Pharmacokinetics: Distribution (Nursing)

00:01 Okay.

00:02 Absorption, was talking about the routes, and it is the time from the route of entry until it gets into the bloodstream.

00:10 Then distribution is the next 1 of the pharmacokinetic processes, and that's the movement of the drug from the bloodstream to the target cells.

00:19 So, if you look at…drugs have to cross the membrane.

00:22 Now, there's a pretty cool picture there of you seeing the capillaries and where they mix in the middle, and you've got the veins.

00:28 But drugs cross membranes either through the pores, they can use an active transport system, or they just directly penetrate the cells.

00:36 So, distribution is from the bloodstream to the point of action, the target site that we want the drug to work on.

00:43 So, what does it take to have effective distribution? Well, you have to have good blood flow.

00:50 Now, we have types of patients that don't have good blood flow.

00:53 They may have like Raynaud syndrome and not have good blood flow to their extremities.

00:57 They might be diabetic and had macrovascular damage.

01:02 In addition to good blood flow, you want the drug to be able to exit the vascular system.

01:07 So part of distribution is moving it through the body in the bloodstream, but then the drug has to get out of the vascular system and to the target cell.

01:15 So we want the drug to be able to easily exit the vascular system, and then the drug has to enter the target cell.

01:22 Okay, so, let's go back and I just wanna make sure that we're clear on that concept.

01:26 Absorption is from the site of entry to the bloodstream.

01:31 Distribution is the bloodstream to the target cell.

01:35 So you need the good blood flow, the drug needs to be able to get out of the bloodstream, and the drug needs to be able to enter the target cell.

01:42 So, that's probably a pretty shocking picture for you to take a look at.

01:47 We want to talk first about who has challenges to distribution.

01:51 Now, I mentioned this before, but this is a picture of a diabetic foot ulcer.

01:55 Here's the problem.

01:57 Diabetic clients often don't have good feeling in their feet.

02:00 They might have pain or neuropathy, or they might have total numbness.

02:05 So if they step on something and there they get a cut or a sore on their foot, and they don't do regular foot care, they can often get an infection that they're completely unaware of.

02:15 That's why we always recommend diabetic clients to wear shoes around the house.

02:19 So if a client gets a wound on their foot and it's not treated, we need to then go in and treat it with an antibiotic.

02:26 Well, we can give them an IV antibiotic.

02:28 That'll go in really quickly, go through the bloodstream, but trying to get it down to that foot is problematic.

02:35 It's a distribution issue, because we don't have the good vasculature to deliver the antibiotic to where the infection is.

02:43 And that's why diabetic foot ulcers can get completely out of control.

02:47 The patient doesn't realize that they have a wound, it becomes infected, and then we have a really difficult time of getting the medication down to where we need it.

02:56 Abscesses don't have good blood supply.

03:00 So they have giant pockets of pus in different places.

03:03 That's why a lot of times, those wounds have to be incised and drained, and then we can get the infection taken care of with the antibiotic.

03:11 The last 1 is tumors.

03:13 Tumors don't have a good blood supply right to the core, so we have a hard time getting chemotherapy to them.

03:19 And patients often require surgery called debulking, where they go in and make the tumor smaller, so that we can get more medication to the tumor.

03:28 So, if distribution is moving from the bloodstream to the target site, we talked about people who don't have good blood flow.

03:36 Diabetic foot ulcers, people have abscesses because of giant pus pockets, or people with tumors, because they have limited blood supply to the core of that tumor.

03:47 Now let's talk about capillary beds.

03:49 Most of the capillary beds, they're pretty loose. and the drugs can pass between the cells and don't have to go right through the cells.

03:56 So they've got these nice, big, open spaces…well, relatively, because they are capillaries.

04:00 But they've got these nice, big, open spaces and the drugs can pass right between the cells.

04:05 They don't have to go through them.

04:07 But there's a really special place in our bodies in the central nervous system where the capillaries form what we call the blood-brain barrier.

04:17 Now, I have to say that slowly because my tongue gets tied when I try to say it.

04:21 But the blood-brain barrier is a great protective device, but can also be problematic.

04:27 Okay, the capillary junctions there are tight.

04:31 There are no gaps between these beds.

04:33 Most capillary beds, they really have nice, easy spaces, and the drug can just go through there.

04:38 But the blood-brain barrier is different.

04:41 Super tight junctions, there's no gaps like most of the other beds.

04:45 So the drugs have to pass through the cells in the capillary bed instead of between them.

04:51 So that's why the blood-brain barrier is able to keep out a lot of substances.

04:57 So, you've got this P-glycolprotein thing, it's super cool, because it'll actually pump blood back into the bloodstream versus the brain; another way that that blood brain barrier protects the CNS, the central nervous system, from drugs entering it.

05:11 So, only lipid-soluble drugs with a transport system can actually cross the blood-brain barrier, and we'll talk about which ones those are later.

05:19 But the purpose of the blood-brain barrier is to protect us from toxins, but it also protects us from helpful medications.

05:25 So, say, you have a CNS infection like meningitis or encephalitis, we have a distribution problem because of that blood-brain barrier.

05:34 There's a lot of antibiotics that can't cross the blood-brain barrier.

05:39 So what you need to do is we found some medications that actually will.

05:44 Cephalosporins 3rd, 4th, and 5th generation will actually cross the blood-brain barrier, where most of them do not.

05:51 So the blood-brain barrier is a good thing.

05:53 It protects toxins from getting to my central nervous system, but remember, it can also be problematic if I'm trying to get a medication into my central nervous system.

06:03 It can be a problem with antibiotics, in treating a CNS infection.

06:08 It can be a problem for people that need more dopamine in their brain, like Parkinson's patients.

06:13 We have to throw another drug across the blood-brain barrier that gets turned into the dopamine that they need.

06:20 Special populations are at risk are newborns.

06:23 Newborns have immature blood-brain barriers, so they can't keep toxins out as well, and they can't keep CNS drugs out as well.

06:32 So they will allow bad things into the CNS.

06:35 So, as nurses, we need to know if it's a CNS drug, it needs to be extreme caution that we ever gave that to a newborn.

06:43 Okay, well, speaking of babies, how about let's talk about the placenta and distribution.

06:48 So, we're not going to go into a lot of detail on that here, but just keep in mind.

06:51 Anytime you have a female who is pregnant, you want to make sure that you're extra careful with the medications that they give, because the placenta is not like the blood-brain barrier.

07:01 It does not prevent drugs from circulating to the baby.

07:05 So, many of the drugs can pass through the placenta, is what you have to be very careful with what drugs a pregnant woman would take.

07:15 Now, they used to be called categories, and how the A, B, C, D and X was the one everyone wanted to pay attention to.

07:21 Because category X drugs means you absolutely do not give them to a pregnant woman because the risk to the baby clearly outweighed any benefit of the drugs.

07:32 Now we're changing to a different system.

07:34 It's being replaced with what they call a narrative.

07:36 And what they found is that not all the drugs that are on the category X list really should be totally forbidden to pregnant women.

07:44 So now they're giving much more information, hence the name narratives.

07:48 They're giving more information so that your healthcare provider and you can make a more informed decision and really weigh out if the risk to the baby outweighed the potential benefits or not.

08:00 So it's just another way you're gonna make a better and informed decision about drugs in the placenta.

08:05 Okay, so that's absorption.

08:08 Pause for a minute and see if you can think through what is the definition of absorption.

08:15 Now take a minute and see if you can come up with at least 6 different routes for absorption.

08:24 What's the definition of distribution?