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Exploring Drug Affinity: A Key to Effective Prescribing · Pearls and Prep

• 0:00
  Foreign.
• 0:05
  Welcome
• 0:05
  back,
• 0:05
  my
• 0:06
  friends,
• 0:06
  to
• 0:06
  another
• 0:06
  episode
• 0:07
  of
• 0:07
  Pearls
• 0:08
  and
• 0:08
  Prep.
• 0:09
  Today
• 0:09
  we're
• 0:09
  going
• 0:10
  to
• 0:10
  talk
• 0:10
  about
• 0:11
  affinity,
• 0:12
  a
• 0:12
  very
• 0:12
  important
• 0:14
  principle
• 0:14
  in
• 0:15
  pharmacology.
• 0:16
  And
• 0:17
  knowing
• 0:18
  this
• 0:19
  concept
• 0:20
  is
• 0:21
  going
• 0:21
  to
• 0:21
  empower
• 0:21
  you
• 0:22
  to
• 0:22
  become
• 0:22
  a
• 0:22
  better
• 0:23
  prescriber,
• 0:24
  to
• 0:24
  have
• 0:24
  a
• 0:24
  much
• 0:25
  richer
• 0:25
  awareness
• 0:26
  of
• 0:26
  what
• 0:26
  is
• 0:26
  going
• 0:26
  on
• 0:27
  when
• 0:28
  you
• 0:28
  prescribe
• 0:28
  a
• 0:28
  medication
• 0:29
  and
• 0:29
  why.
• 0:30
  Affinity
• 0:31
  in
• 0:31
  pharmacology
• 0:32
  is
• 0:32
  the
• 0:32
  measure
• 0:32
  of
• 0:33
  how
• 0:33
  strongly
• 0:33
  a
• 0:33
  drug
• 0:34
  binds
• 0:34
  to
• 0:34
  its
• 0:35
  biological
• 0:35
  target,
• 0:36
  like
• 0:36
  a
• 0:36
  receptor
• 0:37
  or
• 0:37
  a
• 0:37
  transporter.
• 0:38
  A
• 0:38
  high
• 0:38
  affinity
• 0:39
  drug
• 0:39
  will
• 0:39
  cling
• 0:40
  tightly.
• 0:40
  It
• 0:40
  only
• 0:41
  takes
• 0:41
  a
• 0:41
  small
• 0:41
  dose
• 0:41
  to
• 0:42
  activate
• 0:42
  or
• 0:42
  block
• 0:43
  that
• 0:43
  receptor.
• 0:43
  And
• 0:44
  a
• 0:44
  low
• 0:44
  affinity
• 0:45
  drug
• 0:45
  has
• 0:45
  a
• 0:45
  weaker
• 0:45
  pull.
• 0:46
  It
• 0:46
  needs
• 0:46
  a
• 0:46
  higher
• 0:47
  dose
• 0:47
  to
• 0:47
  get
• 0:47
  the
• 0:47
  same
• 0:48
  effect.
• 0:48
  It's
• 0:49
  the
• 0:49
  chemistry
• 0:49
  of
• 0:50
  attraction.
• 0:50
  A
• 0:50
  high
• 0:50
  affinity
• 0:51
  drug
• 0:51
  binds
• 0:52
  like
• 0:52
  Velcro.
• 0:52
  And
• 0:53
  a
• 0:53
  low
• 0:53
  affinity
• 0:53
  drug,
• 0:54
  it's
• 0:54
  more
• 0:54
  like
• 0:55
  a
• 0:55
  post
• 0:55
  it
• 0:55
  note.
• 0:56
  Now,
• 0:56
  why
• 0:57
  does
• 0:57
  affinity
• 0:57
  matter
• 0:58
  to
• 0:58
  you?
• 0:58
  Because
• 0:59
  every
• 0:59
  time
• 1:00
  you
• 1:00
  prescribe
• 1:00
  a
• 1:00
  medication,
• 1:02
  you've
• 1:02
  got
• 1:02
  to
• 1:02
  think
• 1:03
  about
• 1:03
  it.
• 1:03
  What
• 1:04
  are
• 1:04
  going
• 1:04
  to
• 1:04
  be
• 1:04
  the
• 1:04
  first
• 1:04
  and
• 1:05
  second
• 1:05
  and
• 1:05
  third
• 1:05
  order
• 1:05
  effects
• 1:06
  of
• 1:06
  what
• 1:06
  I'm
• 1:06
  doing?
• 1:07
  And
• 1:07
  some
• 1:07
  medications.
• 1:08
  Let's
• 1:08
  take
• 1:08
  Remeron
• 1:09
  as
• 1:09
  an
• 1:09
  example.
• 1:10
  It's
• 1:11
  going
• 1:11
  to
• 1:11
  do
• 1:11
  a
• 1:11
  lot
• 1:11
  of
• 1:12
  different
• 1:12
  things.
• 1:13
  You're
• 1:13
  going
• 1:13
  to
• 1:13
  prescribe
• 1:14
  Remeron
• 1:14
  and
• 1:14
  it's
• 1:15
  going
• 1:15
  to
• 1:15
  make
• 1:15
  that
• 1:15
  patient
• 1:15
  tired.
• 1:16
  Why
• 1:16
  is
• 1:16
  that?
• 1:17
  Because
• 1:17
  it
• 1:17
  has
• 1:17
  a
• 1:18
  very
• 1:18
  high
• 1:18
  affinity
• 1:19
  for
• 1:20
  histamine.
• 1:20
  It
• 1:21
  blocks
• 1:21
  the
• 1:21
  H1
• 1:22
  receptor,
• 1:22
  which
• 1:23
  results
• 1:23
  in
• 1:24
  sedation.
• 1:24
  And
• 1:24
  it
• 1:25
  does
• 1:25
  that
• 1:25
  first
• 1:25
  because
• 1:26
  it
• 1:26
  has
• 1:26
  the
• 1:26
  strongest
• 1:27
  affinity
• 1:28
  for
• 1:29
  histamine.
• 1:30
  Well,
• 1:30
  that's
• 1:30
  really
• 1:31
  important.
• 1:31
  And
• 1:31
  by
• 1:32
  the
• 1:32
  way,
• 1:32
  how
• 1:32
  is
• 1:33
  affinity
• 1:34
  measured?
• 1:35
  It's
• 1:35
  measured
• 1:35
  in
• 1:36
  Ki.
• 1:36
  It's
• 1:36
  an
• 1:36
  inhibition
• 1:37
  constant.
• 1:38
  When
• 1:38
  you
• 1:38
  see
• 1:39
  a
• 1:39
  low
• 1:39
  Ki
• 1:40
  value,
• 1:41
  that
• 1:41
  means
• 1:41
  your
• 1:42
  medication
• 1:42
  has
• 1:42
  a
• 1:43
  very
• 1:43
  high
• 1:43
  affinity
• 1:44
  for
• 1:44
  that
• 1:44
  receptor.
• 1:45
  So
• 1:45
  Remeron
• 1:46
  has
• 1:46
  a
• 1:46
  very
• 1:47
  low
• 1:48
  Ki,
• 1:48
  or
• 1:49
  an
• 1:49
  inhibition
• 1:50
  constant,
• 1:50
  also
• 1:50
  known
• 1:51
  as
• 1:51
  inhibition
• 1:52
  constant
• 1:52
  Ki.
• 1:53
  It
• 1:53
  has
• 1:53
  a
• 1:53
  very
• 1:53
  low
• 1:54
  Ki,
• 1:54
  AKA
• 1:55
  higher
• 1:55
  affinity
• 1:56
  or
• 1:56
  tighter
• 1:56
  binding
• 1:57
  for
• 1:57
  histamine.
• 1:58
  A
• 1:58
  higher
• 1:58
  Ki
• 1:59
  would
• 1:59
  mean
• 1:59
  your
• 1:59
  medication
• 2:00
  has
• 2:00
  a
• 2:00
  very
• 2:00
  weak
• 2:01
  affinity
• 2:01
  for
• 2:03
  a
• 2:03
  particular
• 2:03
  receptor.
• 2:04
  So
• 2:04
  with
• 2:04
  remeron,
• 2:05
  the
• 2:05
  D2
• 2:06
  receptor,
• 2:06
  you
• 2:07
  see
• 2:07
  actually
• 2:07
  a
• 2:07
  very
• 2:07
  high
• 2:08
  Ki,
• 2:08
  because
• 2:10
  it
• 2:11
  needs.
• 2:12
  It
• 2:12
  doesn't
• 2:12
  basically
• 2:13
  affect
• 2:13
  the
• 2:13
  D2
• 2:13
  receptor
• 2:14
  at
• 2:14
  all,
• 2:14
  right?
• 2:15
  So
• 2:15
  when
• 2:15
  you
• 2:15
  see
• 2:16
  a
• 2:16
  crazy
• 2:16
  high
• 2:17
  ki
• 2:17
  level
• 2:17
  of
• 2:18
  10,000,
• 2:19
  that
• 2:19
  means
• 2:20
  your
• 2:21
  medication
• 2:21
  is
• 2:21
  not
• 2:22
  acting
• 2:22
  on
• 2:22
  that
• 2:22
  receptor
• 2:23
  at
• 2:23
  all
• 2:23
  or
• 2:23
  in
• 2:24
  an
• 2:24
  extremely
• 2:24
  weak,
• 2:25
  negligible
• 2:25
  way,
• 2:26
  versus
• 2:26
  a
• 2:26
  low
• 2:26
  Ki
• 2:27
  like
• 2:27
  one.
• 2:28
  And
• 2:28
  histamine
• 2:29
  and
• 2:29
  Remeron,
• 2:29
  where
• 2:29
  it's
• 2:30
  like,
• 2:30
  okay,
• 2:30
  this
• 2:31
  is
• 2:31
  what
• 2:31
  my
• 2:31
  medication
• 2:32
  is
• 2:32
  doing.
• 2:32
  It
• 2:33
  is
• 2:33
  principally
• 2:34
  causing
• 2:34
  sedation
• 2:35
  at
• 2:35
  that
• 2:35
  dose.
• 2:36
  So,
• 2:36
  so
• 2:37
  a
• 2:37
  high
• 2:37
  affinity
• 2:38
  will
• 2:38
  be
• 2:38
  a
• 2:39
  low
• 2:39
  ki,
• 2:39
  like
• 2:40
  1
• 2:40
  or
• 2:40
  2
• 2:41
  or
• 2:41
  3
• 2:41
  or
• 2:41
  4.
• 2:42
  That
• 2:42
  means
• 2:43
  that
• 2:43
  your
• 2:43
  medication
• 2:44
  is
• 2:44
  going
• 2:45
  to
• 2:45
  be
• 2:45
  a
• 2:45
  very
• 2:45
  strong
• 2:46
  magnet
• 2:46
  to
• 2:46
  that
• 2:47
  receptor.
• 2:48
  In
• 2:48
  this
• 2:48
  case
• 2:48
  Remeron
• 2:49
  and
• 2:49
  histamine.
• 2:50
  Very
• 2:50
  interesting,
• 2:51
  right?
• 2:51
  So
• 2:51
  a
• 2:51
  low
• 2:52
  ki
• 2:52
  is
• 2:52
  like
• 2:52
  a
• 2:53
  Velcro
• 2:53
  grip
• 2:54
  and
• 2:54
  a
• 2:54
  high
• 2:54
  ki
• 2:55
  is
• 2:55
  more
• 2:55
  like
• 2:55
  a
• 2:56
  post
• 2:56
  it
• 2:56
  note.
• 2:57
  It
• 2:57
  doesn't
• 2:57
  stick
• 2:57
  on
• 2:58
  there
• 2:58
  very
• 2:58
  well.
• 2:59
  Well,
• 2:59
  that
• 2:59
  really
• 2:59
  matters
• 3:00
  because
• 3:00
  that
• 3:00
  tells
• 3:01
  you
• 3:01
  the
• 3:02
  side
• 3:02
  effects
• 3:02
  that
• 3:02
  you
• 3:02
  can
• 3:02
  expect
• 3:03
  from
• 3:03
  your
• 3:03
  medications
• 3:04
  and
• 3:04
  what
• 3:04
  receptors
• 3:05
  they
• 3:06
  activate
• 3:06
  or
• 3:07
  antagonize
• 3:08
  at
• 3:08
  one
• 3:08
  affinity.
• 3:09
  That's
• 3:09
  going
• 3:09
  to
• 3:10
  tell
• 3:10
  you
• 3:10
  which
• 3:11
  receptors
• 3:11
  get
• 3:12
  hit
• 3:12
  first.
• 3:12
  Highest
• 3:13
  affinity
• 3:13
  receptors,
• 3:14
  usually
• 3:14
  at
• 3:15
  low
• 3:15
  doses,
• 3:15
  tend
• 3:16
  to
• 3:16
  get
• 3:16
  activated
• 3:17
  first.
• 3:17
  That's
• 3:18
  why
• 3:18
  Remeron,
• 3:18
  with
• 3:19
  its
• 3:19
  very
• 3:19
  high
• 3:19
  affinity
• 3:20
  or
• 3:20
  low
• 3:20
  Ki
• 3:21
  for
• 3:21
  histamine,
• 3:22
  is
• 3:22
  going
• 3:22
  to
• 3:23
  affect
• 3:23
  histamine
• 3:24
  and
• 3:24
  cause
• 3:24
  sedation
• 3:25
  first.
• 3:25
  Sure
• 3:25
  enough,
• 3:26
  that's
• 3:26
  what
• 3:26
  happens.
• 3:26
  You
• 3:26
  prescribe
• 3:27
  it,
• 3:27
  people
• 3:27
  get
• 3:28
  sedated.
• 3:29
  But
• 3:29
  it's
• 3:29
  not
• 3:29
  all
• 3:30
  that
• 3:30
  Remeron
• 3:31
  does.
• 3:32
  Remeron
• 3:33
  has
• 3:33
  an
• 3:33
  effect
• 3:34
  on
• 3:34
  multiple
• 3:36
  receptors.
• 3:37
  It's
• 3:37
  an
• 3:37
  Alpha
• 3:38
  2
• 3:38
  antagonist.
• 3:39
  It
• 3:40
  is
• 3:40
  also
• 3:40
  an
• 3:41
  antagonist
• 3:41
  of
• 3:41
  5ht2a,
• 3:43
  it's
• 3:43
  an
• 3:44
  antagonist
• 3:44
  of
• 3:44
  5ht2c,
• 3:48
  it's
• 3:48
  an
• 3:48
  antagonist
• 3:49
  of
• 3:49
  5kt3,
• 3:51
  which
• 3:52
  actually
• 3:52
  makes
• 3:52
  you
• 3:52
  less
• 3:53
  nauseous.
• 3:54
  Now
• 3:54
  its
• 3:54
  affinity
• 3:55
  for
• 3:56
  the
• 3:56
  5ht3
• 3:57
  blockade
• 3:58
  is
• 3:59
  a
• 3:59
  lot
• 3:59
  lower
• 4:00
  than
• 4:00
  its
• 4:00
  ability
• 4:01
  to
• 4:01
  sedate
• 4:01
  you.
• 4:02
  So
• 4:02
  yes,
• 4:03
  it
• 4:03
  can
• 4:03
  make
• 4:03
  you
• 4:03
  less
• 4:04
  nauseous
• 4:04
  and
• 4:04
  promote
• 4:05
  some
• 4:05
  GI
• 4:05
  comfort
• 4:06
  in
• 4:06
  patients
• 4:07
  who
• 4:07
  have
• 4:07
  anxiety
• 4:08
  that
• 4:09
  manifests
• 4:09
  as
• 4:09
  nausea
• 4:10
  or
• 4:10
  vomiting.
• 4:11
  Remeron
• 4:11
  is
• 4:12
  kind
• 4:12
  of
• 4:12
  my
• 4:12
  go
• 4:12
  to
• 4:13
  because
• 4:14
  it
• 4:14
  can
• 4:14
  help
• 4:15
  calm
• 4:15
  them
• 4:15
  down
• 4:15
  a
• 4:16
  little
• 4:16
  bit
• 4:16
  and
• 4:17
  improve
• 4:17
  mood
• 4:18
  via
• 4:18
  its
• 4:19
  alpha
• 4:19
  2
• 4:19
  antagonism.
• 4:20
  Boosts
• 4:20
  norepinephrine
• 4:21
  and
• 4:21
  serotonin
• 4:22
  release.
• 4:23
  It
• 4:23
  also
• 4:23
  blockades
• 4:23
  the
• 4:24
  5ht3
• 4:24
  receptor,
• 4:25
  which
• 4:25
  results
• 4:25
  in
• 4:26
  a
• 4:27
  little
• 4:27
  bit
• 4:27
  of
• 4:27
  an
• 4:27
  anti
• 4:27
  nausea
• 4:28
  effect.
• 4:28
  Notice
• 4:29
  it's
• 4:29
  doing
• 4:29
  multiple
• 4:30
  things
• 4:30
  at
• 4:30
  once.
• 4:31
  But
• 4:31
  to
• 4:31
  understand
• 4:32
  why
• 4:32
  and
• 4:32
  how,
• 4:32
  you've
• 4:33
  got
• 4:33
  to
• 4:33
  understand
• 4:33
  affinity.
• 4:34
  Because
• 4:35
  when
• 4:35
  a
• 4:36
  medication
• 4:36
  like
• 4:36
  Remeron
• 4:37
  has
• 4:37
  a
• 4:37
  really
• 4:37
  high
• 4:38
  affinity
• 4:38
  for
• 4:38
  histamine,
• 4:39
  you're
• 4:40
  gonna
• 4:40
  be
• 4:40
  targeting
• 4:40
  that
• 4:41
  receptor.
• 4:41
  Next.
• 4:41
  When
• 4:42
  it
• 4:42
  has
• 4:42
  lower
• 4:42
  affinities
• 4:43
  for
• 4:43
  the
• 4:44
  anti
• 4:44
  nausea
• 4:44
  effect,
• 4:45
  that
• 4:45
  5ht3
• 4:46
  blockade,
• 4:46
  if
• 4:46
  that
• 4:47
  affinity
• 4:47
  is
• 4:47
  a
• 4:47
  lot
• 4:47
  lower,
• 4:48
  that
• 4:48
  means
• 4:48
  you
• 4:48
  need
• 4:49
  more
• 4:49
  of
• 4:49
  the
• 4:50
  medication
• 4:51
  to
• 4:51
  actually
• 4:51
  exert
• 4:52
  that
• 4:52
  effect
• 4:52
  because
• 4:53
  it's
• 4:53
  a
• 4:53
  low
• 4:53
  affinity.
• 4:54
  I
• 4:55
  want
• 4:55
  you
• 4:55
  to
• 4:55
  think
• 4:55
  of
• 4:56
  high
• 4:56
  affinity
• 4:57
  medications
• 4:58
  like
• 4:58
  snow
• 4:59
  that's
• 4:59
  really
• 4:59
  sticky
• 5:00
  in
• 5:00
  winter.
• 5:00
  It
• 5:01
  doesn't
• 5:01
  take
• 5:01
  a
• 5:01
  lot,
• 5:01
  it
• 5:02
  just
• 5:02
  immediately
• 5:02
  sticks.
• 5:03
  It
• 5:03
  doesn't
• 5:03
  have
• 5:03
  to
• 5:03
  snow
• 5:04
  a
• 5:04
  lot
• 5:04
  and
• 5:04
  your
• 5:05
  sidewalk
• 5:05
  is
• 5:05
  already
• 5:06
  gently
• 5:06
  covered
• 5:07
  and
• 5:07
  stuck
• 5:07
  with
• 5:08
  snow.
• 5:08
  That
• 5:08
  would
• 5:09
  be
• 5:09
  like
• 5:09
  a
• 5:09
  high
• 5:09
  affinity
• 5:10
  medication
• 5:11
  with
• 5:11
  a
• 5:11
  low
• 5:11
  ki
• 5:12
  or
• 5:12
  inhibition
• 5:13
  constant.
• 5:13
  That
• 5:13
  would
• 5:13
  be
• 5:14
  Remeron
• 5:14
  and
• 5:14
  histamine.
• 5:15
  The
• 5:16
  snow
• 5:16
  is
• 5:17
  laying
• 5:18
  it
• 5:18
  on
• 5:18
  thick,
• 5:19
  right?
• 5:19
  It's
• 5:20
  Just
• 5:20
  that
• 5:20
  even
• 5:21
  though
• 5:21
  it
• 5:21
  just
• 5:21
  started
• 5:21
  snowing,
• 5:22
  it's
• 5:22
  sticking
• 5:23
  already
• 5:23
  and
• 5:23
  it's
• 5:23
  covering
• 5:24
  your
• 5:24
  sidewalk.
• 5:25
  That's
• 5:25
  high
• 5:25
  affinity.
• 5:26
  But
• 5:27
  a
• 5:27
  weak
• 5:28
  affinity,
• 5:28
  that
• 5:29
  would
• 5:29
  be,
• 5:29
  let's
• 5:29
  say,
• 5:29
  Remeron.
• 5:30
  It's
• 5:31
  anti
• 5:31
  nausea.
• 5:32
  It's
• 5:32
  not
• 5:32
  gonna
• 5:33
  stick
• 5:33
  as
• 5:33
  easily.
• 5:33
  You
• 5:34
  might
• 5:34
  need
• 5:34
  to
• 5:34
  raise
• 5:34
  the
• 5:35
  dose
• 5:35
  to
• 5:35
  appreciate
• 5:36
  the
• 5:36
  fact
• 5:37
  that
• 5:38
  it's
• 5:39
  causing
• 5:39
  less
• 5:39
  nausea.
• 5:40
  So
• 5:40
  you
• 5:41
  may
• 5:41
  not
• 5:41
  get
• 5:41
  that
• 5:41
  anti
• 5:42
  nausea
• 5:43
  effect
• 5:43
  at
• 5:44
  such
• 5:44
  a
• 5:44
  low
• 5:44
  dose.
• 5:44
  You
• 5:44
  might
• 5:45
  have
• 5:45
  to
• 5:45
  raise
• 5:45
  it
• 5:45
  a
• 5:45
  little
• 5:45
  bit.
• 5:46
  You
• 5:46
  might
• 5:46
  have
• 5:46
  to
• 5:46
  snow
• 5:47
  a
• 5:47
  little
• 5:47
  more
• 5:47
  to
• 5:48
  cover
• 5:48
  the
• 5:49
  sidewalk.
• 5:49
  You
• 5:50
  get
• 5:50
  what
• 5:50
  I'm
• 5:50
  saying?
• 5:51
  I
• 5:51
  love
• 5:51
  that
• 5:51
  analogy.
• 5:52
  Because
• 5:52
  high
• 5:52
  affinity,
• 5:53
  it's
• 5:53
  very
• 5:53
  easy
• 5:54
  to
• 5:54
  cover
• 5:54
  the
• 5:54
  sidewalk.
• 5:55
  It's
• 5:55
  sticking
• 5:55
  or
• 5:56
  the
• 5:56
  magnet
• 5:56
  is
• 5:57
  strong.
• 5:57
  Right?
• 5:57
  Again,
• 5:58
  low
• 5:58
  ki
• 5:59
  value.
• 5:59
  1,
• 6:00
  2,
• 6:00
  10,
• 6:01
  5.
• 6:01
  Okay.
• 6:02
  Histamine,
• 6:03
  it's
• 6:04
  hitting
• 6:04
  that
• 6:04
  receptor
• 6:04
  very
• 6:05
  easily.
• 6:05
  The
• 6:05
  snow
• 6:05
  is
• 6:06
  sticking
• 6:06
  very
• 6:06
  easily.
• 6:07
  But
• 6:07
  these
• 6:08
  other
• 6:08
  effects,
• 6:08
  these
• 6:09
  other
• 6:09
  kind
• 6:09
  of
• 6:09
  doors
• 6:10
  that
• 6:10
  it
• 6:10
  opens,
• 6:10
  these
• 6:10
  other
• 6:11
  receptors
• 6:11
  that
• 6:11
  are
• 6:11
  being
• 6:12
  antagonized
• 6:12
  or
• 6:12
  activated
• 6:13
  to
• 6:13
  exert
• 6:14
  certain
• 6:14
  effects,
• 6:15
  they
• 6:15
  might
• 6:15
  have
• 6:15
  a
• 6:16
  lower
• 6:16
  affinity.
• 6:17
  You
• 6:17
  can
• 6:17
  achieve
• 6:17
  those
• 6:18
  things.
• 6:18
  You
• 6:18
  can
• 6:18
  get
• 6:18
  the
• 6:19
  anti
• 6:19
  nausea
• 6:19
  effect.
• 6:20
  When
• 6:20
  you
• 6:21
  block
• 6:21
  5ht
• 6:22
  2c,
• 6:23
  for
• 6:23
  example,
• 6:24
  with
• 6:24
  Remeron,
• 6:25
  it
• 6:25
  causes
• 6:25
  a
• 6:25
  little
• 6:25
  weight
• 6:26
  gain.
• 6:26
  You
• 6:27
  can
• 6:27
  get
• 6:27
  that
• 6:27
  effect
• 6:28
  and
• 6:29
  it
• 6:29
  will
• 6:29
  cause
• 6:30
  some
• 6:30
  weight
• 6:30
  gain,
• 6:31
  but
• 6:31
  it's
• 6:31
  not
• 6:31
  gonna
• 6:31
  happen
• 6:32
  as
• 6:32
  immediately
• 6:33
  as
• 6:33
  when
• 6:33
  you
• 6:33
  antagonize
• 6:34
  histamine.
• 6:35
  That
• 6:35
  is
• 6:35
  the
• 6:35
  most
• 6:36
  affinity
• 6:36
  for
• 6:37
  Remeron
• 6:37
  right
• 6:38
  off
• 6:38
  the
• 6:38
  bat.
• 6:38
  So
• 6:38
  I
• 6:38
  really
• 6:39
  want
• 6:39
  you
• 6:39
  to
• 6:39
  bear
• 6:39
  with
• 6:39
  me
• 6:40
  here,
• 6:40
  my
• 6:40
  friends,
• 6:40
  because
• 6:40
  it
• 6:41
  all
• 6:41
  kind
• 6:41
  of
• 6:41
  comes
• 6:41
  together
• 6:41
  here.
• 6:42
  Just
• 6:42
  going
• 6:43
  back
• 6:43
  to
• 6:43
  the
• 6:43
  drawing
• 6:44
  board.
• 6:44
  Each
• 6:45
  medication
• 6:45
  you
• 6:46
  take,
• 6:46
  each
• 6:47
  medication
• 6:47
  you
• 6:47
  take
• 6:48
  is
• 6:48
  going
• 6:49
  to
• 6:49
  result
• 6:50
  in
• 6:51
  many
• 6:51
  different
• 6:51
  effects.
• 6:52
  Potentially.
• 6:52
  If
• 6:53
  that
• 6:53
  medication
• 6:54
  has
• 6:54
  an
• 6:54
  affinity
• 6:55
  for,
• 6:55
  let's
• 6:56
  say,
• 6:56
  four
• 6:56
  or
• 6:56
  five
• 6:57
  different
• 6:57
  receptors.
• 6:58
  One
• 6:58
  receptor
• 6:59
  might
• 6:59
  make
• 6:59
  you
• 6:59
  sedated.
• 7:00
  One
• 7:00
  receptor
• 7:01
  like
• 7:01
  alpha
• 7:01
  2
• 7:01
  antagonism
• 7:02
  will
• 7:02
  boost
• 7:02
  norepinephrine
• 7:03
  and
• 7:03
  serotonin.
• 7:04
  Release
• 7:04
  another
• 7:04
  receptor,
• 7:05
  5HT2A.
• 7:06
  We
• 7:06
  talk
• 7:06
  about
• 7:07
  that
• 7:07
  in
• 7:07
  previous
• 7:07
  episodes.
• 7:08
  That
• 7:09
  receptor
• 7:09
  is
• 7:09
  going
• 7:10
  to
• 7:10
  make
• 7:10
  you
• 7:10
  feel
• 7:10
  calmer
• 7:11
  if
• 7:11
  you
• 7:11
  antagonize
• 7:12
  it
• 7:12
  a
• 7:12
  little
• 7:12
  bit,
• 7:13
  right?
• 7:13
  It's
• 7:14
  going
• 7:14
  to
• 7:14
  reduce
• 7:14
  motor
• 7:15
  side
• 7:15
  effects
• 7:16
  in
• 7:16
  folks
• 7:17
  that
• 7:17
  are
• 7:17
  having
• 7:18
  motor
• 7:18
  symptoms
• 7:19
  from
• 7:19
  their
• 7:19
  antipsychotics.
• 7:20
  If
• 7:20
  you
• 7:20
  block
• 7:21
  5Ht2A,
• 7:22
  right?
• 7:23
  If
• 7:23
  you
• 7:24
  block
• 7:25
  5Ht3,
• 7:26
  you're
• 7:26
  going
• 7:26
  to
• 7:27
  get
• 7:27
  an
• 7:27
  anti
• 7:27
  nausea
• 7:27
  effect.
• 7:28
  So
• 7:29
  your
• 7:29
  medication
• 7:29
  is
• 7:30
  going
• 7:30
  to
• 7:30
  do
• 7:30
  many
• 7:30
  different
• 7:30
  things.
• 7:31
  But
• 7:31
  you
• 7:32
  want
• 7:32
  to
• 7:32
  look
• 7:32
  at
• 7:32
  the
• 7:32
  affinities
• 7:33
  and
• 7:33
  how
• 7:34
  well
• 7:34
  it
• 7:34
  does
• 7:34
  those
• 7:35
  things.
• 7:35
  The
• 7:35
  lower
• 7:36
  the
• 7:36
  ki,
• 7:36
  the
• 7:37
  value,
• 7:37
  the
• 7:37
  better
• 7:38
  it
• 7:38
  does
• 7:38
  those
• 7:38
  things
• 7:39
  on
• 7:39
  that
• 7:40
  particular
• 7:40
  receptor.
• 7:41
  And
• 7:41
  that
• 7:41
  is
• 7:42
  really
• 7:42
  the
• 7:42
  key
• 7:42
  to
• 7:42
  this
• 7:43
  episode
• 7:43
  today
• 7:43
  because
• 7:44
  it
• 7:44
  unlocks
• 7:45
  so
• 7:45
  much.
• 7:45
  It
• 7:45
  allows
• 7:45
  you
• 7:45
  to
• 7:46
  Learn
• 7:46
  a
• 7:46
  new
• 7:46
  language,
• 7:47
  if
• 7:47
  you
• 7:47
  will,
• 7:47
  from
• 7:47
  your
• 7:47
  medications.
• 7:48
  Now
• 7:48
  I
• 7:48
  can
• 7:48
  pull
• 7:49
  out
• 7:49
  Risperdol,
• 7:50
  Zyprexide,
• 7:50
  Prozac.
• 7:51
  And
• 7:51
  I
• 7:51
  say,
• 7:51
  okay,
• 7:52
  what
• 7:52
  is
• 7:52
  Prozac's
• 7:53
  affinity
• 7:53
  for
• 7:54
  norepinephrine?
• 7:55
  Well,
• 7:55
  it's
• 7:55
  probably
• 7:55
  a
• 7:55
  very
• 7:56
  weak
• 7:56
  affinity.
• 7:56
  It's
• 7:57
  probably
• 7:57
  very
• 7:57
  low
• 7:57
  affinity
• 7:58
  because
• 7:58
  it's
• 7:58
  not
• 7:59
  an
• 7:59
  snri.
• 8:00
  Is
• 8:00
  it
• 8:00
  zero,
• 8:00
  though?
• 8:01
  Does
• 8:01
  it
• 8:01
  have
• 8:01
  any
• 8:01
  norepinephrine
• 8:02
  effect?
• 8:03
  I
• 8:03
  don't
• 8:03
  know.
• 8:04
  We
• 8:04
  should
• 8:04
  whip
• 8:04
  out
• 8:04
  our
• 8:04
  textbooks
• 8:05
  and
• 8:05
  look
• 8:05
  at
• 8:05
  that.
• 8:06
  Let's
• 8:06
  look
• 8:06
  at
• 8:06
  the
• 8:07
  relative
• 8:07
  affinity
• 8:08
  of
• 8:08
  Effexor,
• 8:09
  Norepinephrine
• 8:10
  and
• 8:10
  Effexor
• 8:11
  and
• 8:11
  Norepinephrine
• 8:12
  and
• 8:12
  Pristiq.
• 8:13
  Right.
• 8:14
  Lo
• 8:14
  and
• 8:14
  behold,
• 8:14
  you
• 8:15
  will
• 8:15
  find
• 8:15
  that
• 8:15
  Pristiq
• 8:16
  has
• 8:16
  more
• 8:16
  of
• 8:16
  a
• 8:16
  norepinephrine
• 8:17
  effect
• 8:18
  at
• 8:18
  its
• 8:19
  introductory
• 8:19
  dose,
• 8:20
  as
• 8:20
  opposed
• 8:20
  to
• 8:20
  Effexor,
• 8:21
  where
• 8:21
  you
• 8:21
  have
• 8:21
  to
• 8:21
  raise
• 8:21
  the
• 8:22
  dose
• 8:22
  to
• 8:22
  150
• 8:22
  to
• 8:23
  appreciate
• 8:23
  more
• 8:24
  of
• 8:24
  a
• 8:24
  norepinephrine
• 8:25
  effect.
• 8:25
  Again,
• 8:26
  very
• 8:26
  interesting,
• 8:26
  right?
• 8:27
  Because
• 8:27
  with
• 8:27
  Pristiq,
• 8:28
  you
• 8:28
  get
• 8:28
  that
• 8:29
  thick
• 8:29
  snow
• 8:29
  right
• 8:30
  away
• 8:30
  because
• 8:30
  it
• 8:30
  has
• 8:30
  a
• 8:30
  higher
• 8:31
  affinity.
• 8:32
  That
• 8:32
  thick
• 8:32
  snow
• 8:32
  is
• 8:33
  laying
• 8:33
  down
• 8:33
  right
• 8:33
  away
• 8:34
  at
• 8:34
  around
• 8:34
  50
• 8:35
  milligrams,
• 8:35
  the
• 8:35
  introdose
• 8:36
  of
• 8:36
  Pristiq.
• 8:37
  Okay?
• 8:37
  But
• 8:38
  with
• 8:38
  Effexor,
• 8:38
  it's
• 8:39
  gotta
• 8:39
  snow
• 8:39
  a
• 8:39
  little
• 8:39
  bit
• 8:40
  more.
• 8:40
  And
• 8:40
  then
• 8:41
  you
• 8:41
  get
• 8:41
  the
• 8:41
  effects
• 8:42
  of
• 8:43
  the
• 8:43
  snow
• 8:44
  and
• 8:44
  the
• 8:44
  norepinephrine
• 8:45
  effect.
• 8:46
  If
• 8:46
  it
• 8:46
  snows
• 8:46
  a
• 8:47
  little
• 8:47
  more
• 8:47
  and
• 8:47
  you
• 8:47
  go
• 8:47
  up
• 8:47
  to
• 8:48
  150,
• 8:48
  more
• 8:49
  snow,
• 8:49
  meaning
• 8:50
  a
• 8:50
  dose
• 8:51
  increase.
• 9:47
  And
• 9:47
  remember,
• 9:47
  high
• 9:48
  affinity
• 9:48
  means
• 9:48
  it
• 9:49
  barely
• 9:49
  has
• 9:49
  to
• 9:49
  snow
• 9:49
  to
• 9:50
  get
• 9:50
  the
• 9:50
  ground
• 8:56
  covered.
• 9:51
  He
• 9:51
  said,
• 9:51
  that's
• 9:51
  a
• 9:52
  very
• 9:52
  important
• 9:52
  principle
• 9:53
  because
• 9:53
  if
• 9:53
  you
• 9:53
  see
• 9:54
  a
• 9:54
  medication
• 9:55
  like
• 9:55
  Remeron
• 9:55
  and
• 9:55
  you
• 9:56
  go,
• 9:56
  I
• 9:56
  would
• 9:56
  actually
• 9:57
  really
• 9:57
  like
• 9:58
  to
• 9:58
  undo
• 9:58
  sexual
• 9:59
  side
• 9:59
  effects
• 10:00
  a
• 10:00
  little
• 10:00
  bit
• 10:00
  by
• 10:01
  blocking
• 10:01
  that
• 10:01
  5ht2a
• 10:02
  receptor.
• 10:03
  And
• 10:03
  you
• 10:03
  look
• 10:03
  at
• 10:03
  Remeron
• 10:03
  and
• 10:04
  you
• 10:04
  go,
• 10:04
  it
• 10:04
  has
• 10:04
  somewhat
• 10:05
  of
• 10:05
  an
• 10:05
  affinity
• 10:05
  for
• 10:05
  that.
• 10:05
  It's
• 10:06
  not
• 10:06
  as
• 10:06
  strong
• 10:06
  of
• 10:07
  an
• 10:07
  affinity
• 10:07
  as
• 10:08
  histamine.
• 10:09
  That
• 10:09
  might
• 10:09
  clue
• 10:09
  you
• 10:09
  in
• 10:10
  to
• 10:10
  saying,
• 10:10
  well,
• 10:11
  we
• 10:11
  might
• 10:11
  have
• 10:11
  to
• 10:11
  raise
• 10:12
  the
• 10:13
  Remeron
• 10:13
  dose
• 10:14
  a
• 10:14
  little
• 10:14
  bit
• 10:14
  because
• 10:14
  the
• 10:14
  affinity
• 10:15
  is
• 10:15
  not
• 10:15
  super
• 10:16
  strong
• 10:16
  at
• 10:16
  5ht
• 10:17
  2a.
• 10:18
  But
• 10:18
  if
• 10:18
  we
• 10:18
  raise
• 10:19
  the
• 10:19
  dose
• 10:19
  of
• 10:19
  Remeron,
• 10:21
  it
• 10:21
  might
• 10:21
  cover
• 10:21
  the
• 10:21
  ground
• 10:22
  and
• 10:22
  start
• 10:23
  actually
• 10:24
  occupying
• 10:25
  those
• 10:25
  receptors
• 10:26
  in
• 10:27
  more
• 10:27
  quantities
• 10:28
  and
• 10:28
  exert
• 10:28
  the
• 10:29
  effect
• 10:29
  that
• 10:29
  we're
• 10:29
  looking
• 10:30
  for,
• 10:30
  which
• 10:30
  would
• 10:30
  be
• 10:30
  to
• 10:30
  reduce
• 10:31
  sexual
• 10:32
  side
• 10:32
  effects.
• 10:33
  So,
• 10:33
  again,
• 10:33
  I
• 10:33
  hope
• 10:34
  you
• 10:34
  have
• 10:34
  an
• 10:34
  appreciation
• 10:35
  for
• 10:35
  this
• 10:35
  a
• 10:35
  little
• 10:35
  bit
• 10:36
  in
• 10:36
  how
• 10:36
  we're
• 10:37
  going
• 10:37
  about
• 10:37
  this.
• 10:38
  And
• 10:38
  knowing
• 10:39
  the
• 10:39
  affinity
• 10:39
  is
• 10:39
  really
• 10:40
  the
• 10:40
  first
• 10:41
  step.
• 10:41
  If
• 10:42
  you
• 10:42
  hear
• 10:42
  that
• 10:42
  Zyprexa
• 10:43
  or
• 10:43
  Haldol
• 10:44
  has
• 10:44
  a
• 10:44
  really,
• 10:45
  really
• 10:45
  strong
• 10:46
  affinity
• 10:46
  for
• 10:46
  D2,
• 10:47
  that
• 10:47
  that
• 10:47
  tells
• 10:47
  you,
• 10:48
  well,
• 10:48
  it's
• 10:48
  really
• 10:48
  good
• 10:48
  at
• 10:48
  blocking
• 10:49
  dopamine
• 10:50
  at
• 10:50
  a
• 10:50
  very
• 10:50
  low
• 10:50
  dose,
• 10:51
  which
• 10:51
  means
• 10:51
  you
• 10:52
  might
• 10:52
  not
• 10:52
  need
• 10:52
  a
• 10:53
  lot
• 10:53
  of
• 10:53
  Zyprexa
• 10:53
  or
• 10:54
  Haldol
• 10:54
  to
• 10:55
  achieve
• 10:55
  your
• 10:56
  desired
• 10:57
  aims
• 10:58
  in
• 10:58
  blocking
• 10:59
  that
• 10:59
  D2
• 10:59
  receptor
• 11:00
  and
• 11:00
  stabilizing
• 11:01
  mood
• 11:01
  and
• 11:02
  reducing
• 11:03
  psychosis.
• 11:04
  Well,
• 11:04
  boy,
• 11:04
  that
• 11:04
  would
• 11:04
  be
• 11:05
  nice,
• 11:05
  wouldn't
• 11:05
  it?
• 11:06
  That's
• 11:06
  what
• 11:06
  we're
• 11:07
  looking
• 11:07
  at
• 11:07
  here.
• 11:07
  It's
• 11:08
  good
• 11:08
  for
• 11:08
  us
• 11:08
  to
• 11:08
  be
• 11:09
  vigilant
• 11:09
  about
• 11:10
  the
• 11:11
  affinity
• 11:11
  of
• 11:11
  a
• 11:12
  particular
• 11:12
  medication.
• 11:13
  With
• 11:13
  Remeron,
• 11:14
  its
• 11:14
  histamine
• 11:15
  antagonism
• 11:15
  is
• 11:15
  about
• 11:16
  20
• 11:16
  times
• 11:16
  stronger
• 11:17
  in
• 11:17
  affinity
• 11:18
  in
• 11:18
  relation
• 11:18
  to
• 11:18
  its
• 11:19
  Alpha
• 11:19
  2
• 11:20
  antagonism.
• 11:20
  That's
• 11:21
  kind
• 11:21
  of
• 11:21
  fascinating
• 11:22
  too,
• 11:22
  right?
• 11:22
  Because
• 11:22
  it's
• 11:22
  going
• 11:22
  to
• 11:22
  be
• 11:23
  really
• 11:23
  good
• 11:23
  at
• 11:23
  sedating
• 11:24
  you
• 11:24
  quickly.
• 11:25
  But
• 11:25
  in
• 11:25
  terms
• 11:25
  of
• 11:26
  blocking
• 11:26
  Alpha
• 11:27
  2,
• 11:27
  being
• 11:27
  an
• 11:27
  Alpha
• 11:27
  2
• 11:28
  antagonist,
• 11:29
  as
• 11:29
  we
• 11:29
  mentioned,
• 11:30
  results
• 11:30
  in
• 11:30
  the
• 11:30
  increase
• 11:31
  in
• 11:31
  norepinephrine
• 11:31
  and
• 11:32
  serotonin
• 11:32
  might
• 11:33
  lift
• 11:33
  mood
• 11:33
  a
• 11:33
  little
• 11:33
  bit.
• 11:34
  Energy
• 11:34
  motivation
• 11:35
  might
• 11:36
  relieve
• 11:36
  hopelessness.
• 11:37
  Well,
• 11:39
  so
• 11:39
  it's
• 11:39
  much
• 11:39
  better
• 11:39
  at
• 11:40
  sedating
• 11:40
  you
• 11:40
  than
• 11:41
  at
• 11:41
  giving
• 11:41
  you
• 11:41
  that
• 11:41
  extra
• 11:42
  energy
• 11:42
  or
• 11:42
  alertness.
• 11:43
  That's
• 11:43
  important
• 11:44
  to
• 11:44
  know.
• 11:44
  So
• 11:44
  we're
• 11:45
  gonna
• 11:45
  have
• 11:45
  to
• 11:45
  raise
• 11:45
  the
• 11:45
  dose
• 11:46
  to
• 11:47
  get
• 11:47
  more
• 11:48
  of
• 11:48
  that
• 11:49
  energy
• 11:49
  and
• 11:49
  alertness
• 11:50
  because
• 11:51
  the
• 11:51
  affinity
• 11:51
  is
• 11:52
  not
• 11:52
  as
• 11:52
  strong.
• 11:52
  Meaning
• 11:53
  at
• 11:53
  7.5,
• 11:54
  you're
• 11:54
  probably
• 11:54
  not
• 11:55
  gonna
• 11:55
  get
• 11:55
  that
• 11:55
  kind
• 11:55
  of
• 11:55
  effect
• 11:56
  for
• 11:56
  norepinephrine.
• 11:58
  And
• 11:58
  therefore
• 11:58
  you
• 11:58
  have
• 11:59
  to
• 11:59
  raise
• 11:59
  the
• 11:59
  dose
• 11:59
  of
• 11:59
  Remeron
• 12:00
  to
• 12:00
  really
• 12:00
  appreciate
• 12:01
  the
• 12:01
  effects
• 12:01
  of
• 12:01
  norepinephrine
• 12:02
  because
• 12:03
  it's.
• 12:03
  The
• 12:03
  affinity's
• 12:04
  not
• 12:04
  as
• 12:04
  strong.
• 12:04
  It's
• 12:04
  not
• 12:04
  like
• 12:05
  histamine.
• 12:05
  Histamine
• 12:06
  is
• 12:06
  the
• 12:06
  principal
• 12:07
  thing.
• 12:07
  It
• 12:07
  antagonizes
• 12:08
  the
• 12:08
  principal
• 12:09
  effect
• 12:09
  at
• 12:10
  early
• 12:10
  on,
• 12:10
  when
• 12:10
  you.
• 12:11
  When
• 12:11
  you
• 12:11
  give
• 12:11
  remeron
• 12:12
  that
• 12:12
  7.5
• 12:13
  milligram
• 12:14
  dose,
• 12:14
  histamine
• 12:15
  is
• 12:16
  kind
• 12:16
  of
• 12:16
  the
• 12:16
  main
• 12:17
  target,
• 12:17
  the
• 12:17
  main
• 12:17
  show
• 12:18
  in
• 12:18
  town,
• 12:18
  right
• 12:19
  at
• 12:19
  that
• 12:19
  low
• 12:19
  dose,
• 12:20
  which
• 12:20
  is
• 12:20
  so
• 12:20
  weird
• 12:20
  with
• 12:21
  Remeron,
• 12:21
  because
• 12:22
  most
• 12:22
  people
• 12:22
  think,
• 12:22
  oh,
• 12:23
  my
• 12:23
  God,
• 12:23
  this
• 12:23
  makes
• 12:23
  me
• 12:23
  tired.
• 12:24
  If
• 12:24
  I
• 12:24
  take
• 12:24
  more,
• 12:24
  I'm
• 12:25
  going
• 12:25
  to
• 12:25
  get
• 12:25
  even
• 12:25
  more
• 12:25
  tired,
• 12:26
  right?
• 12:26
  You
• 12:26
  take
• 12:27
  1
• 12:27
  milligram
• 12:28
  melatonin.
• 12:29
  If
• 12:29
  you
• 12:29
  take
• 12:29
  5
• 12:30
  milligrams
• 12:30
  of
• 12:30
  melatonin,
• 12:31
  you
• 12:31
  should
• 12:31
  feel
• 12:31
  more
• 12:31
  tired,
• 12:32
  right?
• 12:33
  Well,
• 12:33
  Reviron
• 12:33
  is
• 12:34
  kind
• 12:34
  of
• 12:34
  the
• 12:34
  opposite.
• 12:34
  It's
• 12:35
  like,
• 12:35
  well,
• 12:35
  if
• 12:35
  I
• 12:35
  take
• 12:35
  more
• 12:35
  Remeron,
• 12:36
  I'm
• 12:37
  actually
• 12:37
  going
• 12:37
  to
• 12:37
  feel
• 12:37
  more
• 12:38
  activated.
• 12:38
  Why
• 12:38
  is
• 12:39
  that?
• 12:40
  Because
• 12:41
  more
• 12:41
  snow
• 12:41
  is
• 12:42
  covering
• 12:42
  the
• 12:42
  ground,
• 12:42
  which
• 12:43
  means
• 12:43
  you're
• 12:44
  allowing
• 12:45
  the
• 12:46
  Alpha
• 12:46
  2
• 12:47
  antagonism
• 12:47
  to
• 12:47
  take
• 12:48
  place,
• 12:48
  which
• 12:49
  will
• 12:49
  result
• 12:49
  in
• 12:50
  increases
• 12:50
  in
• 12:50
  norepinephrine
• 12:51
  and
• 12:51
  serotonin,
• 12:52
  which
• 12:52
  can
• 12:52
  be
• 12:52
  more
• 12:52
  energizing.
• 12:53
  Now,
• 12:53
  it's
• 12:54
  not
• 12:54
  going
• 12:54
  to
• 12:54
  really
• 12:55
  make
• 12:55
  it
• 12:56
  so
• 12:56
  energizing
• 12:56
  that
• 12:57
  you're
• 12:57
  not
• 12:57
  sedated
• 12:58
  anymore.
• 12:58
  You
• 12:58
  still
• 12:58
  will
• 12:58
  Be
• 12:59
  sedated
• 12:59
  at
• 12:59
  nighttime.
• 13:00
  Why?
• 13:00
  Because.
• 13:00
  Because
• 13:01
  it
• 13:01
  has
• 13:01
  such
• 13:01
  a
• 13:01
  strong
• 13:01
  magnet
• 13:02
  force
• 13:02
  affinity
• 13:03
  for
• 13:03
  that
• 13:03
  histamine
• 13:04
  receptor.
• 13:05
  You
• 13:05
  see
• 13:06
  how
• 13:06
  this
• 13:06
  is
• 13:06
  kind
• 13:07
  of
• 13:07
  interesting,
• 13:07
  right?
• 13:08
  And
• 13:08
  how
• 13:09
  by
• 13:09
  increasing
• 13:10
  the
• 13:10
  dose,
• 13:11
  you
• 13:11
  can
• 13:11
  make
• 13:11
  up
• 13:11
  for
• 13:12
  the
• 13:12
  fact
• 13:12
  that
• 13:12
  the
• 13:13
  affinity
• 13:13
  is
• 13:13
  a
• 13:13
  little
• 13:14
  lower
• 13:14
  on
• 13:14
  those
• 13:14
  other
• 13:15
  receptors.
• 13:15
  AKA
• 13:16
  you're
• 13:16
  letting
• 13:17
  it
• 13:17
  snow
• 13:17
  a
• 13:17
  little
• 13:17
  more
• 13:18
  to
• 13:18
  accumulate
• 13:19
  more
• 13:19
  snow
• 13:19
  on
• 13:19
  the
• 13:19
  sidewalk.
• 13:20
  Cause
• 13:20
  you
• 13:20
  want
• 13:20
  to
• 13:20
  occupy
• 13:21
  those
• 13:21
  receptors
• 13:21
  and
• 13:22
  exert
• 13:22
  the
• 13:22
  desired
• 13:23
  pharmacological
• 13:24
  response.
• 13:25
  Bremeron
• 13:25
  has
• 13:26
  a
• 13:26
  whole
• 13:26
  host
• 13:26
  of
• 13:26
  different
• 13:26
  responses
• 13:27
  that
• 13:27
  you
• 13:27
  may
• 13:27
  be
• 13:28
  interested
• 13:28
  in
• 13:28
  activating.
• 13:29
  Right?
• 13:29
  The
• 13:30
  counter
• 13:30
  to
• 13:30
  the
• 13:30
  sexual
• 13:31
  side
• 13:31
  effects.
• 13:31
  Reduced
• 13:32
  anxiety
• 13:32
  by
• 13:33
  blocking
• 13:33
  5ht
• 13:34
  2a.
• 13:35
  Reducing
• 13:35
  nausea
• 13:36
  by
• 13:36
  blocking
• 13:36
  5ht
• 13:37
  3.
• 13:38
  That's
• 13:38
  a
• 13:39
  pretty
• 13:39
  unique
• 13:39
  one,
• 13:39
  actually.
• 13:40
  Right.
• 13:40
  As
• 13:40
  we
• 13:41
  know,
• 13:41
  SSRIs
• 13:41
  tend
• 13:42
  to
• 13:42
  activate
• 13:42
  5
• 13:43
  HT3.
• 13:43
  That's
• 13:43
  why
• 13:43
  people
• 13:44
  get
• 13:44
  a
• 13:44
  little
• 13:44
  nauseous.
• 13:45
  There's
• 13:45
  a
• 13:45
  lot
• 13:45
  of
• 13:45
  those
• 13:45
  serotonin
• 13:46
  receptors
• 13:46
  in
• 13:46
  the
• 13:47
  gut.
• 13:47
  Well,
• 13:47
  Reviron
• 13:48
  blocks
• 13:48
  that,
• 13:48
  which
• 13:49
  is
• 13:49
  kind
• 13:49
  of
• 13:49
  nice,
• 13:49
  right?
• 13:49
  Because
• 13:50
  not
• 13:50
  a
• 13:50
  lot
• 13:50
  of
• 13:50
  SSRIs
• 13:51
  do
• 13:52
  that.
• 13:52
  Pretty
• 13:52
  cool
• 13:53
  stuff,
• 13:53
  actually.
• 13:53
  Affinity
• 13:54
  is
• 13:54
  pretty
• 13:54
  cool.
• 13:55
  The
• 13:55
  way
• 13:56
  these
• 13:56
  drugs
• 13:57
  work
• 13:57
  on
• 13:57
  receptors
• 13:58
  is
• 13:58
  that
• 13:58
  they
• 13:58
  constantly
• 13:59
  associate
• 13:59
  and
• 14:00
  disassociate
• 14:00
  from
• 14:01
  receptors.
• 14:01
  It's
• 14:02
  like
• 14:02
  people
• 14:02
  walking
• 14:02
  in
• 14:03
  and
• 14:03
  out
• 14:03
  of
• 14:03
  a
• 14:03
  room.
• 14:04
  It's
• 14:04
  kind
• 14:04
  of
• 14:04
  like
• 14:05
  snow
• 14:05
  that
• 14:05
  hits
• 14:05
  the
• 14:05
  sidewalk
• 14:06
  and
• 14:06
  melts.
• 14:06
  It's
• 14:07
  not
• 14:07
  sticking,
• 14:07
  but
• 14:08
  it
• 14:08
  needs
• 14:08
  to
• 14:08
  snow
• 14:09
  more
• 14:09
  to
• 14:09
  compensate
• 14:10
  before
• 14:10
  the
• 14:10
  snow
• 14:10
  piles
• 14:11
  up.
• 14:11
  You
• 14:11
  know
• 14:11
  what
• 14:11
  I
• 14:11
  mean?
• 14:12
  Because
• 14:12
  if
• 14:12
  your
• 14:12
  affinity's
• 14:13
  strong,
• 14:13
  it
• 14:14
  sticks
• 14:14
  right
• 14:14
  away
• 14:14
  and
• 14:15
  it
• 14:15
  keeps
• 14:15
  sticking
• 14:15
  and
• 14:15
  more
• 14:16
  and
• 14:16
  more
• 14:16
  snow
• 14:16
  piles
• 14:17
  up.
• 14:17
  If
• 14:17
  your
• 14:17
  affinity
• 14:18
  is
• 14:18
  kind
• 14:18
  of
• 14:18
  low
• 14:18
  and
• 14:19
  weak,
• 14:19
  the
• 14:19
  snow
• 14:20
  melts
• 14:20
  a
• 14:21
  little
• 14:21
  bit
• 14:21
  and
• 14:21
  sticks,
• 14:22
  but
• 14:22
  it
• 14:22
  also
• 14:22
  melts.
• 14:22
  So
• 14:23
  it
• 14:23
  needs
• 14:23
  to
• 14:23
  snow
• 14:23
  more
• 14:24
  for
• 14:24
  it
• 14:24
  to
• 14:24
  accumulate.
• 14:25
  That's
• 14:25
  the
• 14:25
  same
• 14:25
  analogy
• 14:26
  with
• 14:26
  some
• 14:26
  medications
• 14:27
  like
• 14:27
  Seroquel.
• 14:28
  Right.
• 14:28
  Seroquel
• 14:29
  is
• 14:29
  very
• 14:29
  weak.
• 14:30
  It
• 14:30
  kind
• 14:31
  of
• 14:31
  does
• 14:31
  this.
• 14:32
  They
• 14:32
  call
• 14:32
  it
• 14:32
  kind
• 14:33
  of
• 14:33
  hit
• 14:34
  and
• 14:34
  run
• 14:34
  kinetics.
• 14:34
  Where
• 14:36
  it
• 14:36
  hits
• 14:36
  the
• 14:36
  dopamine
• 14:37
  receptor,
• 14:37
  it
• 14:37
  kind
• 14:37
  of
• 14:38
  blocks
• 14:38
  the
• 14:38
  dopamine
• 14:38
  receptor,
• 14:39
  and
• 14:39
  then
• 14:39
  it
• 14:39
  kind
• 14:39
  of
• 14:39
  melts
• 14:39
  off.
• 14:40
  It's
• 14:40
  like
• 14:40
  snow
• 14:40
  that
• 14:41
  melts
• 14:41
  off
• 14:41
  the
• 14:42
  ground.
• 14:42
  You
• 14:42
  have
• 14:42
  to
• 14:42
  keep
• 14:43
  raising
• 14:43
  the
• 14:43
  dose,
• 14:43
  allowing
• 14:44
  it
• 14:44
  to
• 14:44
  snow
• 14:44
  more
• 14:45
  for
• 14:45
  the
• 14:45
  snow
• 14:45
  to
• 14:45
  accumulate
• 14:46
  on
• 14:46
  the
• 14:46
  sidewalk.
• 14:47
  AKA
• 14:48
  allowing
• 14:49
  enough
• 14:49
  D2
• 14:50
  blockade
• 14:50
  to
• 14:50
  exert
• 14:51
  a
• 14:51
  antipsychotic
• 14:52
  or
• 14:53
  antimanic
• 14:53
  effect.
• 14:54
  That's
• 14:54
  why
• 14:54
  Seroquel
• 14:55
  at
• 14:55
  low
• 14:56
  doses
• 14:56
  is
• 14:56
  really
• 14:57
  just
• 14:57
  hitting
• 14:57
  histamine.
• 14:58
  It's
• 14:58
  making
• 14:58
  you
• 14:59
  sedated
• 15:00
  and
• 15:00
  tired.
• 15:00
  And
• 15:00
  just
• 15:01
  like
• 15:01
  Remeron,
• 15:02
  it
• 15:02
  has
• 15:02
  a
• 15:02
  whole
• 15:03
  host
• 15:03
  of
• 15:03
  receptors
• 15:03
  it
• 15:04
  activates,
• 15:05
  but
• 15:05
  at
• 15:05
  different
• 15:05
  affinities.
• 15:06
  So
• 15:07
  the
• 15:07
  affinity
• 15:07
  for
• 15:08
  dopamine
• 15:09
  D2
• 15:09
  is
• 15:10
  a
• 15:10
  lot
• 15:11
  weaker
• 15:11
  than.
• 15:12
  Let's
• 15:12
  say
• 15:12
  Haldol's
• 15:13
  affinity
• 15:14
  for
• 15:14
  D2,
• 15:14
  right?
• 15:15
  So
• 15:15
  you
• 15:15
  can
• 15:15
  go
• 15:15
  in
• 15:15
  there.
• 15:15
  Haldol's
• 15:16
  like
• 15:16
  that
• 15:16
  thick
• 15:16
  snow.
• 15:17
  It
• 15:17
  occupies
• 15:18
  those
• 15:18
  receptors,
• 15:19
  it
• 15:19
  blocks
• 15:20
  them,
• 15:20
  and
• 15:20
  bam.
• 15:20
  You're
• 15:21
  not
• 15:21
  as
• 15:21
  manic,
• 15:21
  you're
• 15:21
  not
• 15:22
  as
• 15:22
  psychotic.
• 15:23
  But
• 15:23
  Seroquel
• 15:24
  goes
• 15:24
  in
• 15:24
  there
• 15:24
  and
• 15:25
  it
• 15:25
  kind
• 15:25
  of
• 15:25
  melts
• 15:25
  as
• 15:26
  you
• 15:26
  increase
• 15:26
  the
• 15:26
  dose.
• 15:26
  It's
• 15:27
  kind
• 15:27
  of
• 15:27
  hit
• 15:27
  and
• 15:28
  run.
• 15:28
  It's
• 15:29
  sort
• 15:29
  of
• 15:29
  flirting
• 15:29
  with
• 15:30
  the
• 15:30
  receptor,
• 15:31
  but
• 15:31
  it
• 15:32
  kind
• 15:32
  of
• 15:32
  peels
• 15:32
  off
• 15:32
  that
• 15:33
  receptor.
• 15:33
  So
• 15:33
  dopamine's
• 15:34
  not
• 15:34
  always
• 15:34
  blocked
• 15:35
  as
• 15:35
  strongly
• 15:36
  as
• 15:36
  Haldol,
• 15:37
  which
• 15:37
  basically
• 15:37
  just
• 15:37
  bam.
• 15:38
  It's
• 15:38
  like
• 15:38
  a
• 15:38
  strong
• 15:38
  magnet.
• 15:39
  It's
• 15:39
  pretty
• 15:39
  rigid.
• 15:40
  And
• 15:40
  that's
• 15:40
  why
• 15:40
  you
• 15:40
  have
• 15:40
  the
• 15:41
  EPS
• 15:41
  side
• 15:42
  effects.
• 15:42
  But
• 15:42
  Seroquel
• 15:43
  kind
• 15:43
  of
• 15:43
  melts
• 15:44
  off
• 15:44
  like
• 15:44
  a
• 15:44
  melting
• 15:44
  snow.
• 15:45
  So
• 15:45
  you
• 15:45
  have
• 15:45
  to
• 15:46
  raise
• 15:46
  the
• 15:46
  dose
• 15:46
  to
• 15:47
  really
• 15:47
  get
• 15:47
  a
• 15:47
  consistent
• 15:48
  amount
• 15:48
  of
• 15:48
  snow.
• 15:48
  The
• 15:49
  ground
• 15:49
  is
• 15:49
  then
• 15:49
  covered.
• 15:50
  Pretty
• 15:51
  neat,
• 15:51
  right?
• 15:51
  That's
• 15:52
  the
• 15:52
  appreciation
• 15:52
  I
• 15:53
  hope
• 15:53
  you
• 15:53
  can
• 15:53
  gain
• 15:54
  from
• 15:54
  the
• 15:54
  principle
• 15:55
  of
• 15:55
  affinity.
• 15:56
  Affinity
• 15:56
  is
• 15:57
  all
• 15:57
  about
• 15:57
  how
• 15:58
  stuck
• 15:58
  it
• 15:58
  is
• 15:58
  to
• 15:58
  the
• 15:58
  receptor.
• 15:59
  Is
• 15:59
  it
• 15:59
  a
• 16:00
  weak
• 16:00
  connection?
• 16:00
  Is
• 16:00
  it
• 16:01
  a
• 16:01
  strong
• 16:01
  connection?
• 16:02
  And
• 16:02
  what
• 16:02
  do
• 16:03
  you
• 16:03
  do
• 16:03
  about
• 16:03
  it?
• 16:03
  Right?
• 16:03
  What
• 16:04
  do
• 16:04
  you
• 16:04
  do
• 16:04
  when
• 16:04
  the
• 16:04
  affinity
• 16:05
  is
• 16:05
  kind
• 16:05
  of
• 16:05
  weak?
• 16:06
  It
• 16:06
  gives
• 16:06
  you
• 16:06
  some
• 16:07
  sense
• 16:07
  of
• 16:07
  literacy
• 16:07
  about
• 16:08
  the
• 16:08
  medications
• 16:09
  that
• 16:09
  you're
• 16:10
  looking
• 16:10
  at,
• 16:10
  right?
• 16:11
  I
• 16:11
  think
• 16:11
  it's
• 16:11
  a
• 16:12
  pretty
• 16:12
  cool
• 16:12
  thing.
• 16:12
  Remember,
• 16:13
  mechanistically,
• 16:13
  that
• 16:14
  a
• 16:14
  high
• 16:14
  affinity
• 16:15
  is
• 16:15
  going
• 16:15
  to
• 16:15
  help
• 16:15
  you
• 16:15
  understand
• 16:16
  which
• 16:16
  receptor
• 16:17
  gets
• 16:17
  hit
• 16:17
  first,
• 16:18
  which
• 16:18
  really
• 16:18
  dominates,
• 16:19
  which
• 16:20
  side
• 16:20
  effect
• 16:20
  might
• 16:20
  really
• 16:21
  dominate
• 16:21
  here,
• 16:22
  which
• 16:22
  side
• 16:22
  effects
• 16:23
  or
• 16:23
  other
• 16:23
  effects
• 16:24
  might
• 16:24
  not
• 16:24
  kick
• 16:24
  in
• 16:25
  unless
• 16:25
  you
• 16:25
  increase
• 16:25
  the
• 16:26
  dose
• 16:26
  because
• 16:26
  they
• 16:26
  have
• 16:26
  weaker
• 16:27
  affinities.
• 16:27
  That
• 16:28
  might
• 16:28
  give
• 16:28
  you
• 16:28
  an
• 16:28
  appreciation
• 16:29
  for
• 16:29
  what's
• 16:30
  going
• 16:30
  on.
• 16:30
  Remember,
• 16:31
  it's
• 16:31
  also
• 16:31
  a
• 16:31
  little
• 16:32
  more
• 16:32
  complicated
• 16:32
  than
• 16:32
  this.
• 16:33
  There's
• 16:33
  a
• 16:33
  lot
• 16:33
  of
• 16:33
  pharmacokinetics
• 16:34
  at
• 16:34
  play
• 16:35
  and
• 16:35
  other
• 16:35
  dynamics
• 16:36
  at
• 16:36
  play
• 16:37
  that
• 16:37
  affect
• 16:37
  the
• 16:38
  outcome
• 16:38
  of
• 16:38
  the
• 16:38
  meds.
• 16:39
  We're
• 16:39
  prescribing
• 16:40
  blood,
• 16:40
  brain
• 16:41
  barrier
• 16:41
  permeability,
• 16:42
  lipid
• 16:42
  solubility,
• 16:43
  bioavailability
• 16:44
  medication
• 16:45
  interactions,
• 16:45
  how
• 16:46
  you
• 16:46
  metabolize
• 16:46
  these
• 16:46
  medications.
• 16:47
  This
• 16:48
  is
• 16:48
  not
• 16:48
  meant
• 16:48
  to
• 16:48
  be
• 16:49
  as
• 16:49
  simplistic
• 16:49
  as
• 16:50
  every
• 16:50
  time
• 16:50
  you
• 16:51
  do
• 16:51
  this.
• 16:51
  This
• 16:51
  is
• 16:51
  exactly
• 16:52
  what
• 16:52
  you're
• 16:52
  going
• 16:52
  to
• 16:52
  get.
• 16:53
  But
• 16:53
  it
• 16:53
  should
• 16:53
  give
• 16:54
  you
• 16:54
  a
• 16:54
  finer
• 16:54
  appreciation
• 16:55
  for
• 16:55
  what
• 16:56
  happens
• 16:56
  when
• 16:56
  you
• 16:56
  prescribe
• 16:57
  a
• 16:57
  med.
• 16:57
  Why
• 16:57
  does
• 16:58
  affinity
• 16:58
  matter?
• 16:59
  What
• 16:59
  does
• 16:59
  it
• 16:59
  mean
• 17:00
  if
• 17:00
  someone
• 17:01
  tells
• 17:01
  you,
• 17:01
  well,
• 17:01
  reviron
• 17:02
  blocks
• 17:03
  the
• 17:03
  5ht2a
• 17:04
  receptor
• 17:04
  and
• 17:04
  therefore
• 17:04
  it's
• 17:05
  great
• 17:05
  for
• 17:05
  anxiety?
• 17:06
  That's
• 17:06
  an
• 17:06
  incomplete
• 17:07
  concept.
• 17:07
  Your
• 17:08
  first
• 17:08
  question,
• 17:08
  your
• 17:08
  friend,
• 17:09
  would
• 17:09
  be,
• 17:09
  well,
• 17:09
  how
• 17:09
  well
• 17:10
  does
• 17:10
  it
• 17:10
  do
• 17:10
  that?
• 17:10
  Does
• 17:11
  it
• 17:11
  have
• 17:11
  a
• 17:11
  strong
• 17:11
  affinity
• 17:12
  for
• 17:12
  5ht
• 17:12
  2a?
• 17:13
  Because
• 17:13
  if
• 17:13
  it
• 17:13
  does,
• 17:14
  then
• 17:14
  I
• 17:14
  know
• 17:14
  it
• 17:14
  might
• 17:15
  be
• 17:15
  a
• 17:15
  lot
• 17:15
  better
• 17:16
  at
• 17:16
  reducing
• 17:16
  anxiety
• 17:17
  than
• 17:18
  a
• 17:18
  different
• 17:18
  medication
• 17:19
  like
• 17:19
  Seroquel
• 17:20
  that
• 17:21
  may
• 17:21
  not
• 17:21
  block
• 17:22
  5
• 17:22
  HT2A
• 17:23
  as
• 17:23
  well.
• 17:23
  I
• 17:23
  think
• 17:23
  Seroquel
• 17:24
  actually
• 17:24
  does
• 17:24
  have
• 17:24
  a
• 17:24
  very
• 17:24
  strong
• 17:25
  affinity
• 17:25
  for
• 17:25
  5ht
• 17:26
  2a.
• 17:26
  It's
• 17:27
  not
• 17:27
  enough
• 17:27
  to
• 17:27
  just
• 17:27
  say
• 17:28
  it's
• 17:28
  good
• 17:28
  for
• 17:28
  anxiety.
• 17:29
  How
• 17:29
  strong
• 17:29
  is
• 17:30
  the
• 17:30
  affinity?
• 17:30
  And
• 17:30
  what
• 17:31
  receptor
• 17:31
  are
• 17:31
  we
• 17:31
  talking
• 17:32
  about?
• 17:32
  Are
• 17:32
  we
• 17:32
  talking
• 17:33
  about
• 17:33
  receptors
• 17:34
  at
• 17:34
  5ht1a
• 17:36
  or
• 17:36
  5ht2a?
• 17:39
  Right.
• 17:40
  It's
• 17:40
  a
• 17:40
  weight
• 17:41
  gainer.
• 17:41
  Well,
• 17:41
  in
• 17:42
  what
• 17:42
  pathway?
• 17:42
  Histamine?
• 17:43
  Is
• 17:43
  it
• 17:43
  a
• 17:43
  weight
• 17:43
  gainer?
• 17:44
  5ht
• 17:44
  2c?
• 17:45
  Is
• 17:45
  it
• 17:46
  an
• 17:46
  M1
• 17:46
  antagonist?
• 17:47
  A
• 17:47
  muscarinic
• 17:48
  antagonist?
• 17:49
  So
• 17:49
  I
• 17:49
  urge
• 17:50
  you
• 17:50
  to
• 17:50
  do
• 17:50
  a
• 17:50
  deep
• 17:50
  dive
• 17:51
  in
• 17:51
  affinities
• 17:51
  and
• 17:52
  what
• 17:52
  your
• 17:52
  meds
• 17:52
  are
• 17:53
  doing
• 17:53
  at
• 17:53
  what
• 17:53
  affinity,
• 17:54
  at
• 17:54
  what
• 17:54
  receptors,
• 17:54
  and
• 17:55
  you'll
• 17:55
  have
• 17:55
  a
• 17:55
  much
• 17:55
  richer
• 17:56
  appreciation
• 17:57
  for
• 17:57
  what
• 17:57
  you're
• 17:57
  prescribing
• 17:58
  and
• 17:58
  why.
• 17:58
  And
• 17:59
  it'll
• 17:59
  really
• 17:59
  elevate
• 17:59
  your
• 18:00
  game.
• 18:00
  Hope
• 18:01
  you
• 18:01
  like
• 18:01
  this.
• 18:01
  I
• 18:01
  loved
• 18:02
  it.
• 18:02
  Please
• 18:02
  don't
• 18:02
  forget
• 18:02
  to
• 18:03
  become
• 18:03
  Patreon
• 18:04
  members.
• 18:04
  All
• 18:05
  of
• 18:05
  this
• 18:05
  is
• 18:05
  in
• 18:05
  slide
• 18:05
  deck
• 18:06
  form.
• 18:06
  I'm
• 18:07
  a
• 18:07
  visual
• 18:07
  guy.
• 18:07
  If
• 18:08
  you
• 18:08
  become
• 18:08
  a
• 18:08
  member,
• 18:09
  you'll
• 18:09
  have
• 18:09
  access
• 18:10
  to
• 18:10
  all
• 18:10
  these
• 18:10
  slide
• 18:11
  decks
• 18:11
  and
• 18:12
  podcast
• 18:12
  episodes
• 18:13
  that
• 18:13
  come
• 18:13
  out
• 18:14
  well
• 18:14
  in
• 18:14
  advance.
• 18:15
  You'll
• 18:15
  get
• 18:16
  early
• 18:16
  access
• 18:16
  to
• 18:16
  them.
• 18:17
  You
• 18:17
  can
• 18:17
  also
• 18:17
  message
• 18:18
  me
• 18:18
  directly
• 18:18
  if
• 18:18
  you
• 18:19
  have
• 18:19
  any
• 18:19
  questions
• 18:19
  or
• 18:20
  future
• 18:20
  episode
• 18:20
  recommendations.
• 18:21
  And
• 18:21
  we
• 18:21
  can
• 18:22
  build
• 18:22
  a
• 18:22
  community
• 18:22
  of
• 18:22
  really
• 18:23
  good
• 18:23
  mnemonic
• 18:23
  devices,
• 18:24
  ways
• 18:25
  to
• 18:25
  remember
• 18:25
  this
• 18:25
  stuff.
• 18:26
  I
• 18:26
  really
• 18:26
  hope
• 18:27
  you
• 18:27
  become
• 18:28
  a
• 18:28
  member
• 18:28
  and
• 18:28
  if
• 18:28
  nothing
• 18:29
  else,
• 18:29
  march
• 18:29
  over
• 18:30
  to
• 18:30
  Apple.
• 18:30
  Give
• 18:30
  us
• 18:31
  five
• 18:31
  stars
• 18:31
  and
• 18:31
  a
• 18:32
  comment.
• 18:32
  We've
• 18:32
  been
• 18:32
  growing
• 18:33
  really
• 18:33
  fast
• 18:33
  and
• 18:33
  we're
• 18:34
  appreciative
• 18:34
  of
• 18:35
  all
• 18:35
  of
• 18:35
  you
• 18:35
  who
• 18:35
  have
• 18:35
  been
• 18:36
  sharing
• 18:36
  this
• 18:36
  with
• 18:37
  your
• 18:37
  cohort.
• 18:37
  It's
• 18:38
  been
• 18:38
  a
• 18:38
  great
• 18:38
  experience
• 18:39
  to
• 18:39
  talk
• 18:39
  to
• 18:39
  all
• 18:39
  of
• 18:39
  you
• 18:40
  and
• 18:40
  until
• 18:40
  next
• 18:40
  time,
• 18:41
  thank
• 18:41
  you
• 18:41
  all
• 18:41
  very
• 18:41
  much.
• 18:41
  Bye
• 18:42
  bye.