Adrenergic Agents: University of Negros Occidental-Recoletos

University of Negros
Occidental-Recoletos
Adrenergic
Agents
Presented by
Sophia Luz P. Alfiscar
Bessie J. Chavez
Kimberly S. Halipa
Presentation Outline Adrenergic
Neurotransmitter
Today's Topics
Adrenergic Receptor
Drug Affecting Adrenergic
CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Neurotransmission
Sympathomimetic Agents
Overview
Adrenergic Drug Affecting Adrenergic

Neurotransmitter Neurotransmission
Structure and physicochemical Drugs affecting catecholamine
properties storage and release
Biosynthesis

Storage, release, uptake, and
metabolism
Adrenergic Receptor Sympathomimetic Agents

Alpha adrenergic receptors Direct-acting sympathomimetics
Beta adrenergic receptors
NEXT
Overview
Adrenergic agents act on adrenergic
receptors (adrenoceptors, ARs) or
affect the life cycle of adrenergic
neurotransmitters (NTs), including
norepinephrine (NE, noradrenaline),
epinephrine (E, adrenaline), and

dopamine (DA). These NTs modulate
many vital functions, such as the
rate and force of cardiac
contraction, constriction, and
dilation of blood vessels and
bronchioles, the release of
insulin, and the breakdown of fat.
Most Commonly Used Adrenergic Prescription drugs
Major Indication
Mechanism of Action Drug
α1-Agonists Naphazoline (Privine) Nasal & ophthalmic congestion
Clonidine (Catapres)* Hypertension

α2-Agonists
Methyldopa (Aldomet) Hypertension
Hypertension & benign

Prazosin (Minipress)
prostatic hyperplasia (BPH)
Terazosin (Hytrin)* Hypertension & BPH

α1-Blockers
Doxazosin (Cardura)* Hypertension & BPH
Tamsulosin (Flomax) BPH & hypertension

Mechanism of Action Drug Major Indication
ß2-Agonists Albuterol (Ventolin)* Nasal & ophthalmic congestion
Labetalol (Normodyne)* Hypertension

α1-, ß1-, & ß2-
Blockers Carvedilol (Coreg) Hypertension & heart failure
Hypertension, angina,
Acebutolol (Sectral)
& hyperthyroidism
Hypertension, angina,
Atenolol (Tenormin)*
ß1-Blockers & hyperthyroidism
Metoprolol (Lopressor)* Hypertension
Bisoprolol (Zebeta)* Hypertension

Mechanism of Action Drug Major Indication
Hypertension, arrhythmias,
Propranolol (Inderal)*
& angina
Hypertension, angina, &
Nadolol (Corgard)*
hyperthyroidism
ß1-, & ß2-Blockers

Timolol (Timoptic)* Glaucoma & hypertension
Sotalol (Betapace)* Arrhythmias
Levobunolol (Betagan) Glaucoma

Adrenergic
Neurotransmitters:
Structure and
Physicochemical Properties
In a physiological context, the

term usually means Dopamine and

its metabolites Norepinephrine
and Epinephrine. Epinephrine
contains one secondary amino
group and three hydroxyl
groups.
Figure 16.1 Adrenergic neurotransmitters
and related compounds.
Like most phenols, the catechol
functional groups in CAs are highly
susceptible to facile oxidation.
Epinephrine and Norepinephrine
undergo oxidation in the presence
of oxygen (air) or other oxidizing
agents to produce a quinone analog,

which undergoes further reactions
to give mixtures of colored
products, one of which is
adrenochrome.
Figure 16.2 Oxidation of Epinephrine (E).
Biosynthesis
The Catecholamines biosynthesis and

physiological regulation in
neuroendocrine cells has been
reviewed. Catecholamines in
neuroendocrine cells are in a state
of constant flux. They are
continuously being synthesized,

released, and metabolized, yet they
maintain a remarkable constant
level in tissues. Catecholamines
are widely distributed in mammals,
and their levels and physiological
functions are regulated at many
sites. The biosynthesis involves a
sequence of enzymatic reactions.
Figure 16.3 Model of life cycle of NE.

The steps in the biosynthesis of
Catecholamines and related
enzyme inhibitors are as shown
in the following figure. The
first step in CA biosynthesis is
the 3’-hydroxylation of the
amino acid L-tyrosine to form L-
dihydroxyphenylalanine (L-DOPA).
L-Tyrosine is normally present

in the circulation and
transported actively into the
adrenergic neuron, where it is
3’-hydroxylated by tyrosine
hydroxylase (TH, tyrosine-3-
monooxygenase).
Figure 16.4 Biosynthesis of the
catecholamines dopamine, norepinephrine,
and epinephrine.
Storage, Release, Uptake,
and Metabolism:
Storage and Release
Biosynthesis and storage in

granules, the entrance of Ca2+
into these cells results in the
extrusion of Norepinephrine by
exocytosis of the granules.
BIOTIN BENEFITS | AMC

Storage and Release
A large percentage of the

Norepinephrine present is
located within highly
specialized subcellular
particles (later shown to be
synaptic vesicles but
colloquially referred to as
granules) in sympathetic nerve
endings and chromaffin cells.
Much of the Norepinephrine in

CNS is also located within
similar vesicles. The
concentration in the vesicles
is maintained also by the VMAT.
Storage and Release
Ca2+triggered secretion in-

volves interaction of highly
conserved molecular scaffolding
proteins leading to docking of
granules at the plasma mem-
brane and then Norepinephrine
is released from sympathetic
nerve endings into the synaptic
cleft, where it interacts with
specific presynaptic and
postsynaptic adrenoceptors, on

the effector cell, triggering a
biochemical cascade that
results in a physiologic
response by the effector cell.
Storage and Release
These drugs are poor agonists (some

are inactive) at adrenoceptors, but
they are excellent substrates for
VMAT. They are avidly taken up into
noradrenergic nerve endings by
Norepinephrine reuptake transporter
(NET) responsible for Norepinephrine
Indirectly acting and mixed reuptake into the nerve terminal.
In the nerve ending, they are then
sympathomimetics (e.g.,
transported by VMAT into the
tyramine, amphetamines, and
vesicles, displacing NE, which is

ephedrine) are capable of subsequently expelled into the
releasing stored transmitter synaptic space by re- verse transport
from noradrenergic nerve via NET. Their action does not
endings by a calcium- require vesicle exocytosis
independent process
Uptake
Once Norepinephrine has exerted its

effect at adrenergic receptors, there
must be mechanisms for removing the
Norepinephrine from the synapse and
terminating its action at the receptors
a. Reuptake of Norepinephrine into

the presynaptic neuron (recycling,
major mechanism) by NET and into
extra neuronal
b. Conversion of Norepinephrine to an

inactive metabolite
c. diffusion of the Norepinephrine
away from the synapse
Metabolism
The second mechanism of

Catecholamine removal is
metabolism. The major mammalian
enzymes of importance in the
Catecholamine metabolism are
monoamine oxidase (MAO) and
catechol-O-methyltransferase
(COMT).

monoamine oxidase catechol-O-methyltransferase
Mechanism of Action (MAO) (COMT)
In neuronal mitochondria Not in sympathetic neuron
Location in Neurons
metabolism of intraneuronal metabolism of extraneuronal
Catecholamines Catecholamines
Deaminate Catecholamines O-methylate CAs to 3’-

Reactions
to aldehydes OMe-CAs
Compounds with a terminal

Aliphatic amino group Catechol-containing
(primary or N-methyl-amino molecules
groups)preference: Dopamine, Epinephrine,
Substrates MAO-A MOA-B Norepinephrine,
NE and 5-HT DA Isoproterenol, etc.
ß-phenylethylamine
benzylamine
Metabolism
Both Epinephrine and

Norepinephrine are orally
inactive and have short
durations of action because of
their high hydrophilicity,
ionization, and extensive
first-pass metabolic
deactivation by COMT and MAO.
The lack of substrate

specificity of COMT and MAO is
manifested in the metabolism of
Norepinephrine and Epinephrine
Adrenergic Receptors:
Adrenergic Receptors
Subtypes
In 1948, Ahlquist proposed and designated α-

and ß- adrenoceptors based on their apparent
drug sensitivity. The diverse physiological

responses of Catecholamines are mediated via
α1-, α2-, and ß-adrenoceptors, which are
further divided into α1A, α1B, α1D, α2A,
α2B, α2C, ß1, ß2, and ß3. They all belong to
the superfamily of guanine nucleotide (G)-
regulatory proteins (G-protein)–coupled
receptors (GPCR), which have seven-
transmembrane (7TM) helical regions
This table describes various tissues they
predominate, types of adrenoceptors, the result
of activating these receptors, and the principal
therapeutic uses of adrenergic agonists and
antagonists. The clinical use of receptors-
selective drugs becomes obvious when one
considers the adrenoceptor subtypes and their
locations.
a1-Agonists as Vasoconstrictors and
Nasal Decongestants
Agonists acting selectively on

a1-receptors cause
vasoconstriction and thus can be
used alongside local anesthetics
in dentistry to localize and
prolong the effect on the

anesthetic at the site of
injection. They are also used as
nasal decongestants
(vasoconstriction of mucous
membranes) and for raising blood
pressure (vasoconstriction of
blood vessels) in shock.
a1-Antagonists for Treatment of
Hypertension
a1-antagonists would be expected to be

vasodilators and hypotensive with clear
implications of treating hypertension.
Similarly, they should block α1A-
receptor in prostate smooth muscle and
relax the muscle with implication of
treating benign prostatic hyperplasia
(BPH)

a2-Agonists for Treatment of Hypertension
a2-Agonists (e.g., clonidine) act at CNS

sites to decrease sympathetic outflow to
the periphery, resulting in decreased
Norepinephrine release at sympathetic
nerve terminal and, therefore, relaxed
vascular smooth muscle
b1-Blockers for Treatment of Hypertension,
Angina, and Certain Cardiac Arrhythmiasa1-
Antagonists for Treatment of Hypertension
Activation of the b1- receptors in heart

causes an increase in rate and force of
contraction and b1-blockers should be
expected to slow the heart rate and
decrease the force of contraction. They
are used in treating hypertension,
angina, and certain cardiac arrhythmias.

ob2-Blockers for Treatment of Asthma and
Premature Labor
A major clinical use for adrenergic

agonists is in treatment of asthma.
Activation of b2-receptors relaxes the
smooth muscles in the bronchi, thus
dilating and opening airways
Similarly, activation of b2-receptors in the
uterus relaxes the muscle, and some b2-agonists
are thus used to inhibit uterine contractions.

This table summarizes the subtypes of
adrenoceptor and their effector systems. In
the early 1970s, the discovery that certain
adrenergic agonists and antagonists exhibited
various degrees of selectivity for
presynaptic and postsynaptic a-receptors led
to the proposal that postsynaptic a-receptors
be designated a1 and that presynaptic a-
receptors be referred to as a2. Later, a
functional classification of the a-receptors
was proposed wherein a1-receptors were
designated as those that were excitatory,

while a2-receptors purportedly mediated
inhibitory responses. Further developments
revealed, however, that both a1- and a2-
receptors could be either presynaptic or
postsynaptic and either excitatory or
inhibitory in their responses. However, the
physiologic significance of postsynaptic a2-
receptors is less well understood.
Figure 16.6 Mechanism
of a1-receptor-mediated
signal transduction
b-Adrenergic Receptors
The b-adrenoceptor subtypes also
differ in terms of the rank order of potency of
the adrenergic receptor agonists Norepinephrine,
Epinephrine, and Isoproterenol. The use of b2-
agonists as bronchodilators and b1- or b1/ b2-
blockers as antihypertensives is well established.
The b1-receptors are located mainly in the heart,
where they mediate the positive inotropic and
chronotropic effects of the Catecholamines. They
are also found on the juxtaglomerular cells of the
kidney, where they are involved in increasing
renin secretion. The b2-receptors are located on

smooth muscle throughout the body, where they are
involved in relaxation of the smooth muscle,
producing such effects as bronchodilation and
vasodilation. They are also found in the liver,
where they promote glycogenolysis. The b3-receptor
is located on brown adipose tissue and is involved
in the stimulation of lipolysis. All three b-
receptors are coupled to Adenylyl cyclase, which
catalyzes the conversion of ATP to cAMP.
Figure 16.7 Mechanism of b2-receptor-
mediated signal transduction
Drugs Affecting Adrenergic
Neurotransmission
Drugs Affecting Catecholamine
Biosynthesis
1. Metyrosine (a-Methyl-L-tyrosine,
Demser).

Metyrosine is a much more effective
competitive inhibitor of EPINEPHRINE
and NE production than agents that
inhibit any of the other enzymes
involved in CA biosynthesis. It is
often possible to “fool” the enzymes
into accepting a structurally similar
and unnatural substrate such as
metyrosine.
Demser).
Metyrosine differs structurally

from tyrosine only in the presence
of an a-methyl group. It is one
example of a CA-biosynthesis
inhibitor in clinical use.
Although metyrosine is used as a

racemic mixture, it is the (-)
isomer that possesses the
inhibitory activity. Metyrosine,
which is given orally in dosages
ranging from
Demser).
a-methyl-m-tyrosine in the treatment

of shock. It differs structurally
from metyrosine only in the
presence of m-OH instead of p-OH in
metyrosine. This unnatural amino acid
is accepted by the enzymes of the
biosynthetic pathway and converted to
metaraminol (an a-agonist) as shown.

Inhibitors of AADC (e.g., carbidopa)
have proven to be clinically useful,
but not as modulators of peripheral
adrenergic transmission. Rather these
agents are used to inhibit the
metabolism of drug L-DOPA
administered in the treatment of
Parkinson disease
Drugs Affecting
Catecholamine Storage and
Release
1. Reserpine (an NT Depleter)
Reserpine, a prototypical and

historically important drug, is an
indole alkaloid obtained from the

root of Rauwolfia serpentina found
in India. As is typical of many
indole alkaloids, reserpine is
susceptible to decomposition by
light and oxidation.
Reserpine is extensively
metabolized through hydrolysis of
the ester function at position 18
and yields methyl reserpate and
3,4,5-trimethoxybenzoic acid. It
not only depletes the vesicle
storage of NE in sympathetic
neurons in PNS, neurons of the

CNS, and E in the adrenal medulla,
but also depletes the storage of
serotonin and DA in their
respective neurons in the brain.
Reserpine binds extremely tightly
with and blocks VMAT that
transports NE and other biogenic
amines from the cytoplasm into the
storage vesicles.
In sympathetic neurons, NE, which

normally is transported into the
storage vesicles, is instead
metabolized by mitochondrial MAO
in the cytoplasm. In addition,
there is a gradual loss of
vesicle-stored NE as it is used up
by release resulting from

sympathetic nerve activity so that
the storage vesicles eventually
become dysfunctional. The end
result is a depletion of NE in the
sympathetic neuron. Analogous
effects are seen in the adrenal
medulla with E and with 5-HT in
serotonergic neurons.
When reserpine is given orally, its maximum

effect is seen after a couple of weeks. A
sustained effect up to several weeks is seen
after the last dose has been given. This is
because the tight binding of reserpine to
storage vesicles continues for a prolonged
time, and recovery of sympathetic function
requires synthesis of new vesicles over a
period of days to weeks after discontinuation

of the drug. Most adverse effects of reserpine
(log P = 4.37) are caused by CNS effects
because it readily enters the CNS. Sedation and
inability to concentrate or perform complex
tasks are the most common adverse effects. More
serious is the occasional psychotic depression
that can lead to suicide, which support
monoamine theory of pathology of depression.
Agents with fewer side effects have largely
replaced reserpine in clinical use
2. Guanethidine (Ismelin) and guanadrel
(Hylorel)
are seldom used orally active

antihypertensives. Drugs of this type enter
the adrenergic neuron by way of the uptake-1
process and accumulate within the neuronal
storage vesicles. There they bind to the
storage vesicles and stabilize the neuronal
storage vesicle membranes, making them less
responsive to nerve impulses. The ability of

the vesicles to fuse with the neuronal
membrane is also diminished, resulting in
inhibition of NE release into the synaptic
cleft in response to a neuronal impulse and
generalized decrease in sympathetic tone.
Long-term administration of some of these
agents also can produce a depletion of NE
stores in sympathetic neurons.
2. Guanethidine (Ismelin) and guanadrel
(Hylorel)
Although guanethidine and guanadrel have

virtually the same mechanism of action on
sympathetic neurons, they differ in their
pharmacokinetic properties. For example,
although guanethidine is absorbed
incompletely after oral administration (3%–
50%), guanadrel is well absorbed, with a
bioavailability of 85%.32 These two agents

also differ in terms of half-life:
Guanethidine has a half-life of about 5 days,
whereas guanadrel has a half-life of 12
hours. Both agents are partially metabolized
(~50%) by the liver, and both are used to
treat moderate-to-severe hypertension, either
alone or in combination with another
antihypertensive agent.
SYMPATHOMIMETIC AGENTS
Sympathomimetic agents produce effects

resembling those produced by
stimulation of the sympathetic nervous
system. They may be classified as
agents that produce effects by a
direct, indirect, or mixed mechanism
of action.
Direct-acting agents elicit a
sympathomimetic response by

interacting directly with adrenergic
receptors. Indirect-acting agents
produce effects primarily by causing
the release of NE from adrenergic
nerve terminals; the NE that is
released by the indirect-acting
agent activates the receptors to
produce the response.
Direct-Acting Sympathomimetics
STRUCTURE–ACTIVITY RELATIONSHIPS
The structure–activity relationships
(SARs) summary
Comprehensive reviews of the SARs of a-
and b-agonists and antagonists covered
their developments in the late 1980s.
The parent structure with the features
in common for many of the adrenergic
drugs is b- phenylethylamine. The

manner in which b-phenylethylamine is
substituted on the meta- and para-
positions of the aromatic ring, on the
amino (R1), and on a-, (R2)-, and b-
positions of the ethylamine side chain
influences not only their mechanism of
action, the receptor selectivity, but
also their absorption, oral activity,
metabolism, degradation, and thus
duration of action (DOA).
Optical Isomerism
A critical factor in the interaction of

adrenergic agonists with their receptors is
stereoselectivity. Substitution on either
carbon-1 or carbon-2 yields optical
isomers. (1R,2S) isomers seem correct
configuration for direct-acting activity.
For CAs, the more potent enantiomer has the
(1R) configuration. This enantiomer is
typically several 100-fold more potent than

the enantiomer with the (1S) configuration.
It appears that for all direct-acting,
phenylethylamine-derived agonists that are
structurally similar to NE, the more potent
enantiomer is capable of assuming a
conformation that results in the
arrangement in space of the catechol group,
the amino group, and the (1R)-OH group in a
fashion resembling that of (1R)-NE.
Separation of Aromatic Ring and
Amino Group
By far, the greatest adrenergic activity occurs

when two carbon atoms separate the aromatic ring
from the amino group. This rule applies with few
exceptions to all types of activities
R1, Substitution on the Amino

Nitrogen Determines a- or b-

Receptor Selectivity
The amine is normally ionized at physiological pH.

This is important for direct agonist activity,
because replacing nitrogen with carbon results in
a large decline in activity. The activity is also
affected by the number of substituents on the
nitrogen. Primary and secondary amines have good
adrenergic activity, whereas tertiary amines and
quaternary ammonium salts do not.
R2, Substitution on the a-Carbon
(Carbon-2)
Substitution by small alkyl group (e.g., CH3- or

C2H5-) slows metabolism by MAO but has little overall
effect on DOA of catechols because they remain
substrates for COMT. However, the resistance to MAO
activity is more important in noncatechol indirect-
acting phenylethylamines. The DOA of drugs such as
ephedrine or amphetamine is thus measured in hours
rather than in minutes. Because addition of small
alkyl group increases the resistance to metabolism

and lipophilicity, such compounds often exhibit
enhanced oral effective- ness and greater CNS
activity than their counterparts that do not contain
an a-alkyl group. In addition, compounds with an a-
methyl substituent persist in the nerve terminals and
are more likely to release NE from storage sites. For
example, metaraminol is an a-agonist and also
exhibits a greater degree of indirect sympathomimetic
activity.
OH substitution on the b-carbon
(carbon-1)
Generally decreases CNS activity largely

because it lowers lipid solubility. However,
such substitution greatly enhances agonist
activity at both a- and b-receptors. For
example, ephedrine is less potent than
methamphetamine as a central stimulant, but
it is more powerful in dilating bronchioles
and increasing blood pressure and heart

rate. Compounds lacking the b-OH group (e.g.
DA) have a greatly reduced adrenergic
receptor activity. Some of the activity is
retained, indicating that the OH group is
important but not essential. The R-
enantiomer of NE is more active than the S-
enantiomer, indicating that the secondary
alcohol is involved in an H-bonding
interaction.
Substitution on the Aromatic
Ring
Maximal a- and b-activity also depends

on the presence of 3’ and 4’ OH
groups. Tyramine, which lacks two OH
groups, has no affinity for

adrenoceptors, indicating the
importance of the OH groups. Studies
of b-adrenoceptor structure suggest
that the OH groups on serine residues
204 and 207 probably form H- bonds
with the catechol OH groups at
positions 3’ and 4’, respectively.
CAs without OH Groups
Phenylethylamines that lack OH groups

on the ring and the b-OH group on the
side chain act almost exclusively by
causing the release of NE from
sympathetic nerve terminals and thus

results in a loss of direct
sympathomimetic activity. Because
substitution of OH groups on the
phenylethylamine structure makes the
resultant compounds less lipophilic,
unsubstituted or alkyl- substituted
compounds cross the BBB more readily
and have more central activity.
Imidazolines and a-Adrenergic
Agonists
Although nearly all b-agonists are b-

phenylethanolamine derivatives, it is
-adrenoceptors that exhibit a far more
diverse assortment of structures. A
second chemical class of a-agonists,
the imidazolines, which give rise to

a-agonists and are thus
vasoconstrictors. These imidazolines
can be nonselective, or they can be
selective for either a1- or a2-
receptors. Structurally, most
imidazolines have their heterocyclic
imidazoline nucleus linked to a
substituted aromatic moiety via some
type of bridging unit
ENOLOGOUS CATECHOLAMINES
The three naturally occurring

catecholamines DA, NE, and E are
used as therapeutic agents
Dopamine
(DA, 3’,4’-dihydroxyphenylethylamine)
differs from NE in lacking of 1-OH group.
It is the immediate precursor of NE and is
a central NT particularly important in the
regulation of movement . As a catechol and
primary amine, DA is rapidly metabolized
by COMT and MAO and has a short DOA with
no oral activity. It is used intravenously
in treatment of shock. In contrast with

the NE and E, DA increases blood flow to
the kidney in doses that have no
chronotropic effect on the heart or that
cause no increase in blood pressure. The
increased blood flow to the kidneys
enhances glomerular filtration rate, Na+
excretion, and, in turn, urinary output.
The dilation of renal blood vessels
produced by DA is the result of its
agonist action on the D1-DA receptor.
Norepinephrine (NE, Levophed)
Differs from DA only by addition of a 1-OH

substituent (b-OH-DA) and from E only by
lacking the N-methyl group. Like DA, it is
polar and rapidly metabolized by both COMT
and MAO, resulting in poor oral
bioavailability and short DOA (1 or 2
minutes even when given intravenously). It
is a stimulant of a1-, a2-, and b1-
adrenoceptors (notice that lacking the N-

methyl group results in lacking b2- and
b3-activity). It is used to counteract
various hypotensive crises, because its b-
activity raises blood pressure and as an
adjunct treatment in cardiac arrest
because its b-activity stimulates the
heart. It has limited clinical application
caused by the nonselective nature of its
activities.
Epinephrine (E, Adrenalin)
Like the other CAs, E is light

sensitive and easily oxidized on
exposure to air because of the
catechol ring system. The development
of a pink-to-brown color indicates
oxidative breakdown. To minimize
oxidation, solutions of the drug are
stabilized by the addition of reducing
agents such as sodium bisulfite.

Epinephrine is also destroyed readily
in alkaline solutions and by metals
(e.g., Cu, Fe, Zn) and weak oxidizing
agents. It is used in aqueous solution
for inhalation as the free amine. Like
other amines, it forms salts with
acids, hydrochloride, and the
bitartrate being the most common
Dipivefrin (Propine, Dipivalyl
Epinephrine)
Most of the advantages of this prodrug

over E stem from improved
bioavailability. The greatly increased
lipophilicity allows much greater
penetrability into the eye through the
corneal epithelial and endothelial
layer. The stroma in between requires

hydrophilicity for penetration.
Dipivefrin has that, too, due to the
1-OH group and cationic nitrogen (the
eyedrops contain the hydrochloride
[HCl] salt). This dual solubility
permits much greater penetrability
into the eye than the very hydrophilic
E hydrochloride.
Words to Live By
"Wherever the art of Medicine is loved,

there is also a love of Humanity".
HIPPOCRATES

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University of Negros

Drug Affecting Adrenergic

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Adrenergic Drug Affecting Adrenergic

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Adrenergic Receptor Sympathomimetic Agents

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Clonidine (Catapres)* Hypertension

Hypertension & benign

Terazosin (Hytrin)* Hypertension & BPH

Tamsulosin (Flomax) BPH & hypertension

Labetalol (Normodyne)* Hypertension

Bisoprolol (Zebeta)* Hypertension

ß1-, & ß2-Blockers

Sotalol (Betapace)* Arrhythmias

Levobunolol (Betagan) Glaucoma

In a physiological context, the

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

The Catecholamines biosynthesis and

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Biosynthesis and storage in

BIOTIN BENEFITS | AMC

A large percentage of the

BIOTIN BENEFITS | AMC

Ca2+triggered secretion in-

BIOTIN BENEFITS | AMC

These drugs are poor agonists (some

BIOTIN BENEFITS | AMC

Once Norepinephrine has exerted its

a. Reuptake of Norepinephrine into

BIOTIN BENEFITS | AMC

The second mechanism of

BIOTIN BENEFITS | AMC

Deaminate Catecholamines O-methylate CAs to 3’-

Compounds with a terminal

Both Epinephrine and

BIOTIN BENEFITS | AMC

In 1948, Ahlquist proposed and designated α-

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Agonists acting selectively on

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

a1-antagonists would be expected to be

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

a2-Agonists (e.g., clonidine) act at CNS

Activation of the b1- receptors in heart

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

A major clinical use for adrenergic

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

Metyrosine differs structurally

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

a-methyl-m-tyrosine in the treatment

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

1. Reserpine (an NT Depleter)

Reserpine, a prototypical and

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

CENTRAL NERVOUS SYSTEM STIMULANTS | UNO-R

In sympathetic neurons, NE, which