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Understanding Receptor Occupancy: A Key Concept for Clinicians · Pearls and Prep

• 0:00
  Foreign.
• 0:05
  Welcome
• 0:05
  back,
• 0:05
  my
• 0:06
  friends,
• 0:06
  to
• 0:06
  another
• 0:07
  episode
• 0:07
  of
• 0:07
  Pearls
• 0:08
  and
• 0:09
  Prep.
• 0:10
  This
• 0:10
  is
• 0:10
  an
• 0:10
  exciting
• 0:11
  one.
• 0:12
  Today
• 0:12
  we're
• 0:12
  going
• 0:12
  to
• 0:13
  talk
• 0:13
  about
• 0:14
  receptor
• 0:15
  occupancy.
• 0:16
  Occupancy
• 0:17
  is
• 0:17
  a
• 0:17
  very
• 0:17
  important
• 0:19
  concept
• 0:20
  for
• 0:20
  us
• 0:20
  to
• 0:21
  tackle.
• 0:21
  It
• 0:21
  will
• 0:22
  empower
• 0:22
  you
• 0:23
  significantly
• 0:24
  in
• 0:24
  your
• 0:24
  practice
• 0:25
  if
• 0:26
  you
• 0:26
  understand
• 0:27
  the
• 0:27
  concept
• 0:27
  of
• 0:28
  occupancy.
• 0:28
  Our
• 0:29
  last
• 0:29
  episode
• 0:30
  tackled
• 0:30
  the
• 0:30
  concept
• 0:31
  of
• 0:31
  affinity.
• 0:32
  Affinity
• 0:32
  is
• 0:33
  also
• 0:33
  very
• 0:33
  fascinating.
• 0:35
  The
• 0:35
  F
• 0:36
  in
• 0:36
  affinity
• 0:37
  actually
• 0:37
  stands
• 0:38
  for
• 0:38
  fascinating.
• 0:39
  The
• 0:39
  O
• 0:40
  in
• 0:40
  occupancy
• 0:41
  stands
• 0:41
  for
• 0:42
  outstanding.
• 0:43
  Because
• 0:43
  this
• 0:43
  is
• 0:43
  an
• 0:43
  outstanding
• 0:44
  topic
• 0:44
  that
• 0:44
  we're
• 0:45
  going
• 0:45
  to
• 0:45
  have
• 0:45
  a
• 0:45
  lot
• 0:45
  of
• 0:45
  fun
• 0:45
  with
• 0:46
  today.
• 0:46
  Now,
• 0:47
  what
• 0:47
  is
• 0:48
  occupancy?
• 0:49
  You
• 0:49
  can
• 0:49
  think
• 0:50
  of
• 0:50
  it
• 0:50
  as
• 0:51
  the
• 0:52
  number
• 0:52
  of
• 0:53
  seats
• 0:53
  on
• 0:53
  the
• 0:53
  school
• 0:54
  bus
• 0:54
  that
• 0:54
  are
• 0:54
  occupied.
• 0:55
  And
• 0:55
  let's
• 0:56
  say
• 0:57
  your
• 0:57
  driver
• 0:58
  is
• 0:58
  telling
• 0:58
  you
• 1:00
  that
• 1:00
  he's
• 1:01
  only
• 1:01
  going
• 1:01
  to
• 1:01
  take
• 1:01
  you
• 1:01
  to
• 1:02
  school
• 1:02
  once
• 1:02
  80%
• 1:03
  of
• 1:04
  the
• 1:04
  bus
• 1:04
  seats
• 1:04
  are
• 1:05
  occupied.
• 1:06
  Well,
• 1:06
  you
• 1:06
  can
• 1:06
  think
• 1:07
  of
• 1:07
  it
• 1:07
  that
• 1:07
  way
• 1:07
  in
• 1:08
  terms
• 1:08
  of
• 1:08
  antipsychotics.
• 1:10
  D2
• 1:10
  receptor
• 1:11
  occupancy,
• 1:11
  right?
• 1:12
  There's
• 1:12
  a
• 1:12
  certain
• 1:13
  percentage
• 1:13
  by
• 1:13
  which,
• 1:14
  if
• 1:14
  you
• 1:15
  antagonize
• 1:15
  the
• 1:15
  D2
• 1:16
  receptor,
• 1:17
  you
• 1:17
  will
• 1:17
  exert
• 1:18
  the
• 1:18
  desired
• 1:19
  pharmacological
• 1:20
  effect
• 1:20
  and
• 1:21
  therefore
• 1:21
  the
• 1:21
  bus
• 1:22
  can
• 1:22
  start
• 1:22
  driving.
• 1:23
  The
• 1:23
  bus
• 1:23
  doesn't
• 1:24
  drive
• 1:24
  on
• 1:24
  its
• 1:24
  own.
• 1:24
  In
• 1:24
  this
• 1:25
  analogy,
• 1:25
  the
• 1:25
  bus
• 1:25
  driver
• 1:26
  would
• 1:27
  drive
• 1:27
  the
• 1:27
  bus.
• 1:28
  It's
• 1:28
  a
• 1:28
  real
• 1:28
  bus
• 1:28
  driver.
• 1:29
  And
• 1:29
  he
• 1:29
  goes,
• 1:29
  oh,
• 1:30
  80%
• 1:30
  of
• 1:30
  our
• 1:30
  seats
• 1:31
  are
• 1:31
  occupied.
• 1:32
  Boom.
• 1:32
  I'm
• 1:33
  going,
• 1:33
  he's
• 1:33
  not
• 1:33
  waiting
• 1:33
  for
• 1:34
  100%.
• 1:35
  Okay,
• 1:35
  now,
• 1:36
  every.
• 1:37
  Every
• 1:37
  kind
• 1:38
  of
• 1:38
  draw,
• 1:38
  let's
• 1:39
  put
• 1:39
  it
• 1:39
  this
• 1:39
  way,
• 1:39
  every
• 1:40
  kind
• 1:40
  of
• 1:40
  medication
• 1:42
  may
• 1:42
  entail
• 1:43
  a
• 1:43
  different
• 1:44
  level
• 1:44
  of
• 1:45
  occupancy
• 1:45
  for
• 1:46
  it
• 1:46
  to
• 1:46
  exert
• 1:46
  the
• 1:47
  desired
• 1:47
  effect.
• 1:47
  It's
• 1:47
  not
• 1:48
  always
• 1:48
  80%.
• 1:49
  Sometimes
• 1:49
  it's
• 1:49
  60,
• 1:50
  50%.
• 1:51
  Right.
• 1:51
  With
• 1:51
  second
• 1:52
  generation
• 1:52
  antipsychotics,
• 1:54
  they're
• 1:54
  able
• 1:54
  to
• 1:55
  address
• 1:56
  specific
• 1:57
  symptom
• 1:57
  clusters
• 1:58
  at
• 1:59
  a
• 1:59
  lower
• 1:59
  occupancy
• 2:00
  than
• 2:00
  the
• 2:00
  first
• 2:01
  generation
• 2:01
  antipsychotics,
• 2:02
  thus
• 2:03
  sparing
• 2:03
  people
• 2:04
  from
• 2:04
  a
• 2:04
  lot
• 2:04
  of
• 2:05
  the
• 2:05
  worsening
• 2:06
  side
• 2:06
  effects.
• 2:06
  Those
• 2:07
  EPS
• 2:07
  side
• 2:07
  effects
• 2:08
  because
• 2:08
  they're
• 2:09
  able
• 2:09
  to
• 2:09
  occupy
• 2:10
  a
• 2:10
  smaller
• 2:11
  percentage
• 2:11
  of
• 2:12
  receptors
• 2:13
  and
• 2:13
  not
• 2:14
  cause
• 2:14
  as
• 2:14
  many
• 2:14
  side
• 2:15
  effects.
• 2:15
  Okay.
• 2:15
  And
• 2:15
  we're
• 2:16
  going
• 2:16
  to
• 2:16
  go
• 2:16
  into
• 2:16
  some
• 2:16
  of
• 2:16
  this
• 2:16
  a
• 2:17
  little
• 2:17
  bit
• 2:17
  later.
• 2:17
  But
• 2:18
  think
• 2:18
  about
• 2:18
  that
• 2:18
  school
• 2:19
  bus
• 2:19
  in
• 2:20
  the
• 2:20
  beginning
• 2:20
  here.
• 2:21
  And
• 2:21
  in
• 2:21
  order
• 2:21
  for
• 2:22
  an
• 2:22
  effect
• 2:22
  to
• 2:22
  happen,
• 2:23
  you
• 2:24
  need
• 2:24
  a
• 2:24
  certain
• 2:24
  percentage
• 2:25
  of
• 2:25
  those
• 2:25
  receptors
• 2:26
  to
• 2:27
  be
• 2:27
  occupied.
• 2:28
  The
• 2:28
  precise
• 2:28
  definition
• 2:29
  that
• 2:29
  we
• 2:29
  can
• 2:29
  go
• 2:29
  off
• 2:30
  of
• 2:30
  here
• 2:30
  as
• 2:30
  it
• 2:31
  relates
• 2:31
  to
• 2:31
  occupancy
• 2:32
  is
• 2:32
  the
• 2:32
  percentage
• 2:32
  of
• 2:33
  receptors
• 2:33
  in
• 2:33
  the
• 2:33
  body
• 2:34
  that
• 2:34
  are
• 2:34
  currently
• 2:35
  occupied
• 2:35
  or
• 2:35
  bound
• 2:36
  by,
• 2:36
  by
• 2:36
  a
• 2:37
  drug
• 2:37
  at
• 2:37
  any
• 2:37
  given
• 2:38
  time.
• 2:38
  Okay.
• 2:39
  That's
• 2:39
  the
• 2:39
  simple
• 2:40
  definition
• 2:40
  we
• 2:40
  can
• 2:40
  go
• 2:41
  by
• 2:41
  right
• 2:41
  now.
• 2:42
  A
• 2:43
  key
• 2:43
  takeaway
• 2:43
  is
• 2:44
  that
• 2:44
  it's
• 2:44
  not
• 2:45
  as
• 2:45
  simple
• 2:45
  as
• 2:46
  I'm
• 2:46
  going
• 2:46
  to
• 2:46
  prescribe
• 2:48
  this
• 2:48
  one
• 2:48
  medication
• 2:50
  and
• 2:50
  I'm
• 2:51
  going
• 2:51
  to
• 2:51
  occupy
• 2:53
  this
• 2:53
  percentage
• 2:55
  of
• 2:55
  receptors.
• 2:55
  It
• 2:56
  is
• 2:56
  not
• 2:56
  that
• 2:56
  simple
• 2:57
  as
• 2:57
  you
• 2:57
  as
• 2:57
  we
• 2:57
  will
• 2:57
  understand,
• 2:58
  and
• 2:58
  it's
• 2:59
  not
• 2:59
  that
• 2:59
  simple.
• 2:59
  And
• 3:00
  I
• 3:00
  hope
• 3:00
  this
• 3:00
  is
• 3:00
  a
• 3:00
  very
• 3:01
  stimulating
• 3:01
  episode
• 3:02
  for
• 3:02
  you
• 3:02
  and
• 3:02
  it
• 3:02
  really
• 3:02
  gets
• 3:03
  you
• 3:03
  thinking
• 3:04
  because
• 3:04
  this
• 3:05
  is
• 3:05
  what
• 3:05
  will
• 3:05
  separate
• 3:06
  you
• 3:06
  as
• 3:07
  a
• 3:07
  higher
• 3:07
  order
• 3:08
  clinician,
• 3:09
  as
• 3:09
  a
• 3:09
  prescriber
• 3:10
  is
• 3:10
  having
• 3:10
  a
• 3:10
  finer
• 3:11
  conceptual
• 3:11
  appreciation
• 3:12
  for
• 3:12
  these
• 3:13
  types
• 3:13
  of
• 3:13
  things.
• 3:13
  Okay,
• 3:14
  so
• 3:15
  occupancy,
• 3:15
  you
• 3:16
  want
• 3:16
  to
• 3:16
  set
• 3:16
  out
• 3:17
  and
• 3:17
  occupy
• 3:17
  a
• 3:17
  certain
• 3:18
  percentage
• 3:18
  of
• 3:18
  receptors
• 3:19
  to
• 3:19
  exert
• 3:19
  a
• 3:20
  specific
• 3:20
  clinical
• 3:21
  effect.
• 3:22
  Whether
• 3:22
  it
• 3:22
  is
• 3:23
  an
• 3:23
  anti
• 3:23
  histaminergic
• 3:24
  effect
• 3:24
  to
• 3:24
  sedate
• 3:25
  a
• 3:25
  patient,
• 3:26
  whether
• 3:26
  it
• 3:26
  is
• 3:27
  antagonizing
• 3:28
  a
• 3:29
  dopamine
• 3:29
  receptor
• 3:30
  to
• 3:30
  stabilize
• 3:31
  mood
• 3:31
  or
• 3:31
  psychosis,
• 3:32
  you're
• 3:33
  striving
• 3:33
  for
• 3:33
  a
• 3:34
  specific
• 3:34
  percentage.
• 3:35
  The
• 3:35
  problem
• 3:35
  with
• 3:36
  that
• 3:36
  is
• 3:36
  that
• 3:37
  like
• 3:37
  everything
• 3:38
  else
• 3:38
  in
• 3:38
  the
• 3:38
  body,
• 3:40
  it's
• 3:40
  not
• 3:40
  always
• 3:41
  that
• 3:41
  simple.
• 3:41
  There
• 3:41
  are
• 3:42
  specific
• 3:43
  factors
• 3:44
  that
• 3:45
  can
• 3:45
  interrupt
• 3:45
  your
• 3:46
  ability
• 3:46
  to
• 3:46
  occupy
• 3:47
  those
• 3:48
  receptors.
• 3:49
  So
• 3:49
  similar
• 3:49
  to
• 3:51
  getting
• 3:51
  on
• 3:51
  a
• 3:52
  bus
• 3:52
  at
• 3:52
  80%,
• 3:53
  well,
• 3:53
  there's
• 3:54
  specific
• 3:54
  problems
• 3:55
  that
• 3:56
  might
• 3:56
  impede
• 3:56
  you
• 3:56
  from
• 3:57
  getting
• 3:57
  onto
• 3:58
  that
• 3:58
  seat.
• 3:59
  Maybe
• 4:01
  there
• 4:01
  are
• 4:02
  other
• 4:02
  kids
• 4:03
  trying
• 4:03
  to
• 4:03
  compete
• 4:04
  to
• 4:04
  get
• 4:05
  on
• 4:05
  those
• 4:05
  seats
• 4:05
  as
• 4:06
  well.
• 4:06
  They're
• 4:06
  playing
• 4:07
  musical
• 4:07
  chairs
• 4:07
  and
• 4:08
  not
• 4:08
  everybody
• 4:08
  can
• 4:08
  get
• 4:09
  into
• 4:09
  a
• 4:09
  seat.
• 4:09
  Or
• 4:10
  maybe
• 4:10
  there's
• 4:10
  a
• 4:10
  different
• 4:11
  kid
• 4:11
  in
• 4:11
  the
• 4:11
  seat
• 4:12
  and
• 4:12
  it's
• 4:12
  not
• 4:13
  you.
• 4:13
  Right.
• 4:14
  And
• 4:14
  you
• 4:14
  want
• 4:14
  to
• 4:14
  get
• 4:14
  on
• 4:15
  that
• 4:15
  seat
• 4:15
  so
• 4:15
  you
• 4:15
  can
• 4:16
  go
• 4:16
  to
• 4:16
  school,
• 4:16
  get
• 4:16
  in
• 4:17
  that
• 4:17
  seat
• 4:17
  and
• 4:17
  get
• 4:17
  the
• 4:17
  desired
• 4:18
  pharmacological
• 4:19
  effect.
• 4:19
  Well,
• 4:19
  there's
• 4:20
  another
• 4:21
  kid,
• 4:21
  a
• 4:21
  bully,
• 4:22
  on
• 4:22
  that
• 4:22
  seat,
• 4:23
  competing
• 4:23
  with
• 4:23
  you
• 4:23
  for
• 4:24
  that
• 4:24
  seat,
• 4:24
  and
• 4:24
  he's
• 4:24
  going
• 4:24
  to
• 4:25
  knock
• 4:25
  you
• 4:25
  off.
• 4:25
  So
• 4:25
  now
• 4:26
  you're
• 4:26
  not
• 4:26
  going
• 4:26
  to
• 4:26
  school,
• 4:27
  AKA
• 4:28
  you're
• 4:28
  not
• 4:29
  achieving
• 4:30
  the
• 4:30
  desired
• 4:30
  effect
• 4:31
  of
• 4:31
  going
• 4:31
  to
• 4:31
  school.
• 4:32
  And
• 4:32
  that
• 4:32
  bully
• 4:33
  was
• 4:34
  another
• 4:35
  medication
• 4:35
  that
• 4:36
  has
• 4:36
  competed
• 4:36
  for
• 4:37
  you,
• 4:37
  for
• 4:37
  has
• 4:38
  competed
• 4:38
  and
• 4:39
  not
• 4:39
  allowed
• 4:39
  you
• 4:39
  to
• 4:39
  get
• 4:40
  into
• 4:40
  that
• 4:40
  seat.
• 4:40
  We're
• 4:40
  going
• 4:40
  to
• 4:41
  go
• 4:41
  into
• 4:41
  what
• 4:41
  that
• 4:41
  means,
• 4:41
  what
• 4:42
  that
• 4:42
  looks
• 4:42
  like.
• 4:43
  But
• 4:43
  I
• 4:43
  want
• 4:43
  you
• 4:43
  to
• 4:44
  have
• 4:44
  an
• 4:44
  appreciation
• 4:44
  for
• 4:45
  the
• 4:45
  fact
• 4:45
  that
• 4:45
  many
• 4:45
  things
• 4:46
  can
• 4:46
  thwart
• 4:46
  your
• 4:46
  ability
• 4:47
  to
• 4:47
  occupy
• 4:48
  receptors,
• 4:50
  including
• 4:50
  yourself.
• 4:50
  Your
• 4:51
  own
• 4:51
  genetic
• 4:52
  metabolism
• 4:53
  can
• 4:54
  influence
• 4:55
  how
• 4:56
  many
• 4:56
  kids
• 4:56
  are
• 4:56
  getting
• 4:56
  on
• 4:57
  that
• 4:57
  bus.
• 4:57
  If
• 4:58
  you
• 4:58
  will,
• 4:58
  I
• 4:58
  can
• 4:59
  prescribe
• 4:59
  you
• 4:59
  5
• 5:00
  milligrams
• 5:00
  of
• 5:00
  Lexapro,
• 5:01
  10
• 5:01
  milligrams
• 5:02
  of
• 5:02
  Lexapro,
• 5:02
  15
• 5:03
  milligrams
• 5:03
  of
• 5:03
  Lexapro.
• 5:04
  And
• 5:04
  you
• 5:05
  are
• 5:05
  such
• 5:05
  an
• 5:05
  ultra
• 5:06
  rapid
• 5:06
  metabolizer
• 5:07
  of
• 5:07
  that
• 5:07
  Lexapro.
• 5:08
  It's
• 5:09
  like
• 5:09
  kids
• 5:09
  that
• 5:09
  are
• 5:09
  getting
• 5:09
  on
• 5:09
  the
• 5:10
  bus
• 5:10
  and
• 5:10
  then
• 5:10
  running
• 5:10
  away
• 5:10
  from
• 5:11
  the
• 5:11
  bus.
• 5:11
  They're
• 5:11
  never
• 5:11
  really
• 5:12
  sitting
• 5:12
  in
• 5:12
  the
• 5:12
  seats.
• 5:13
  They're
• 5:13
  going
• 5:13
  up
• 5:13
  there,
• 5:13
  they're
• 5:13
  eyeballing
• 5:14
  the
• 5:14
  bus
• 5:14
  and
• 5:14
  they're
• 5:14
  running
• 5:15
  away.
• 5:15
  It's
• 5:16
  almost
• 5:16
  like
• 5:16
  snow
• 5:17
  that
• 5:17
  hits
• 5:17
  the
• 5:17
  pavement
• 5:18
  and
• 5:18
  then
• 5:18
  kind
• 5:18
  of
• 5:18
  melts
• 5:18
  right
• 5:19
  away
• 5:19
  rather
• 5:20
  than
• 5:20
  sticks.
• 5:21
  The
• 5:21
  drug
• 5:21
  is
• 5:22
  being
• 5:22
  metabolized
• 5:22
  so
• 5:23
  quickly
• 5:23
  that
• 5:23
  it's
• 5:24
  not
• 5:24
  able
• 5:24
  to
• 5:24
  have
• 5:24
  time
• 5:25
  to
• 5:25
  occupy
• 5:25
  those
• 5:25
  receptors
• 5:26
  to
• 5:26
  begin
• 5:26
  with,
• 5:27
  right?
• 5:28
  And
• 5:28
  some
• 5:28
  people
• 5:29
  just
• 5:29
  churn
• 5:29
  out
• 5:29
  these
• 5:29
  medications.
• 5:30
  They
• 5:30
  metabolize
• 5:31
  them
• 5:31
  genetically.
• 5:32
  They
• 5:32
  have
• 5:32
  genotypes
• 5:33
  that
• 5:33
  metabolize
• 5:33
  the
• 5:34
  medications
• 5:34
  too
• 5:34
  quickly.
• 5:35
  And
• 5:35
  therefore
• 5:35
  the
• 5:36
  desired
• 5:36
  occupancy
• 5:37
  is
• 5:37
  undermined
• 5:38
  because
• 5:38
  of
• 5:38
  hyper
• 5:39
  metabolism.
• 5:40
  You
• 5:40
  can
• 5:41
  can
• 5:41
  get
• 5:41
  in
• 5:41
  the
• 5:41
  way
• 5:41
  of
• 5:41
  your
• 5:42
  own
• 5:43
  medication
• 5:44
  that
• 5:44
  is
• 5:44
  trying
• 5:44
  to
• 5:44
  exert
• 5:45
  a
• 5:45
  desired
• 5:46
  effect.
• 5:47
  And
• 5:47
  it's
• 5:48
  not
• 5:48
  letting
• 5:48
  you
• 5:49
  sit
• 5:49
  in
• 5:49
  that
• 5:49
  seat,
• 5:49
  occupy
• 5:50
  that
• 5:51
  receptor.
• 5:52
  And
• 5:52
  again,
• 5:52
  we
• 5:52
  want
• 5:53
  to
• 5:53
  occupy
• 5:53
  those
• 5:53
  receptors.
• 5:54
  Now
• 5:54
  we
• 5:54
  don't
• 5:54
  want
• 5:54
  to
• 5:55
  over
• 5:55
  occupy
• 5:55
  the
• 5:55
  receptors,
• 5:56
  right?
• 5:56
  There's
• 5:57
  100
• 5:57
  seats
• 5:57
  on
• 5:57
  the
• 5:58
  bus.
• 5:58
  We
• 5:59
  don't
• 5:59
  want
• 6:00
  all
• 6:00
  100
• 6:00
  kids
• 6:01
  to
• 6:01
  sit
• 6:01
  on
• 6:01
  the
• 6:01
  bus.
• 6:01
  That
• 6:02
  might
• 6:02
  be
• 6:02
  a
• 6:02
  really
• 6:02
  crowded,
• 6:03
  loud
• 6:03
  bus
• 6:04
  ride.
• 6:04
  It
• 6:04
  might
• 6:05
  be
• 6:05
  very
• 6:05
  chaotic.
• 6:05
  It
• 6:06
  might
• 6:06
  be
• 6:06
  hard
• 6:06
  to
• 6:06
  drive.
• 6:07
  The
• 6:07
  analogy
• 6:08
  here
• 6:08
  would
• 6:08
  be
• 6:08
  side
• 6:09
  effects,
• 6:09
  right?
• 6:09
  If
• 6:09
  you
• 6:09
  are
• 6:10
  oversaturating
• 6:11
  those
• 6:11
  receptors,
• 6:12
  if
• 6:12
  you
• 6:12
  are
• 6:12
  raising
• 6:13
  the
• 6:13
  dose
• 6:14
  well
• 6:14
  past
• 6:15
  the
• 6:15
  point
• 6:15
  of
• 6:15
  80%,
• 6:16
  let's
• 6:16
  say,
• 6:16
  in
• 6:16
  an
• 6:17
  SSRI,
• 6:18
  and
• 6:18
  now
• 6:18
  you're
• 6:18
  at
• 6:19
  a
• 6:19
  really
• 6:19
  super
• 6:19
  high
• 6:20
  dose
• 6:20
  of
• 6:20
  Prozac
• 6:20
  or
• 6:21
  Lexapro
• 6:21
  or
• 6:21
  Zoloft,
• 6:22
  now
• 6:22
  you
• 6:23
  might
• 6:23
  just
• 6:23
  get
• 6:23
  side
• 6:23
  effects,
• 6:24
  right?
• 6:24
  We
• 6:24
  don't
• 6:24
  necessarily
• 6:25
  want
• 6:25
  to
• 6:26
  saturate
• 6:26
  these
• 6:27
  receptors
• 6:27
  beyond
• 6:28
  80%
• 6:28
  because
• 6:29
  now
• 6:29
  remember,
• 6:30
  these
• 6:30
  receptors
• 6:30
  are
• 6:31
  not
• 6:31
  just
• 6:31
  in
• 6:31
  sweet
• 6:32
  spots
• 6:32
  in
• 6:32
  the
• 6:32
  brain
• 6:32
  that
• 6:33
  calm
• 6:33
  you
• 6:33
  down
• 6:33
  and
• 6:33
  make
• 6:34
  you
• 6:34
  feel
• 6:34
  less
• 6:34
  anxious.
• 6:35
  You
• 6:35
  also
• 6:35
  have
• 6:35
  serotonin
• 6:36
  receptors
• 6:36
  in
• 6:37
  the
• 6:37
  gut.
• 6:37
  When
• 6:38
  you
• 6:38
  stimulate
• 6:39
  the
• 6:39
  5ht3
• 6:41
  receptors,
• 6:41
  you're
• 6:42
  getting
• 6:42
  more
• 6:42
  nauseous.
• 6:42
  GI
• 6:43
  discomfort
• 6:44
  when
• 6:44
  you
• 6:44
  overstimulate
• 6:45
  5ht2A,
• 6:46
  you're
• 6:47
  becoming
• 6:47
  a
• 6:47
  little
• 6:47
  too
• 6:48
  anxious
• 6:48
  and
• 6:48
  ruminative.
• 6:49
  You
• 6:49
  want
• 6:49
  to
• 6:50
  stimulate
• 6:50
  specific
• 6:51
  receptors.
• 6:51
  But
• 6:51
  as
• 6:52
  we
• 6:52
  talked
• 6:52
  about
• 6:52
  in
• 6:52
  previous
• 6:53
  episodes,
• 6:54
  when
• 6:54
  you
• 6:55
  prescribe
• 6:55
  an
• 6:55
  ssri,
• 6:57
  it's
• 6:57
  going
• 6:58
  to
• 6:58
  act
• 6:58
  broadly
• 6:58
  on
• 6:59
  many
• 6:59
  different
• 6:59
  receptors.
• 7:01
  And
• 7:01
  the
• 7:01
  key
• 7:01
  is
• 7:02
  to
• 7:02
  occupy
• 7:02
  a
• 7:03
  specific
• 7:03
  percentage
• 7:04
  of
• 7:04
  those
• 7:05
  receptors
• 7:05
  at
• 7:06
  a
• 7:06
  specific
• 7:06
  time
• 7:06
  to
• 7:07
  exert
• 7:07
  a
• 7:07
  specific
• 7:08
  effect
• 7:08
  while
• 7:09
  mitigating
• 7:09
  the
• 7:09
  side
• 7:10
  effects.
• 7:10
  You
• 7:10
  might
• 7:10
  get
• 7:11
  more
• 7:11
  nauseous,
• 7:11
  you
• 7:11
  might
• 7:11
  get
• 7:12
  more
• 7:12
  anxious.
• 7:13
  So
• 7:13
  it's
• 7:13
  a
• 7:13
  fine
• 7:14
  line.
• 7:14
  It's
• 7:14
  an
• 7:14
  art
• 7:14
  and
• 7:15
  a
• 7:15
  science.
• 7:15
  And
• 7:15
  we
• 7:15
  have
• 7:16
  to
• 7:16
  really
• 7:16
  get
• 7:16
  good
• 7:17
  at
• 7:17
  asking
• 7:17
  our
• 7:17
  patients
• 7:18
  those
• 7:18
  granular
• 7:18
  questions
• 7:19
  about,
• 7:19
  okay,
• 7:20
  you're
• 7:20
  on
• 7:20
  Prozac.
• 7:21
  We
• 7:21
  just
• 7:21
  started
• 7:21
  you
• 7:21
  on
• 7:21
  Prozac.
• 7:22
  Why
• 7:23
  at
• 7:23
  a
• 7:23
  very
• 7:23
  low
• 7:24
  dose,
• 7:24
  are
• 7:25
  you
• 7:25
  having
• 7:25
  so
• 7:26
  many
• 7:26
  side
• 7:26
  effects?
• 7:27
  They
• 7:27
  might
• 7:27
  be
• 7:27
  occupying
• 7:28
  that
• 7:28
  small
• 7:29
  dose
• 7:29
  of
• 7:29
  Prozac,
• 7:30
  and
• 7:30
  that
• 7:30
  low
• 7:30
  dose
• 7:30
  of
• 7:30
  Prozac
• 7:31
  might
• 7:31
  be
• 7:31
  occupying
• 7:32
  way
• 7:32
  more
• 7:32
  receptors
• 7:33
  than
• 7:33
  you
• 7:34
  wanted
• 7:34
  it
• 7:34
  to.
• 7:34
  And
• 7:35
  you're
• 7:35
  like,
• 7:35
  wait
• 7:35
  a
• 7:35
  minute,
• 7:35
  it's
• 7:36
  only
• 7:36
  10
• 7:36
  milligrams.
• 7:37
  Why
• 7:37
  would
• 7:38
  this
• 7:38
  be
• 7:38
  occupying
• 7:38
  so
• 7:39
  many
• 7:39
  receptors?
• 7:39
  Well,
• 7:40
  maybe
• 7:40
  the
• 7:40
  patient
• 7:40
  is
• 7:40
  a
• 7:41
  slow
• 7:41
  metabolizer
• 7:42
  of
• 7:43
  Prozac
• 7:44
  and
• 7:44
  therefore
• 7:45
  has
• 7:45
  a
• 7:45
  hard
• 7:45
  time
• 7:45
  clearing
• 7:46
  it
• 7:46
  genetically
• 7:48
  via
• 7:48
  the
• 7:48
  liver
• 7:49
  enzymes,
• 7:49
  the
• 7:49
  CYP
• 7:50
  system.
• 7:50
  And
• 7:51
  now
• 7:51
  you
• 7:51
  have
• 7:52
  a
• 7:52
  disproportionately
• 7:53
  high
• 7:54
  level
• 7:54
  of
• 7:55
  Prozac
• 7:56
  in
• 7:56
  the
• 7:56
  system.
• 7:57
  So
• 7:57
  now
• 7:57
  that's
• 7:58
  another
• 7:58
  thing
• 7:58
  you
• 7:58
  have
• 7:58
  to
• 7:58
  contend
• 7:59
  with
• 7:59
  and
• 7:59
  think
• 7:59
  about.
• 8:01
  So
• 8:01
  we
• 8:01
  talked
• 8:01
  about
• 8:02
  your
• 8:02
  own
• 8:03
  genetic
• 8:03
  metabolism
• 8:04
  and
• 8:04
  how
• 8:04
  that
• 8:04
  can
• 8:05
  influence
• 8:06
  the
• 8:06
  occupancy
• 8:07
  percentage.
• 8:08
  We
• 8:08
  also
• 8:08
  have
• 8:08
  to
• 8:09
  think
• 8:09
  about
• 8:10
  dehydration,
• 8:10
  right?
• 8:11
  Less
• 8:11
  plasma
• 8:12
  volume
• 8:12
  means
• 8:13
  drug
• 8:13
  is
• 8:13
  more
• 8:13
  concentrated,
• 8:14
  and
• 8:14
  it
• 8:14
  raises
• 8:15
  the
• 8:15
  free
• 8:15
  levels
• 8:16
  in
• 8:16
  the
• 8:16
  blood,
• 8:17
  and
• 8:17
  therefore
• 8:18
  it
• 8:18
  can
• 8:18
  exert
• 8:19
  more
• 8:19
  of
• 8:19
  an
• 8:20
  effect
• 8:20
  on
• 8:20
  your
• 8:21
  receptors.
• 8:21
  Now,
• 8:22
  I
• 8:22
  don't
• 8:22
  wanna
• 8:22
  lose
• 8:23
  you
• 8:23
  here.
• 8:23
  It's.
• 8:23
  It's
• 8:23
  pretty
• 8:24
  simple.
• 8:24
  It's
• 8:25
  a
• 8:25
  crude
• 8:25
  analogy,
• 8:25
  but
• 8:26
  I
• 8:26
  think
• 8:26
  it's
• 8:26
  a
• 8:26
  decent
• 8:27
  analogy.
• 8:28
  Think
• 8:28
  of
• 8:29
  dehydration
• 8:30
  as
• 8:31
  what
• 8:31
  it
• 8:31
  is,
• 8:31
  right?
• 8:31
  Everything's
• 8:32
  more
• 8:32
  concentrated,
• 8:33
  your
• 8:33
  drug,
• 8:33
  including
• 8:34
  the
• 8:34
  drug.
• 8:34
  So
• 8:34
  you
• 8:34
  prescribe
• 8:35
  Prozac,
• 8:35
  this
• 8:36
  patient's
• 8:36
  really
• 8:36
  dehydrated.
• 8:37
  The
• 8:37
  concentration
• 8:38
  of
• 8:38
  the
• 8:38
  drug
• 8:38
  is
• 8:38
  going
• 8:39
  to
• 8:39
  be
• 8:39
  just
• 8:39
  more
• 8:40
  intense.
• 8:40
  It's
• 8:41
  no
• 8:41
  different
• 8:41
  than
• 8:42
  if
• 8:43
  you
• 8:43
  take
• 8:43
  a
• 8:43
  tablespoon
• 8:44
  of
• 8:44
  salt
• 8:44
  and
• 8:44
  you
• 8:45
  put
• 8:45
  it
• 8:45
  in
• 8:45
  a
• 8:45
  small
• 8:45
  glass
• 8:46
  of
• 8:46
  water
• 8:46
  and
• 8:46
  drink
• 8:46
  that
• 8:47
  glass
• 8:47
  of
• 8:47
  water
• 8:47
  that's
• 8:48
  really
• 8:48
  powerful.
• 8:48
  It's
• 8:49
  like,
• 8:49
  oh,
• 8:49
  my
• 8:49
  God,
• 8:49
  this
• 8:49
  water's
• 8:50
  so
• 8:50
  salty.
• 8:51
  If
• 8:51
  you
• 8:51
  put
• 8:51
  it
• 8:51
  in
• 8:51
  a
• 8:52
  gallon
• 8:52
  of
• 8:52
  water,
• 8:52
  it
• 8:52
  might
• 8:53
  actually
• 8:53
  be
• 8:53
  a
• 8:53
  little
• 8:54
  easier.
• 8:54
  It
• 8:55
  won't
• 8:55
  be
• 8:55
  as
• 8:55
  salty
• 8:56
  because
• 8:56
  there's
• 8:56
  so
• 8:57
  much
• 8:57
  more
• 8:57
  water
• 8:58
  to
• 8:58
  dilute
• 8:58
  the
• 8:58
  salt.
• 8:59
  It's
• 8:59
  not
• 8:59
  going
• 8:59
  to
• 8:59
  taste
• 8:59
  great
• 9:00
  to
• 9:00
  drink
• 9:01
  that
• 9:01
  salt
• 9:01
  water,
• 9:02
  but
• 9:02
  it's
• 9:02
  just
• 9:02
  going
• 9:02
  to
• 9:02
  be
• 9:03
  a
• 9:03
  lot
• 9:03
  less
• 9:03
  intense
• 9:04
  than
• 9:04
  if
• 9:04
  you
• 9:04
  have
• 9:04
  one
• 9:05
  little
• 9:05
  glass
• 9:05
  with
• 9:05
  a
• 9:06
  whole
• 9:06
  tablespoon
• 9:06
  of
• 9:07
  salt.
• 9:07
  Same
• 9:08
  with
• 9:08
  your
• 9:08
  medications.
• 9:09
  If
• 9:09
  you
• 9:10
  prescribe
• 9:10
  Prozac
• 9:11
  or
• 9:11
  Zoloft
• 9:12
  or
• 9:12
  what
• 9:12
  have
• 9:12
  you,
• 9:12
  and
• 9:12
  the
• 9:13
  patient
• 9:13
  is
• 9:13
  super
• 9:13
  dehydrated,
• 9:14
  the
• 9:14
  reduction
• 9:15
  in
• 9:15
  plasma
• 9:15
  volume
• 9:16
  means
• 9:17
  your
• 9:17
  drug
• 9:17
  doesn't
• 9:17
  have
• 9:17
  to
• 9:17
  travel
• 9:18
  as
• 9:19
  far.
• 9:19
  Let's
• 9:20
  say
• 9:20
  you
• 9:20
  have
• 9:20
  a
• 9:20
  pool,
• 9:21
  and
• 9:21
  the
• 9:22
  pool
• 9:22
  is
• 9:22
  completely
• 9:23
  full
• 9:23
  and
• 9:23
  you're
• 9:24
  draining
• 9:24
  it,
• 9:24
  you
• 9:25
  have
• 9:25
  a
• 9:25
  little
• 9:26
  bit
• 9:26
  of
• 9:26
  pink
• 9:26
  dye
• 9:26
  in
• 9:27
  the
• 9:27
  pool.
• 9:27
  It's
• 9:27
  going
• 9:27
  to
• 9:28
  take
• 9:28
  a
• 9:28
  long
• 9:28
  time
• 9:28
  for
• 9:29
  all
• 9:29
  that
• 9:29
  pink
• 9:29
  dye
• 9:29
  to
• 9:30
  drain
• 9:30
  because
• 9:30
  it's
• 9:30
  a
• 9:30
  large
• 9:31
  pool,
• 9:31
  right?
• 9:32
  But
• 9:32
  if
• 9:32
  your
• 9:32
  pool
• 9:32
  is
• 9:32
  very
• 9:33
  small
• 9:33
  and
• 9:33
  you
• 9:33
  still
• 9:33
  have
• 9:34
  the
• 9:34
  same
• 9:34
  amount
• 9:34
  of
• 9:34
  pink
• 9:35
  dye
• 9:35
  and
• 9:35
  you're
• 9:35
  draining
• 9:36
  the
• 9:36
  pool,
• 9:37
  it's
• 9:37
  going
• 9:37
  to
• 9:37
  drain
• 9:38
  faster
• 9:38
  because
• 9:38
  that
• 9:39
  dye
• 9:39
  is
• 9:39
  way
• 9:39
  more
• 9:40
  concentrated.
• 9:40
  It's
• 9:40
  just
• 9:40
  in
• 9:41
  a
• 9:41
  small
• 9:41
  puddle.
• 9:41
  And
• 9:42
  it
• 9:42
  doesn't
• 9:42
  take
• 9:42
  long
• 9:43
  to
• 9:43
  drain
• 9:43
  that
• 9:43
  puddle
• 9:44
  because
• 9:44
  it's
• 9:44
  A
• 9:44
  small
• 9:44
  amount
• 9:44
  of
• 9:45
  volume.
• 9:45
  The
• 9:45
  same
• 9:45
  principle
• 9:46
  is
• 9:46
  taking
• 9:46
  place
• 9:47
  when
• 9:47
  you
• 9:47
  give
• 9:47
  a
• 9:48
  drug
• 9:48
  like,
• 9:48
  like
• 9:48
  Prozac
• 9:49
  and
• 9:49
  the
• 9:50
  plasma
• 9:50
  is
• 9:51
  super
• 9:51
  dehydrated.
• 9:52
  It
• 9:52
  gets
• 9:52
  super
• 9:52
  concentrated
• 9:53
  in
• 9:53
  the
• 9:53
  plasma
• 9:53
  and
• 9:54
  it
• 9:54
  can
• 9:54
  flow
• 9:54
  through
• 9:54
  the
• 9:54
  blood
• 9:55
  brain
• 9:55
  barrier
• 9:55
  more
• 9:56
  readily
• 9:56
  because
• 9:57
  it's
• 9:57
  less
• 9:57
  volume
• 9:58
  and
• 9:58
  way
• 9:58
  more
• 9:58
  concentrated.
• 9:59
  Right.
• 9:59
  That
• 10:00
  same
• 10:00
  amount
• 10:00
  of
• 10:01
  pink
• 10:01
  dye,
• 10:01
  but
• 10:01
  in
• 10:02
  a
• 10:02
  small
• 10:02
  puddle.
• 10:02
  So
• 10:03
  it's
• 10:03
  like
• 10:03
  really
• 10:03
  pink
• 10:04
  and
• 10:04
  really
• 10:04
  intense.
• 10:04
  And
• 10:05
  therefore
• 10:05
  it
• 10:06
  exerts
• 10:06
  a
• 10:06
  much
• 10:07
  greater
• 10:07
  side
• 10:07
  effect.
• 10:08
  So
• 10:08
  I
• 10:08
  want
• 10:09
  you
• 10:09
  to
• 10:09
  have
• 10:09
  an
• 10:09
  appreciation
• 10:10
  for
• 10:10
  the
• 10:10
  fact
• 10:10
  that
• 10:11
  if
• 10:11
  your
• 10:11
  patient
• 10:11
  is
• 10:11
  just
• 10:12
  dehydrated,
• 10:12
  that
• 10:13
  alone
• 10:13
  can
• 10:13
  increase
• 10:14
  the
• 10:14
  occupancy
• 10:15
  of
• 10:16
  those
• 10:16
  receptors
• 10:16
  to
• 10:17
  achieve
• 10:17
  the
• 10:17
  desired
• 10:17
  clinical
• 10:18
  effect.
• 10:18
  And
• 10:19
  not
• 10:19
  just
• 10:19
  desired
• 10:19
  effect,
• 10:19
  but
• 10:20
  side
• 10:20
  effects.
• 10:20
  Right.
• 11:15
  Your
• 11:15
  patient
• 11:16
  might
• 11:16
  have
• 11:16
  a
• 11:16
  lot
• 11:16
  of
• 11:16
  side
• 10:22
  effects.
• 11:17
  They're
• 11:18
  dehydrated.
• 11:18
  They
• 11:19
  might
• 11:19
  be
• 11:19
  slow
• 11:19
  metabolizers
• 11:20
  like
• 11:20
  we
• 11:20
  talked
• 11:21
  about.
• 11:21
  And
• 11:22
  so
• 11:22
  that
• 11:22
  can
• 11:23
  all
• 11:23
  affect
• 11:23
  things
• 11:24
  a
• 11:24
  lot.
• 11:25
  We
• 11:25
  talked
• 11:25
  about
• 11:25
  affinity
• 11:26
  last
• 11:26
  time
• 11:26
  and
• 11:26
  how
• 11:27
  that
• 11:27
  affects
• 11:27
  occupancy.
• 11:28
  We
• 11:28
  talked
• 11:28
  about
• 11:28
  the
• 11:28
  snowflake
• 11:29
  analogy.
• 11:29
  And
• 11:29
  I
• 11:30
  encourage
• 11:30
  you
• 11:30
  to
• 11:30
  go
• 11:30
  to
• 11:30
  our
• 11:30
  previous
• 11:31
  episode
• 11:31
  all
• 11:32
  about
• 11:32
  affinity.
• 11:33
  If
• 11:33
  a
• 11:33
  drug
• 11:34
  has
• 11:34
  a
• 11:34
  very
• 11:34
  high
• 11:34
  affinity,
• 11:35
  like
• 11:35
  Remeron,
• 11:36
  has
• 11:36
  a
• 11:36
  very
• 11:36
  high
• 11:36
  affinity
• 11:37
  for
• 11:37
  blocking
• 11:37
  histamine.
• 11:38
  Well,
• 11:39
  if
• 11:39
  a
• 11:39
  drug
• 11:39
  has
• 11:40
  a
• 11:40
  high
• 11:40
  affinity
• 11:40
  for
• 11:41
  something,
• 11:41
  it's
• 11:41
  going
• 11:41
  to
• 11:41
  occupy
• 11:42
  those
• 11:43
  receptors
• 11:44
  more
• 11:44
  readily
• 11:45
  at
• 11:45
  lower
• 11:45
  doses.
• 11:46
  So
• 11:46
  that's
• 11:46
  another
• 11:46
  factor
• 11:47
  that
• 11:47
  can
• 11:48
  influence
• 11:49
  the
• 11:49
  occupancy.
• 11:50
  And
• 11:50
  that
• 11:50
  matters
• 11:51
  because
• 11:51
  very
• 11:51
  low
• 11:51
  doses
• 11:52
  of
• 11:52
  something
• 11:52
  can
• 11:53
  be
• 11:53
  enough
• 11:53
  to
• 11:53
  achieve
• 11:54
  the
• 11:54
  desired
• 11:54
  effect
• 11:55
  and
• 11:55
  occupy
• 11:56
  the
• 11:56
  right
• 11:56
  percentage
• 11:56
  of
• 11:57
  receptors,
• 11:58
  because
• 11:58
  the
• 11:58
  affinity
• 11:59
  of
• 11:59
  your
• 11:59
  medication
• 12:00
  towards
• 12:00
  that
• 12:01
  receptor,
• 12:01
  in
• 12:01
  this
• 12:01
  case
• 12:02
  Renron
• 12:02
  and
• 12:02
  histamine,
• 12:03
  is
• 12:04
  significant.
• 12:05
  So
• 12:05
  think
• 12:05
  about
• 12:06
  that.
• 12:06
  We
• 12:06
  talked
• 12:06
  about
• 12:07
  dehydration.
• 12:07
  We
• 12:07
  talked
• 12:08
  about
• 12:08
  affinity.
• 12:08
  We
• 12:09
  talked
• 12:09
  about
• 12:09
  your
• 12:09
  own
• 12:10
  metabolism
• 12:10
  and
• 12:11
  how
• 12:11
  you
• 12:11
  metabolize
• 12:12
  medications
• 12:12
  and
• 12:13
  their
• 12:13
  ability
• 12:14
  either
• 12:14
  if
• 12:14
  it's
• 12:14
  too
• 12:14
  slow
• 12:15
  or
• 12:15
  too
• 12:15
  fast
• 12:15
  to
• 12:16
  influence
• 12:16
  the
• 12:17
  percentage
• 12:17
  of
• 12:17
  receptors
• 12:18
  that
• 12:18
  are
• 12:18
  occupied.
• 12:19
  But
• 12:19
  it's
• 12:20
  almost
• 12:20
  like
• 12:20
  when
• 12:21
  blood
• 12:21
  levels
• 12:22
  build
• 12:22
  up
• 12:22
  and
• 12:22
  side
• 12:22
  effects
• 12:23
  build
• 12:23
  up
• 12:23
  quickly,
• 12:24
  it's
• 12:25
  like
• 12:25
  people
• 12:25
  getting
• 12:25
  you
• 12:26
  on
• 12:26
  that
• 12:26
  bus
• 12:27
  even
• 12:27
  faster.
• 12:27
  They're
• 12:28
  just
• 12:28
  like,
• 12:28
  get
• 12:28
  on
• 12:28
  the
• 12:28
  bus.
• 12:29
  And
• 12:29
  now
• 12:29
  all
• 12:30
  those
• 12:30
  seats
• 12:30
  are
• 12:30
  occupied
• 12:31
  and
• 12:31
  they
• 12:31
  build
• 12:31
  up
• 12:31
  and
• 12:31
  nobody's
• 12:32
  leaving
• 12:32
  the
• 12:32
  bus.
• 12:33
  Not
• 12:33
  my
• 12:33
  favorite
• 12:34
  analogy,
• 12:34
  but
• 12:35
  you
• 12:35
  get
• 12:35
  the
• 12:35
  idea
• 12:35
  here,
• 12:36
  right?
• 12:36
  It's
• 12:36
  all
• 12:37
  about
• 12:37
  how
• 12:37
  quickly
• 12:38
  your
• 12:39
  enzymes
• 12:40
  are
• 12:40
  metabolizing
• 12:41
  this,
• 12:41
  or
• 12:42
  how
• 12:42
  slowly.
• 12:43
  Quickly
• 12:43
  would
• 12:43
  mean
• 12:44
  you're
• 12:44
  not
• 12:44
  getting
• 12:44
  the
• 12:45
  therapeutic
• 12:45
  effects
• 12:46
  as
• 12:47
  easily.
• 12:47
  And
• 12:48
  slowly
• 12:48
  would
• 12:48
  mean
• 12:48
  you're
• 12:48
  getting
• 12:49
  them
• 12:49
  probably
• 12:50
  at
• 12:50
  lower
• 12:50
  doses
• 12:51
  and
• 12:51
  with
• 12:51
  some
• 12:52
  side
• 12:52
  effects.
• 12:53
  So
• 12:53
  just
• 12:53
  think
• 12:53
  about
• 12:53
  that,
• 12:54
  my
• 12:54
  friends.
• 12:54
  Now,
• 12:55
  protein
• 12:55
  binding
• 12:55
  is
• 12:56
  a
• 12:56
  very
• 12:56
  unique
• 12:56
  concept.
• 12:56
  We're
• 12:57
  probably
• 12:57
  going
• 12:57
  to
• 12:57
  do
• 12:57
  a
• 12:57
  whole
• 12:58
  episode
• 12:58
  on
• 12:58
  protein
• 12:58
  binding.
• 12:59
  So
• 12:59
  you
• 12:59
  have
• 12:59
  A
• 12:59
  better
• 12:59
  appreciation
• 13:00
  for
• 13:00
  it.
• 13:01
  But
• 13:01
  just
• 13:01
  remember
• 13:02
  that
• 13:02
  when
• 13:02
  you
• 13:02
  prescribe
• 13:03
  a
• 13:03
  medication
• 13:03
  and
• 13:03
  if
• 13:04
  it
• 13:04
  is
• 13:04
  highly
• 13:04
  protein
• 13:05
  bound,
• 13:05
  it
• 13:05
  is
• 13:05
  inactive,
• 13:06
  it
• 13:06
  is
• 13:07
  not
• 13:07
  exerting
• 13:07
  a
• 13:07
  real
• 13:08
  pharmacological
• 13:08
  effect
• 13:09
  when
• 13:09
  it
• 13:09
  is
• 13:09
  bound
• 13:09
  to
• 13:10
  a
• 13:10
  protein.
• 13:10
  It's
• 13:11
  the
• 13:11
  amount
• 13:11
  of
• 13:11
  free
• 13:11
  drug
• 13:12
  or
• 13:12
  unbound
• 13:13
  drug
• 13:13
  that
• 13:14
  is
• 13:14
  actually
• 13:14
  active
• 13:15
  and
• 13:15
  can
• 13:15
  exert
• 13:16
  pharmacological
• 13:16
  effects.
• 13:18
  So
• 13:18
  highly
• 13:19
  protein
• 13:19
  bound
• 13:19
  meds
• 13:20
  like
• 13:20
  Prozac,
• 13:20
  they
• 13:20
  occupy
• 13:21
  those
• 13:21
  receptors
• 13:21
  more
• 13:22
  slowly.
• 13:23
  So
• 13:23
  keep
• 13:23
  that
• 13:23
  in
• 13:23
  mind,
• 13:24
  because
• 13:24
  if
• 13:24
  you're
• 13:24
  prescribing
• 13:25
  something
• 13:25
  and
• 13:26
  it's
• 13:26
  highly
• 13:26
  protein
• 13:27
  bound,
• 13:27
  it's
• 13:27
  not
• 13:27
  gonna
• 13:27
  occupy
• 13:28
  your
• 13:28
  receptors
• 13:28
  as
• 13:29
  quickly
• 13:29
  as
• 13:29
  something
• 13:29
  that
• 13:29
  is
• 13:30
  really
• 13:30
  not
• 13:30
  as
• 13:30
  protein
• 13:31
  bound.
• 13:31
  But
• 13:31
  you
• 13:32
  have
• 13:32
  multiple
• 13:32
  other
• 13:33
  filters
• 13:33
  to
• 13:33
  put
• 13:33
  that
• 13:34
  through,
• 13:34
  right?
• 13:34
  The
• 13:35
  genetic
• 13:35
  makeup
• 13:36
  of
• 13:36
  your
• 13:36
  patient,
• 13:36
  how
• 13:36
  dehydrated
• 13:37
  they
• 13:37
  are,
• 13:38
  the
• 13:38
  affinity
• 13:38
  for
• 13:38
  the
• 13:38
  medication
• 13:39
  that
• 13:40
  you're
• 13:40
  prescribing,
• 13:41
  right?
• 13:41
  If
• 13:42
  you're
• 13:42
  prescribing
• 13:42
  Remeron
• 13:43
  and
• 13:43
  you're
• 13:43
  looking
• 13:43
  for
• 13:44
  a
• 13:44
  really
• 13:44
  good
• 13:44
  elevation
• 13:45
  in
• 13:45
  mood
• 13:45
  and
• 13:45
  energy,
• 13:45
  you
• 13:46
  want
• 13:46
  that
• 13:46
  Norepinephrine
• 13:47
  kick.
• 13:47
  Well,
• 13:48
  Remeron
• 13:48
  doesn't
• 13:49
  have
• 13:49
  a
• 13:49
  very
• 13:49
  high
• 13:49
  affinity
• 13:50
  for
• 13:50
  Norepinephrine.
• 13:51
  Right
• 13:51
  away
• 13:51
  at
• 13:51
  7.5,
• 13:52
  you
• 13:52
  have
• 13:52
  to
• 13:52
  raise
• 13:53
  the
• 13:53
  dose
• 13:54
  for
• 13:54
  it
• 13:54
  to
• 13:54
  start
• 13:55
  accumulating
• 13:56
  a
• 13:56
  little
• 13:56
  bit
• 13:57
  for
• 13:57
  that
• 13:57
  effect.
• 13:58
  So
• 13:58
  keep
• 13:58
  that
• 13:59
  in
• 13:59
  mind,
• 13:59
  right?
• 13:59
  If
• 13:59
  you
• 13:59
  want
• 14:00
  more
• 14:00
  Norepinephrine
• 14:01
  release,
• 14:01
  you've
• 14:01
  got
• 14:02
  to
• 14:03
  increase
• 14:03
  the
• 14:03
  amount
• 14:04
  of
• 14:05
  Remeron.
• 14:06
  But
• 14:06
  again,
• 14:07
  you
• 14:07
  might
• 14:07
  have
• 14:07
  a
• 14:07
  patient
• 14:08
  who's
• 14:08
  a
• 14:08
  super
• 14:09
  slow
• 14:09
  metabolizer
• 14:10
  of
• 14:10
  Remeron
• 14:10
  and
• 14:11
  those
• 14:11
  drug
• 14:11
  levels
• 14:11
  will
• 14:12
  build
• 14:12
  up
• 14:12
  quicker.
• 14:13
  So
• 14:13
  you
• 14:14
  see
• 14:14
  how
• 14:14
  this
• 14:14
  is
• 14:14
  all
• 14:14
  coming
• 14:15
  full
• 14:15
  circle.
• 14:15
  A
• 14:16
  lot
• 14:16
  of
• 14:16
  these
• 14:16
  things
• 14:16
  are
• 14:16
  coming
• 14:17
  together
• 14:18
  when
• 14:18
  circling
• 14:19
  back
• 14:19
  to
• 14:19
  protein
• 14:19
  binding.
• 14:21
  Take
• 14:21
  Zoloft
• 14:21
  and
• 14:22
  Depakote.
• 14:22
  Maybe
• 14:22
  you
• 14:23
  prescribe
• 14:23
  Zoloft
• 14:24
  and
• 14:25
  Depakote
• 14:26
  comes
• 14:26
  in
• 14:27
  and
• 14:27
  just
• 14:27
  whacks
• 14:28
  it
• 14:28
  off
• 14:28
  those
• 14:28
  protein
• 14:29
  molecules.
• 14:29
  And
• 14:30
  now
• 14:30
  you
• 14:30
  have
• 14:30
  way
• 14:31
  more
• 14:31
  Zoloft
• 14:32
  in
• 14:33
  the
• 14:33
  bloodstream,
• 14:34
  exerting
• 14:35
  clinical
• 14:35
  effects
• 14:36
  and
• 14:36
  potentially
• 14:36
  really
• 14:36
  bad
• 14:37
  side
• 14:37
  effects.
• 14:37
  More
• 14:38
  sexual
• 14:38
  dysfunction,
• 14:38
  more
• 14:39
  anxiety
• 14:39
  because
• 14:40
  Depakote
• 14:40
  came
• 14:41
  in
• 14:41
  and
• 14:41
  kicked
• 14:41
  it
• 14:41
  off,
• 14:42
  because
• 14:42
  they're
• 14:42
  both
• 14:43
  protein
• 14:43
  bound.
• 14:44
  So
• 14:44
  you
• 14:44
  have
• 14:44
  to
• 14:44
  think
• 14:45
  about
• 14:45
  that
• 14:45
  too.
• 14:45
  Just
• 14:45
  the
• 14:46
  protein
• 14:46
  binding
• 14:47
  competition.
• 14:47
  It's
• 14:48
  almost
• 14:48
  like
• 14:48
  musical
• 14:48
  chairs,
• 14:49
  right?
• 14:49
  It's
• 14:50
  almost
• 14:50
  like
• 14:50
  a
• 14:50
  life
• 14:50
  raft.
• 14:51
  Depakote
• 14:52
  comes
• 14:52
  in
• 14:52
  and
• 14:52
  kicks
• 14:52
  Zoloft
• 14:53
  off
• 14:53
  the
• 14:53
  life
• 14:53
  raft.
• 14:53
  And
• 14:54
  now
• 14:54
  Zoloft
• 14:54
  is
• 14:54
  in
• 14:55
  the
• 14:55
  water
• 14:55
  scrambling
• 14:55
  and
• 14:56
  yelling.
• 14:56
  And
• 14:56
  those
• 14:56
  are
• 14:56
  your
• 14:57
  side
• 14:57
  effects.
• 14:57
  It's
• 14:58
  important
• 14:58
  that
• 14:59
  you
• 14:59
  think
• 14:59
  about
• 14:59
  occupancy
• 15:00
  each
• 15:00
  time
• 15:00
  you
• 15:01
  see
• 15:01
  your
• 15:01
  patient
• 15:01
  and
• 15:01
  ask
• 15:02
  yourself,
• 15:02
  why
• 15:03
  is
• 15:03
  this
• 15:03
  patient
• 15:03
  having
• 15:04
  side
• 15:04
  effects?
• 15:04
  Because
• 15:04
  there's
• 15:05
  many
• 15:05
  different
• 15:05
  reasons
• 15:06
  they
• 15:06
  could
• 15:06
  have
• 15:06
  side
• 15:06
  effects
• 15:06
  that
• 15:07
  we
• 15:07
  just
• 15:07
  explained,
• 15:07
  right?
• 15:08
  And
• 15:08
  it
• 15:08
  has
• 15:08
  to
• 15:08
  do
• 15:09
  with
• 15:09
  occupancy.
• 15:10
  And
• 15:10
  maybe
• 15:11
  those
• 15:11
  receptors
• 15:12
  are
• 15:12
  oversaturated
• 15:13
  with
• 15:13
  too
• 15:14
  many
• 15:14
  neurotransmitters
• 15:15
  on
• 15:15
  them.
• 15:16
  You
• 15:16
  need
• 15:16
  to
• 15:16
  change
• 15:17
  course
• 15:17
  and
• 15:17
  what
• 15:17
  do
• 15:17
  you
• 15:17
  do?
• 15:18
  Right,
• 15:18
  so.
• 15:18
  So
• 15:18
  if
• 15:18
  you
• 15:19
  have
• 15:19
  a
• 15:19
  patient
• 15:20
  where
• 15:20
  the
• 15:20
  receptor
• 15:21
  occupancy
• 15:22
  is
• 15:22
  maybe
• 15:22
  too
• 15:22
  high,
• 15:22
  and
• 15:23
  we
• 15:23
  can't
• 15:23
  go
• 15:23
  in
• 15:23
  there
• 15:24
  necessarily
• 15:24
  and
• 15:24
  do
• 15:24
  a
• 15:25
  PET
• 15:25
  scan
• 15:25
  and
• 15:25
  prove
• 15:26
  how
• 15:26
  many
• 15:27
  serotonin
• 15:28
  receptors
• 15:28
  are
• 15:29
  blocked,
• 15:29
  we
• 15:30
  don't
• 15:30
  have
• 15:30
  that
• 15:30
  luxury.
• 15:30
  What
• 15:30
  we
• 15:31
  can
• 15:31
  do,
• 15:31
  my
• 15:31
  friends,
• 15:32
  is
• 15:32
  if
• 15:33
  you're
• 15:33
  giving
• 15:33
  Prozac
• 15:34
  or
• 15:34
  let's
• 15:34
  say
• 15:34
  you're
• 15:34
  giving
• 15:35
  Lexapro,
• 15:35
  and
• 15:36
  you're
• 15:36
  like,
• 15:36
  man,
• 15:37
  I'm
• 15:37
  at
• 15:37
  20
• 15:37
  milligrams
• 15:38
  of
• 15:38
  Lexapro
• 15:38
  and
• 15:39
  this
• 15:39
  patient's
• 15:39
  not
• 15:39
  getting
• 15:39
  any
• 15:40
  less
• 15:40
  anxious.
• 15:40
  Their
• 15:41
  mood
• 15:41
  is
• 15:41
  still
• 15:41
  not
• 15:41
  great.
• 15:42
  They
• 15:42
  have
• 15:42
  morning
• 15:43
  fatigue.
• 15:43
  Their
• 15:43
  energy's
• 15:44
  low.
• 15:44
  Well,
• 15:45
  you
• 15:45
  might
• 15:45
  be
• 15:46
  at
• 15:46
  80%
• 15:46
  occupancy
• 15:47
  with
• 15:48
  DE
• 15:48
  Lexapro.
• 15:48
  You
• 15:48
  can't
• 15:49
  really
• 15:49
  do
• 15:49
  much
• 15:49
  else
• 15:50
  as
• 15:50
  it
• 15:50
  relates
• 15:50
  to
• 15:50
  serotonin
• 15:51
  because
• 15:51
  you're
• 15:51
  at
• 15:52
  full
• 15:52
  receptor
• 15:52
  occupancy,
• 15:53
  exerting
• 15:54
  the
• 15:54
  clinical
• 15:54
  effect
• 15:54
  that
• 15:55
  you
• 15:55
  need.
• 15:55
  Maybe
• 15:55
  they're
• 15:56
  ruminating
• 15:56
  less,
• 15:56
  but
• 15:57
  they
• 15:57
  still
• 15:57
  don't
• 15:57
  get
• 15:58
  any
• 15:58
  joy
• 15:58
  out
• 15:58
  of
• 15:58
  anything.
• 15:59
  If
• 15:59
  they're
• 15:59
  not
• 16:00
  metabolizing
• 16:00
  this
• 16:01
  well,
• 16:01
  that
• 16:01
  20
• 16:01
  milligrams
• 16:02
  might
• 16:02
  feel
• 16:02
  like
• 16:02
  30
• 16:03
  milligrams
• 16:03
  to
• 16:03
  them.
• 16:04
  They
• 16:04
  even
• 16:05
  have
• 16:05
  a
• 16:05
  blunted
• 16:06
  dopamine
• 16:06
  response.
• 16:06
  Remember
• 16:07
  we
• 16:07
  talked
• 16:07
  about
• 16:07
  in
• 16:08
  previous
• 16:08
  episodes
• 16:09
  that
• 16:09
  when
• 16:09
  serotonin
• 16:10
  is
• 16:10
  increased
• 16:11
  more
• 16:11
  broadly,
• 16:11
  it
• 16:12
  can
• 16:12
  actually
• 16:12
  act
• 16:12
  as
• 16:12
  a
• 16:13
  brake
• 16:13
  on
• 16:13
  dopamine
• 16:14
  in.
• 16:14
  In
• 16:14
  other
• 16:15
  receptors.
• 16:15
  So
• 16:16
  now
• 16:16
  you're
• 16:16
  like,
• 16:16
  what
• 16:16
  do
• 16:16
  I
• 16:17
  do?
• 16:17
  Could
• 16:17
  lower
• 16:17
  the
• 16:17
  dose
• 16:18
  of
• 16:18
  Lexapro
• 16:19
  to
• 16:19
  ease
• 16:19
  off
• 16:20
  on
• 16:20
  that
• 16:20
  dopamine
• 16:21
  break.
• 16:21
  You
• 16:22
  could
• 16:22
  also
• 16:22
  go
• 16:22
  for
• 16:22
  a
• 16:23
  dopaminergic
• 16:23
  medication
• 16:24
  like
• 16:24
  Wellbutrin.
• 16:25
  Remember,
• 16:26
  when
• 16:26
  you
• 16:26
  reach
• 16:26
  a
• 16:27
  certain
• 16:27
  occupancy
• 16:28
  and
• 16:28
  you
• 16:28
  have
• 16:28
  to
• 16:29
  tease
• 16:29
  out
• 16:29
  where
• 16:29
  your
• 16:30
  patient
• 16:30
  is
• 16:30
  with
• 16:30
  respect
• 16:30
  to
• 16:31
  that
• 16:31
  occupancy,
• 16:32
  you
• 16:32
  have
• 16:32
  to
• 16:32
  ask,
• 16:32
  do
• 16:33
  I
• 16:33
  need
• 16:33
  to
• 16:33
  switch
• 16:34
  neurotransmitter
• 16:35
  class
• 16:35
  or
• 16:35
  augment
• 16:36
  to
• 16:36
  a
• 16:37
  different
• 16:37
  neurotransmitter
• 16:38
  class?
• 16:38
  Because
• 16:39
  I'm
• 16:39
  reaching
• 16:39
  full
• 16:40
  occupancy
• 16:40
  here,
• 16:41
  and
• 16:41
  you
• 16:41
  may
• 16:41
  have
• 16:42
  to
• 16:42
  do
• 16:42
  that.
• 16:42
  So
• 16:42
  in
• 16:42
  other
• 16:42
  words,
• 16:43
  there
• 16:43
  are
• 16:43
  diminishing
• 16:43
  returns
• 16:44
  at
• 16:44
  a
• 16:44
  certain
• 16:44
  point,
• 16:45
  and
• 16:45
  it's
• 16:46
  not
• 16:46
  always
• 16:46
  clear
• 16:46
  to
• 16:46
  determine
• 16:47
  where
• 16:47
  that
• 16:47
  certain
• 16:47
  point
• 16:48
  is.
• 16:48
  Again,
• 16:49
  for
• 16:49
  all
• 16:49
  the
• 16:49
  other
• 16:49
  factors
• 16:50
  that
• 16:50
  we
• 16:50
  talked
• 16:51
  about.
• 16:51
  Genotype,
• 16:52
  dehydration,
• 16:53
  drug
• 16:53
  affinity,
• 16:53
  protein
• 16:54
  binding,
• 16:54
  all
• 16:55
  of
• 16:55
  those
• 16:55
  things.
• 16:56
  Right.
• 16:57
  And
• 16:57
  I
• 16:57
  think
• 16:58
  that's
• 16:58
  pretty
• 16:58
  interesting
• 16:59
  circling
• 16:59
  back
• 16:59
  to
• 16:59
  Prozac.
• 17:00
  Interesting
• 17:00
  medication,
• 17:01
  long
• 17:01
  half
• 17:01
  life.
• 17:02
  Prozac
• 17:02
  will
• 17:03
  maintain
• 17:03
  occupancy
• 17:04
  even
• 17:04
  after
• 17:04
  you
• 17:04
  discontinue
• 17:05
  it,
• 17:05
  which
• 17:06
  can
• 17:06
  be
• 17:06
  nice.
• 17:06
  It's
• 17:07
  kind
• 17:07
  of
• 17:07
  a
• 17:07
  slow,
• 17:07
  graceful
• 17:08
  withdrawal
• 17:09
  rather
• 17:09
  than
• 17:10
  this
• 17:10
  abrupt
• 17:10
  withdrawal.
• 17:11
  So
• 17:11
  if
• 17:11
  you
• 17:11
  imagine
• 17:12
  that
• 17:12
  school
• 17:12
  bus
• 17:12
  again,
• 17:13
  Prozac
• 17:14
  is
• 17:14
  kind
• 17:14
  of
• 17:14
  like
• 17:14
  a
• 17:14
  little
• 17:15
  old
• 17:15
  lady
• 17:15
  who
• 17:15
  gracefully
• 17:16
  walks
• 17:16
  off
• 17:17
  the
• 17:17
  bus
• 17:17
  really
• 17:17
  slowly
• 17:18
  because
• 17:18
  she
• 17:18
  doesn't
• 17:18
  want
• 17:19
  to
• 17:19
  fall
• 17:19
  on
• 17:20
  her
• 17:20
  face.
• 17:20
  And
• 17:21
  she
• 17:21
  just
• 17:21
  slowly,
• 17:21
  she
• 17:22
  grabs
• 17:22
  the
• 17:22
  railings,
• 17:23
  she
• 17:23
  holds
• 17:23
  on
• 17:24
  to
• 17:24
  other
• 17:24
  passengers.
• 17:25
  She
• 17:25
  slowly
• 17:26
  gets
• 17:26
  off
• 17:26
  the
• 17:26
  bus.
• 17:27
  And
• 17:27
  there's
• 17:28
  no
• 17:28
  withdrawal
• 17:28
  effect
• 17:29
  because
• 17:29
  it's
• 17:30
  slow
• 17:30
  and
• 17:30
  graceful,
• 17:31
  as
• 17:31
  opposed
• 17:31
  to
• 17:31
  a
• 17:32
  fexor
• 17:32
  very
• 17:33
  short
• 17:33
  half
• 17:33
  life.
• 17:33
  The
• 17:34
  withdrawal
• 17:35
  can
• 17:35
  be
• 17:35
  very
• 17:35
  unpleasant.
• 17:36
  It's
• 17:36
  kind
• 17:36
  of
• 17:37
  like
• 17:37
  a
• 17:37
  kid
• 17:37
  who's
• 17:37
  impatient
• 17:38
  and
• 17:38
  just
• 17:38
  jumps
• 17:38
  out
• 17:38
  the
• 17:39
  window
• 17:39
  trying
• 17:39
  to
• 17:39
  squeeze
• 17:40
  out.
• 17:40
  It's
• 17:40
  like,
• 17:40
  oh,
• 17:40
  my
• 17:40
  God,
• 17:41
  this
• 17:41
  is
• 17:41
  miserable.
• 17:41
  Like,
• 17:42
  I'm
• 17:42
  trying
• 17:42
  to
• 17:42
  squeeze
• 17:43
  out
• 17:43
  this
• 17:43
  tiny
• 17:43
  window.
• 17:44
  This
• 17:44
  is
• 17:45
  really
• 17:45
  miserable
• 17:45
  and
• 17:45
  awful.
• 17:46
  And
• 17:46
  I'm
• 17:46
  jumping
• 17:47
  out
• 17:47
  right
• 17:47
  away.
• 17:47
  And
• 17:48
  that's
• 17:49
  how
• 17:49
  I
• 17:49
  view
• 17:50
  again,
• 17:50
  Receptor
• 17:51
  occupancy
• 17:51
  half
• 17:51
  lives.
• 17:52
  There's
• 17:53
  a
• 17:53
  slow,
• 17:53
  graceful
• 17:54
  way
• 17:54
  to
• 17:54
  get
• 17:54
  off
• 17:54
  the
• 17:54
  bus.
• 17:54
  There's
• 17:55
  a
• 17:55
  really
• 17:55
  hectic,
• 17:55
  unpleasant
• 17:56
  way
• 17:56
  to
• 17:56
  get
• 17:56
  off
• 17:57
  the
• 17:57
  bus.
• 17:57
  But
• 17:58
  you
• 17:58
  know
• 17:58
  what?
• 17:58
  In
• 17:58
  the
• 17:59
  same
• 17:59
  analogy
• 17:59
  here,
• 18:00
  some
• 18:00
  kids
• 18:00
  are
• 18:01
  thin
• 18:01
  and
• 18:01
  agile,
• 18:02
  and
• 18:02
  they
• 18:02
  can
• 18:03
  get
• 18:03
  off
• 18:03
  the
• 18:03
  bus
• 18:03
  really
• 18:04
  quickly.
• 18:04
  And
• 18:05
  they
• 18:05
  don't
• 18:05
  have
• 18:05
  weird
• 18:06
  withdrawal
• 18:06
  symptoms.
• 18:07
  Believe
• 18:07
  it
• 18:07
  or
• 18:07
  not,
• 18:07
  some
• 18:07
  people
• 18:08
  just
• 18:08
  don't
• 18:08
  withdraw
• 18:09
  that
• 18:09
  hard.
• 18:09
  Even
• 18:10
  on
• 18:10
  Effexor,
• 18:10
  it's
• 18:11
  definitely
• 18:11
  the
• 18:11
  more
• 18:11
  common
• 18:12
  one
• 18:12
  you
• 18:12
  withdraw
• 18:12
  off
• 18:13
  of.
• 18:13
  But
• 18:13
  again,
• 18:13
  it
• 18:14
  all
• 18:14
  kind
• 18:14
  of
• 18:14
  depends
• 18:15
  on
• 18:15
  that
• 18:15
  unique
• 18:16
  genetic
• 18:16
  makeup,
• 18:17
  other
• 18:17
  factors
• 18:18
  at
• 18:18
  play.
• 18:19
  And
• 18:19
  some
• 18:19
  people
• 18:19
  can
• 18:20
  just
• 18:20
  get
• 18:20
  off
• 18:20
  of
• 18:21
  Xor.
• 18:21
  Fine.
• 18:22
  In
• 18:22
  my
• 18:22
  experience,
• 18:22
  most
• 18:23
  people
• 18:23
  don't.
• 18:23
  It
• 18:24
  is
• 18:24
  more
• 18:24
  difficult.
• 18:25
  The
• 18:25
  brain
• 18:25
  zaps.
• 18:26
  The
• 18:26
  GI
• 18:27
  issues
• 18:27
  when
• 18:27
  you
• 18:27
  get
• 18:27
  off.
• 18:28
  The
• 18:28
  irritability,
• 18:28
  the
• 18:29
  insomnia,
• 18:29
  the
• 18:29
  anxiety.
• 18:30
  But
• 18:30
  again,
• 18:31
  it's
• 18:31
  not
• 18:31
  as
• 18:31
  simple
• 18:31
  as
• 18:32
  every
• 18:32
  single
• 18:33
  time.
• 18:33
  Someone's
• 18:33
  gonna
• 18:33
  have
• 18:34
  a
• 18:34
  hellish
• 18:34
  time
• 18:34
  getting
• 18:34
  off
• 18:35
  of
• 18:35
  Zola.
• 18:35
  But
• 18:35
  you
• 18:35
  do
• 18:36
  wanna
• 18:36
  proceed
• 18:36
  cautiously
• 18:37
  because
• 18:38
  it
• 18:38
  can
• 18:38
  feel
• 18:38
  like
• 18:38
  that
• 18:39
  kid
• 18:39
  jumping
• 18:39
  out
• 18:39
  of
• 18:39
  the
• 18:39
  bus
• 18:40
  window.
• 18:40
  Right.
• 18:41
  And
• 18:41
  that's
• 18:41
  why
• 18:41
  we
• 18:41
  want
• 18:42
  to
• 18:42
  mitigate
• 18:43
  that
• 18:43
  again,
• 18:43
  that's
• 18:44
  probably
• 18:44
  a
• 18:44
  different
• 18:45
  episode,
• 18:46
  though,
• 18:46
  my
• 18:46
  friends.
• 18:47
  I
• 18:47
  hope
• 18:47
  you
• 18:47
  really
• 18:47
  enjoyed
• 18:48
  this
• 18:48
  episode
• 18:48
  on
• 18:49
  occupancy
• 18:49
  theory.
• 18:50
  How
• 18:50
  to
• 18:50
  define
• 18:51
  it
• 18:51
  and
• 18:51
  what
• 18:51
  it
• 18:52
  means
• 18:52
  and
• 18:52
  why
• 18:52
  it's
• 18:52
  important
• 18:53
  and
• 18:53
  what
• 18:53
  things
• 18:53
  can
• 18:53
  compete
• 18:54
  for
• 18:54
  occupancy.
• 18:55
  And
• 18:55
  I
• 18:55
  love
• 18:55
  this.
• 18:56
  I
• 18:56
  think
• 18:56
  it's
• 18:56
  so
• 18:56
  important.
• 18:57
  It
• 18:57
  unlocks
• 18:58
  so
• 18:58
  many
• 18:58
  principles
• 18:59
  at
• 18:59
  once
• 18:59
  to
• 18:59
  really
• 19:00
  give
• 19:00
  you
• 19:00
  depth
• 19:00
  into
• 19:01
  why
• 19:01
  you
• 19:01
  prescribe
• 19:02
  things.
• 19:03
  I've
• 19:03
  said
• 19:03
  it
• 19:03
  in
• 19:03
  previous
• 19:04
  episodes.
• 19:04
  It
• 19:05
  was
• 19:05
  always
• 19:05
  odd
• 19:05
  to
• 19:06
  me
• 19:06
  to
• 19:06
  explain
• 19:07
  to
• 19:07
  a
• 19:07
  patient,
• 19:07
  well,
• 19:07
  things
• 19:08
  didn't
• 19:08
  work
• 19:08
  on
• 19:08
  Lexapro,
• 19:09
  so
• 19:09
  let's
• 19:09
  move
• 19:09
  to
• 19:09
  Prozac.
• 19:10
  It
• 19:10
  almost
• 19:11
  feels
• 19:11
  like
• 19:11
  this
• 19:11
  pointless
• 19:12
  exercise.
• 19:13
  Sometimes
• 19:13
  your
• 19:14
  patients
• 19:14
  will
• 19:14
  look
• 19:14
  at
• 19:14
  you,
• 19:14
  like,
• 19:15
  why?
• 19:15
  And
• 19:15
  they
• 19:15
  lose
• 19:16
  hope,
• 19:16
  right?
• 19:16
  Because
• 19:16
  they're
• 19:16
  like,
• 19:17
  that
• 19:17
  didn't
• 19:17
  work
• 19:17
  and
• 19:18
  that
• 19:18
  went
• 19:18
  so
• 19:18
  poorly.
• 19:18
  Why
• 19:19
  would
• 19:19
  I
• 19:19
  hold
• 19:19
  out
• 19:19
  for
• 19:19
  Prozac?
• 19:20
  I
• 19:20
  don't
• 19:20
  think
• 19:20
  this
• 19:21
  is
• 19:21
  going
• 19:21
  to
• 19:21
  help
• 19:21
  me.
• 19:21
  But
• 19:22
  when
• 19:22
  you
• 19:22
  understand
• 19:22
  the
• 19:23
  nitty
• 19:23
  gritty
• 19:23
  of,
• 19:23
  hey,
• 19:24
  some
• 19:24
  people
• 19:24
  metabolize
• 19:25
  Lexapro
• 19:26
  way
• 19:26
  too
• 19:26
  quickly,
• 19:27
  and
• 19:27
  maybe
• 19:28
  you
• 19:28
  just
• 19:28
  didn't
• 19:28
  get
• 19:28
  a
• 19:28
  great
• 19:29
  effect
• 19:29
  on
• 19:29
  that.
• 19:29
  Maybe
• 19:30
  there
• 19:30
  are
• 19:30
  these
• 19:30
  other
• 19:31
  variables
• 19:32
  that
• 19:32
  might
• 19:33
  affect
• 19:33
  the
• 19:34
  fact
• 19:34
  that
• 19:34
  Lexapro
• 19:35
  wasn't
• 19:35
  the
• 19:35
  best
• 19:35
  for
• 19:36
  you.
• 19:36
  And
• 19:36
  we
• 19:37
  can
• 19:37
  modulate
• 19:37
  that.
• 19:37
  We
• 19:38
  can
• 19:38
  shape
• 19:38
  that.
• 19:38
  A
• 19:38
  lot
• 19:39
  of
• 19:39
  my
• 19:39
  episodes
• 19:39
  are
• 19:40
  attempts
• 19:40
  by
• 19:40
  which
• 19:41
  you
• 19:41
  can
• 19:41
  think
• 19:41
  about
• 19:41
  this
• 19:42
  and
• 19:42
  look
• 19:42
  at
• 19:43
  this
• 19:43
  with
• 19:43
  HD
• 19:44
  glasses,
• 19:45
  right?
• 19:45
  You
• 19:45
  can
• 19:46
  look
• 19:46
  at
• 19:46
  this
• 19:46
  with
• 19:46
  laser
• 19:47
  glasses
• 19:47
  and
• 19:47
  be
• 19:47
  like,
• 19:48
  wait
• 19:48
  a
• 19:48
  minute,
• 19:48
  I
• 19:48
  know
• 19:49
  the
• 19:49
  nuances
• 19:49
  here.
• 19:49
  This
• 19:50
  is
• 19:50
  what
• 19:50
  I'm
• 19:50
  going
• 19:50
  to
• 19:50
  try
• 19:50
  instead,
• 19:51
  and
• 19:51
  this
• 19:51
  is
• 19:52
  why
• 19:52
  I'm
• 19:52
  going
• 19:52
  to
• 19:52
  try
• 19:52
  instead.
• 19:53
  Empowering
• 19:54
  you
• 19:54
  is
• 19:54
  key.
• 19:55
  That's
• 19:55
  all
• 19:55
  I
• 19:55
  have
• 19:55
  today.
• 19:56
  I
• 19:56
  can't
• 19:57
  emphasize
• 19:57
  enough
• 19:58
  to
• 19:59
  go
• 19:59
  into
• 19:59
  my
• 19:59
  show
• 20:00
  notes,
• 20:00
  become
• 20:01
  a
• 20:01
  Patreon
• 20:01
  member
• 20:02
  because
• 20:02
  you
• 20:03
  have
• 20:03
  slide
• 20:03
  decks
• 20:04
  full
• 20:04
  of
• 20:04
  this
• 20:04
  information
• 20:05
  at
• 20:05
  your
• 20:05
  fingertips.
• 20:05
  You
• 20:06
  can
• 20:06
  study
• 20:06
  or
• 20:07
  review
• 20:07
  this
• 20:07
  to
• 20:07
  empower
• 20:08
  you
• 20:08
  in
• 20:08
  your
• 20:08
  practice
• 20:08
  or
• 20:09
  in
• 20:09
  school
• 20:09
  as
• 20:09
  a
• 20:09
  student
• 20:10
  and
• 20:10
  pass
• 20:10
  your
• 20:11
  boards.
• 20:11
  I
• 20:11
  can't
• 20:11
  emphasize
• 20:12
  enough
• 20:12
  to
• 20:12
  become
• 20:12
  a
• 20:12
  Patreon
• 20:13
  member.
• 20:13
  There
• 20:14
  are
• 20:14
  some
• 20:14
  freebies
• 20:14
  for
• 20:15
  Patreon
• 20:15
  members,
• 20:16
  and
• 20:16
  then
• 20:16
  there's
• 20:16
  also
• 20:17
  a
• 20:17
  paid
• 20:18
  $5
• 20:18
  and
• 20:18
  $10
• 20:19
  tier
• 20:19
  a
• 20:19
  month.
• 20:20
  We'd
• 20:20
  very
• 20:20
  much
• 20:20
  appreciate
• 20:21
  your
• 20:21
  membership.
• 20:22
  We
• 20:22
  also
• 20:22
  release
• 20:23
  episodes
• 20:24
  early
• 20:24
  to
• 20:24
  those
• 20:24
  members,
• 20:25
  pretty
• 20:25
  much
• 20:26
  right
• 20:26
  away
• 20:26
  when
• 20:26
  they
• 20:26
  drop,
• 20:27
  rather
• 20:27
  than
• 20:27
  waiting
• 20:27
  four
• 20:28
  or
• 20:28
  five
• 20:28
  months
• 20:29
  for
• 20:29
  that
• 20:29
  episode
• 20:29
  to
• 20:30
  show
• 20:30
  up
• 20:30
  in
• 20:30
  your
• 20:30
  feed.
• 20:30
  So
• 20:31
  there's
• 20:31
  pretty
• 20:31
  cool
• 20:31
  things
• 20:31
  there.
• 20:32
  I
• 20:32
  highly
• 20:33
  encourage
• 20:33
  you.
• 20:33
  If
• 20:33
  nothing
• 20:33
  else,
• 20:34
  jump
• 20:34
  on
• 20:34
  Apple,
• 20:35
  give
• 20:35
  us
• 20:35
  five
• 20:35
  stars,
• 20:36
  Write
• 20:36
  a
• 20:36
  comment.
• 20:36
  If
• 20:37
  we've
• 20:37
  helped
• 20:37
  you
• 20:37
  out,
• 20:38
  that
• 20:38
  really
• 20:38
  helps.
• 20:39
  But
• 20:39
  we'd
• 20:39
  love
• 20:39
  for
• 20:39
  you
• 20:40
  to
• 20:40
  become
• 20:40
  a
• 20:40
  Patreon
• 20:40
  member
• 20:41
  because
• 20:41
  you
• 20:42
  can
• 20:42
  also
• 20:42
  message
• 20:42
  me
• 20:42
  directly.
• 20:43
  I
• 20:43
  love
• 20:43
  thinking
• 20:44
  in
• 20:44
  analogies,
• 20:44
  so
• 20:44
  I
• 20:45
  would
• 20:45
  love
• 20:45
  to
• 20:46
  open
• 20:46
  the
• 20:46
  floor
• 20:46
  to
• 20:46
  you
• 20:46
  and
• 20:47
  pick
• 20:47
  your
• 20:47
  brain.
• 20:47
  What
• 20:48
  can
• 20:48
  we
• 20:48
  talk
• 20:48
  about
• 20:48
  next
• 20:49
  that
• 20:49
  you're
• 20:49
  struggling
• 20:49
  with
• 20:50
  or
• 20:50
  curious
• 20:50
  about?
• 20:51
  I
• 20:51
  love
• 20:51
  analogies,
• 20:52
  so
• 20:52
  I
• 20:52
  would
• 20:52
  love
• 20:53
  to
• 20:53
  learn
• 20:53
  the
• 20:53
  ways
• 20:54
  you
• 20:54
  guys
• 20:54
  are
• 20:54
  conceptualizing
• 20:55
  these
• 20:56
  topics.
• 20:56
  If
• 20:57
  we
• 20:57
  share
• 20:57
  that
• 20:57
  together,
• 20:57
  it
• 20:58
  will
• 20:58
  be
• 20:58
  like
• 20:58
  the
• 20:58
  most
• 20:58
  empowering
• 20:59
  study
• 20:59
  hall
• 21:00
  of
• 21:00
  all
• 21:00
  time.
• 21:01
  I
• 21:01
  think
• 21:01
  it
• 21:01
  would
• 21:01
  be
• 21:02
  really
• 21:02
  remarkable.
• 21:03
  Remember,
• 21:04
  every
• 21:04
  pearl
• 21:05
  you
• 21:05
  learn
• 21:05
  is
• 21:05
  not
• 21:06
  just
• 21:06
  an
• 21:06
  opportunity
• 21:06
  to
• 21:07
  pass
• 21:07
  the
• 21:07
  boards.
• 21:07
  It's
• 21:08
  not
• 21:08
  just
• 21:08
  a.
• 21:09
  A
• 21:09
  feather
• 21:09
  in
• 21:09
  your
• 21:09
  cap
• 21:09
  and
• 21:10
  some
• 21:10
  extra
• 21:10
  knowledge.
• 21:11
  It's
• 21:11
  an
• 21:11
  unique
• 21:12
  opportunity
• 21:12
  to
• 21:13
  make
• 21:13
  someone's
• 21:13
  life
• 21:13
  tangibly
• 21:14
  better.
• 21:14
  That's
• 21:15
  why
• 21:15
  we're
• 21:15
  here.
• 21:15
  That's
• 21:15
  why
• 21:15
  we
• 21:16
  tune
• 21:16
  into
• 21:16
  this
• 21:16
  stuff
• 21:17
  because
• 21:17
  if
• 21:17
  we
• 21:17
  even
• 21:18
  learn
• 21:18
  one
• 21:18
  thing
• 21:19
  throughout
• 21:19
  this
• 21:19
  episode
• 21:20
  that
• 21:20
  empowers
• 21:21
  us
• 21:21
  to
• 21:22
  change
• 21:22
  a
• 21:22
  human
• 21:23
  life
• 21:23
  or
• 21:23
  even
• 21:23
  make
• 21:23
  a
• 21:24
  day
• 21:24
  better
• 21:24
  for
• 21:25
  somebody
• 21:25
  out
• 21:25
  there,
• 21:26
  it's
• 21:26
  worth
• 21:26
  grabbing
• 21:27
  the
• 21:27
  pearl
• 21:28
  and
• 21:28
  prepping
• 21:28
  for
• 21:29
  practice.
• 21:29
  Thank
• 21:29
  you
• 21:29
  all
• 21:30
  very
• 21:30
  much.
• 21:30
  I'm
• 21:31
  grateful
• 21:31
  to
• 21:31
  each
• 21:32
  and
• 21:32
  every
• 21:32
  one
• 21:32
  of
• 21:32
  you,
• 21:32
  and
• 21:32
  we
• 21:33
  will
• 21:33
  see
• 21:33
  you
• 21:33
  next
• 21:33
  time
• 21:33
  here
• 21:34
  on
• 21:34
  pearls
• 21:35
  and
• 21:35
  prep.