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Okay I'm back and I brought some friends.

We're gonna talk about affinity potency and efficacy.

Uh These guys are my three year old sons

collection of stuffed dogs.

He actually has paid more than this but this is how I can carry in my hands.

This is bo Brittany Wish and Murphy dog um affinity is the extent

at which a drug binds to the receptor at a certain concentration.

So how tightly

Does the drug bind to the receptor? Um out of these four dogs

Wish

has the greatest affinity for Reef. He loves Wish Wish.

I don't know because he's little or what but he goes everywhere with my son Reef.

Um He is attached to him at all times.

It was very hard for me not too hard for him not to bring him to school this morning.

So which binds very tightly to my son,

my three year old and is with him at all times as close as possible

if wishes dirty needs to go in the wash.

Um He has other friends that he can hang

out with but which has the strongest affinity.

Um For reef, Reef has the strongest affinity for Wish actually.

But okay so these are usually shown in dissociation constant.

KD sometimes shown as K. I don't get hung up on K. D.

Or hang on their very similar ones more broad ones more specific. So if you see K. D.

Or K. I just know that they're inversely related to the affinity. So a lower

K. D. Or K. I means a higher affinity or stronger bond to the receptor

and a higher K. D. Or K. I. Has a lower affinity to the receptor.

So and a good example of this that we're going to keep coming back to

because I think it's just such a great real life example is the button orphan.

buprenorphine has a stronger affinity for the

opiate receptors than mu receptors than morphine.

So if you're giving it in the presence of morphine,

morphine is not going to be able to get to the receptors because buprenorphine

is going to get there faster stronger and stick and knock it off.

So the morphine is not gonna be able to

kick the buprenorphine off with the beauty of this an

opiate treatment is is that you're not going to have

that full response because buprenorphine is a partial agonist.

Um But it will stay on the receptors so that opiates will not be

able to find or you're like OxyContin or whatever you end up taking.

So below is some examples of some K. D. S. Or K. I. S.

I guess for these different opiates but one orphan is 10.221 point seven.

So remember the lower the K. Ii the stronger the affinity fentaNYL is 70.7 to 1.9.

So if you put fentaNYL in the presence of

an orphan that's going to be a

that's going to be a match right there on which one is going to activate the receptors

it could be probably either they're very similar um

morphine is 1.2 to 4 and then codeine.

If you put codeine in the presence of buprenorphine, codeine has no chance.

It's definitely not going to win that battle. Uh 65 to 1 35.

So you can see there that the

K. I.

Goes up the chances of it competing with the button orphan

for the receptors is lower and lower and no chance,

you know.

So efficacy is the ability to reach the max response.

So all of my buddies in my hand right here have the same efficacy.

They all can cause when and when they're individually given to reef.

He will love them equally when he has them if that's the only one that he has now this

this is salty dog,

this is Noelle's dog, this is my daughter's dog.

So

he likes salty dog but salty dog will never

be as effective as one of these guys because

it's not his it's his sister's dog and he just he's just not as cuddly and he said I

don't love him as much. So poor.

Salty dog is definitely just not as effective as bo Brittany wish and Murphy are

um you can see here in the graph B is showing the effectiveness

of this drug like what's the max effectiveness usually done as a max.

What is the max effectiveness? Okay, potency as we showed in that graph earlier.

Um like an espresso is more potent than a cup of folders or whatever.

Um This is how much of the drug you need to produce a response. This is a comparative

term. So drug A. On our slide there is more potent than drug B. You need less of drug A.

To produce a response than you need of drug B. So it is a relative term.

Um For example, fentaNYL is more potent than morphine. 50 times more potent.

When we're trying to convert opiate doses, we're going to use our mm. E.

Which you'll see very often is the morphine milligram equivalent.

So if you're trying to get them from like for example last month was a nightmare.

oxyCODONE. 15 was on backorder. oxyCODONE.

30 was basically all the oxyCODONE products were on back order was a nightmare.

So a lot of the doctors had to switch them to HYDROmorphone or morphine or

HYDROcodone or something else that I had.

That uh we could give them just for the month until that darn shortage was ending.

So how do you convert somebody from oxyCODONE to HYDROmorphone?

You're going to use the morphine milligram equivalent to

see how much HYDROmorphone you would need two.

You can convert it to the morphine and then convert it to the oxyCODONE.

So how much would you need to do that conversion there.

Um that is used in clinical real life on the rag. You'll use it.

So good to know that that's there and it exists.

Alright we're gonna get rid of our dogs

up regulation and down regulation.

So down regulation is a decreased number of receptors that are available.

So you actually going to need more of a drug to produce the same response over time.

Um opiates do this so over time you may need more opiates.

Um I used to have a couple girls that had sickle cell and

they have been on opiates since they were six years old unfortunately.

Um So by the time they were in their thirties they were

on these insanely dangerous doses of opiates that would kill anybody else.

But they were so tolerant to it,

this is not good this picture. Oh sorry

there um they were so tolerant to it that it didn't it didn't affect them in any way.

And a lot of pharmacists you know it's kind of sad because a

lot of pharmacist wouldn't fill medications for

them because these doses were lethal.

They were lethal doses but for them

they weren't lethal because their receptors have

been so down regulated because they had been on them for so long.

Uh The cannabinoid receptors are known for doing this and insulin receptors are

known for doing this so we're gonna need more insulin over time.

Also

now up regulation would be if the body produces more receptors over time.

So this happens in the third trimester of pregnancy.

Your body starts producing more oxytocin receptors and

preparation for that birth so that we can have

those strong contractions there um And everything we

need for breastfeeding and that sort of thing.

So you can see in this little picture here

the up regulation more receptors are produced by those

little blue ones and then down the bottom those

that down regulations as less receptors are produced.

Selectivity versus specificity.

Selectivity is the ability to bind to one subtype versus another subtype.

So as we get to our next lecture on tomorrow we will see that there's very

many Colin ergic subtypes um for the muscular

neck and then yeah you have the nicotine

and the most moronic and one of them has five subtypes and

the other one I was like three or whatever and you can

you bind to one of those subtypes that only is in like

two places in the body versus non selectively binding to the muscular

receptors in general and then you're going to

activate all the receptors all over the body.

Or can you do just the one receptor that works on the glands or whatever.

Um We'll talk about that more tomorrow.

So it likes to buy into one subtype of receptors.

So vera's veranda milk is a calcium channel blocker. It is an

antagonists of the calcium channels.

Um That's why it's in the class of

calcium channel blockers along with um loaded pine and

there's a bunch of them in there but at high doses it

can also block the sodium channels now it doesn't normally block the

sodium channels and it doesn't like to block the sodium channels but

if you give enough wrapping millet will block the sodium channels also.

But I want you to note that verapamil is technically a calcium channel blocker.

Okay then specificity specificity is the ability to

buy into just one type of receptor.

So our best friend from last week atropine

binds to the acetylcholine receptors but it's non

selective so it binds to all the acetylcholine

receptors causing a wide variety of responses.

Can we name them?

Blind as a bat mad as a hatter dry as a bone ridges beat

was I always forget that last one

tachycardia and there's one more.

Um but it's going to produce a wide variety

of um responses throughout the entire body because it is

I'm going to activate all types of acetylcholine

receptors and not just one subtype versus another.

Synergism versus additive additive effects.

Now this is a little bit tricky when I was looking up different examples of these.

They're kind of all over the place.

I think it's very difficult to tell if something

is synergistic versus additive additive means if you take

one drug like

Aspirin and one drug like Tylenol.

The aspirin is gonna cause blood thinning effect.

And the talent I was gonna fight cause pain reliever and you take them together,

you're gonna have blood thinning pain relief basically one plus one equals two.

Um synergism is one plus one equals three. So that means that you take to drugs.

So they one of them had to use an example of aspen causing 30% blood

thinning and Plavix causing 30% blood thinning and

then together they cost 90% blood thinning.

So one plus one equals three so that

some of both of them together causes an

amplified response more than just the additive effect

important to know but not that important.

I mean you'll see this a lot if you're giving

like an opiate plus a benzo plus muscle relaxant,

you know that sort of thing.

So just know that that's the thing where you can have these

drug interactions where they combine and

produce produce an increase amplified effect.

Um

Okay,

I think that's all I have for you guys for pharma

code dynamics today I will start getting you some kinetics out and

and then we'll get started on that one and

understand now what the body does to the drug.

And I will see you tomorrow.

I will be there at noon if anybody wants to come a little early and talk to

me and we'll do a little bit of reviewing on this um while we're in class.

Okay you guys have a great day. Bye.

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