BY: PROFESSOR EMILIANO Z. SISON JR.

 The adrenergic drugs affect receptors that are stimulated by

norepinephrine or epinephrine.
 Some adrenergic drugs act directly on the adrenergic
receptor (adrenoceptor) by activating it and are said to be
sympathomimetic.
 Others will block the action of the neurotransmitters at the
receptors (sympatholytics), whereas still other drugs affect
adrenergic function by interrupting the release of
norepinephrine from adrenergic neurons.
 DRUGS UNDER ADRENERGIC AGONISTS
DIRECT-ACTING INDIRECT-ACTING DIRECT & INDIRECT ACTING
(mixed action)
 Albuterol  Amphetamine  Ephedrine
 Clonidine  Cocaine  Pseudophrine
 Dobutamine  Tyramine

 Dopamine
 Epinephrine
 Isoproterenol
 Metaproterenol
 Methoxamine
 Norepinephrine
 Phenylphrine
 Piruterol
 Salmeterol
 Terbutaline
 CARDIAC HEADACHE HYPERACTIVITY INSOMIA NAUSEA TREMORS
ARRHYTHMIAS
Adrenergic neurons release norepinephrine as the primary
neurotransmitter.
These neurons are found in the central nervous system (CNS) and also in
the sympathetic nervous system, where they serve as links between
ganglia and the effector organs.
The adrenergic neurons and receptors, located either presynaptically on
the neuron or postsynaptically on the effector organ, are the sites of
action of the adrenergic drugs.
1. SYNTHESIS OF NOREPINEPHRINE
 Hydroxylation of tyrosine is the rate-limiting step

2. UPTAKE INTO STORAGE VESICLES

 Dopamine enters vesicle & is converted to norepinephrine
 Norepinephrine is protected from degradation in vesicle
 Transport into vesicle is inhibited by reserpine
3. RELEASE OF NEUROTRANSMITTER
 Influx of calcium causes fusion of vesicle w/ cell membrane
 Release blocked by guanethidine & bretylium

4. BINDING TO RECEPTOR
 Postsynaptic receptor activated by binding of
neurotransmitter

5. REMOVAL OF NOREPINEPHRINE
 Released norepinephrine is rapidly taken into neuron
 Uptake is inhibited by cocaine & imipramine

6. METABOLISM
 Norepinephrine is methylated by COMT & oxidized by
monoamine oxidase
 ADRENOCEPTORS

α- β-
RECEPTORS RECEPTORS

α1-receptor α2-receptor β1-receptor β2-receptor β3-receptor

 The α-adrenoceptors show a weak response to the
synthetic agonist isoproterenol, but they are
responsive to the naturally occurring catecholamines
epinephrine and norepinephrine.
 For α receptors, the rank order of potency is
epinephrine ≥ norepinephrine >> isoproterenol.
 The α-adrenoceptors are subdivided into two
subgroups, α1 and α2, based on their affinities for α
agonists and blocking drugs.
 For example, the α1 receptors have a higher affinity for
phenylephrine than do the α2 receptors.
 β Receptors exhibit a set of responses different from those
of the α receptors.
 These are characterized by a strong response to
isoproterenol, with less sensitivity to epinephrine and
norepinephrine.
 For β receptors, the rank order of potency is
isoproterenol > epinephrine > norepinephrine.
 The β-adrenoceptors can be subdivided into three major
subgroups, β1, β2, and β3, based on their affinities for
adrenergic agonists and antagonists, although several others
have been identified by gene cloning.
 β1 Receptors have approximately equal affinities for
epinephrine and norepinephrine, whereas β2 receptors have a
higher affinity for epinephrine than for norepinephrine.
Most of the adrenergic drugs are derivatives of β-phenylethylamine.

Two important structural features of these drugs are:

1. the number and location of OH substitutions on the benzene ring &
2. the nature of the substituent on the amino nitrogen.
 Sympathomimetic amines that contain the 3,4-dihydroxybenzene group:
(such as epinephrine, norepinephrine, isoproterenol, and dopamine)
are called catecholamines.

 These compounds share the following properties:

2. Rapid inactivation
3. Poor penetration into
1. High potency
the CNS
 Compounds lacking the catechol hydroxyl groups
have longer half-lives, because they are not
inactivated by COMT.

 These include:
 phenylephrine,
 ephedrine, and
 amphetamine.
 Epinephrine is synthesized from tyrosine in the adrenal
medulla and released, along with small quantities of
norepinephrine, into the bloodstream.
 Epinephrine interacts with both α and β receptors.
 At low doses, β effects (vasodilation) on the vascular system
predominate, whereas at high doses, α effects
(vasoconstriction) are strongest.
CARDIOVASCULAR RESPIRATORY HYPERGLYCEMIA LIPOLYSIS

Epinephrine Epinephrine causes Epinephrine has a Epinephrine initiates

strengthens the powerful significant lipolysis through its
contractility of the bronchodilation by hyperglycemic effect agonist activity on the β
myocardium (positive acting directly on because of increased receptors of adipose
inotropic: β1 action) and bronchial smooth glycogenolysis in the tissue, which upon
increases its rate of muscle (β2 action). liver (β2 effect), stimulation activate
contraction (positive increased release of adenylyl cyclase to
chronotropic: β1 action). glucagon (β2 effect), increase cAMP levels.
and a decreased release
of insulin (α2 effect).
BRONCHOSPASM GLAUCOMA ANAPHYLACTIC CARDIAC ARREST ANESTHETICS
SHOCK
Epinephrine is the In Epinephrine is the Epinephrine may The effect of the
primary drug used ophthalmology, a drug of choice for be used to restore drug is to greatly
in the emergency two-percent the treatment of cardiac rhythm in increase the
treatment of any epinephrine Type I patients with duration of the
condition of the solution may be hypersensitivity cardiac arrest local anesthesia.
respiratory tract used topically to reactions in regardless of the
when reduce response to cause.
bronchoconstriction intraocular allergens.
has resulted in pressure in open-
diminished angle glaucoma.
respiratory
exchange.
CNS DISTURBANCE HEMORRHAGE CARDIAC PULMONARY
ARRYTHMIAS EDEMA

Includes: anxiety, fear, tension,

headache, and tremor.
HYPERTHYROIDISM COCAINE DIABETES β-BLOCKERS INHALATION
ANESTHETICS
 Because norepinephrine is the neuromediator of adrenergic
nerves, it should theoretically stimulate all types of
adrenergic receptors.
 In practice, when the drug is given in therapeutic doses to
humans, the α-adrenergic receptor is most affected.
VASOCONSTRICTION BARORECEPTOR REFLEX EFFECTS OF ATROPINE
PRE-TREATMENT
Norepinephrine causes a rise in In isolated cardiac tissue, If atropine, which blocks the
peripheral resistance due to norepinephrine stimulates transmission of vagal effects, is
intense vasoconstriction of most cardiac contractility; however, in given before norepinephrine,
vascular beds, including the vivo, little if any cardiac then norepinephrine stimulation
kidney (α1 effect). stimulation is noted. of the heart is evident as
tachycardia.
 Isoproterenol is a direct-acting synthetic catecholamine that
predominantly stimulates both β1- and β2-adrenergic
receptors.
 Its nonselectivity is one of its drawbacks and the reason why
it is rarely used therapeutically.
 Its action on α receptors is insignificant.
CARDIOVASCULAR PULMONARY OTHER EFFECTS
Isoproterenol produces Isoproterenol is as active as Other actions on β
intense stimulation of the epinephrine and rapidly receptors, such as increased
heart to increase its rate and alleviates an acute attack of blood sugar and increased
force of contraction, causing asthma when taken by lipolysis, can be
increased cardiac output. inhalation (which is the demonstrated but are not
recommended route). clinically significant.
 Dopamine, the immediate metabolic
precursor of norepinephrine, occurs naturally
in the CNS in the basal ganglia, where it
functions as a neurotransmitter, as well as in
the adrenal medulla.
 Dopamine can activate α- and β-adrenergic
receptors.
CARDIOVASCULAR RENAL & VISCERAL
Dopamine exerts a stimulatory effect on the Dopamine dilates renal and splanchnic
β1 receptors of the heart, having both arterioles by activating dopaminergic
inotropic and chronotropic effects. receptors, thus increasing blood flow to the
kidneys and other viscera.
Therefore, dopamine is clinically useful in
the treatment of shock, in which significant
increases in sympathetic activity might
compromise renal function.
 Dobutamine is a synthetic, direct-acting catecholamine that
is a β1-receptor agonist.
 One of the stereoisomers has a stimulatory activity.
 It increases cardiac rate and output with few vascular effects.
 Dobutamine is used to increase cardiac output in congestive
heart failure as well as for inotropic support after cardiac
surgery.
 Oxymetazoline is a direct-acting synthetic adrenergic
agonist that stimulates both α1- and α2-adrenergic receptors.
 It is primarily used locally in the eye or the nose as a
vasoconstrictor.
 Oxymetazoline is found in many over-the-counter short-
term nasal spray decongestant products as well as in
ophthalmic drops for the relief of redness of the eyes
associated with swimming, colds, or contact lens.
 Phenylephrine is a direct-acting, synthetic adrenergic drug
that binds primarily to α receptors and favors α1 receptors
over α2 receptors.
 It is not a catechol derivative and, therefore, not a substrate
for COMT.
 Phenylephrine is a vasoconstrictor that raises both systolic
and diastolic blood pressures.
 Methoxamine is a direct-acting, synthetic adrenergic drug
that binds primarily to α-receptors, with α1 receptors favored
over α2 receptors.
 Methoxamine raises blood pressure by stimulating α1
receptors in the arterioles, causing vasoconstriction.
 This causes an increase in total peripheral resistance.
 Clonidine is an α2 agonist that is used in essential
hypertension to lower blood pressure because of its action in
the CNS.
 It can be used to minimize the symptoms that accompany
withdrawal from opiates or benzodiazepines.
 Clonidine acts centrally to produce inhibition of sympathetic
vasomotor centers, decreasing sympathetic outflow to the
periphery.
 Metaproterenol, although chemically similar to
isoproterenol, is not a catecholamine, and it is resistant to
methylation by COMT.
 Metaproterenol produces dilation of the bronchioles and
improves airway function.
 The drug is useful as a bronchodilator in the treatment of
asthma and to reverse bronchospasm.
 Albuterol, pirbuterol, and terbutaline are short-
acting β2 agonists used primarily as
bronchodilators and administered by a metered-
dose inhaler.
 Salmeterol and formoterol are β2-adrenergic selective,
long-acting bronchodilators.
 Salmeterol and formoterol are the agents of choice for
treating nocturnal asthma in symptomatic patients taking
other asthma medications.
 The marked central stimulatory action of amphetamine is
often mistaken by drug abusers as its only action.
 The CNS stimulant effects of amphetamine and its
derivatives have led to their use for treating hyperactivity in
children, narcolepsy, and appetite control.
 Its use in pregnancy should be avoided because of adverse
effects on development of the fetus.
 Tyramine is not a clinically useful drug, but it is important
because it is found in fermented foods, such as ripe cheese
and Chianti wine.
 It is a normal by-product of tyrosine metabolism.
 Normally, it is oxidized by MAO in the gastrointestinal tract,
but if the patient is taking MAO inhibitors, it can precipitate
serious vasopressor episodes.
 Cocaine is unique among local anesthetics in having the
ability to block the Na+/K+-activated ATPase (required for
cellular uptake of norepinephrine) on the cell membrane of
the adrenergic neuron.
 Like amphetamines, it can increase blood pressure by α-
agonist actions and β-stimulatory effects.
 Ephedrine, and pseudoephedrine are plant alkaloids, that
are now made synthetically.
 These drugs are mixed-action adrenergic agents.
 They not only release stored norepinephrine from nerve
endings but also directly stimulate both α and β receptors.
 Thus, a wide variety of adrenergic actions ensue that are
similar to those of epinephrine, although less potent.
 Ephedrine enhances contractility and improves motor
function in myasthenia gravis.
 Ephedrine has been used to treat asthma, as a nasal
decongestant (due to its local vasoconstrictor action), and to
raise blood pressure.
 Pseudoephedrine is primarily used to treat nasal and sinus
congestion or congestion of the eustachian tubes.
SEE YOU ALL NEXT MEETING!!!

ADRENERGIC
ANTAGONISTS