Pharmacokinetics: Visualising Omeprazole as it gets Absorbed, Distributed, Metabolised and Excreted — Transcript

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1. 0:01let's do something completely different
2. 0:03right now I think it's best to review
3. 0:05the process of pharmacokinetics well
4. 0:08we've got that information from last
5. 0:10chapter fresh in our mind but the way in
6. 0:13which we're going to be doing that is
7. 0:14we're going to be taking the main drug
8. 0:16we're going to be discussing in this
9. 0:18chapter and just to picture each one of
10. 0:21those processes that the body is going
11. 0:23to be doing to the drugs so the
12. 0:24absorption distribution metabolism and
13. 0:27excretion
14. 0:28so the point of this lesson is not to
15. 0:30memorize anything but rather to picture
16. 0:33each one of the processes and to
17. 0:36understand the terms we're using so we
18. 0:38can apply that information to any of our
19. 0:41other medications so let's go for it
20. 0:45when a person is orally administered and
21. 0:48omeprazole the medication goes down the
22. 0:51esophagus and into the stomach
23. 0:54proton pump inhibitors like Omeprazole
24. 0:57are enteric coated
25. 1:00and the enteric coating is a coating
26. 1:03that we put on medications to make sure
27. 1:05that they dissolve in the small
28. 1:07intestine rather than the stomach that
29. 1:11type of coating is put on a medication
30. 1:14mostly if that medication is destroyed
31. 1:17in the stomach acids or if it's an
32. 1:21irritant to the stomach
33. 1:23let's go back up to the stomach right
34. 1:26now because I'd like to make a note on
35. 1:28something else
36. 1:30Omeprazole and other proton pump
37. 1:33inhibitors work on a specific enzyme
38. 1:37found in a specific type of cell the
39. 1:41parietal cell that's in the stomach
40. 1:45recall the appearance of the stomach
41. 1:48wall if you zoomed into the stomach wall
42. 1:51you'd find that the stomach has gastric
43. 1:55pits and that those pits are composed of
44. 1:59several different types of cells
45. 2:03one of the types of cells is the
46. 2:06parietal cell which are depicted right
47. 2:09here
48. 2:10taking an even closer look at the
49. 2:13parietal cell it would look like this
50. 2:16remember that Omeprazole is not going to
51. 2:20access the parietal cells from the
52. 2:23stomach
53. 2:24it's going to go all the way through the
54. 2:26entire process of absorption in the
55. 2:30small intestine metabolism and
56. 2:33distribution before it accesses the
57. 2:36parietal cell from the blood vessels and
58. 2:39the interstitial spaces that are in this
59. 2:42area right here
60. 2:45as Omeprazole goes from the stomach to
61. 2:48the next structure of the git it'll
62. 2:50enter the small intestine where it is
63. 2:53absorbed normally for Omeprazole it will
64. 2:57finish the absorption process in about
65. 3:00three hours
66. 3:02when the Omeprazole is absorbed into the
67. 3:05bloodstream from the small intestine
68. 3:06about 95 of it will bind to the proteins
69. 3:13recall that this protein binding is
70. 3:17variable the medications can have a very
71. 3:21high binding to the proteins and other
72. 3:23medications might have a very very low
73. 3:26binding and sometimes no binding to
74. 3:29proteins for Omeprazole it's 95 percent
75. 3:32Bound by proteins which will help carry
76. 3:35it through the bloodstream
77. 3:37then the proteins carry it off toward
78. 3:41the liver in the portal venous system
79. 3:45when the millions of tiny little drug
80. 3:48particles go through the liver the
81. 3:51Unbound
82. 3:53Omeprazole the Omeprazole that's not
83. 3:55bound to the proteins most of that is
84. 3:58going to go into the hepatic cells or
85. 4:01the liver cells from the hepatic
86. 4:04capillaries into the hepatocytes
87. 4:07and you may be wondering right now what
88. 4:10is it that is so special about the liver
89. 4:13why is it that all of our medications
90. 4:16want to go straight to the liver and go
91. 4:18into the liver cells
92. 4:20well while most cells can help
93. 4:23metabolize medications the liver cells
94. 4:26have full access to hundreds of what we
95. 4:30call cytochrome
96. 4:32p450 enzymes
97. 4:35which are abbreviated as cyp enzymes
98. 4:41individual enzymes from that super
99. 4:43family of enzymes are known as cyp
100. 4:47something something something at least
101. 4:50three letters and numbers after that cyp
102. 4:55you have to remember that our body
103. 4:57thinks of all medications as being
104. 5:00toxins so it wants to metabolize them as
105. 5:04quickly as possible and the liver cells
106. 5:07can do this quicker than any cells in
107. 5:09the body
108. 5:10the first time the Omeprazole goes
109. 5:13through the liver into the hepatocyte or
110. 5:16in other words on the hepatic first pass
111. 5:20one of the hundreds of hepatic
112. 5:23cytochrome p450 enzymes will alter that
113. 5:27medication slightly
114. 5:30and jumping ahead for a moment later the
115. 5:33already altered medication that has been
116. 5:36circulating around will go back to the
117. 5:39liver where a phase two reaction will
118. 5:43make it very water soluble and easily
119. 5:46excreted
120. 5:47ultimately you're going to hear the word
121. 5:51bioavailability quite frequently so we
122. 5:53should know a little bit about what that
123. 5:55is
124. 5:56bioavailability is the fraction the
125. 5:59percentage of the administered dose that
126. 6:04enters into systemic circulation
127. 6:06unchanged
128. 6:09if we injected the medication into a
129. 6:11vein for instance or in other words
130. 6:14intravenously administered the
131. 6:16Omeprazole the bioavailability would be
132. 6:20a hundred percent
133. 6:22one hundred percent of that medication
134. 6:24would get into the circulation unchanged
135. 6:29but we took the medication orally
136. 6:31so for Omeprazole the bioavailability is
137. 6:35about 60 percent
138. 6:38and you may be thinking why does only 60
139. 6:42percent of the Omeprazole get into the
140. 6:45circulation unchanged well a bit of the
141. 6:49Omeprazole is not absorbed and some of
142. 6:52it gets metabolized on the first pass
143. 6:54through the liver but there is also
144. 6:57something that occurs to about 20
145. 7:00percent of it right here at the liver
146. 7:04I'll let you think about what that might
147. 7:07be and we'll come back to that in the
148. 7:10applying your knowledge quiz we don't
149. 7:13need to concern ourselves too much about
150. 7:15the bioavailability but we should
151. 7:18understand some of the basics like the
152. 7:21fact that if a drug has a very low
153. 7:23bioavailability it may have to be
154. 7:26injected or administered in a different
155. 7:29way
156. 7:30or if one proton pump inhibitor had a
157. 7:34bioavailability of 30 percent and
158. 7:38omeprazole had a bioavailability of 60
159. 7:41percent you can understand that you'd
160. 7:44have to take less of the Omeprazole in
161. 7:47order to get the same effect as the
162. 7:49other medication
163. 7:50and once again you don't have to worry
164. 7:53too much about that as long as you
165. 7:55understand the basics
166. 7:58once the Omeprazole goes through the
167. 8:01liver it goes off into General
168. 8:03circulation and it will have access to
169. 8:06the capillaries or sometimes called
170. 8:08capillaries near the parietal cells so
171. 8:12that the action of the drug will start
172. 8:15to occur because the medication is
173. 8:17actually getting to those enzymes that
174. 8:20it will affect
175. 8:22for Omeprazole the inhibitory effect
176. 8:25begins in about an hour after you take
177. 8:28the medication and the maximum effect is
178. 8:31seen in about two hours after the
179. 8:33medication is taken
180. 8:36one important note is that the proton
181. 8:39pump inhibitors only work on the acid
182. 8:43pumps that are working at the time that
183. 8:47the Omeprazole is there in the parietal
184. 8:50cell
185. 8:51so the way that we have to take the
186. 8:55medication
187. 8:56Omeprazole needs to be taken on an empty
188. 8:59stomach and then about a half an hour
189. 9:01later or an hour later the person should
190. 9:04consume food
191. 9:06and what that does is starts to activate
192. 9:09those proton pumps and as those proton
193. 9:14pumps are activated and the drug is
194. 9:16there at the same time then the drug can
195. 9:20work on the proton pumps
196. 9:24in the case of Omeprazole as we said
197. 9:26before it only works in the cells that
198. 9:29have the enzyme hydrogen potassium
199. 9:31atpase
200. 9:33so that makes it pretty specific to the
201. 9:37parietal cells so it's really good that
202. 9:39there is a limited number of cells that
203. 9:42will have the enzyme that we're working
204. 9:45on that ensures that this medication
205. 9:48doesn't have widespread side effects
206. 9:52throughout the body
207. 9:54and because of that
208. 9:56Omeprazole has a very good what we call
209. 9:59adverse effect profile or in other words
210. 10:03it's well tolerated
211. 10:05just to add a bit more information about
212. 10:08what happens right here at the parietal
213. 10:10cells when the molecule of Omeprazole
214. 10:13passes the capillaries near the parietal
215. 10:16cells most of the free drug is going to
216. 10:19go through the capillaries into the
217. 10:21interstitial space around the parietal
218. 10:24cells and then it's going to penetrate
219. 10:26into the parietal cells where it's going
220. 10:29to work inside the parietal cell once
221. 10:33Omeprazole goes through the liver a
222. 10:35couple times it's been degraded to the
223. 10:37point that it becomes water soluble and
224. 10:40we excrete it mainly by the kidneys as a
225. 10:43matter of fact about 80 percent of the
226. 10:45drug will be excreted by the kidneys and
227. 10:48most of the remaining 20 percent will be
228. 10:51excreted in the feces
229. 10:53with respect to the half-life of
230. 10:56Omeprazole and other proton pump
231. 10:58inhibitors that's about 1.2 to 1.5 hours
232. 11:03and normally that would mean that the
233. 11:07drug would have to be taken quite
234. 11:08frequently for instance if a drug had a
235. 11:11half-life of 1.5 hours you'd expect
236. 11:14there to be about five percent remaining
237. 11:17after four and a half half-lives or
238. 11:20about seven hours after it reaches Peak
239. 11:23concentrations in the blood but
240. 11:25Omeprazole and other proton pump
241. 11:27inhibitors only need to be taken on a
242. 11:30daily dose
243. 11:32so how could that be possible I'll let
244. 11:35you think about that question as well
245. 11:37and we'll come back to it in the
246. 11:39applying your knowledge quiz coming up
247. 11:43for right now I'd like to congratulate
248. 11:44you if you've understood what we've been
249. 11:46talking about with respect to the review
250. 11:48of pharmacokinetics remember that our
251. 11:51goal was not to memorize the
252. 11:53pharmacokinetics of Omeprazole and other
253. 11:56proton pump inhibitors we were just
254. 11:58aiming to understand and picture the
255. 12:01pharmacokinetics of Omeprazole and with
256. 12:04that Foundation you'll be able to add to
257. 12:07your knowledge each time you hear about
258. 12:10the pharmacokinetics of another
259. 12:12medication