Adrenergic agonists

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

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

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

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

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

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

 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

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

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

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.

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

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.

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

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

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

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

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

norepinephrine Cardiovascular actions Vasoconstriction Baroreceptor reflex Effect of atropine pretreatment:

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.

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

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.

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