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Adrenergic neurons release norepinephrine (NE) as the primary neurotransmitter. Found in
CNS ans in sympathetic nervous system .
Norepinephrine also relased from adrenal medulla
Most of the postganglionic sympathetic neurons are adrenergic
However; the postganglionic sympathetic nerve fibers to the sweat glands, piloerector
muscles of the hair and to a very few blood vessels are cholinergic.
Substance activate adrenoreceptor called sympthatomimtic and the one block it
called sympatholytic
Neurotransmission at adrenergic neurons:
synthesis, storage, release, receptor binding of norepinephrine, removal of the
neurotransmitter from the synaptic gap
-hydroxylation of tyrosine is the rate limiting step , in the synthesis of norepinephrine.
-norepinephrine is hydrolysed by monoamine oxidase (MAO) and Catechol-O-methyl
transferase
Tow type of adrenoreceptor are α (alpha) and β (beta),
α (alpha)  weak response to synthetic agonist but well response to natural agonist
subdivided into alpha 1 and alpha 2
β (beta) : subdivided to
1β
Equal affinity to epi =
norepi
2β
Affinity for epi > norepi
3β
lipolysis
Mechanisms of adrenergic receptor activation:
1. Direct receptor binding  Direct interaction with receptors.
2. Promotion of norepinephrine release  acting on terminals of sympathetic nerves to
cause release of NE
3. Blockade of norepinephrine reuptake  blocking NE reuptake cause NE to accumulate
within the synaptic gap, and thereby increase receptor activation.
4. Inhibition of norepinephrine inactivation  Some of the NE inside the terminals of
adrenergic neurons is subject to inactivation by monoamine oxidase (MAO).
Hence, drugs that inhibit MAO will increase the amount of NE available for release
Classification of adrenergic drugs:
1.Direct acting:
1-non-selctive  act on
more than one receptors
subtype
2-selctive  act on one
certain receptor subtype
2.Indirect-acting drugs:
3.mixed-acting
sympathomimetic
(1) by releasing or displacing NE from
indirectly release
sympathetic nerve varicosities (vesicles ) and also directly
(2) by blocking the transport of NE into
activate receptors
sympathetic neurons (prevent reuptake)
(3) by blocking the metabolizing
enzymes, MAO or catechol-Omethyltransferase
Catecholamines versus Noncatecholamines:
Catecholamine as NE, epinephrine,
dopamine, dobutamine, isoproterenol.
1. They cannot be taken orally.
2. They have a brief duration of
action.
3.They cannot cross the blood brain
barrier
Noncatecholamines as ephedrine,
phenylphrine, terbutaline
1- can be given orally .
2- longer duration of action
3- ,ore able to penetrate BBB
Characteristic responses mediated by each adrenoceptors:
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All this effect is the same that mediated by Epinephrine since it activate all this receptors
On GIT decrease muscle activity and relaxation
The B2 receptors of the bladder wall mediate relaxation of the wall
Insulin secretion is stimulated by B receptors and inhibited by a2 receptors.
Renin secretion is stimulated by B1 and inhibited by a2 receptors
Desensitization of receptors:
Prolonged exposure to the catecholamine and other sympathomimetic drugs reduces the
responsiveness of these receptors
Mechanisms:
1. sequestration of the receptors
2. down-regulation of the receptors
3. inability to couple to G protein
Catecholamine act on B recptorc  activate enzyme adenylcyclase inside the cell 
increase the level of CAMP  this second massnger make other reaction responsible for the
response .
Note alpha2  decrase cAMP and alpha 1  increase cAMP
Epinephrine (adrenaline)
Norepinephrine
(Noradrenaline)
Isoproterenol
alpha1, alpha2, beta1, beta2.
And Considered the
prototype of the
sympathomimetic drugs.
The drug cannot be given
orally and Epinephrine has a
short half life because of 2
processes: enzymatic
inactivation (MAO and
COMT), and uptake into
adrenergic nerves.
alpha1, alpha2, beta1.
NE does not promote
hyperglycemia, a response
that is mediated by beta2
receptors.
NE has limited clinical
applications. The only
recognized indications are
hypotensive states and
cardiac arrest.
beta1, beta2
The drug has positive
chronotropic and inotropic
actions
Mediated by B1
-Beta2 selective agonists are
preferred more than
Isoproterenol
In treatment of asthma
Therapeutic uses :
1.Cardiovascular: By
activating beta1 receptors on
the heart, isopreterenol can
be used in
1.Can help overcome AV
heart block.
2. In cardiac arrest.
3.Can increase cardiac
output during shock.
2.Asthma: By activitating
beta2 receptors in the lung,
isoproterenol can cause
bronchodilation
Dopamine
in low doses, acts on
dopamine receptors only.
At moderate doses activates
beta1 receptors in addition
to dopamine receptors
At very high doses,
dopamine activates alpha1
receptors along with beta1
and dopamine receptors
Dobutamine
beta1
1.Shock: by activating beta1
receptors in the heart,
dopamine can increase
cardiac output
By activating dopamine
receptors in the kidney,
dopamine can dilate renal
blood vessels, thereby
improving renal perfusion,
which in turn reduces the
risk of renal failure.
2. Heart failure. Dopamine
can help alleviate symptoms
by activating beta1 receptors
on the heart
The only indication for the
drug is heart failure.
Phenylephrine
alpha 1
it is not a catechol derivative,
it is not inactivated by COMT
and has a much longer
duration of action than the
catecholamines.
Therapeutic uses:
1- Locally as nasal drops to
reduce nasal
congestion.
2- Parenterally to elevate
blood pressure.
3- As eye drops to dilate the
pupil (Mydriatic).
Terbutaline
beta2
noncatecholamine
Terbutaline is preferred to
isoproterenol and related
drugs for therapy of asthma,
because it is selective for B2
only without activation of B1
1.Asthma: stimulation of
beta2 receptors in the
bronchi, causing
bronchodilation.
2. Delay of preterm labor:
By activating beta2 receptors
in the uterus, terbutaline can
relax uterine smooth muscle
Factor that determine suitable drug to be used :
1.Whether activation of alpha or beta is required
2.preffered route of administration
3.duration of action desired
Therapeutic uses of alpha 1 activation:
Adverse effects of alpha 1 activation:
1.Hemostasis  cause vasoconstriction and
arrest bleeding
1- Hypertension due to side spread
vasoconstriction
2.Nasal decongestion  cause vasoconstriction
of dilated and engorged blood vessels of nasal
mucosa  this lead to stop congestion
2- Necrosis  lack of blood flow secondary
to excessive vasoconstriction
3.Adjunct to local anesthesia :
Alpha 1 agonist combined with anesthetic
agent ( lidocaine ) to
a- to prolong anesthetic action
b- reduction in anesthetic dose
c- reduce systemic effect ( toxicity ) of
anesthetic agent
d-delay anesthetic absorption
epinephrine is the most commonly used .
3- Bradycardia  vasoconstriction elevate
blood pressure  barorecptors reflex cause
decrease in heart rate
4.Elevation of blood pressure  cause
vasoconstriction and elevate blood pressure
and used in hypotensive state but not
primary therapy
5.Mydriasis
Therapeutic uses of alpha 2 activation:
Centrally acting alpha 2 agonists: Includes clonidine and methyldopa.
They reduce sympathetic outflow centrally to heart and blood vessel
Their activation inhibits NE release.
These drugs are used as antihypertensive drugs.
Therapeutic uses of Beta 1 activation:
1.Cardiac arrest  activate cardiac B1
receptor initiate beat in heart that stopped
baeting
Adverse effects of beta 1 activation:
Over stimulation of B1  tachycardia and
dysrhythmia
2.Heart failure  activate cardiac B1 has
positive intropic effect  increase force of
cardiac contraction
2. Angina pectoris  increased work of
heart  increase oxygen demand  in
patient with compromised coronary blood
flow in risk of angina
3.Shock  increase heart rate and
contraction  increase cardiac output and
improve tissue perfusion
4.Atrioventricular heart block  B1
activation enhance impulse conduction
through AV node
Therapeutic uses of beta 2 activation:
1.Asthma  activation of B2 receptor in
lung lead to bronchiodilation
Adverse effects of beta 2 activation:
1.Hyperglycemia  activation of B2 lead to
increase liver and muscle glycogenolysis
2.Delay of preterm labor  activation of B2
receptor in uterus relax uterine smooth
muscles
2. Tremor  activation of B2 in skeletal
muscle enhance contraction .
Therapeutic uses of alpha blockade
1. Essential hypertension
Adverse effects of alpha adrenergic blocking
agents:
1. Orthostatic hypotension
2. Reversal of toxicity from alpha 1 agonists
2. Reflex tachycardia
3. Benign prostatic hyperplasia
3. Nasal congestion
4. Pheochromocytoma.
4. Inhibition of ejaculation
5. Raynaud's disease
Therapeutic uses of Beta
blockade:
1.Angina pectoris
Adverse effects of beta
blockade:
1.Bronchoconstriction.
Contraindications
1. Asthma.
2.Hypertension
2.Heart block.
2. Chronic obstructive
pulmonary disease.
3.Cardiac dysrhythmias
3.Decrease peripheral blood
flow causing cold
extremities.
3. Peripheral vascular
diseases
(vasospasm).
4.Myocardial infarction
4.Decrease blood flow to the
liver and kidneys
4. Combination with Ca
channel blockers,
particularly verapamil.
5.Hyperthyroidism
5.Increase lipids
Concentration.
5. IDDM patients.
6. Migraine
6.Mask hypoglycemic
symptoms.
6. Heart failure and
bradycardia.
7.Pheochromocytoma
7.CNS.
7. Psychiatric disorders.
8. Glaucoma
8.Allergy: skin rash, fever.
9.Impotence (sexual
dysfunction).