq

so gq and what gq is it's a very

interesting type of g protein so let's

say that we have a drug binds to this

receptor domain changes the shape of the receptor

receptor

and then what it does is it stimulates a

particular g protein now g proteins

normally they're bound to something called

called

gdp but what we're going to do is we

want to activate this even more

so what we do is we have them pop out

gdp and have them bind what's called gtp

and this really stimulates this gq protein

protein

what gq will do then is it'll move along

the cell membrane and stimulate

this enzyme okay that's embedded into

the cell membrane you know what this

enzyme is called it's a very important

one for you guys to remember especially

for this it's called phospholipase c

and what phospholipase c will do is is

it'll break down different components of

the cell membrane a molecule called pip2

it'll break it down into two components

one is called diacylglycerol and the

other one is called ionocytotriphosphate

and what these things do is is this will

activate something called a protein

kinase particularly a protein kinase c

and this will work to increase calcium

ions inside of the cell

what this may do is you might be like

okay zach i have no idea what the

significance of this is

protein kinases you know what's really

interesting about these is they

phosphorylate things so if there's let's

say channels that are on the cell

membrane that currently

currently they're inactivated

currently they're inactivated but i

have this drug bind to this receptor

activate this gq protein

it then activates this enzyme which

activates these second messengers like

diacetyl glycerol or inositol

triphosphate what do they do well this

will increase calcium let me explain why

this could be cool

protein kinase c can then go

and phosphorylate all of these channels

if it adds a phosphate group to these

channels it may activate them or

inactivate them let's say it activates them

them

if it activates them it opens them up so

allow for maybe positive ions to easily

flow into the cell

bringing positive ions into the cell

could potentially stimulate this cell

let's give an example

let's say i have a drug here like

norepinephrine here's norepinephrine and

i want norepinephrine to act on the

heart cells the heart muscle

what norepinephrine will do is it'll

bind onto this receptor activate the gq

protein activate this enzyme

diacetyl glycerol phospho protein

kinases will go phosphorylate particular

channels to increase calcium ion influx

or sodium ion influx

and anesthetic triphosphate will

activate what's called your smooth er or

in this case the rough endoplasm i'm

sorry the particular endoplasmic reticulum

reticulum

to activate or the sarcoplasmic

reticulum to release calcium into the

actual muscle cell the whole concept is

that i increase ions inside the muscle

cell particularly calcium i'm going to

increase the contraction of the heart

muscle cell so you guys see the clinical

response if this was norepinephrine

working on the heart muscle cell it

would increase the amount of ions

rushing into the cell stimulating its

ability to contract that's the whole

concept of its cellular response so the

cellular response for this if this was a

heart muscle

would be that it would increase

contraction do you guys get the whole

point here right so the same concept

exists for these other two components

so there was a gq protein guess what we

can actually make our lives a little bit

easier for these two there's a g

stimulatory protein and a g

inhibitory protein

so what i'm going to do is i'm going to

explain this one and this one is the g

inhibitor is the exact opposite so let's

say i have another drug

this drug binds to this receptor

when it binds to this receptor the

receptor changes its shape

it then activates the g-stimulatory

protein in order for this protein to be

truly activated needs to get rid of gdp

gdp

and bind on to gtp

gtp

then when it's super activated it then

will go

move along the cell membrane and

stimulate this particular enzyme

embedded in the cell membrane which is called

called

adenylate cyclase

adenylate cyclase adenylate cyclase is a

really interesting enzyme once it's

activated it takes atp

and converts it into cyclic amp

and cyclic amp will activate a molecule

called protein kinase a what do we say

protein kinase a does

it phosphorylates things so if there's

particular channels that are on this

particular cell membrane

it may go

and phosphorylate this cell membrane and

if it phosphorylates these proteins on

the cell membrane it can either open up

the ion channel or close the ion channel

either way ions will move in or out of

the cell it'll potentially cause some

cellular response this could be

norepinephrine as well acting on a heart

muscle cell it can do both of these

concepts here but you get the point it's

going to be causing some type of a

cellular response now

with that being said

g inhibitory is just the opposite

you have a drug

it binds to this g protein coupled

receptor changes its shape

activates a g inhibitory protein

the g inhibitory protein will then

release a

gdp and bind a gtp

this g inhibitory protein will then go

and inhibit

it'll inhibit this enzyme the same

enzyme here which is adenylate cyclase

cyclase

the adenylate cyclase is supposed to

convert atp into

cyclic amp and then supposed to activate

protein kinase a

which is then supposed to do what

maybe go and phosphorylate specific

types of proteins this could be

structural proteins these could be

enzymatic proteins or functional

proteins any kind of protein you can

think of it can go

and phosphorylate

which could either inactivate or

activate the particular protein or enzyme

enzyme

in this situation with g-inhibitory

protein you inhibit adenylate cyclase

you inhibit the ability to convert atp

into cyclic amp you decrease protein

kinase a you decrease the

phosphorylation of these particular

proteins and again depending upon what

you're looking for this could produce a

particular cellular response so when a

drug interacts with a receptor to

produce a cellular response it either

can act on a ligand-gated ion channel

binding to a spot opening up the channel

closing the channel one of the two which

produces a cellular response or

it can bind to a protein that is

connected on the outside of it changes

the shape of the protein the morphology

of the protein that activates second

messenger systems to produce a cellular

response what's the last one

the last one for extracellular receptors

is what's called a tyrosine kinase

receptor it's the same concept here i

have a receptor on the out outside here

and i'm going to have a particular drug

let's just say for example i pick

something like insulin

insulin will bind to this receptor now

now

because insulin will bind to this

receptor domain what happened is in

g-protein it changed its morphology right

right

when you bind to this what it does is it

activates these like enzymes that are a

part of the receptor you see these blue

components here these are called your

tyrosine kinases and so on this kind of

receptor there's these little residues

called tyrosine residues they're little

amino acids

when insulin binds on to this receptor

the receptor kinases become activated

and what they do is

they cross phosphorylate so this

tyrosine kinase will phosphorylate

these tyrosine residues and this

tyrosine kinase will phosphorylate these

tyrosine residues

once you phosphorylate these it causes

them to have a change in their structure

once you change the structure it then

makes it easier for these guys to be

able to bind to specific types of

proteins or second messengers and when

that happens these second messengers

that you're going to activate will go

down and do the same thing

that the protein kinases or the ionosol

tile for triphosphate or all of these

other molecules cyclic amp it's going to

act like a second messenger which will

produce the cellular response so this is

an important concept so we can have

three extracellular receptor pathways

that i want you guys to remember that a

drug can work on the cell to produce a

cellular response through one

ligand-gated ion channels

two g-protein coupled receptors three

tyrosine kinase receptors now

this is particularly important that i

want you guys to remember for

ligand-gated g-protein coupled receptors

and tyrosine kinase receptors this is

for what kind of drugs here's what i

really want you to remember this is specifically

specifically for

for hydrophilic

large

drugs i want you to remember that

these drugs that are hydrophilic they're

large they're not going to be able to

move through the cell membrane and act

on different types of receptors in the

cell they're also polar they're charged

they're not going to be able to crash

through the phospholipid bilayer but if

i talk about intracellular receptors my

friend those are hydrophobic those are

small molecules those are non-polar they

can easily pass across the cell membrane

and bind to intracellular receptors

don't forget that let's talk about that

now all right so when we talk about

intracellular receptors what did i tell

you remember for intracellular receptors

this is for what kind of drugs this is

for drugs that are hydrophobic or lipid

soluble non-polar and small drugs

because of that these drugs such as

steroids nitric oxide things of that

nature so examples of this would be

something like maybe like a

corticosteroid so if someone's taking

some type of steroid of some kind

corticosteroid mineral mineral corticoid

one of those some type of steroid drug

or maybe even they contain something

like a nitric oxide molecule

these drugs are small enough or

hydrophobic enough that they can cross

right through the cell membrane

because they can cross right through the

cell membrane they can bind onto an

intracellular receptor

when they bind onto the intracellular

receptor that receptor can then

translocate into the nucleus where it'll

bind to you see these like little

turquoise proteins here that are

connected with the dna these are called

transcription factors

transcription factors obviously regulate

the degree of transcription of dna

converting dna into

rna because rna is important to be able

to make proteins

proteins so

if i give a particular drug that

activates this receptor intracellular

receptor then goes and translocates and

works to stimulate a transcription

factor i can then increase the

transcription process of making more rna

making more proteins to produce a

cellular response

so this is an important thing to think

about also

this pathway of intracellular receptors

takes time it may take some time to be

able to produce this response in

comparison to extracellular that's a lot

faster and more amplified so there's a

lot of amplification one drug can

activate multiple second messenger

system producing a massive clinical response

response

this you have one drug interacting with

one receptor which will take some time

for it to trigger this transcription

process protein synthesis process and

kick into high gear so that's an

important thing to remember this is a

little bit quicker but it can stay

around a lot stay around for a very very

long time this takes some time to be

able to produce a very good clinical effect

effect

all right so that's your intracellular

receptor pathways between drugs and

receptor interaction all right so when

we talk about this next concept is a

very interesting concept called

tachyphylaxis intolerance it's really

important when drug receptor interactions

interactions

so when a drug works on a receptor

whether it's an extracellular receptor

intracellular receptor and produces a

cellular response what can happen is is

when a patient is exposed to maybe a

particular dose of a drug maybe a lot of

it let's say that you give a very large

dose of a particular drug and what

happens is that drug will bind on to

many different receptors and keep trying

to stimulate the living crap out of this

cell producing a massive cellular response

response

what happens is when you produce this

massive cellular response and again

here's the key term i need you to

remember that it could come up on the

exam for tachyphylaxis is it is a rapid

type of response so a rapid response to

maybe a initial dose maybe you gave a

very a large initial dose of a drug and

it caused a very intense stimulation of

the cell

because these drugs are binding on to

many many different receptors the cell's like

whoa bro you're stimulating way too

intensely i got to protect myself here

so what i'm going to do is is i'm going

to desensitize myself to how much drug

is actually out there right now and so

the way it does this is very very

interesting has a couple of different mechanisms

mechanisms one

one

is it can say okay what i'm going to do

is i'm making these receptors right so

what i'm going to do is

is since i have to make these receptors

to plug them into the actual cell

membrane what i'm going to do is i'm

going to decrease the synthesis of these

receptors so this pathway is decreased

or inhibited so there's less receptors

that are actually available for the drug

to bind to so one of the ways that i can

do this is i can decrease the number of

receptors so there could be drug out

here trying to be able to produce this

clinical effect but there's no receptor

for it to bind to

the second thing that it can do which is

also pretty cool here

is they can also

work particularly to have specific

enzymes if you will maybe there are

specific types of enzymes

and what these enzymes will do is maybe

they're like kinases of some type

they'll add phosphate residues

onto this particular receptor and what

it does is it inhibits or inactivates

the receptor because you know what

happens is certain kinases what these

kinases could do is they could phosphorylate

phosphorylate

these particular receptors right and

when they phosphorylate them what it

does is it actually tags them and then a

protein called arrestin so a protein

called arrested if you just wanted to

think about it let's say i have a

protein here

and purple

once these receptors get phosphorylated

this protein called arrestin will bind

with that and basically say hey these

receptors no good inactivate them don't

let them respond to a particular drug

and then eventually they get internalized

internalized

but again we're inhibiting it so even if

the drug is present it's not going to be

able to work on the receptor because the

receptor is arrested in the phase of

inactivation pretty cool right

the third thing that this actual

receptor and drug interaction can do is

we can say okay bro

way too much stimulation what i'm going

to do is is i'm going to take this

receptor and i'm going to internalize

the receptor via an endocytosis

mechanism i'm going to bring this receptor

receptor

into the actual cell and if i bring this

receptor into the cell you won't be able

to stimulate him so therefore i down

regulate my number of receptors so i can

do three things via this process of tachyphylaxis

tachyphylaxis one

one

is i can internalize my receptors

two i can inactivate the receptors by

phosphorylating them and then having a

rest and protein bind to them the third

way is i can decrease the synthesis of

these actual receptors and the whole

purpose is trying to have a less

significant cellular response in

response to a rapid

dose a rapid response to a very high

dose of a drug very very quickly so

that's a very important thing to be able

to remember

now with tachyphylaxis the other thing

that's important to remember that

sometimes they'll ask you is between

tachyphylaxis and tolerance

if i increase the concentration of the

drug will it change the actual cellular response

response

it's important to remember that it won't

so the reason why is because i'm getting

rid of particular receptors i'm

decreasing the synthesis of the

receptors or i'm inactivating the receptors

receptors

tolerance is a little bit different tolerance

tolerance

is usually more of a

chronic response so usually just a

chronic response it's over

you know weeks for let's say just say

for example weeks

or let's even be a little bit more you

know less intense here let's say hours

days weeks whatever we can go hours

to weeks so it's way more delayed it's

not the initial dose so it's a chronic

response it's over time okay so it's

important to remember that this is

usually just repeated exposure to a drug

so repeated exposure

to a particular drug it's not like a

one-time initial rapid response this is

chronic exposure you're being exposed to

a drug constantly every single day for a

long period of time

this response develops over a decent

amount of time this doesn't happen

rapidly or initially it's usually over time

time

what happens is the same concept here

you have a drug that you're exposed to

it's basically

binding on to these particular receptors

and trying to cause this excessive

stimulation of the receptors

your cell says yo bro can't handle all

this we need to be able to change this

up a little bit it does all the same

kinds of things it says okay what i'm

going to do is i'm not going to make as

many of these particular proteins i'm

going to internalize

these actual receptor proteins so it's

going to do two things just like we did

up here above it's going to internalize

and it's also going to reduce the

synthesis of these particular proteins

right so this process is inhibited and

this process is actually going to be

also occurring

the other thing that happens is it

doesn't do this arrestin type of process

where it phosphorylates it do something

else you know that drugs

sometimes they need to be metabolized by

particular enzymes

so sometimes drugs are metabolized

especially think about alcohol

in that sense sometimes drugs need to be

metabolized by particular enzymes so

here's this enzyme here

what happens is if what if i'm exposed

to a drug and i increase the number of

enzymes so i'm going to increase the

number of metabolic enzymes that

basically works to break down that drug

and patients who have tolerance what

happens is when they're exposed to this

drug over a long period of time chronic

exposure repeated doses what we do is we

increase the number of metabolic enzymes

and what these metabolic enzymes will do

is it'll continue to keep breaking down

the drug so it'll keep breaking down the drug

drug

all right

and that'll reduce the actual efficacy

of the drug that'll reduce the response

that the actual drug can produce on the

body and so that's the whole point is

trying to be able to have a compensation

mechanism what's important to remember

though is is i can overcome the activity

of this enzyme if i over saturate the

enzyme so if i increase the number of

metabolic enzymes theoretically if i

increase the drug dosage super super

high eventually causes this enzyme to be

so saturated where they'll still be drug

left over that it won't be able to break

down and metabolize

and so one of the big things with

tolerance is that if you increase the

you can overcome

the decreased response slash effect

and that is an important concept the

reason why is

tolerance is an example of something

like opioid over opioid abuse so if a

patient is taking opioids they're

exposed to opioids chronically what

happens is that continuous opioid kind

of working on the particular cells will

cause this excessive activity of the

cells to again a diminished pain

response what will happen is particular

cells will try to develop a particular

way of metabolizing that drug a little

bit easier quickly

and because of that maybe what you have

to do is because you're metabolizing or

your receptors are becoming less

sensitive is you need to increase the

number of drug to be able to work on

these receptors or overcome the

metabolic enzymes to produce the same

clinical effect and this is a very

important concept with things like

opioid overdose or alcohol opioid abuse

alcohol abuse cocaine methamphetamines

things of that nature all right that

covers tachyphylaxis intolerance now

what i need to do is we need to say okay

we take a drug it interacts with the

particular receptor when it binds with

that receptor what's the affinity that

the receptor has between the drug so

what's the the bondage the actual

connection between them how strong is

the actual connection between the

receptor and the drug and the next thing

is what's the maximum clinical effect

that that drug receptor interaction can

produce and then we'll talk about some

other things called therapeutic index

all right my friend so now we're going

to talk about what's called the dose

response relationship so this is

actually a pretty cool concept and it's

going to be something that you'll

definitely be tested on so you have to

know this for your exam especially for

the step one

so when we talk about this we're going

to have two curves here that are going

to compare two particular components one

thing is we're going to talk about the

potency of the drug and the other things

we're going to talk about is the

efficacy of the drug and we'll have some

quick kind of clinical points in there

and the big pearls to take out of this

so on this type of graph here on the

x-axis what i want you to remember is

whenever you see these types of graphs

on your questions or on your exam on the

x-axis we're taking the concentration of

the drug or the dosage of the drug

particularly but you know on a

logarithmic scale and then on the y-axis

you're looking at the response of the

actual drug dosages therefore it's the

dose response curve or relationship now

what's really important is when we're

talking about these curves let's

actually say that we have

the same concept here so we're going to

have in black here we're going to have

we give a drug we give a particular

dosage of a drug what happens is when

you start off with the low dosage of the

drug only small amounts of drug are

going to bind on to a very little of

these receptors okay so what happens is

if you only have a little bit of drug

only binding onto a few out of the tons

of receptors that you have the clinical

response that you're going to see is

pretty minimal

and so what we'll see here is we'll see

like a pretty like flattish curve

but then what happens is as you start to

have more drug binding onto more

receptor you start seeing what you start

seeing an increase in the response

now what's really really interesting

is that as i have more and more and more

drug that's actually increasing based

upon an increase in the drug dosage

eventually all of these receptors are

going to become saturated with drug

and no matter how much more drug i give

there's not going to be enough receptors

for that drug to bind to to produce

a cellular

response so therefore

it'll plateau or remain constant that

cellular response because all of my

receptors are saturated and activated

and so because of that what we'll see is

we'll see this kind of trail off and

become flat

that's a very important concept so we

kind of say this kind of looks like an

s-shaped curve or a sigmoidal curve and

again the first component here is where

it's initially flat that again is

whenever there's very little drug

binding on to not very many receptors so

we're not producing a massive clinical response

response

phase two of it is when we're actually

seeing tons of drug binding to tons of

receptors producing a good cellular

response and the third part here is

where we have all the drugs saturating

all of the complete number of receptors

that we have

and this point here is the e-max that's

the max amount of drug that you can give

to produce the maximum response or

effect that you're looking for and so

this is an important concept now another

thing that we have to talk about here so

we're going to say let's say that this

is a hundred percent effect or response

and then somewhere in the middle here

we're going to say is about a 50

response and then here is going to be

about a zero percent response we'll see

the same thing over here on this curve

i'm just comparing potency and efficacy

so let's say same thing here i draw this

curve here just to kind of make it representative

representative

this was a little bit too much of a

slope here so let's bring that less of a slope

slope

okay so here's our sigmoidal curve same

concept here here's one so that's

whenever little of the drug is binding

to very little receptors as we increase

the concentration of the drug we start

to see again more drug binding to more

receptors and then eventually we

saturate all of those particular

receptors so that's our concept there

this should be this dose response curve

what it should look like sigmoidal

now here's what i want you to think about

about

with respect to potency of the drug what

i want you to remember terminology wise

is potency is correlational with affinity

affinity

so in other words so i want you to think potency

potency

correlational with affinity

affinity

so as i

increase the affinity i increase the

potency of the drug and this is

basically the strength so this is the strength

of drug

drug receptor

interaction

so the stronger the bond is between the

drug and the receptor the more affinity

the more potent the drug is

now if i have an actual drug and it's

binding onto this receptor and the

strength of this actual bond is very

very powerful that doesn't necessarily

produce the same efficacy okay so you

can have a drug

that has a very high potency but what is

the significance of having a drug with a

very high affinity or a high potency let

me explain

let's say here that as i what do i know

then if i have a very high affinity that

that that that drug has for the

particular receptor okay so this drug

has a very high affinity for this

receptor meaning it's very very potent

what i can do is very very cool here

is when we look at this we actually can

take into consideration something called

the ec 50 which is a measure of potency

and so the ec 50 is the concentration

of the drug so it's the concentration

of the drug that will reach 50 percent

of the max response or effect so what is

this called this is called your ec50

that is a measure of potency or affinity

so what i want you to remember is the ec

50 is basically kind of a measure of potency

potency

now why is this important because when

you guys get a graph you have to be able

to consider this okay watch

as the ec 50 increases meaning you go

towards the right the concentration of

drug that you have to give to reach 50

of the mass effect as that increases

what am i saying that i have to give

more drug to produ produce 50 of the max

effect that means the potency is doing what

what

it's decreasing i don't have a strong of

a drug receptor interaction so what i

want you to remember is is that as you

increase your ec

50 you decrease

the potency meaning that these are

inversely proportional

if i decrease my ec 50

meaning i don't require as much of a

drug concentration to be able to produce

50 percent of the max effect what does

that mean for my potency that means this

potential so because of

that we have a very very good situation

here now watch what would this curve

look like if i actually took this into

consideration where i had one situation

where i want to change the potency so

let's say i want to have a decreased

potency that means that this curve would

go which way

it means it would go this way

right because now look at where my ec50

is my ec 50

is all the way

over here

so what i see is as i see that whenever

the potency is actually decreasing what

happens to the sigmoidal curve where

does it shift shifts to the right

if i want to increase the potency let's

say that i do this in a different color here

here

this way

so my

ec50 is shifted to the left and if it's

a decrease ec50 that means a higher

potency of the drug so it's important to

be able to remember that so whenever you

see these particular curves here and

they say which one of these if i were to

say this is medication a medication b

medication c which one of these has the

d the lowest potency you'd say a b c

which one has the highest potency it

would be a so it's important to be able

to remember that concept all right

we have to now take into consideration

something called efficacy

so efficacy is actually a very

interesting concept and it's actually

dependent upon two things it's dependent

upon the drug

receptor interaction

right so basically how

many receptors

the actual drug is occupying

so if i give a drug and this drug is

occupying 100 of the receptors that

means it's probably going to have an

increased efficacy if i give a drug and

it's only occupying some of those

receptors the efficacy is going to be decreased

decreased

that's one component

the other component is the intrinsic activity

activity

intrinsic activity of the drug meaning

meaning

if this drug binds to this receptor

if this drug binds to this receptor will

produce a 100 clinical response will it

produce a 70 clinical response will it

produce a 50 of a clinical response

that's dependent upon the intrinsic

activity of the drug so some drugs are

what's called full agonists meaning that

when they bind to the receptor the

effect that they have is 100 some are

partial agonists meaning that when they

bind to the drug even if they occupy all

the receptors the effect that they will

give you is never going to be maxed it's

not going to be 100

and so that's another important concept

so when i think about efficacy it's

really determined by what what we set up

here the point when all of the receptors

are stimulated so drug receptor

interaction you have to have at least

you'd like to 100 of the receptors that

are occupied

but it's also dependent upon the

intrinsic activity so even if you had

let's say i had a cell where 100 of the

receptors are occupied

if i had 100 of their cells uh all the

receptors occupied and the intrinsic

activity of that drug was very high a

full agonist

it would give me this type of emax then

it would give me this

where my hundred percent

or my emacs the point where

all my receptors are occupied doesn't

matter if i increase the drug anymore

the maximal effect that i have will be

at this point

all the receptors are occupied

if i take a drug that has a decreased efficacy

efficacy

meaning that maybe it has less receptors

that it's bound to or meaning it has

less intrinsic activity what would it

look like while i'd expect the e-max to

come down it wouldn't shift to the right

or shift to the left they should they

could actually keep the potency about

the same so what would i see with this curve

curve

if i were to compare here

i would actually see something like this

you see how it trails off like that so

this would be

the emax

and this here the difference between

these two is the difference in efficacy

so this here is the difference in efficacy

efficacy

this here between each one of these

between this component here

and this component here is the

difference in potency

potency

so remember that if my curve is shifting

down i'm changing the efficacy if my

curve is shifting to the right or the

left i'm shifting potency but again the

same concept here exists so again if i

take this difference here between on the

y-axis this tells me my response to the

actual drug right so the max effect and

again same thing this drug a would have

the highest efficacy this drug would

have the lowest efficacy but if i even

wanted to make it even more intense i

keep the same potency but again trail

off here so my emacs is even lower so if

they were to say okay

in a question you have drug a which is

black drug blee which is pink drug c

which is going to be green which one of

these has the highest efficacy you would

say would be the top one a which one has

the lowest it'd be the green the bottom

one and so this is an important concept

to be able to understand

all right

now sometimes the question may come up

and say okay if

i have a particular situation where

let's say i have a drug for example a

commonly utilized one bumetanide and

furosemide those are diuretics

when you think about these the efficacy

so let's actually just put here bumetanide

bumetanide

and furosemide

be metanide and furosemide

when you think about this

bumetanide i can actually give a very

low dose

to be able to produce 50

of the max effect

so because of that if i give a very low

dose what's the potency of that drug

it's very very good it's very high

potency so in that situation bumetanide

can be more potent than furosemide

because i can give a low dose

to be able to produce 50 of the mass

effect max effect whereas with

furosemide i'd have to give a little bit

of a higher dose

so we can say that the potency of these

are different

but the literature has actually shown

that just because the potency is

different doesn't mean that the efficacy

is different

so if i actually take bumet nine

ferocity and compared them around the

same like level of actual dose

comparison with their potency i could

actually see that these do have an equal

efficacy so just because a drug has a

different potency does not mean that it

doesn't have the same efficacy so just

make sure you remember that as well

all right my friends so we talked about

efficacy we talked about potency the

last thing that we got to talk about

here for this section of dose response

is something called the therapeutic

index alright guys so now let's talk

about the therapeutic index so

therapeutics is actually a really

important thing is in terms like the

safety of the drug if you will

so what i want us to think about is same

kind of concept here we're still going

to have like this dose response curve if

you will it's just on the x-axis it's

logarithmic concentration of the dose

but instead of it being a response or

effect on the y-axis with the dose

response curve for therapeutic index we

determine a patient population so the

percentage of patient population if you

will but it's still going to be the same

dose response curve so i'm going to

start here

move up like this that's my dose

response curve same thing over here i'm

going to move up and there's my dose

response curve okay so same concept here now

now

we use that terminology where we said

okay here's 100 that's emax right and

then somewhere in the middle here we're

going to be about 50

that was the ec 50 for the dose response

curve well now we're talking about

something different okay we're talking

about the percentage of patient population

population

so remember here at about 50 percent of

the patient population just like 50

percent of the max effect that you can

produce at this drug concentration that

was called ec50 all we're doing is we're saying

saying

this is now the ed50

for therapeutic index

same thing over here here's i'm going to

bring this response curve up just a

little bit higher okay

okay

so here if we look at this

this would be our max effect or 100

percent and somewhere here in the middle

of about 50. so again here

is going to be 50 of the patient

population i'm giving this concentration

or dose of the drug now this is also

called the ed50 now let's compare ec50

was the concentration of drug that i

would give to produce 50 of the max effect

effect

the ed50 is the dose of drug that i

would give to 50 of the population to

produce the clinically desired effect

okay so let's put desired effect this is good

good

good stuff right so this is clinically

desired effect within 50 of the

population if i give this dose of the drug

drug

now what i'm gonna do is is i'm gonna be

a little evil

and i'm gonna give a toxic dose

but on one situation

the the actual toxic dose that i can give

give

to 50 of the population that actually

produces that toxic effect

is not very large so what i can say is

like let's say it's like right here

so that's my toxic dose

so this is a toxic effect

so if that's the toxic effect then right here

here

at giving 50 of the population this dose

of drug

that is my toxic dose so td50

same thing over here i'm going to give

it but now what i'm going to do is it

takes a very large dose of that drug to

give to 50 of the population to produce

the toxic effect if you will so now this

is the toxic effect

effect

and the td50 the dose that i got to give

to 50 of the population

is right here

there's my td50 now

now

the therapeutic index is the difference

between these two that is the

therapeutic index

so this is a therapeutic index which is small

small

and small therapeutic index that's a

scary situation that's not a good thing

ones with a large therapeutic index is a

good thing it's very hard to be able to

you know make a mistake with these types

of drugs giving a particular dosage you

won't kill the patient or cause a very

toxic effect so it's important to

remember that so how do we determine

therapeutic index therapeutic index is

dependent upon the td50 divided by the

ed50 so

td50 divided by ed50

so think about this in this situation

here the td50 is relatively low it's

decreased so the therapeutic index if we think

think low

low

low they're directly proportional so a

decreased td-50 and i don't have a very

i don't have to give a very large dose

to produce the toxic effect of 50 of the

population this very low td50 will give

me a very small or

narrow therapeutic index and this is

scary because they have high risk

of side effects or toxicity if you will

meaning let's say i take for example you

know i remember the drugs in this

category remember a guy a guy right

warning these drugs are lethal all right

so it goes guy warning

warning

these drugs are lethal

and if you like this and it helps you

remember it great it just makes me laugh

but it goes gentamicin gentamicin

gentamicin

warfarin which is a really big one

it's theothen which we probably don't

use too much anymore nowadays

for copd

digoxin good one for afib and heart failure

failure

aeds and i think one of the big ones to

remember is phenytoin

and the last last one is lithium okay

which we use for bipolar so what's

important to remember about these is

that you could give a dosage of this

drug that produces a clinically desired

effect and increasing the dose just a

little bit is a very risky situation to

put you in a toxic effect of the dose

that's why it's important whenever drugs

have a very small therapeutic index you

monitor these drugs through particular

like serum levels or labs so one of the

best ones to give an example about is warfarin

warfarin

i determine it by its inr right the

other ones i can check their levels i

can check the level of an aminoglycoside

or i can check the level of digoxin i

can check the level of phenytoin and

lithium because i want to make sure that

the concentration i have in the blood is

not too high but it with risk of toxic

effect so the margin of error for a

therapeutic index when it's small is

very very

very tiny and there's a high risk of

side effects and the opposite you

probably already know now that this is a

large therapeutic index you have to give

a very high td50 so you increase the

td50 you increase the therapeutic index

and so this is a large

therapeutic index and so because of that

there's less risk

of side effects so i could give a pretty

heavy dosage you know what a good

example of this one is uh steroids and

penicillin so good examples of this one

is penicillin g i can give like massive

amounts of penicillin g and small

amounts of penicillin g and i would have

a very difficult time being able to get

to the toxic effect of it

corticosteroids so steroids are another

one as well you can get pretty like

large doses of steroids as well and again

again

less risk of a toxic side effect so i

think this is an important really really

important concept to remember especially

for clinicals and as well as your exams

all right now let's talk about intrinsic

activity so agonist and antagonists

alright guys so now let's talk about

intrinsic activity between drug receptor

interactions this is actually a pretty

cool concept very high yield so we

should know this as well

so whenever you have a drug that binds

to a particular receptor we want to try

to in some way compare it to our

endogenous system

and so i think one of the really cool

examples to think about is let's say

that um

let's say a very common one is you have

a blood vessel and on that blood vessel

you have what's called alpha-1 receptors

so here's an alpha-1 receptor what we

know is that norepinephrine and

epinephrine are basically molecules that

will bind onto this receptor stimulate

it and trigger vasoconstriction that's the

the

response or the effect if you will of

the drug binding onto that receptor

now let's assume that there's 100

receptor binding by norepinephrine we

know that its effect is vasoconstriction

vasoconstriction

if i give a drug that also can act like norepinephrine

norepinephrine

whenever it binds on to 100 percent of

the receptors are completely saturated

with this drug and it produces the same

intensity or maximal effect 100

vasoconstriction just like

norepinephrine it's a full agonist

if i give another drug drug b

and i have it bind on to 100 of the

receptors are saturated by this other

type of agonist drug b

but it doesn't produce the same maximal

effect or efficacy

as drug a did we call that a partial agonist

agonist

and then when you have another drug drug c

and this binds on to the alpha-1

receptor and all it does is it keeps the

actual receptor completely inactivated

then you significantly reduce the actual

efficacy and the maximal effect of that

drug to below the basal activity of the

receptor because normally receptors have

some degree of basal activity

that degree of basal activity is about

12 percent

so no matter what if i give a particular

drug all we're doing is we're increasing

the efficacy of that drug above its

basal activity 12 percent about most

textbooks will say

so say i say a full agonist with the

first case so full agonist so for

example norepinephrine i can give a drug

just like norepinephrine norepinephrine

i can just give it exogenously so

levofed norepinephrine another agonist

would be phenylephrine or epinephrine

they both can bind onto the alpha

receptors and produce the same type of

you know maximal effect so that would be

an example of a full agonist so if i

were to give let's say these are all

alpha one receptors i could give a drug

like norepinephrine

epinephrine or i can give something

called phenylephrine okay

okay

and these will all produce the same type

of clinical response when they bind to

so 100 percent of the receptors are

bound by a drug and they produce the

clinical response the clinical effect

that they have will be the max

effect that you can produce the e max

okay so if we were to drop that off on

the curve here log mere the

concentration of the drug on the x-axis

response on the y-axis just like the

dose response curve what we're going to

see is is that there's 12 basal activity

i'm going to increase it from that point

that would be the curve at 100 max

efficacy if i give a full agonist so

remember this is a full

full

agonist it will produce the same it'll

mimic the basic endogenous system okay

a partial agonist will be something a

little bit different

so i think a really interesting example

about a partial agonist could be

something for example you know there's a

opioid receptors so let's say that this

is what's called a mu

receptor a mu receptor is a type of

opioid receptor and it loves to bind

onto something called morphine

and so what happens is

if you give something

uh like a partial agonist this is really interesting

interesting

partial agonists they'll bind on to

these receptors these mu receptors let's

just say an example of this could be

something called buprenorphine buprenorphine

and what happens is this will actually

bind onto these new receptors

if it saturates 100 of the mu receptors

it'll produce a clinical effect that is below

below

the max effect it's sub-par sub

max effect maybe like if we were to say

this is 100 this is like 70 or 60

percent but it's below the max effect

that's a partial agonist it will not

produce the max effect

but there's something really interesting

about partial agonist that i'm going to

talk about in just a second but let's

say that we graph this out in a pink so

now we have another one where we're

going to start this off beyond the basal

activity of the receptor i'll see that

as i increase the concentration of the

drug i will do what

i'm going to drop off my efficacy

because no matter what i'll never reach

max effect so this one i'm going to even

i'm going to make it a little bit more

drastic so we're going to drop this one

off even a little bit more than that so

this is going to be a partial

agonist now here's something that's

really interesting about partial agonist

partial agonists if you keep giving

higher concentrations of a partial

agonist and you give it in combination

with an agonist so for example what did

we say would bind on to the mu receptors

let's say that you give buprenorphine

and you're giving it with morphine

and let's make sure morphine is like in

a different color here let's make him in

this red color here so here's morphine

in red and then buprenorphine is going

to be in black here

if you give buprenorphine what it'll do

is it'll bind to all of these mu receptors

receptors

and basically as you increase the

concentration of it it's going to block

the actual morphine from being able to

bind into that receptors because it's

kind of in the same active site as the

buprenorphine and so that's blocking

that morpheme from being able to bind to

that actual receptor so what's really

interesting is that when you give an

agonist and a partial agonist together

this is a partial agonist

again full agonist partial agonist when

you give these together what you see is

is you see something called competitive inhibition

inhibition where

where

this buprenorphine is going to compete

with morphine for the actual mu receptor

blocking it and the only way that you're

going to be able to see the morphine

produce max effect meaning that whenever

this guy binds to the receptor it

produces the max effect is if i keep

trying to increase and increase and

increase the concentration of my

morphine to eventually displace the

buprenorphine out of that active site

that's a really interesting concept to

remember so partial agonist can also act

like antagonists

so remember that okay sometimes partial

agonists if you increase the

concentration of them they can act like

antagonists specifically competitive

antagonists all right off my soapbox

with that one

the next one that i want you guys to

think about is called inverse agonist

now inverse agonists are a little funky

they're weird ones so what happens is

these drugs will bind to the receptor

and when they bind to the receptor

they will significantly decrease the

effect of this drug like

less than 12 which is the basal activity

of the drug you're like what the heck so

what would i see that i would see this

that's that's my inverse agonist so for

my inverse agonist

i'm going to see this particular drug reduce

reduce

the actual effect of the um it's going

to reduce the actual maximal effects

significantly to the point where it's

less than the basal activity how the heck

heck

do you decrease the drug receptor

interaction where you go below the basal

activity you inactivate the receptor

that's what this thing does so basically

what it does is you have receptors that

can exist in two forms so let's say

here's one receptor here's another receptor

receptor

and if i want to go back and forth

between these two forms here so let's

say i want to go back and forth so this

is going to be r which let's say that

this is the active form

and then we're going to make this one

so make this r

let's make this one r prime this is the in

active form

what we do here is that when an inverse

agonist interacts

it tries to be able to push the reaction

and keep it in this inactive form so

what it does it tries to be able to keep

this receptor in the inactive form it

shifts this reaction to keep it

inactivated so now no other agonist will

be able to bind to it so it completely

reduces the drug receptor interaction

below the basal activity that's an

important thing to think about

inverse agonists there's not too many

drugs that you can think about for this one

one

one of them could be something like

antihistamines can act like this on the

h1h2 receptors but don't get too bogged

down in the details focus more on full

and partial

now the next thing is that sometimes we

have to talk about antagonists and what

antagonists do which we're going to talk

about next is they work to be able to

oppose the agonists and what they try to

do is they try to be able to act like a

neutral component here and so they'll

basically kind of like inhibit any type

of agonist being able to bind to the

receptor but at least allow for the

receptor to maintain basal activity and

so this will be the antagonist and

that's what we're going to talk about

next we're going to talk about

competitive and non-competitive

antagonists let's talk about that now

all right so now we're going to talk

about the same concept we talked about

agonists full agonist partial agonist

inverse agonist with antagonists

these are basically going to be working

in the opposite function of an agonist

so they're completely opposite so

take for example

um let's use this example here we had up

above we have a blood vessel has a alpha 1

alpha 1 receptor norepinephrine will

bind to that and cause vasoconstriction

an antagonist

to that drug

would be something that is an alpha one blocker

blocker

so i would give something like an alpha

one blocker

and that would basically bind on to this

little receptor site

inhibiting or preventing norepinephrine

from being able to exert its effect on

it therefore there would be no vasoconstriction

vasoconstriction

that is what an antagonist does is it

opposes the action of the agonist in

this case we're using norepinephrine as

an example

so how does it do this

well what happens is let's say here we

have our cell

and here's the receptor let's say we have

have

in general our agonist and we're going

to represent agonist here in black okay

so here's our agonist and what we're

going to do is we're going to give

what's called a competitive antagonist

and we'll just use this example here

here's our

neuroepinephrine which is going to bind

onto these alpha-1 receptors and then

over here i have my alpha i'm going to

put alpha blocker all right so one of

the alpha blockers you can have tons of

these dang things but an alpha blocker

of some kind right we could use

phentolamine whatever we'll just say phentolamine it's just an example of one

phentolamine it's just an example of one of these so phentolamine

what phentolamine will do is is it'll come and basically norepinephrine is

come and basically norepinephrine is supposed to bind to these receptors the

supposed to bind to these receptors the phentolamine will plug into these

phentolamine will plug into these receptors

receptors and basically block

and basically block the norepinephrine from being able to

the norepinephrine from being able to bind here so if we were to look at the

bind here so if we were to look at the normal curve let's say that we have the

normal curve let's say that we have the normal dose response curve when

normal dose response curve when norepinephrine binds to these receptors

norepinephrine binds to these receptors we know that it produces a nice

we know that it produces a nice sigmoidal curve so same thing effect you

sigmoidal curve so same thing effect you can say response it's the same concept

can say response it's the same concept this is the dose response curve i'm

this is the dose response curve i'm going to see something like this right

going to see something like this right that's my dose response curve this is a

that's my dose response curve this is a 100 max effect and this right here will

100 max effect and this right here will be somewhere around 50 max effect right

be somewhere around 50 max effect right now what i know is is that this would be

now what i know is is that this would be what would happen if neuroepinephrine

what would happen if neuroepinephrine was to bind to the actual alpha and

was to bind to the actual alpha and receptor

receptor now what i'm going to do is is i'm going

now what i'm going to do is is i'm going to give phentolamine

to give phentolamine and when i give so this is actually

and when i give so this is actually going to be my agonist if you will so

going to be my agonist if you will so this is my agonist whenever it's

this is my agonist whenever it's supposed to bind so norepinephrine what

supposed to bind so norepinephrine what i'm going to do is i'm going to give it

i'm going to do is i'm going to give it a competitive antagonist like

a competitive antagonist like phantolamine it's going to work to block

phantolamine it's going to work to block these receptors

these receptors now if there is any receptors that are

now if there is any receptors that are available norepinephrine will still bind

available norepinephrine will still bind so if there is any receptors that are

so if there is any receptors that are actually available norepinephrine will

actually available norepinephrine will bind to these and still produce some

bind to these and still produce some type of response

type of response but if i still want it to be able to

but if i still want it to be able to produce the maximum response what do i

produce the maximum response what do i have to do

have to do what i need to do is is i need to

what i need to do is is i need to increase

increase the concentration

the concentration of my norepinephrine or my agonist to

of my norepinephrine or my agonist to overcome and displace

overcome and displace the antagonist out of the active site i

the antagonist out of the active site i want to pop those

want to pop those out of the active site so that i have

out of the active site so that i have the ability to beat that guy out and

the ability to beat that guy out and bind onto these receptors and produce

bind onto these receptors and produce the same type of clinical response that

the same type of clinical response that i want

i want but in order for me to do that in the

but in order for me to do that in the presence of this antagonist i need to

presence of this antagonist i need to increase the concentration heavily

increase the concentration heavily so let's say now

so let's say now i have a new curve

i have a new curve and this new curve what am i going to

and this new curve what am i going to have to do if i need to be able to

have to do if i need to be able to produce the same clinical effect the

produce the same clinical effect the same response as an agonist would by

same response as an agonist would by itself

itself i'm going to have to

i'm going to have to increase the concentration of the drugs

increase the concentration of the drugs significantly

significantly to be able to produce the same type of

to be able to produce the same type of clinical response

clinical response and so this would be a combination of my

and so this would be a combination of my agonist

agonist and

and antagonist

antagonist and specifically which one competitive

and specifically which one competitive antagonist so what i'm seeing is is in

antagonist so what i'm seeing is is in order for me to be able to produce the

order for me to be able to produce the same kind of

same kind of maximal effect i'm going to have to do

maximal effect i'm going to have to do what to my dosage

what to my dosage increase the dosage so i have to

increase the dosage so i have to increase

increase the dosage do you guys remember off of

the dosage do you guys remember off of that curve

that curve what that looks like so remember this is

what that looks like so remember this is our e

our e max the maximal effect that this actual

max the maximal effect that this actual drug receptor interaction can perform

drug receptor interaction can perform and then at 50 percent

this was our ec 50

50 and then this was our ec 50.

and then this was our ec 50. what was happening if i increased or i

what was happening if i increased or i shifted the actual curve to the right

shifted the actual curve to the right what did that do that increased my ec 50

what did that do that increased my ec 50 what does that do to the potency then

what does that do to the potency then it decreased the potency so competitive

it decreased the potency so competitive antagonists do what to your potency they

antagonists do what to your potency they decrease your potency but what do they

decrease your potency but what do they do to the emacs

do to the emacs nothing so here's what i want you to

nothing so here's what i want you to remember

remember no change

no change in emacs

in emacs but what do they do to the ec 50 they

but what do they do to the ec 50 they decrease your ec

decrease your ec 50 which is going to do what

50 which is going to do what it's going to require if i'm sorry if

it's going to require if i'm sorry if you're actually increasing your ec50 i

you're actually increasing your ec50 i apologize if you're increasing the ec50

apologize if you're increasing the ec50 what is that doing to the potency it's

what is that doing to the potency it's decreasing the potency because these are

decreasing the potency because these are inversely proportional so we're shifting

inversely proportional so we're shifting it to the right increasing our ec 50

it to the right increasing our ec 50 which means i have to give more of the

which means i have to give more of the drug to be able to have the same type of

drug to be able to have the same type of potent effect that's what i want you to

potent effect that's what i want you to remember so for one thing for

remember so for one thing for competitive no change in e-max

competitive no change in e-max but it does decrease the potency so you

but it does decrease the potency so you have to give more of the drug to

have to give more of the drug to displace the competitive inhibitor out

displace the competitive inhibitor out of that spot so that you can produce the

of that spot so that you can produce the same type of maximal effect or clinical

same type of maximal effect or clinical response all right i hope that made

response all right i hope that made sense

sense for non-competitive antagonists it's a

for non-competitive antagonists it's a teensy bit different so let's use the

teensy bit different so let's use the same example here that we talked about

same example here that we talked about this blood vessel

this blood vessel let's say here this actually kind of

let's say here this actually kind of worked out well i didn't even think

worked out well i didn't even think about this but here you have an alpha-1

about this but here you have an alpha-1 receptor again norepinephrine's supposed

receptor again norepinephrine's supposed to bind so i'm going to give an alpha

to bind so i'm going to give an alpha blocker

blocker that's going to work to

that's going to work to basically block prevent work against the

basically block prevent work against the activity of the agonist right so we know

activity of the agonist right so we know normally if we were to give

normally if we were to give norepinephrine by itself it would look

norepinephrine by itself it would look something like this right same kind of

something like this right same kind of curve there that's our dose response

curve there that's our dose response curve this is the agonist

curve this is the agonist by itself okay just the agonist

by itself okay just the agonist now

now here is my norepinephrine

here is my norepinephrine and then down here same color here in

and then down here same color here in blue i'm going to have my

blue i'm going to have my antagonist but this is a non-competitive

antagonist but this is a non-competitive i didn't plan this but this actually

i didn't plan this but this actually worked out perfectly so another alpha

worked out perfectly so another alpha blocker so this is actually

blocker so this is actually noroepinephrine

noroepinephrine there's another alpha blocker that acts

there's another alpha blocker that acts as a non-competitive antagonist and it's

as a non-competitive antagonist and it's called phenoxybenzamine

called phenoxybenzamine benza

benza mean

mean now the difference here

now the difference here is that phentol mean bound to the actual

is that phentol mean bound to the actual active site so you see a little pocket

active site so you see a little pocket there that's called the active site the

there that's called the active site the same site

same site where the actual

where the actual agonist binds to

agonist binds to now

now phenoxybenzamine does not bind to the

phenoxybenzamine does not bind to the active site so when you have a

active site so when you have a non-competitive inhibitor like

non-competitive inhibitor like phenoxybenzamine it binds to another

phenoxybenzamine it binds to another site besides the active site so let's

site besides the active site so let's say that it binds to like right here

say that it binds to like right here binds to like right here binds to here

binds to like right here binds to here binds to here it's not the active site

binds to here it's not the active site this site here if we were to kind of

this site here if we were to kind of like let's say that we zoomed in on this

like let's say that we zoomed in on this theoretically let's say here's the

theoretically let's say here's the receptor

receptor i'm going to put a little kind of like

i'm going to put a little kind of like divot here so here's the receptor when

divot here so here's the receptor when we really zoom in on it

we really zoom in on it here's the active site that right there

here's the active site that right there is called the allosteric site so it's a

is called the allosteric site so it's a site

site on the actual protein or receptor other

on the actual protein or receptor other than the active site

than the active site when this phenoxybenzemian or

when this phenoxybenzemian or non-competitive antagonist binds to this

non-competitive antagonist binds to this it changes the shape

it changes the shape of the actual receptor to where now

of the actual receptor to where now it changes it in such a way where maybe

it changes it in such a way where maybe it's not even the same shape here

it's not even the same shape here or maybe maybe it looks like this now

or maybe maybe it looks like this now maybe it's like

and now it's going to be harder for that to be able to bind to the agonist

to be able to bind to the agonist norepinephrine

norepinephrine so because of that norepinephrine

so because of that norepinephrine wants to be able to bind here but it

wants to be able to bind here but it can't even know that there's a site

can't even know that there's a site available

available these non-competitive antagonists

these non-competitive antagonists bind to the allosteric site changing its

bind to the allosteric site changing its shape that no matter what even if i try

shape that no matter what even if i try to increase and increase and increase

to increase and increase and increase the concentration of norepinephrine it's

the concentration of norepinephrine it's not going to matter because it's going

not going to matter because it's going to have tons of active sites available

to have tons of active sites available that's not going to make a difference

that's not going to make a difference and if i increase the concentration

and if i increase the concentration it'll still have a difficult time being

it'll still have a difficult time being able to bind to the active sites

able to bind to the active sites but what i know is that no matter what i

but what i know is that no matter what i do to the concentration if i can

do to the concentration if i can increase it increase and increase it

increase it increase and increase it it's not going to be able to produce any

it's not going to be able to produce any improvement

improvement in the overall response or cellular

in the overall response or cellular effect and that's a really important

effect and that's a really important concept so the response

concept so the response i can't spell a response for the life of

i can't spell a response for the life of me the response or the clinical effect

me the response or the clinical effect is going to plummet

is going to plummet it's going to plummet even if i increase

it's going to plummet even if i increase the concentration of this dang drug or

the concentration of this dang drug or agonist it's not going to matter because

agonist it's not going to matter because this

this not non competitive inhibitor

not non competitive inhibitor phenoxy benzamine is binding to the

phenoxy benzamine is binding to the allosteric site changing its shape to no

allosteric site changing its shape to no matter what it's not going to be able to

matter what it's not going to be able to bind properly to the agonist so what

bind properly to the agonist so what would the graph look like here

would the graph look like here well i know that if with respect to

well i know that if with respect to concentration or potency that's not

concentration or potency that's not going to change it's going to stay the

going to change it's going to stay the same so if i were to look here it would

same so if i were to look here it would should look just like this i shouldn't

should look just like this i shouldn't shift the curve i'm going to do it just

shift the curve i'm going to do it just a little so you guys can see the

a little so you guys can see the difference here but what i'm going to

difference here but what i'm going to notice here is that this is

notice here is that this is son of a gun

son of a gun this is my max effect this is my emacs

this is my max effect this is my emacs so that's at a hundred percent

so that's at a hundred percent response or effect here i'm going to

response or effect here i'm going to come right in the middle about 50

come right in the middle about 50 so i know that this right here

so i know that this right here is my ec 50. they're about exactly the

is my ec 50. they're about exactly the same and that should make sense because

same and that should make sense because even if i increase the concentration of

even if i increase the concentration of my monopoly it's not going to make any

my monopoly it's not going to make any difference in the response

difference in the response there's no effect on potency with

there's no effect on potency with respect to non-competitive inhibitors

respect to non-competitive inhibitors but what i am going to see is that the

but what i am going to see is that the response the effect that it's going to

response the effect that it's going to have is going to decrease significantly

have is going to decrease significantly because the agonists can't bind to the

because the agonists can't bind to the dang active site and produce the

dang active site and produce the response it wants to because the

response it wants to because the non-competitive inhibitor changed its

non-competitive inhibitor changed its shape by binding to the allosteric site

shape by binding to the allosteric site so what will i see i'll see this thing

so what will i see i'll see this thing drop off before reaching maximal

drop off before reaching maximal response or effect so it'll drop off

response or effect so it'll drop off like this and here will be its emacs

like this and here will be its emacs this

this is the agonist

is the agonist and the

and the non-competitive

antagonist and what do i see with respect to the

and what do i see with respect to the e-max

e-max i see a decrease in the e-max if i see a

i see a decrease in the e-max if i see a decrease

decrease in the e-max

what do i know then i know that non-competitive inhibitors do what

non-competitive inhibitors do what they

they decrease the efficacy of the drugs so

decrease the efficacy of the drugs so what would they do to the ec 50 the

what would they do to the ec 50 the ec-50 will be the same no effect

ec-50 will be the same no effect no change that's one thing but the e-max

no change that's one thing but the e-max that will change you'll decrease the

that will change you'll decrease the e-max with respect to non-competitive

e-max with respect to non-competitive inhibitors the only way you can actually

inhibitors the only way you can actually prevent this and improve the efficacy is

prevent this and improve the efficacy is getting rid of the non-competitive

getting rid of the non-competitive inhibitor you increase the drug

inhibitor you increase the drug concentration trying to decrease the

concentration trying to decrease the potency is not going to affect it so

potency is not going to affect it so that's an important thing to

that's an important thing to remember all right initiatives we

remember all right initiatives we covered pharmacodynamics now let's do a

covered pharmacodynamics now let's do a couple practice problems see if we can

couple practice problems see if we can test you guys knowledge and review or

test you guys knowledge and review or your understanding now let's get to it

your understanding now let's get to it all right engineer so we finished our

all right engineer so we finished our pharmacodynamic video but now we got to

pharmacodynamic video but now we got to really put everything that we talked

really put everything that we talked about on the whiteboard to practice to

about on the whiteboard to practice to see if you guys really understand this

see if you guys really understand this okay

okay so first question here which of the

so first question here which of the following best describes how a drug that

following best describes how a drug that acts as a agonist

acts as a agonist on the gaba a receptor affects signal

on the gaba a receptor affects signal transduction in a neuron i went through

transduction in a neuron i went through this example very specifically so a gaba

this example very specifically so a gaba a receptor is an example of what kind of

a receptor is an example of what kind of receptor is it a ligand-gated type of

receptor is it a ligand-gated type of ion channel that it will act as right

ion channel that it will act as right whenever gaba-a receptors are

whenever gaba-a receptors are particularly is it a ligand-gated

particularly is it a ligand-gated is it a g-protein g-protein-coupled

is it a g-protein g-protein-coupled receptor or is it some type of tyrosine

receptor or is it some type of tyrosine kinase receptor or is it an

kinase receptor or is it an intracellular receptor i use this one as

intracellular receptor i use this one as a very specific example

a very specific example as a ligand-gated ion channel and so

as a ligand-gated ion channel and so whenever you give a agonist of the gaba

whenever you give a agonist of the gaba a receptor it'll bind onto that little

a receptor it'll bind onto that little pocket open up the channel to allow for

pocket open up the channel to allow for chloride ions to flow into the cell

chloride ions to flow into the cell decreasing the chance of generating a

decreasing the chance of generating a action potential

action potential so would it be activating the

so would it be activating the intracellular receptor process

intracellular receptor process so no

so no would it be opening up ion channels that

would it be opening up ion channels that allow sodium no would it be activation

allow sodium no would it be activation of this receptor subtype that opens up

of this receptor subtype that opens up ion channels that allow chloride to

ion channels that allow chloride to enter in

enter in yes that's likely the one or does it

yes that's likely the one or does it activate the receptor the g protein

activate the receptor the g protein remember i told you it was not a g

remember i told you it was not a g protein

protein it's not an intracellular receptor

it's not an intracellular receptor it does act as a ligand-gated ion

it does act as a ligand-gated ion channel so it is opening up for sodium

channel so it is opening up for sodium or chloride it's particularly for

or chloride it's particularly for chloride remember that example i showed

chloride remember that example i showed you on the whiteboard this was the one

you on the whiteboard this was the one and we used this kind of way of being

and we used this kind of way of being able to treat anxiety and seizures etc

able to treat anxiety and seizures etc all right next question after one

all right next question after one milligram if one milligram of lorazepam

milligram if one milligram of lorazepam produces the same anxiolytic response as

produces the same anxiolytic response as 10 milligrams

10 milligrams of diazepam

of diazepam which is correct

which is correct think about your dose response curve

think about your dose response curve so remember as we increase the dosage

so remember as we increase the dosage going towards the right

going towards the right what happens to the potency of the drug

what happens to the potency of the drug remember i have one drug here it's going

remember i have one drug here it's going to be towards the left i can give a very

to be towards the left i can give a very low dose of that drug to produce the

low dose of that drug to produce the same efficacious response

same efficacious response if i have to give a higher dosage to

if i have to give a higher dosage to produce the same efficacious anxiolytic

produce the same efficacious anxiolytic response what is happening to the

response what is happening to the potency of that drug that means the

potency of that drug that means the potency of diazepam

potency of diazepam is decreased that means i have to give a

is decreased that means i have to give a higher con a higher dose of that drug to

higher con a higher dose of that drug to be able to produce the same effect so

be able to produce the same effect so what i say lorazepam is more potent than

what i say lorazepam is more potent than in this case i would i would say that

in this case i would i would say that one milligram is definitely that

one milligram is definitely that lorazepam is more efficacious no because

lorazepam is more efficacious no because remember doses were producing the same

remember doses were producing the same anxiolytic response so the efficacy is

anxiolytic response so the efficacy is the same it's just the dosage that i

the same it's just the dosage that i have to give to change that to reach

have to give to change that to reach that efficacious response is different

that efficacious response is different so it's not b lorazepam is a full

so it's not b lorazepam is a full agonist and diazepam as a partial

agonist and diazepam as a partial agonist don't worry about that that has

agonist don't worry about that that has nothing to do with this lorazepam is a

nothing to do with this lorazepam is a better drug to take for anxiety than

better drug to take for anxiety than diazepam again has nothing to do with

diazepam again has nothing to do with this so it's either efficacy or potency

this so it's either efficacy or potency and in this case lorazepam is more

and in this case lorazepam is more potent than diazepam again remember that

potent than diazepam again remember that as you have to

as you have to increase the concentration of your drug

increase the concentration of your drug so the ec50 so that was the actual

so the ec50 so that was the actual concentration to reach 50 of the max

concentration to reach 50 of the max effect

effect as that goes more towards the right or

as that goes more towards the right or increases the potency of the drug

increases the potency of the drug decreases so that's an important concept

decreases so that's an important concept all right

all right next one here so we have 10 milligrams

next one here so we have 10 milligrams of oxycodone produces a greater

of oxycodone produces a greater analgesic response than does aspirin at

analgesic response than does aspirin at any dose which is correct so now we're

any dose which is correct so now we're looking at the response

looking at the response so the response is actually a degree of

so the response is actually a degree of efficacy of 10 milligrams of oxycodone

efficacy of 10 milligrams of oxycodone will produce a higher efficacious

will produce a higher efficacious response than compared to aspirin at any

response than compared to aspirin at any dose that means that oxycodone is more

dose that means that oxycodone is more efficacious than aspirin is because

efficacious than aspirin is because again we're looking at the response not

again we're looking at the response not the dose that we need to attain the same

the dose that we need to attain the same response so in this case it's more

response so in this case it's more efficacious for oxycodone

efficacious for oxycodone okay

okay all right in the presence of propanol

all right in the presence of propanol a higher concentration of epinephrine is

a higher concentration of epinephrine is required to elicit full anti-asthmatic

required to elicit full anti-asthmatic activity propanol has no effect on

activity propanol has no effect on asthma symptoms which is correct

asthma symptoms which is correct regarding these medications

regarding these medications so what you're trying to look at is

so what you're trying to look at is you're trying to look at particularly

you're trying to look at particularly here again for presence of propranolol a

here again for presence of propranolol a higher concentration of epinephrine is

higher concentration of epinephrine is required to elicit a full

required to elicit a full anti-asthmatic activity propanol has no

anti-asthmatic activity propanol has no effect on asthma symptoms which is

effect on asthma symptoms which is correct regarding these medications

correct regarding these medications so when you look at this we're looking

so when you look at this we're looking at now agonist and partial agonists etc

at now agonist and partial agonists etc so

so if i get propanol

if i get propanol i need to increase the concentration of

i need to increase the concentration of my epinephrine

my epinephrine to be able to reach the full antismatic

to be able to reach the full antismatic activity well epinephrine will act in

activity well epinephrine will act in this case is kind of like wanting to be

this case is kind of like wanting to be able to act as a full agonist in this

able to act as a full agonist in this situation that's what epinephrine wants

situation that's what epinephrine wants to be able to do it wants to be able to

to be able to do it wants to be able to produce bronchodilation

produce bronchodilation if you give her panel off her panel law

if you give her panel off her panel law is going to try to be able to block that

is going to try to be able to block that in a particular way

in a particular way because of that propanol since it has no

because of that propanol since it has no effect on asthma symptoms it's not

effect on asthma symptoms it's not really going to act as like you know in

really going to act as like you know in this situation here it's not really

this situation here it's not really going to work as an agonist because it

going to work as an agonist because it has no effect on asthma symptoms so

has no effect on asthma symptoms so therefore it can't act as an agonist

therefore it can't act as an agonist if that's the case then i have to

if that's the case then i have to increase the concentration of my

increase the concentration of my epinephrine to be able to reach the full

epinephrine to be able to reach the full activity that means the propanol is

activity that means the propanol is acting as a beta blocker so i'm going to

acting as a beta blocker so i'm going to have to increase the concentration of

have to increase the concentration of epinephrine to block to push him out of

epinephrine to block to push him out of that beta receptor site to produce the

that beta receptor site to produce the same effect

same effect if you remember

if you remember this diagram here this was competitive

this diagram here this was competitive antagonist non-competitive antagonist

antagonist non-competitive antagonist so if you look here for competitive

so if you look here for competitive antagonists what do we need to do to

antagonists what do we need to do to produce the same efficacious response so

produce the same efficacious response so imagine here

imagine here is just going to be epinephrine okay

is just going to be epinephrine okay here's its efficacious response this is

here's its efficacious response this is the dose that we can give if we give

the dose that we can give if we give propanol propanol is actually going to

propanol propanol is actually going to take up some of those receptors and

take up some of those receptors and block epinephrine so then what i'm going

block epinephrine so then what i'm going to have to do is increase the

to have to do is increase the concentration of my epinephrine even

concentration of my epinephrine even more so my ec50 is going to increase so

more so my ec50 is going to increase so the potency of my drug is less

the potency of my drug is less and so because of that i'm going to have

and so because of that i'm going to have to increase the concentration of

to increase the concentration of epinephrine to push some of the

epinephrine to push some of the perpendicular out to get the same

perpendicular out to get the same efficacy

efficacy so in this situation i would say

so in this situation i would say epinephrine is definitely a full agonist

epinephrine is definitely a full agonist propanol is a partial agonist no because

propanol is a partial agonist no because it has it says here propanol has no

it has it says here propanol has no effect on asthma symptoms so usually

effect on asthma symptoms so usually that means that it's an antagonist

that means that it's an antagonist so epinephrine is an agonist that is

so epinephrine is an agonist that is true and propanol is a non-competitive

true and propanol is a non-competitive antagonist no because if you look at

antagonist no because if you look at this situation

this situation even if i increase the concentration

even if i increase the concentration here

here of my actual epinephrine again it's not

of my actual epinephrine again it's not going to be able to reach the max effect

going to be able to reach the max effect so again usually with non-competitive

so again usually with non-competitive antagonists there's no change in actual

antagonists there's no change in actual potency potency changes with only

potency potency changes with only competitive antagonists efficacy changes

competitive antagonists efficacy changes with non-competitive antagonists we're

with non-competitive antagonists we're still trying to elicit the full

still trying to elicit the full antisemitic activity so in this

antisemitic activity so in this situation i would say epinephrine is the

situation i would say epinephrine is the agonist trying to produce the

agonist trying to produce the bronchodilation per panel is the

bronchodilation per panel is the competitive antagonist trying to produce

competitive antagonist trying to produce no actual benefit on asthma symptoms but

no actual benefit on asthma symptoms but if i increase the concentration of my

if i increase the concentration of my epinephrine i can beat some of the upper

epinephrine i can beat some of the upper panel out of the beta receptor site and

panel out of the beta receptor site and increase the actual efficacy of its

increase the actual efficacy of its effect but it's going to have to be at

effect but it's going to have to be at higher dosages so with this being said i

higher dosages so with this being said i would say that epinephrine is an agonist

would say that epinephrine is an agonist and propanol is a competitive antagonist

and propanol is a competitive antagonist the key thing here is here is the

the key thing here is here is the antagonist and you can tell it's an

antagonist and you can tell it's an antagonist because when it says

antagonist because when it says perpendicular has no effect on asthma

perpendicular has no effect on asthma symptoms that meaning it can't be as an

symptoms that meaning it can't be as an it can't be an agonist if you give a

it can't be an agonist if you give a drug and you're trying to look at the

drug and you're trying to look at the actual effect of that drug in this

actual effect of that drug in this situation because it has no effect

situation because it has no effect we're going to say it's more of an

we're going to say it's more of an antagonist it definitely won't have

antagonist it definitely won't have agonistic effects so it automatically

agonistic effects so it automatically gets rid of

gets rid of b then you come down to the point here

b then you come down to the point here where you're trying to look at is it a

where you're trying to look at is it a competitive and non-competitive

competitive and non-competitive antagonist well the way that we tell is

antagonist well the way that we tell is based upon the way they write this we

based upon the way they write this we know in the presence of perpendicular a

know in the presence of perpendicular a higher concentration of epinephrine is

higher concentration of epinephrine is required to produce the same efficacy

required to produce the same efficacy so efficacy is staying the same look

so efficacy is staying the same look efficacy changes here

efficacy changes here but i require a larger dosage of the

but i require a larger dosage of the drug meaning that the curve shifts to

drug meaning that the curve shifts to the right i have to increase the

the right i have to increase the concentration of my epinephrine my

concentration of my epinephrine my agonist

agonist in the presence of a competitive

in the presence of a competitive antagonist and that's why this answer is

antagonist and that's why this answer is the correct answer c

the correct answer c all right

all right let's see if we can actually test your

let's see if we can actually test your knowledge again here we go in the

knowledge again here we go in the presence of picker toxin diazepam is

presence of picker toxin diazepam is less efficacious

less efficacious at causing sedation regardless of the

at causing sedation regardless of the dose you see the way the word of that

dose you see the way the word of that picker toxin has no sedative effect

picker toxin has no sedative effect meaning it's not an agonist

meaning it's not an agonist even at the highest dose which of the

even at the highest dose which of the following is correct regarding these

following is correct regarding these agents so think about this guys

agents so think about this guys in the presence of picker toxin diazepam

in the presence of picker toxin diazepam which is going to be in this situation

which is going to be in this situation providing sedation so it's an agonist

providing sedation so it's an agonist if you give picrotoxin diazepam is less

if you give picrotoxin diazepam is less efficacious meaning that this is not

efficacious meaning that this is not going to shift to the right it shifts

going to shift to the right it shifts down efficacy is decreasing in this

down efficacy is decreasing in this situation here where you have your

situation here where you have your agonist and then the presence of an

agonist and then the presence of an agonist and some type of antagonist in

agonist and some type of antagonist in this situation picrotoxin is a

this situation picrotoxin is a non-competitive antagonist and it's

non-competitive antagonist and it's decreasing the efficacy of diazepam

decreasing the efficacy of diazepam so in this situation picker toxin is a

so in this situation picker toxin is a competitive no picker toxin a

competitive no picker toxin a non-competitive yes diazepam is less

non-competitive yes diazepam is less efficacious than has nothing to do with

efficacious than has nothing to do with it because again we're looking at

it because again we're looking at in the situation here diazepam

in the situation here diazepam is less efficacious in the presence of

is less efficacious in the presence of picker toxin not in comparison to this

picker toxin not in comparison to this because picker toxin has no effect on

because picker toxin has no effect on sedation diazepam is less potent than

sedation diazepam is less potent than pickertox and again not a comparison

pickertox and again not a comparison that we're making in this situation

that we're making in this situation picrotoxin is a non-competitive

picrotoxin is a non-competitive antagonist all right let's move on to

antagonist all right let's move on to another question here so it says here in

another question here so it says here in this question which of the following up

this question which of the following up regulates post-synaptic alpha-1

regulates post-synaptic alpha-1 adrenergic receptors

adrenergic receptors all right so daily use of amphetamine

all right so daily use of amphetamine that causes release of neural

that causes release of neural epinephrine

epinephrine okay so it's just saying if you use

okay so it's just saying if you use amphetamine basically the amphetamines

amphetamine basically the amphetamines will potentially continue to cause

will potentially continue to cause the release of norepinephrine and maybe

the release of norepinephrine and maybe that'll act on those alpha-1 adrenergic

that'll act on those alpha-1 adrenergic receptors and potentially help to

receptors and potentially help to upregulate them because of repeated

upregulate them because of repeated exposure that doesn't actually

exposure that doesn't actually completely

completely kind of go in line with this and the

kind of go in line with this and the reason why

reason why is that if a patient is using

is that if a patient is using amphetamines daily and that causes the

amphetamines daily and that causes the release of norepinephrine it'll act on

release of norepinephrine it'll act on those alpha-1 adrenergic receptors

those alpha-1 adrenergic receptors pretty consistently and they'll get kind

pretty consistently and they'll get kind of like over-stimulated and a way to

of like over-stimulated and a way to protect themselves is to regulate so i

protect themselves is to regulate so i don't think that's the correct answer

don't think that's the correct answer and being a

and being a a disease that causes an increase in the

a disease that causes an increase in the activity of norepinephrine

activity of norepinephrine neurons

neurons so in this situation here we're saying

so in this situation here we're saying some disease that causes an increase in

some disease that causes an increase in the activity of these norepinephrine

the activity of these norepinephrine neurons so it's saying that these

neurons so it's saying that these neurons are releasing more

neurons are releasing more norepinephrine consistently meaning that

norepinephrine consistently meaning that it's acting on the alpha one and or

it's acting on the alpha one and or adrenergic receptors over stimulating

adrenergic receptors over stimulating them

them if they're over stimulating them they

if they're over stimulating them they wouldn't up regulate they would

wouldn't up regulate they would potentially develop a response to down

potentially develop a response to down regulate in response to all of that so

regulate in response to all of that so that again can't be the right answer

that again can't be the right answer saying that a and b are the same thing

saying that a and b are the same thing daily use of phenylephrine an alpha one

daily use of phenylephrine an alpha one receptor agonist

receptor agonist so again this is another way of saying

so again this is another way of saying okay you have

okay you have daily use of phenylephrine it's going to

daily use of phenylephrine it's going to act on the alpha-1 receptor

act on the alpha-1 receptor overstimulate it cause it to again cause

overstimulate it cause it to again cause an increase in vasoconstriction and

an increase in vasoconstriction and again over time the cell will say this

again over time the cell will say this is too much of this type of response

is too much of this type of response can't tolerate it don't like it i'm

can't tolerate it don't like it i'm going to decrease the number of

going to decrease the number of receptors that you can't bind to me so

receptors that you can't bind to me so again it's the same as a b and c so that

again it's the same as a b and c so that leaves d so d has got to be the right

leaves d so d has got to be the right answer then right

answer then right well how would it be that answer

well how would it be that answer daily use of prasasin is an alpha 1

daily use of prasasin is an alpha 1 receptor antagonist so it's going to

receptor antagonist so it's going to bind to the alpha 1 adrenergic receptor

bind to the alpha 1 adrenergic receptor and block

and block any other drug from being able to bind

any other drug from being able to bind to it now that's kind of a problem and

to it now that's kind of a problem and the reason why is is what in certain

the reason why is is what in certain situations we maybe want to stimulate

situations we maybe want to stimulate that alpha-1 adrenergic receptor you're

that alpha-1 adrenergic receptor you're not going to be able to because you have

not going to be able to because you have a practicing bound to it

a practicing bound to it and so if you need an agonist to come

and so if you need an agonist to come and stimulate it guess what it's blocked

and stimulate it guess what it's blocked by praises in so in that situation where

by praises in so in that situation where maybe you do need to stimulate that that

maybe you do need to stimulate that that receptor guess what i'm going to have to

receptor guess what i'm going to have to kind of up regulate more risk more

kind of up regulate more risk more receptors available

receptors available for one of those agonists like

for one of those agonists like phenylephrine or norepinephrine or

phenylephrine or norepinephrine or epinephrine to bind to that's the only

epinephrine to bind to that's the only way i'm going to make more receptors so

way i'm going to make more receptors so that because of practicing binding to

that because of practicing binding to the alpha-1 receptors right now if i

the alpha-1 receptors right now if i make more receptors maybe i'll have more

make more receptors maybe i'll have more spots for the agonists like

spots for the agonists like phenylephrine and norepinephrine or

phenylephrine and norepinephrine or epinephrine to bind to so it's got to be

epinephrine to bind to so it's got to be d

d okay so up regulates because again it

okay so up regulates because again it needs receptors that are available for

needs receptors that are available for it to bind to agonists because right now

it to bind to agonists because right now let's say that right here is your alpha

let's say that right here is your alpha 1 receptor and let's pretend that these

1 receptor and let's pretend that these were not here you only have two

were not here you only have two receptors and processing down here

receptors and processing down here processing bound here

processing bound here well now you have no other receptor for

well now you have no other receptor for epinephrine norepinephrine epinephrine

epinephrine norepinephrine epinephrine to bind to so what's going to happen is

to bind to so what's going to happen is you're going to try to make more and

you're going to try to make more and more receptors that'll be open for

more receptors that'll be open for epinephrine norepinephrine or

epinephrine norepinephrine or phenylephrine to bind to to be able to

phenylephrine to bind to to be able to produce an agonistic response so that's

produce an agonistic response so that's a little concept

a little concept there okay question number nine

there okay question number nine methylphenidate helps patients with

methylphenidate helps patients with attention deficit hyperactivity disorder

attention deficit hyperactivity disorder maintain attention to perform better at

maintain attention to perform better at school or at work

school or at work with an ed50 and again that's the dose

with an ed50 and again that's the dose that you want to give to

that you want to give to 50 percent of the population that would

50 percent of the population that would have an actual clinically desired effect

have an actual clinically desired effect that's 10 milligrams

that's 10 milligrams however methylfinity can also cause side

however methylfinity can also cause side effects so significant nausea at higher

effects so significant nausea at higher doses so td50 which is the dose that you

doses so td50 which is the dose that you would give to 50 of the population to

would give to 50 of the population to cause a toxic effect that's 30

cause a toxic effect that's 30 milligrams

milligrams so what is the correct

so what is the correct what is which one of the following is

what is which one of the following is correct regarding methylphenidate

correct regarding methylphenidate so in this situation i would need to

so in this situation i would need to take what

take what i would need to be able to take my

i would need to be able to take my in this situation here my td 50 and my

in this situation here my td 50 and my ed50 and plug it into a particular

ed50 and plug it into a particular equation

equation and that equation is the therapeutic

and that equation is the therapeutic index the therapeutic index is the td50

index the therapeutic index is the td50 so 30 milligrams divided by the ed50

so 30 milligrams divided by the ed50 which is 10 milligrams what does that

which is 10 milligrams what does that give me 30 divided by 10 is 3. so my

give me 30 divided by 10 is 3. so my therapeutic index is 3.

therapeutic index is 3. what that helps me to understand is

what that helps me to understand is is the range that i have

is the range that i have to basically what's the window what's my

to basically what's the window what's my margin of error

margin of error that i have so if i give 10 milligrams

that i have so if i give 10 milligrams i'll produce my desired effect

i'll produce my desired effect and at 30 milligrams i'll produce a

and at 30 milligrams i'll produce a toxic effect the kind of window where i

toxic effect the kind of window where i have a good degree of desired effect

have a good degree of desired effect before i reach a toxic effect is my

before i reach a toxic effect is my therapeutic index the narrower your

therapeutic index the narrower your therapeutic index the

therapeutic index the you know the risk of toxic adverse

you know the risk of toxic adverse effects are higher because the margin of

effects are higher because the margin of error is very very tiny with a very

error is very very tiny with a very large therapeutic index there's a very

large therapeutic index there's a very low risk of toxic side effects because

low risk of toxic side effects because the margin of error is huge you could

the margin of error is huge you could give a very large dose and still not

give a very large dose and still not produce that toxic effect so remember

produce that toxic effect so remember that relationship here but the basic

that relationship here but the basic answer to the question is that the

answer to the question is that the therapeutic index of methylphenidate is

therapeutic index of methylphenidate is three

three all right and again take that into

all right and again take that into consideration when you're talking about

consideration when you're talking about the safety of a drug all right guys

the safety of a drug all right guys let's move on to question number ten so

let's move on to question number ten so again we're going to talk a little bit

again we're going to talk a little bit about safety here so which of the

about safety here so which of the following is the correct answer

following is the correct answer concerning the safety of using warfarin

concerning the safety of using warfarin small therapeutic index versus

small therapeutic index versus penicillin with a large therapeutic

penicillin with a large therapeutic index

index so we know that with this being said

so we know that with this being said here the higher your therapeutic index

here the higher your therapeutic index right the safer the actual drug is

right the safer the actual drug is likely to be okay that's for most

likely to be okay that's for most patients but it wouldn't be for like

patients but it wouldn't be for like every single patient

every single patient okay but i'd say for most patients so

okay but i'd say for most patients so the smaller the therapeutic index more

the smaller the therapeutic index more dangerous higher the therapeutic index

dangerous higher the therapeutic index more safe but again that's not for every

more safe but again that's not for every single patient there's obviously

single patient there's obviously contingencies in that situation here

contingencies in that situation here so let's go through this answer here

so let's go through this answer here orphan is a safer drug because it has a

orphan is a safer drug because it has a low therapeutic index now we already

low therapeutic index now we already said low is dangerous

said low is dangerous um this is kind of the same situation

um this is kind of the same situation the higher the therapeutic index the

the higher the therapeutic index the high therapeutic index makes penicillin

high therapeutic index makes penicillin a safer drug for all patients i'd say

a safer drug for all patients i'd say for most patients not for all patients

for most patients not for all patients okay again

okay again not absolutely the correct answer it's

not absolutely the correct answer it's relatively close but it's not the best

relatively close but it's not the best answer here

answer here warfarin treatment has a high chance of

warfarin treatment has a high chance of resulting in dangerous adverse effects

resulting in dangerous adverse effects if bioavailability is altered

if bioavailability is altered i'd say that's yeah it's likely the

i'd say that's yeah it's likely the right answer the reason why is look at

right answer the reason why is look at warfarin it's a small therapeutic index

warfarin it's a small therapeutic index so because that has a high risk of

so because that has a high risk of dangerous adverse effects and if you

dangerous adverse effects and if you alter his bioavailability so let's say

alter his bioavailability so let's say for whatever reason

for whatever reason i don't know

i don't know you give this particular drug and in

you give this particular drug and in some way shape or form you know

some way shape or form you know you are taking something with it that

you are taking something with it that actually has the amount of the drug that

actually has the amount of the drug that usually it's supposed to be

usually it's supposed to be bioavailability a bioavailable uh

bioavailability a bioavailable uh bioavailability of that dosage is

bioavailability of that dosage is usually i'm just making it up 50

usually i'm just making it up 50 okay when you take it orally

okay when you take it orally and then afterwards you

and then afterwards you have another medication that you're

have another medication that you're taking it with you have a problem with

taking it with you have a problem with your absorption process something

your absorption process something happens where you're taking another drug

happens where you're taking another drug with it and the bioavailability of that

with it and the bioavailability of that drug the amount of drug that gets into

drug the amount of drug that gets into the systemic circulation is increase

the systemic circulation is increase from 50 to 80 percent now there's more

from 50 to 80 percent now there's more of that drug in the bloodstream and

of that drug in the bloodstream and therefore the actual toxic effect is

therefore the actual toxic effect is going to be higher easier to reach

going to be higher easier to reach so because of that i would say that this

so because of that i would say that this would be the right answer warfarin

would be the right answer warfarin definitely has a very small therapeutic

definitely has a very small therapeutic index so anything that alters its

index so anything that alters its bioavailability which can actually cause

bioavailability which can actually cause higher amounts of the drug to be in the

higher amounts of the drug to be in the circulation can definitely produce

circulation can definitely produce dangerous adverse effects so i would say

dangerous adverse effects so i would say would be b

would be b okay and again you can remember this by

okay and again you can remember this by the sad face again the drugs with a very

the sad face again the drugs with a very small therapeutic index

small therapeutic index very very dangerous side effects if it's

very very dangerous side effects if it's actually going to lead to higher

actually going to lead to higher concentrations of the drug

concentrations of the drug with this one smiley face is a large

with this one smiley face is a large therapeutic index you could give this

therapeutic index you could give this and the bioavailability wouldn't

and the bioavailability wouldn't actually be a big deal because again

actually be a big deal because again it's going to be really hard to cause

it's going to be really hard to cause adverse effects you could give it

adverse effects you could give it and even at high concentrations of the

and even at high concentrations of the drug you're still not going to produce

drug you're still not going to produce the toxic side effect you have a very

the toxic side effect you have a very larger you know range to be able to kind

larger you know range to be able to kind of give drug dosages without causing

of give drug dosages without causing that nasty toxic effect so i'd say this

that nasty toxic effect so i'd say this would definitely be the right answer

would definitely be the right answer here b

here b all right guys we went through a couple

all right guys we went through a couple examples here we went through a lot in

examples here we went through a lot in this video i hope it made sense i hope

this video i hope it made sense i hope that you guys really did enjoy it and as

that you guys really did enjoy it and as always until next time

[Music] you

Click on any text or timestamp to jump to that moment in the video

Most transcripts ready in under 5 seconds

One-Click Copy125+ LanguagesSearch ContentJump to Timestamps

Paste YouTube URL

Enter any YouTube video link to get the full transcript

Most transcripts ready in under 5 seconds

Get Our Chrome Extension

Get transcripts instantly without leaving YouTube. Install our Chrome extension for one-click access to any video's transcript directly on the watch page.

Add to Chrome — Free

Works with YouTube, Coursera, Udemy and more educational platforms

Get Instant Transcripts: Just Edit the Domain in Your Address Bar!

YouTube

←

→

↻

https://www.youtube.com/watch?v=UF8uR6Z6KLc

YoutubeToText

←

→

↻

https://youtubetotext.net/watch?v=UF8uR6Z6KLc

YouTube TranscriptPreparing your results…

YouTube Transcript:Pharmacodynamics

AutoDub

Video Transcript

Paste YouTube URL

Transcript Extraction Form

Get Our Chrome Extension

Get Instant Transcripts: Just Edit the Domain in Your Address Bar!

YouTube Transcript:
Pharmacodynamics