Affinity Potency Selectivity — Transcript

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1. 0:00hi there and welcome back to an
2. 0:02understanding medications we've just
3. 0:04explained the four types of cellular
4. 0:06receptors that our medications can bind
5. 0:09to and in this lesson we're going to
6. 0:11understand a lot more about those
7. 0:13receptors and by investigating things
8. 0:16like receptor binding Affinity
9. 0:18selectivity and potency
10. 0:21we're going to start out this lesson by
11. 0:23understanding the medications how they
12. 0:27bind to The receptors we very
13. 0:29simplistically think that it's a
14. 0:31molecular shape and if this molecular
15. 0:33shape meets this molecular shape then
16. 0:36that's fine it's bound
17. 0:37but it really does have a lot to do with
18. 0:40the molecular forces as well so recall
19. 0:44how the phospholipid bilayer is held
20. 0:47together by Van Der waals forces the uh
21. 0:50the tails are held together by Van Der
22. 0:52waals forces the heads are held together
23. 0:54by hydrogen bonds well The Binding of
24. 0:58the ligand to the receptor are going to
25. 1:02use those forces as well and they're
26. 1:04going to use other things like ionic
27. 1:07bonding ionic bonding is is a fairly
28. 1:09strong it's a lot stronger than those
29. 1:11other two forces I've just discussed I
30. 1:14like to use the analogy of our modern
31. 1:17electronic devices which have some
32. 1:20snap-in features you know when the
33. 1:22accessory comes into close proximity to
34. 1:25the receptor the magnetic forces guide
35. 1:28the accessory into place and they snap
36. 1:31together now in applying that analogy to
37. 1:34our medications the molecular properties
38. 1:37of the drug have various attractant
39. 1:40forces to the molecular properties of
40. 1:43the receptor the drug is therefore
41. 1:46attracted to the receptor and just like
42. 1:49The Binding of the accessory to the
43. 1:52electronic device most of our binding of
44. 1:56drugs to The receptors is not permanent
45. 2:00there can be a lot of differences though
46. 2:03in the strength of the binding and that
47. 2:06is termed Affinity the drugs Affinity to
48. 2:09the receptor so sometimes a medication
49. 2:12is said to have a high Affinity or a low
50. 2:15Affinity to a receptor and using that
51. 2:19electronic device analogy let's say that
52. 2:23for instance there are usually five
53. 2:25magnets that are holding unit in place
54. 2:27and we've lost three of those magnets
55. 2:29well it's still going to have the same
56. 2:32shape isn't it and it's still going to
57. 2:34have a little bit of a binding but it
58. 2:36can snap off a lot easier
59. 2:38so in applying that to our medications
60. 2:41if the medication has a low affinity for
61. 2:44a particular receptor the molecular
62. 2:47binding holding it into place is not as
63. 2:49strong and the receptor and Drug just
64. 2:53kind of pop off and then conversely if
65. 2:56it's got a higher Affinity it's going to
66. 2:59result in being bound to that receptor a
67. 3:03lot longer having a lot more difficulty
68. 3:05being pulled apart and later we'll see
69. 3:09how Affinity is going to contribute to
70. 3:12potency and potency it is is described
71. 3:15as the measure of the drugs activity in
72. 3:20terms of the amount of the drug that is
73. 3:22needed to produce a certain effect so if
74. 3:25two drugs do exactly the same thing and
75. 3:28one only needs three milligrams the
76. 3:31other one needs 30 milligrams obviously
77. 3:34the one that has the three milligram
78. 3:37dose is going to be having the stronger
79. 3:40potency and it may have a lot to do with
80. 3:43The Binding of the medication to its
81. 3:47receptor
82. 3:48another concept that we should overview
83. 3:50right now has to do with selectivity
84. 3:54selectivity has to do with how selective
85. 3:57a medication is for a certain receptor
86. 4:02and I'll use the common example for this
87. 4:04of the adrenergic drugs in other words
88. 4:06the medications that mimic adrenaline or
89. 4:10sometimes called epinephrine
90. 4:13recall that we use adrenaline in the
91. 4:16fight or flight response when we're
92. 4:19running away from something that's about
93. 4:21to do us harm The receptors for
94. 4:24adrenaline are all the way through the
95. 4:26body but I'm just going to use two
96. 4:28receptors in this simple example we have
97. 4:31adrenergic Alpha One receptors on the
98. 4:35peripheral blood vessels the blood
99. 4:36vessels to the skin the blood vessels to
100. 4:38the extremities and The Binding of
101. 4:41adrenaline to those receptors will
102. 4:43constrict those blood vessels and in
103. 4:46turn that may very well increase the
104. 4:49blood pressure we also have the beta 2
105. 4:52receptors on the bronchi and they will
106. 4:55be acted on by adrenaline itself as well
107. 4:58so if adrenaline would hit those beta 2
108. 5:02receptors dilating the bronchi and
109. 5:05allowing more air to go into the lungs
110. 5:08so that the person would have plenty of
111. 5:10air when they're running away in a fight
112. 5:12or flight response the adrenaline will
113. 5:14find both the Alpha One and the beta 2
114. 5:19receptor we can simplistically represent
115. 5:22that with this diagram the adrenaline
116. 5:25fits both the Alpha One receptor and the
117. 5:29beta 2 receptor and it has a strong
118. 5:32molecular bond to both of those
119. 5:35receptors
120. 5:37but suppose we just wanted to get the
121. 5:40therapeutic effects of adrenaline for a
122. 5:42person with asthma and all we wanted to
123. 5:45do was open up the bronchi
124. 5:48if we developed a selective beta-2
125. 5:52adrenergic medication we could do that
126. 5:55without constricting the blood vessels
127. 5:57so we could do that without the major
128. 6:00side effects
129. 6:02that can be simplistically represented
130. 6:04by these diagrams where the beta 2
131. 6:07medication has a strong binding to the
132. 6:10beta 2 receptor but the very weak
133. 6:14binding in other parts of the adrenergic
134. 6:17receptor
135. 6:18we also have drugs that will bind to
136. 6:22another receptor receptor that doesn't
137. 6:24seem to be related to the original
138. 6:26receptor at all
139. 6:28so for instance the early antihistamines
140. 6:31bound to and blocked the histamine one
141. 6:35receptor that was what they were
142. 6:38supposed to do but they bound to another
143. 6:41receptor the acetylcholine receptor
144. 6:43blocked that receptor and a lot of these
145. 6:46side effects of that medication were
146. 6:49going to be found because of that
147. 6:51binding to the acetylcholine receptor
148. 6:54so you'll find that our medications will
149. 6:57be trying to get more and more selective
150. 7:00as time goes on
151. 7:02in summary of this lesson Affinity has
152. 7:05to do with how well the drug binds to
153. 7:08the receptor selectivity has to do with
154. 7:12the degree to which the drug acts on a
155. 7:15given receptor relative to how well it
156. 7:19binds to other receptors and potency has
157. 7:23to do with a measure of the drug
158. 7:25activity expressed in terms of the
159. 7:27amount that is required to produce and
160. 7:31effect
161. 7:34let's try to gain an understanding of
162. 7:36the terms Affinity selectivity and
163. 7:39potency by applying our knowledge to the
164. 7:43opioid medications
165. 7:45recall that we were saying that opioid
166. 7:47analgesics work by binding to the opioid
167. 7:50receptors mainly in the spinal cord at
168. 7:54this level here
169. 7:55at that point there's what we can
170. 7:58simplistically think of as a gate the
171. 8:02pain is being transmitted from the
172. 8:04extremities and we have a gate there
173. 8:06that can decrease the number of impulses
174. 8:10allowed to go to the brain
175. 8:12so the opioid binding right here will
176. 8:16decrease the perception of pain at the
177. 8:19level of the brain
178. 8:20there are a number of subsets of opioid
179. 8:23receptors in the body but the main one
180. 8:25that is involved in analgesic effects
181. 8:28right here is the MU receptor
182. 8:31one of our opioids morphine binds to
183. 8:35these mu receptors and that decreases
184. 8:39the messages to the brain and the
185. 8:41perception of pain decreases
186. 8:45another one of our opioid analgesics
187. 8:47called fentanyl also binds to the MU
188. 8:51receptors right here but fentanyl is 100
189. 8:55times more potent than morphine in other
190. 9:00words the dose of fentanyl that would be
191. 9:03needed to get the same pain relief as
192. 9:06morphine is just 1 100th the amount and
193. 9:10using what we just learned in the last
194. 9:12lesson develop a hypothesis about why
195. 9:15fentanyl would be so much more potent
196. 9:18than morphine
197. 9:22and while there could be a number of
198. 9:24reasons why a medication is more potent
199. 9:27than a similar one that acts by the same
200. 9:29mechanism one of the main reasons that
201. 9:31fentanyl is so much more potent than
202. 9:34morphine is that the Affinity to the MU
203. 9:37receptor is much stronger
204. 9:40in other words when fentanyl binds to
205. 9:43that same receptor it is much more
206. 9:45difficult to get it off that receptor
207. 9:48and this strong Affinity to the receptor
208. 9:51ends up with the drug simplistically
209. 9:54speaking sending many more messages to
210. 9:56the cell to decrease the transmission of
211. 9:59pain impulses the Affinity to the
212. 10:03receptor can affect the potency of the
213. 10:06medication
214. 10:08let's take another quick question to
215. 10:10apply our knowledge of selectivity
216. 10:13the MU receptor has two major subsets
217. 10:17meaning that The receptors differ just a
218. 10:21little bit from each other
219. 10:23the mu1 receptor is responsible for the
220. 10:26analgesic or pain relieving effect and
221. 10:29the mu2 receptor is responsible for
222. 10:33respiratory depression constipation and
223. 10:36the euphoric effect that makes the
224. 10:38medication addictive
225. 10:40so which one of the following do you
226. 10:42think would be correct a drug Discovery
227. 10:46scientists would be looking to develop
228. 10:47opioids that are selective for the MU 1
229. 10:51receptor
230. 10:52B drug Discovery scientists would
231. 10:55develop a very potent opioid if the drug
232. 10:59they discovered had a strong Affinity to
233. 11:02the MU 1 receptor
234. 11:04or C both of the above are correct
235. 11:10and you were correct if you had said c
236. 11:13both of the above are correct we're
237. 11:16always looking for new medications that
238. 11:19have fewer side effects and one of the
239. 11:22ways that can happen is if we develop
240. 11:25more selective medications some of the
241. 11:28most valuable medications bind only to
242. 11:31one receptor that gives the most
243. 11:34therapeutic effect without binding to
244. 11:37other receptors which yields the side
245. 11:40effects