5. The adrenergic neuron
- In the CNS and sympathetic nervous
system
- Neurotransmission at adrenergic
neurons:
1. Synthesis of norepinephrine
2. Storage of norepinephrine in vesicles
3. Release of norepinephrine
4. binding by receptors
5. Removal of norepinephrine
5
6. Drugs can activate adrenergic receptors by:
- direct receptor binding
- promotion of NE release (Ephedrine,
amphetamines)
- inhibition of NE reuptake (cocaine, tricyclic
antidepressants)
- inhibition of NE inactivation
6
8. Chemical classification of adrenergic
agonists:
a. Catecholamines:
Cannot be used orally: have short half life and
cannot be used orally because of the action of
MAO and COMT. Located in the liver and
intestinal wall. So catecholamine that are
administered orally inactivated before reaching
the circulation
Have a brief duration of action
Cannot cross the BBB
Catecholamine-containing solutions should be
discarded as soon as discoloration appears
8
9. Chemical classification of
adrenergic agonists:
b. Noncatecholamines:
Longer half-lives longer than
catecholamine
Can be given orally: not a substrate for
COMT and metabolized slowly by MAO
Penetrate BBB
9
11. Clinical Consequences of Alpha1
activation:
vasoconstriction of blood vessels of the skin,
viscera, and mucous membranes
Mydriasis
Hemostasis (arrest of bleeding): alpha1
stimulants are given to stop bleeding in the
skin and mucous membranes. e.g. epinephrine
applied topically
Adjunct to local anesthesia (epinephrine): to
delay anesthetic absorption by causing
vasoconstriction reduces blood flow to the
site of anesthetic administration (benefits:
prolong anesthesia, allows a reduction in
anesthetic dose and reduce systemic effects)
Elevation of BP: not the primary therapy for
hypotension.
11
12. Adverse effects of Alpha1 activation
(all are a results of vasoconstriction)
Hypertension: sever hypertension is most likely
with systemic administration you must monitor
CV status, never leave the patient
Necrosis: if the IV line employed become
leaking drug may cause necrosis due to lack of
blood flow secondary to intense
vasoconstriction. Area should be infiltrated with
alpha1 blocking agent phentolamine to minimize
injury
Bradycardia: reflex slowing of the heart
12
13. Clinical Consequences of Beta1
activation:
heart
treatment of:
Cardiac arrest: epinephrine injected directly into the heart
Heart failure: positive inotropic effect (increases the force of
contraction)
Shock: characterized by profound hypotension and reduced tissue
perfusion. Primary goal of treatment is to maintain blood flow to
vital organ. By increasing heart rate and force of contraction beta1
stimulants can inc cardiac output and improve tissue perfusion
Atrioventricular heart block: a condition in which impulse
conduction from the atria to the ventricles is impeded or blocked
entirely. Beta1 receptors can enhance impulse conduction through
the AV node so help to overcome AV block. This is just for
temporary treatment. For long term treatment a pacemaker is
implanted
13
14. Adverse effects of Beta1
activation:
results from activating beta1 receptors in the heart
tachycardia and dysrhythmias
Angina pectoris
14
15. Clinical Consequences of Beta2
activation:
Asthma: promote bronchodilation.
Adrenergic agonists that are selective for
beta2 receptors (terbutaline)
By inhalation: to minimize systemic effect.
Warn patient against inhaling too much
Delay of preterm labor: beta2 receptor in the
uterus relaxes uterine smooth muscle
15
16. Adverse effects of Beta2 activation:
Hyperglycemia in patients with diabetes: by promoting
breakdown of glycogen in the liver and skeletal muscle
Tremor: most common side effect. Activation of beta2
receptors in muscle
16
17. Clinical Consequences of dopamine
receptor activation:
dilation of the vasculature of the kidneys
improve renal perfusion reduce risk of renal
failure in shock
dopamine
17
19. Epinephrine:
Therapeutic uses:
Mydriasis during ophthalmic procedures
Overcome AV heart block
Restore cardiac function
Bronchodilation in asthma
Saja Hamed, Ph.D
19
20. Epinephrine:
Therapeutic uses:
Treatment of choice for anaphylactic shock:
• manifestation of sever allergy
• hypotension, bronchoconstriction, and edema of
the glottis
• bee venom, certain drugs (e.g. penicillin)
• Epinephrine SC
Saja Hamed, Ph.D
20
22. Epinephrine:
Adverse effects:
Hypertensive crisis: parenteral epinephrine
continuous cardiovascular monitoring
Dysrhythmias: high risk in hyperthyroid patients
Angina pectoris: especially in patients with
coronary atherosclerosis
Necrosis
Hyperglycemia: in diabetic patients
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23. Epinephrine:
Drug interactions:
MAO inhibitors: used to treat depression. Prolong and
intensify epinephrine’s effects.
Tricyclic antidepressants: block uptake
General anesthetics
Alpha adrenergic blocking agents: phentolamine treat
toxicity caused by excessive epinephrine- induced alpha
activation
Beta adrenergic blocking agents: propranolol can reduce
adverse effects caused by epinephrine
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24. Isoproterenol:
beta1 and beta2
catecholamine
beta selective
Therapeutic uses:
help overcome AV heart block
restart the heart following cardiac arrest
increase cardiac output during shock
treatment of bronchospasm during anesthesia
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25. Isoproterenol:
Adverse effects:
fewer than NE and epinephrine
dysrhythmias and angina pectoris
hyperglycemia in diabetic patients
Drug Interactions (identical to epinephrine)
25
26. Dopamine:
dopamine, beta1, and at high doses alpha1
low doses dopamine receptors only
moderate doses dopamine and beta1 receptors
high doses dopamine, beta1, and alpha1 receptors
catecholamine
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28. Dopamine:
Adverse effects:
tachycardia, dysrhythmias, and anginal pain
high concentrations activate alpha1
extravasationnecrosis
Drug interactions:
MAO inhibitors: the dosage of dopamine must be
reduced by at least 90%
Administration:
Continuous IV infusion: bec of rapid inactivation
by MAO and COMT. Monitor CV status and
extravasations. If extravasations occur stop
infusion and infilter area with phentolamine
28
30. Terbutaline:
beta2
Noncatecholamine
Therapeutic uses:
Asthma: patients should not exceed the
recommended dose undesired cardiac
stimulation
Delay of preterm labor: beta2 receptors in the
uterus
Adverse effects:
tremor
tachycardia in excessive dosage
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31. Ephedrine:
alpha1, alpha2, beta1, beta2
noncatecholamine
mixed-acting drug
Therapeutic uses:
Nasal congestion: alpha1 mediated
vasoconstriction. Topically is preferred over
orally.
Narcolepsy: sudden and irresistible attacks of
sleep. Benefits from activation of adrenergic
receptors in the brain
Adverse effects:
Same as epinephrine
In addition to insomnia
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