1. Adrenergic agonists

2. overview
The adrenergic drugs affect receptor that are stimulated by norepinephrine or epinephrine

3. The adrenergic neuron
Adrenergic neurons release norepinephrine as the neurotransmitter.
CNS, and between ganglia and the effector organs in sympathetic nervous system.

5. Neurotransmission at adrenergic neurons
Synthesis of norepiephrine
Storage of norepiephrine in vesicles
Release of norepiephrine
Binding by receptor
Removal of norepiephrine
Potential fates of recaptured norepiephrine

7. Adrenergic receptor
, were initially identified on the basis of their responses the adrenergic agonists, epinephrine, norepinephrine, isoproterenol
1 receptors have a higher affinity for phenylephrine. The drug clonidine selectively binds to 2 receptors

9. 1 receptors
these receptors are present on the postsynaptic membrane of the effector organs. G-protein coupling

10. 2receptors
Located primarily on the presynaptic nerve endings and on other cells.
The stimulation of the 2receptors causes feedback inhibition of the ongoing release of norepinephrine from the stimulated adrenergic neuron

11.  receptor Characterized by a strong response to isoproterenol.
1 receptor and 2 receptor
Results in activation of adenylyl cyclase and therefore increased concentration of cAMP within the cell

12. Distribution of receptors
Vasculature to skeletal muscle have both 1 and 2 receptors, but the 2 receptors predominate. The heart contains predominantly 1 receptors

13. Desensitization of receptors
Prolonged exposure to the catecholamines reduces the responsivity of these receptors.

15. Characteristics of adrenergic agonists
Derivatives of -phenylethylamine
Catecholamines: sympathomimetic amines that contain the 3,4-dihydroxybenzene group
Non- catecholamines: lacking the catechol
hydroxyl groups have longer half-lives.

16. Mechanism of action of adrenergic agonists
Direct-acting agonists
indirect-acting agonists
Mixed-action agonists

17. Direct-acting adrenergic agonists
Epinephrine is synthesized from tyrosine in the adrenal medulla and released.
Interacts with both  and  receptors. At low doses,  effects(vasodilation) on the vascular system predominate, whereas at high doses,  effects(vasoconstriction) are strongest.

19. actions
Cardiovascular: strengthen the contractility of the myocardium(1 effect)
Respiratory: causes powerful bronchodilation(2 effect)
Hyperglycemia:
lipolysis

20. Therapeutic uses
Bronchospasm: emergency treatment of any condition of the respiratory tract where the presence of bronchoconstriction has resulted in diminished respiratory exchange.
Acute asthma
Anaphylactic shock

21. Therapeutic uses
Glaucoma: epinephrine solution reduce intraocular pressure in open-angle glaucoma.
Anaphylactic shock: for the treatment of Type I hypersensitivity reaction in response to allergens
In anesthetics: increase the duration of the local anesthesia

22. Pharmacokinetics Intravenously for the most rapid onset of action
Subcutaneously, by endotracheal tube, by inhalation, or topically to the eye
Oral administration is ineffective

23. Adverse effects
CNS disturbance: anxiety, fear, tension, headache, and tremor
Hemorrhage: induce cerebral hemorrhage
Cardiac arrhythmias:

24. norepinephrine Cardiovascular actions Vasoconstriction
Baroreceptor reflex
Effect of atropine pretreatment:

25. Therapeutic uses
Is uses to treat shock because it increases vascular resistance
Other actions of norepinephrine are not considered clinically significant. It is never used for asthma.

26. Isoproterenol
Isoproterenol is a direct-acting synthetic catecholamine.
Stimulates both beta1 and beta2 adrenergic receptors.

27. actions
Cardiovascular: increase heart rate and force of contraction, cause increased cardiac output.
Beta2 on arterioles of skeletal muscle result in a decreased peripheral resistance
May increase systolic blood pressure slightly

28. pulmonary A profound and rapid bronchodilation is produced by the drug
Other effects: other actions on beta receptor, such as increases in blood sugar and increased lipolysis

29. Therapeutic uses Stimulate heart in emergency situations
Rarely used as bronchodilator in asthma

30. dopamine Dopamine, the immediate metabolic precursor of norepinephrine
Can activate alpha and beta adrenergic receptors

31. Actions
Cardiovascular: stimulatory effect on the beta1 receptors of the heart, having both inotropic and chronotropic effects. At high doses, vasoconstriction
Renal and visceral: dopamine dilates renal arterioles by activating dopaminergic receptors, thus increases blood flow to the kidneys and other viscera

32. Therapeutic uses
Shock: dopamine is the drug of choice for shock. It raises the blood pressure by stimulating the heart(beta1 action). Dopamine is far superior to norepinephrine.

33. Adrenergic antagonists
Overview: bind to adrenoceptors but do not trigger the usual receptor-mediated intracellular effects

34. Alpha adrenergic blocking agents
Reduces the sympathetic tone of the blood vessels, resulting in decreased peripheral vascular resistance.

35. Phenoxybenzamine
Non-selective, alpha1 postsynaptic and alpha2 presynaptic receptors
Last about 24h after a single administration

36. Actions
Cardiovascular effects: the decreased peripheral resistance provokes a reflex tachycardia
Epinephrine reversal: reverse the alpha agonist actions of epinephrine

37. Therapeutic uses
Is used in the treatment of pheochromocytoma, a catecholamine-secreting tumor of cells derived from the adrenal medulla.

38. Adverse effects
Can cause postural hypotension, nasal stuffiness, and nausea and vomiting.

39. Prazosin, terazosin and doxazosin
Cardiovascular effects: prazosin and terazosin decrease peripheral resistance and lower arterial blood pressure

40. Therapeutic uses The “first dose” effects
as an alternative to surgery in patients with symptomatic benign prostatic hypertrophy. Decreases tone in the smooth muscle of the bladder neck and prostate and improve urine flow.

41. Adverse effects
Prazosin and terazosin may cause dizziness, a lack of energy, nasal congestion, headache, and orthostatic hypotension