Adrianagic egonist receptor explanation

1. Adrenergic agonists
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2. adrenergic drugs affect receptors that are
stimulated by nor-epinephrine or
epinephrine
Sympathomimetics
Adrenergic Receptors:
- α receptors: α1 & α2 receptors
- β receptors: β1 & β2 & β3 receptors
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3. vasculature to skeletal muscle: both α1 &
β2 but β2 predominates
the heart: β1 receptors
α2 receptors: presynaptic nerve ending
and β cell of the pancreas
In general:
- α1: vasoconstriction (skin and abdominal
viscera), increase in blood pressure
- β1: cardiac stimulation
- β2: vasodilation (in skeletal vascular beds)
and bronchiolar relaxation
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4. Saja Hamed, Ph.D 4

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
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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
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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
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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
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Receptor specificity:

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.
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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
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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
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14. Adverse effects of Beta1
activation:
results from activating beta1 receptors in the heart
tachycardia and dysrhythmias
Angina pectoris
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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
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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
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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
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18. Epinephrine:
 alpha1, alpha2, beta1, beta2
 Catecholamine
Therapeutic uses:
 Alpha1-mediated vasoconstriction:
• delay absorption of local anesthetics
• control superficial bleeding
• reduce nasal congestion
• elevate blood pressure
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19. Epinephrine:
Therapeutic uses:
 Mydriasis during ophthalmic procedures
 Overcome AV heart block
 Restore cardiac function
 Bronchodilation in asthma
Saja Hamed, Ph.D
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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
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21. Epinephrine:
Pharmacokinetics:
 topically, by injection, by inhalation
 No oral??
Saja Hamed, Ph.D
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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)
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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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27. Dopamine:
Therapeutic uses:
shock:
beta 1 in heart  increase cardiac output 
improve tissue perfusion
dopamine receptors in kidney  dilate renal
blood vessels  improve renal perfusion
(monitor output of urine to evaluate success)
heart failure: increase cardiac output
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28. Dopamine:
Adverse effects:
 tachycardia, dysrhythmias, and anginal pain
 high concentrations  activate alpha1
extravasationnecrosis
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
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29. Phenylephrine:
alpha1
noncatecholamine
locally to reduce nasal congestion
parenterally to elevate BP
eye drops to dilate the pupil
co-administered with local anesthetics to
retard absorption of anesthetic
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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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