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2011 06 Pharmacology Anti Allergy Drugs

2011 06 Pharmacology Anti Allergy Drugs

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05/22/2012

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 1 
HISTAMINE
y
 
Primary
 
mediator
 
of 
 
allergic
 
reactions
 
 
D
rugs
 
that
 
are
 
commonly
 
used
 
for
 
allergic
 
reactions
(
antihistamines)
 
are
 
intended
 
to
 b
lock
 
the
 
effects
 
of 
 
histamine
 
y
 
F
ormed
b
y
 
decar
b
oxylation
 
of 
 
histidine
b
y
L-
histidine
 
decar
b
oxylase
 
y
 
I
t
 
is
 
in
 
the
 
mast
 
cell
 
if 
 
it
 
is
 
stored
 
in
 
the
 
tissues,
 b
ut
 
it
 
is
 
stored
 
in
 
the
b
asophils
 
if 
 
it
 
is
 
in
 
the
 b
lood
 
y
 
O
ther
 
non
-
mast
 
cell
 
sites
 
include
 
the
 
epidermis,
 
gastric
 
mucosa,
 
neurons
w
ithin
 
the
 CNS
and
 
regenerating
 
or
 
rapidly
 
gro
w
ing
 
tissues;
 
these
 
areas
 
also
 
contain
 
some
 
mast
 
cells
 
y
 
B
efore
 
histamine
 
is
 
released
 
from
 
the
 
mast
 
cell
 
to
 
have
 
manifested
 
an
 
allergic
 
reaction,
 
it
 
has
 
to
 
have
 
a
 
sensitizing
 
exposure.
 
 
O
nce
 
exposed
 
to
 
the
 
allergen,
 
the
b
ody
 w
ill
 
produce
 
anti
b
odies
 
against
 
that
 
allergen
 
for
 
the
 
next
 
exposure
 
 
R
eaction
 
occurs
 
on
 
second
 
exposure:
 w
hen
 
allergen
 
is
 
re
-
introduce
 
to
 
the
b
ody,
 
the
 
antigen
-
anti
b
ody
 
complex
 
is
 
no
w
formed
w
hich
 
attaches
 
itself 
 
to
 
the
 
mast
 
cell,
 
then
 
a
 
series
 
of 
 
processes
 
occurs,
 
leading
 
to
 
degranulation
 
of 
 
that
 
mast
 
cell
 
to
 
release
 
mediators.
 
y
 
Produces
 
an
 
effect
b
y
 
interacting
w
ith
 
histaminergic
 
receptors.
 
Histaminergic Receptors
  G-
protein
 
coupled
 
receptors
 
y
 
H
1
coupled
 
to
GS
;
 
the
 
phosphoinositol
 
path
w
ay
 
is
 
involved;
 
peripheral
 
nerve
 
ending,
 b
ronchial
 
and
 
intestinal
 
smooth
 
muscles,
 
small
 b
lood
 
vessels
 
y
 
H
2
linked
 
to
 
the
 
cyclic
AM
P
 
system
 
that
w
ill
 
release
 
cyclic
AM
P
 
as
 
second
 
messenger;
 
primarily
 
in
 
gastric
 
parietal
 
cells
 
y
 
H
3
presynaptic
 
autoreceptors
 
in
 
neurons
 
that
 
mediate
 
feed
b
ack
 
inhi
b
ition
 
of 
 
the
 
release
 
and
 
synthesis
 
of 
 
histamine
 
y
 
H
4
similar
 
to
 
H
3
,
 
expressed
 
in
 
cells
 
of 
 
the
 
hematopoietic
 
lineage
 
Type
 
Major TissueLocations
 
Major BiologicEffects
 
H
1
 
B
ronchial
&
intestinal
 
smooth
 
muscles,
 A
cute
 
allergic
 
responses
 
endothelial
 
cells,
 CNS
,
 
peripheral
 
nerve
 
endings
 
H
2
 G
astric
 
parietal
 
cells,
 
heart,
CNSS
ecretion
 
of 
 
gastric
 
acid
 
H
3
 CNS
:
 
presynaptic
 
neuron
 M
odulates
 
neurotransmission
--
mediates
 
feed
b
ack
 
mechanism
 
H
4
 
H
ematopoietic
 
cells
 
R
egulates
 
immune
 
responses
 
HistamineEffects:1.
 
CV
S
a.
 
D
ilatation
 
of 
 
resistance
 
vessels
(
arterioles)
 
o
 
H
1
 
and
 
H
2
 
receptors
 
distri
b
uted
 
throughout
 
the
 
resistance
 
vessels
 
in
 
most
 
vascular
b
eds
 
o
 
H
1
(
rapid
 
in
 
onset
 
and
 
short
-
lived),
 
H
2
 (
slo
w b
ut
 
more
 
sustained)
 b
.
 
D
ecrease
 
systemic
b
lood
 
pressure
 
c.
 
I
ncrease
 
capillary
 
permea
b
ility
 
o
 
E
ffect
 
on
 
postcapillaryvenules
 
o
 
O
ut
w
ard
 
passage
 
of 
 
plasma
 
protein
 
and
 
fluid
 
 
edema
 
formation
 
o
 
M
ediated
b
y
 
H
1
 
receptors
 
on
 
endothelial
 
cells
 
Subject: PharmacologyTopic: Anti-allergy DrugsLecturer: Dr. Ma. Luisa DelacruzDate of Lecture:06/29/2011Transcriptionist: ChooOoosSs 01Pages: 5
   S   Y   2   0   1   1  -   2   0   1   2
 
 
2
 
d.
 
Triple
 
R
esponse
L
e
w
is
 1
.
 
L
ocalized
 
red
 
spot
 
y
 
C
apillary
 
dilatation
(
same
 
as
 "
petichiae:
 
red
 
spots)
 
2
.
 
B
righter
 
red
 
flush
 
or
 
flare
 
around
 
the
 
area
 
of 
 
the
 
red
 
spot
 
y
 
A
xon
 
reflex
 
3
.
 
W
heal
 
y
 
F
ormed
b
ecause
 
of 
 
increase
 
capillary
 
permea
b
ility,
 
the
 
fluid
 
and
 
protein
 
go
 
out
 
into
 
interstitial
 
area
(
edema
 
formation)
 
*
F
ig.
 
Produced
b
y
 
scratching
 
the
 
skin
->
elicit
 
the
 
triple
 
response
 
le
w
is
 *W
heal
-
elevated
 
area
 *
F
lare
-
reddened
 
area
 
surrounding
 
th
w
heal
 
2.
 
Heart
o
 
H
2
:
(+
)
 
inotropic
 
effect,
(+
)
 
chronotropic
 
effect
 
y
 
I
ncrease
 
force
 
of 
 
contraction
 
of 
 
atrial
 &
ventricular
 
muscles
 
promoting
 
influx
 
of 
C
a
++
(
H
2
)
 
y
 
I
ncrease
 
heart
 
rate
b
y
 
hastening
 
diastolic
 
depolarization
 
in
 
the
 
sinoatrial
 
node
(
H2
)
 
o
 
H
1
:
 
increase
 
automaticity
 
 
arrhythmias
 
o
 
H
istamine
 
shock
 
y
 
I
n
 
large
 
doses
(
systemic
 
anaphylaxis)
 
causes
 
a
 
profound
 
and
 
progressive
 
fall
 
in
b
lood
 
pressure
 
y
 
R
esem
b
les
 
surgical
 
or
 
traumatic
 
shock
 
 
R
esults
 
in
 
diminish
 
effective
 b
lood
 
volume,
 
reduce
 
venous
 
return
 
and
 
marked
 
decrease
 
in
 
cardiac
 
output
 
 
C
irculatory
 
collapse
=
decrease
 
in
 
venous
 
return
 
 
decreased
 
cardiac
 
output
 
3.
 
Extravascular smooth muscle
a.
 
C
ontraction
 
due
 
to
 
H
1
 
activation
 
y
 
H
istamine
 
induces
 b
ronchoconstriction
 b
.
 
R
elaxation
 
due
 
to
 
H
2
 
activation
 
c.
 
I
ntense
b
ronchoconstriction
 
in
 
patients
 w
ith
 
asthma
 
and
 
other
 
pulmonary
 
diseases
 
y
 
A
sthmatic
 
attack
 
due
 
to
 
allergic
 
reactions
 
d.
 
H
istamine
-
induced
b
ronchospasm
 
may
 
involve
 
an
 
additional
 
reflex
 
component
 
that
 
arises
 
from
 
irritation
 
of 
 
efferent
 
vagal
 
nerve
 
endings
 
e.
 
C
ontraction
 
of 
 
intestinal
 
smooth
 
muscles
 
4.
 
C
NS
a.
 
N
ociception
pain
 
perception
 b
.
 
A
rousal
 
c.
 
S
atiation
 
d.
 
C
ognitive
 
function
 
e.
 
C
ontrol
 
of 
 
pituitary
 
hormone
 
release
 
f.
 
N
ausea
&
vomiting
 
*V
esti
b
ular
 
center
 
and
C
hemoreceptor
 
Trigger
Z
one
 
has
 
H
1
receptor
w
hich
w
hen
 
activated
 
can
 
produce
 
nausea
 
and
 
vomiting,
b
ecause
 
they
 
are
 
linked
 
to
 
vomiting
 
center.
 
5
.
 
Dizziness, vertigo
6
.
 
P
eripheral nerve endings
i.
 
Perception
 
of 
 
itchiness
&
pain
 
is
 
due
 
to
 
the
 
activation
 
of 
 
H
1
 
receptors
 
in
 
the
 
nerve
 
endings
 
a.
 
S
timulation
 
of 
 
various
 
nerve
 
endings
 
and
 
sensory
 
effects
 b
.
 
I
 
released
 
in
 
the
 
epidermis
(
superficial
 
stimulation)
 
 
itch
 
c.
 
I
 
released
 
in
 
the
 
dermis
(
deep
 
stimulation)
 
 
pain
 
sometimes
 
accompanied
b
y
 
itching
 
y
 
N
arro
w
margin
 
for
 
itch
 
and
 
pain
 
perception
 
 
 
3
 
ANA
P
HYLAXIS
y
 
S
evere
 
form
 
of 
 
allergic
 
reaction
 
y
 
Potentially
 
fatal
 
y
 
M
anifestations:
 
 
A
ngioderma,
 
pruritus
 
 
D
yspnea
 
 
Tachycardia
 
 
H
ypotension
 
 
L
oss
 
of 
 
consciousness
 
C
lassification of Anti-allergy Drugs (H1 receptorantagonists, epinephrine, histamine releaseinhibitors, corticosteroids)
I
.
 
H
1
 
R
eceptor
A
ntagonists
(C
lassical
 A
ntihistamines)
 
a.
 
1st generation
o
 
C
hlorpheniramine
 
o
 
C
yclizine
 
o
 
D
imenhydrinate
 
o
 
H
ydroxyzine
 
o
 
M
eclizine
 
o
 
Promethazine
 
o
 
D
iphenhydramine
 
H
C
l:
 
prototype
 
of 
1
st
 
generation
 
drugs
 
y
 
P
harmacokinetics
 
R
apidly
 
a
b
sor
b
ed
 
after
 
oral
 
administration
 
y
 
U
sually
 
given
 
orally
b
ut
 
also
 
has
 
parenteral
 
administration
 
 
Peak
 
plasma
 
concentration
 
in
1-
2
 
hours
 
y
 
E
limination
 
half 
 
life
 
is
 
4
-8
hours
 
y
 
W
idely
 
distri
b
uted
 
throughout
 
the
 b
ody
 
including
 
the
CNS
y
 
M
eta
b
olized
 
in
 
the
 
liver
b
y
CY
P
 
enzymes
isoenzymes
 
not
 
yet
 
identified
 
y
 
E
xcreted
 
in
 
small
 
amounts
 
in
 b
reast
 
milk
 
y
 
S
mall
 
amount
 
excreted
 
unchanged
 
in
 
the
 
urine
 
y
 
Therapeutic Uses:
1
.
 
Type
1
hypersensitivity
 
reaction
 - A
cute
 
allergic
 
reaction
 
 
S
econdary
 
to
 
food,
 
drugs,
 
insect
 b
ites,
 
etc.
 
 
S
easonal
 
rhinitis
&
conjunctivitis
 - L
imited
 
efficacy
 
in
 
asthma
 
since
 
in
 
asthma,
 
other
 
mediators
 
are
 
involved
 (
not
 
 just
 
histamine)
 
2
.
A
djunct
 
role
 
to
 
epinephrine
 
in
 
the
 
treatment
 
of 
 
severe
 
allergic
 
reactions/anaphylaxis
 
y
 
E
pinephrine
-
reverses
 
the
 
effect
 
of 
 
histamine
b
ut
 
needs
 
anti
-
histamine
 
to
 
prevent
 
further
 
inflammatory
 
reactions
 
3
.
A
ntipruritic
 
4
.
M
otion
 
sickness,
 
vertigo
 - M
eclizine
(
aka
 
B
onamine)
 
is
 
an
 
antihistamine
w
idely
 
used
 
for
 
motion
 
sickness
 5
.
 
Prophylaxis
&
treatment
 6
.
A
nti
-
emetic
 -
Prevention
 
of 
 
vomiting
 7
.
 
Parkinson's
 
disease
 -
D
iphenhydramine
(
B
enadryl®)
 
has
 b
een
 
used
 
to
 
decrease
 
muscle
 
stiffness
 
and
 
tremors,
w
hich
 
are
 
associated
w
ith
 
the
 
disease.
 (W
ellness.com)
 8
.
 
D
rug
-
induced
 
extrapyramidal
 
adverse
 
effects
 
Adverse Effects
1
.
 
CNS
y
 
D
ro
w
siness
(
often
 
transient)
 
o
 
M
ay
b
e
 
a
 
good
 
thing,
w
hen
 
trying
 
to
 
avoid
 
scratching
 
and
 
the
 
feeling
 
of 
 
itchiness
 
y
 
S
edation,
 
dizziness,
 
faintness,
 
distur
b
ed
 
coordination
 
2
.
 
G
I
T
 
y
 
L
oss
 
of 
 
appetite,
 
epigastric
 
distress,
 
constipation
 
or
 
diarrhea
 
3
.
 
H
ematologic
 
y
 
H
emolytic
 
anemia,
 
leukopenia,
 
throm
b
ocytopenia,
 
agranulocytosis
 
4
.
 
M
eta
b
olic
-
not
 
very
 
common
 
y
 
I
ncreased
 
appetite,
w
eight
 
gain
 
y
 
S
ome
 
drug
 
preparations
(
H
1
 
receptor
b
locker;
 
Pizotifen)
 
for
 
children
 
contain
 
appetite
 
stimulants
 

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