Distribution of Drugs — Transcript

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1. 0:00hi there and welcome back we're
2. 0:03continuing our discussions of
3. 0:05pharmacokinetics which includes the
4. 0:07absorption distribution metabolism and
5. 0:09excretion of drugs and right now we'll
6. 0:12be talking about the distribution of
7. 0:14drugs
8. 0:15we finished our last video as the orally
9. 0:18consumed medication was going down to
10. 0:21the microvilli of the small intestine
11. 0:24and being absorbed in the microvilli and
12. 0:27from there it's going to go into the
13. 0:29hepatic portal venous system
14. 0:32we'll discuss more that when we talk
15. 0:34about metabolism but it's important to
16. 0:37note that right now orally consumed
17. 0:40medications will go through what we call
18. 0:43the hepatic first pass mechanism or in
19. 0:46other words go through the liver before
20. 0:49it's distributed to other tissues or any
21. 0:53other part of the body
22. 0:55oftentimes before the drug even gets to
23. 0:58the liver it acts as a protein carrier
24. 1:02molecule many of our drugs are carried
25. 1:04by proteins such as albumin or the
26. 1:07globulins especially if the drug is
27. 1:09highly lipophilic or in other words fat
28. 1:12soluble
29. 1:13each drug will have a different Affinity
30. 1:16to that protein carrier molecule and as
31. 1:20such each drug will have a certain
32. 1:23percentage that is normally bound to
33. 1:25proteins
34. 1:27and importantly it's only the Unbound
35. 1:31portion of the drug that can be
36. 1:33metabolized and it's only the Unbound
37. 1:36portion of the drug that can exert its
38. 1:39effect
39. 1:40and as you hear that you may be thinking
40. 1:42well if 80 percent is bound to the
41. 1:44proteins then the 80 percent is going to
42. 1:47be ineffective right because as you just
43. 1:50said the Unbound portion of the drug is
44. 1:53the only portion that can be metabolized
45. 1:56or exert its effect but you have to
46. 1:58remember that this binding is going to
47. 2:01establish what's called a chemical
48. 2:03equilibrium
49. 2:05so for instance if the drug is in the
50. 2:08liver and 80 is bound to the proteins
51. 2:10and 20 is free the 20 this free is going
52. 2:14to go into the hepatocytes to be
53. 2:16metabolized but what does that do to the
54. 2:20percentage that is bound in the blood
55. 2:23well that raises the percentage doesn't
56. 2:26it but that chemical equilibrium must be
57. 2:29re-established at that point so some of
58. 2:32the drug is going to disassociate from
59. 2:35the protein carriers right then
60. 2:38and in the end all of the medication
61. 2:41that's reversibly bound to the proteins
62. 2:43will eventually disassociate from that
63. 2:45protein carrier and be available to
64. 2:48perform its actions or be metabolized a
65. 2:51highly bound drug however may take
66. 2:54longer for that to happen
67. 2:57the other important concept about
68. 3:00distribution is the way in which the
69. 3:02drug is distributed among the four major
70. 3:05body compartments the blood the fats the
71. 3:10extracellular fluid and the
72. 3:11intracellular fluid
73. 3:13and as a drug enters a compartment for
74. 3:17instance the blood the Unbound drug
75. 3:19begins to distribute into other body
76. 3:24compartments and once again establishing
77. 3:26an equilibrium between those body
78. 3:29compartments until the drug reaches
79. 3:31equilibrium throughout the body
80. 3:34in the quiz on this lesson we're going
81. 3:37to take a couple clinical scenarios that
82. 3:39are going to reinforce these Concepts
83. 3:41we'll see you there
84. 3:47we were just talking about the fact that
85. 3:49many of our medications bind to protein
86. 3:53carrier molecules in order to get
87. 3:55distributed around the body and we're
88. 3:58saying that only the Unbound portion of
89. 4:01the drug is going to exert its effect
90. 4:05albumin and globulins are the proteins
91. 4:08that are most frequently used to carry
92. 4:10those drugs and which protein carries a
93. 4:15particular drug depends on the
94. 4:17properties of the drug itself so for
95. 4:19instance one drug that is highly acidic
96. 4:22may be carried by albumin and another
97. 4:26drug may be carried by the globulins but
98. 4:29it's important to realize that we don't
99. 4:32have a limitless capacity to carry drugs
100. 4:35on proteins The Binding spots on our
101. 4:37proteins can be completely saturated
102. 4:40meaning that despite the fact that a
103. 4:44drug is normally for instance 80 percent
104. 4:46bound to proteins there may be certain
105. 4:49instances in which there's not enough
106. 4:51free proteins to carry that drug
107. 4:55using that information let's take a
108. 4:58clinical scenario Mrs Ling is stabilized
109. 5:02on a medication let's call that
110. 5:03medication a that is highly bound to
111. 5:06albumin she is then prescribed an
112. 5:09additional new medication let's call
113. 5:12that medication B that is also highly
114. 5:15bound to albumin
115. 5:17but it's got a much stronger Affinity to
116. 5:21albumin what do you suspect would happen
117. 5:25one there would be no change in the
118. 5:28effective drug a
119. 5:30or two drug B the one that binds more
120. 5:34strongly to albumin may knock a lot of
121. 5:37drug a off the albumin leaving more of
122. 5:41the Unbound drug a to possibly exert
123. 5:45toxic effects
124. 5:48and you were correct if you said two
125. 5:51drug B may knock a lot of drug a off the
126. 5:55albumin binding sites leaving more of
127. 5:59drug a free and if there's more of drug
128. 6:03a free then there's a greater potential
129. 6:06of adverse and toxic effects of that
130. 6:09drug
131. 6:10while the potential for this type of
132. 6:12reaction to occur is really
133. 6:14overestimated in Pharmacology books it's
134. 6:18one of the reasons that two medications
135. 6:20are oftentimes contraindicated together
136. 6:25it can also contribute to adverse
137. 6:27reactions in people who are deficient in
138. 6:30proteins for instance in liver disease
139. 6:32where the person isn't making adequate
140. 6:35proteins and in some types of kidney
141. 6:37disease where the person is losing their
142. 6:39proteins
143. 6:41and to be clear most of the problems
144. 6:43associated with drug toxicity in people
145. 6:46with liver disease comes from the fact
146. 6:48that the liver metabolizes most drugs
147. 6:51and in liver disease the liver is simply
148. 6:55not doing its job very well but the low
149. 6:58protein levels still seem to play some
150. 7:01role in the toxicity of drugs in liver
151. 7:04failure with that we're going to move
152. 7:07into the next process of
153. 7:09pharmacokinetics and get a much better
154. 7:11picture of the role of the liver in the
155. 7:13metabolism of drugs