1. Adrenergic agonists
Saja Hamed, Ph.D

2. Adrenergic Receptors: - α receptors: α1 & α2 receptors
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
Saja Hamed, Ph.D

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
Saja Hamed, Ph.D

4. Saja Hamed, Ph.D

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
Saja Hamed, Ph.D

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
Saja Hamed, Ph.D

7. Saja Hamed, Ph.D

8. Saja Hamed, Ph.D

9. 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
Saja Hamed, Ph.D

10. 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
Saja Hamed, Ph.D

11. Saja Hamed, Ph.D

12. Receptor specificity:
Saja Hamed, Ph.D

13. 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.
Saja Hamed, Ph.D

14. 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
Saja Hamed, Ph.D

15. 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
Saja Hamed, Ph.D

16. Adverse effects of Beta1 activation:
results from activating beta1 receptors in the heart
tachycardia and dysrhythmias
Angina pectoris
Saja Hamed, Ph.D

17. 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
Saja Hamed, Ph.D

18. 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
Saja Hamed, Ph.D

19. Clinical Consequences of dopamine receptor activation:
dilation of the vasculature of the kidneys  improve renal perfusion  reduce risk of renal failure in shock
dopamine
Saja Hamed, Ph.D

20. 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
Saja Hamed, Ph.D

21. Epinephrine: Therapeutic uses: Mydriasis during ophthalmic procedures
Overcome AV heart block
Restore cardiac function
Bronchodilation in asthma
Saja Hamed, Ph.D

22. 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

23. Epinephrine: Pharmacokinetics: topically, by injection, by inhalation
No oral??
Saja Hamed, Ph.D

24. 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
Saja Hamed, Ph.D

25. 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
Saja Hamed, Ph.D

26. 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
Saja Hamed, Ph.D

27. Isoproterenol: Adverse effects: fewer than NE and epinephrine
dysrhythmias and angina pectoris
hyperglycemia in diabetic patients
Drug Interactions (identical to epinephrine)
Saja Hamed, Ph.D

28. 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
Saja Hamed, Ph.D

29. 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
Saja Hamed, Ph.D

30. 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
Saja Hamed, Ph.D

31. 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
Saja Hamed, Ph.D

32. 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
Saja Hamed, Ph.D

33. 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
Saja Hamed, Ph.D