Pharm. Chap. 17 Adrenergic Agonists

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Sympathomimetic

Because of similarity of sympathetic nervous system, adrenergic agonists referred as sympathomimetic.

Clinical Consequence of Alpha 1 Activation

Activation of alpha 1 receptors elicits two responses that be therapeutica Therapeutic Uses: 1) Vasoconstriction (in blood vessels of the skin, vicers an mucous membrane) 2) Mydriasis *vasoconstriction is used more often for activation of adrenergic receptor alpha 1. Hemostasis-alpha 1 stimulants are given to stop bleeding in skin and muscous. Can relieve congestion. increase BP and cause mydriasis (dilation of the pupil) Adverse Effects: caused by alpha 1 activation 1)Hypertension-alpha1 agonist cause widespread vasoconstriction 2)Necrosis-If IV line to adminsiter alpha 1 agonist becomes leaking, drug can cause tissue death 3) Bradycardia-Alpha 1 agonist can cause slowing reflex of the heart. Alpha 1 agonist vasoconstricts elevating the blood pressure, which triggers the baroreceptors causing the heart rate to decline leading to decrease cardiac ouput compromising tissue perfusion.

Clinical Consequence of Beta 1 Activation (Epineprhine, NE, Isoproterelol, dopamine)_

Activation of beta 1 receptors results from activated beta1 receptors in the heart. Therapeutic Application of Beta 1 activation: 1) Heart failure-Can improve cardiac performance by increasing force of contraction. 2)Shock-Condition is severe hypotension and greatly reduced tissue perfusion. Primary goal of tx is to maintain blood flow to vital organs, by increasing HR and force of contraction. Beta 1 increases cardiac output=improve tissue perfusion. Adverse Effect: Altered heart rate or rhythm-overstimulation of ardiac beta 1 receptors can produce tachycardia and dysrthymias. & Angina Pectoris

Mydriasis

Activation of the alpha receptors on the radial muscle of the iris causes mydriasis (dilation of the pupil)

Adrenergic Agonist

Adrenergic agonists produce their effects by activating adrenergic receptors. Stimulation of sympathetic nervous system are similar.

Clinical Consequence of Alpha 2 activation

Alpha 2 receptors in the periphery are located PRESYNAPTICALLY and their activation inhibits NE release. Several adrenergic agonists (Epinephrine and NE) are capable of causing alpha 2 activation. However ability to activate alpha 2 receptors in periphery has no significance. TEHRE ARE NO therapeutic applications related to activation of peripheral alpha 2 receptors and activation of these receptor cause no adverse effects in PERIPHERY. Alpha 1 receptors in the CNSare great clinical use. Activating CNS alpha 2 receptors can produce 1)REDUCTION of sympathetic outflow to the heart and blood vessels. 2)Relief of severe pain.

Clinical Consequences of Beta2 activation

Beta 2 activations limited to the lungs and uterus. Drugs used for beta 2 activation is epinieprhine, isoprotereol, albuterol. Therapeutic Uses: Asthma:Chronic condition by inflammation and bronchoconstriction. During sever attack airflow reduction can be life threatening. Drugs that can activate beta 2 receptors in the lung promote bronchodilation and helps to relieve or prevent asthma attacks. Selective for beta 2 receptors ex. Albuterol is best. Delay of preterm labor: Actiation of Beta2 receptors in the uterus relaxes the uterine smooth muscle. Adverse Effects: Hyperglycemia-Activation of beta 2 receptors can elevate bloog glucose and cause hyperglycemia ONLY in patient with diabetes. -Tremor

Anaphylaxis

Can be triggered by variety of substances, bee venom, wasp venom, latex rubber, certain foods (peanuts, shellfish) certain drugs like penicillin.

Receptor Specificity

Catecholamines: Epinephrine: Receptors activated A1, A2, B1, B2 NE: Receptors activated A1, A2, B1 Isoproterenol: Receptors activated B1, B2 Dopaine: Receptors activated are A1, B1 and dopamine Albuterol: Recpetors are B2

Catecholamines

Chemical class of adrenergic agonist. Due to the chemistry all catcholamines have three protperties in common: 1)CANNOT be used orally 2)Brief duration of action 3)Cannot cross blood brain barrier MAO & COMT located in liver and active enzymes that quickly destroy the catecholamines administered by any route.

Catecholamine Structure

Contain a catechol group (Benzene ring) and an amine group (ethylamine). Structural formulas for all major catecholamines (Epi, NE, isoproterenol, dopamine)

Direct Adrenergic Receptor Activation

Direct interaction with receptor is most common mechanism by which drugs activate peripheral adrenergic receptors. Through direct receptor binding mimicks the actions of natural transmitters (NE, Epi, and dopemine). Direct Mechanism- Receptor activation through direct binding Dopamine, epi, Isoproternol, ephedrine

Anaphylactic Shock

Manifestation of sever allergy. Reaction is characterized by HYPOTENSION (widespread vasodilation), BRONCHOCONSTRCITION and EDEMA of the glottis. Tx: EPINEPHRINE, inject IM. Activates three types of adrenergic receptors A1, B1, B2.Can reverse severe manisfestations. activated B1-increase cardiac output, by elevating BP activating A1-Vasoconstriction hand in hand with increasing BP. Activating B2-epi can counteract bronchoconstriction.

The EPIPEN

Ppl who are prone to severe allergic responses should carry an epipen auto injector at all times.

Indirect Adrenergic Receptor Activation

Promotion of NE release (amphetamines, epheprine) Inhibition of NE reuptake (Cocaine, tricyclic antidepressants) Inhibition of MAO (MAO inhbitors)

Dopamine

Receptor Specificity: Alpha 1 (high doses), Beta 1, & Dopamine Chemical Classification: Catecholamine Dose dependent receptor. LOW therapeutic doses acts on dopamine receptors. -Moderate therapeutic doses dopamine activates beta 1 receptors -High doses dopamine activates alpha 1 Therapeutic Uses: -Shock-major indication for dopamine is shock (effects heart and renal blood vessels). Dopamine can increase cardiac output & dilute renal blood vessels to improve renal perfusion. -Heart Failure-Dopamine can help alleviate symptoms by activating beta 1 receptors on the heart to increase myocardial contraction and cardiac output. -Acute renal failure-dilute renal blood vessels to improve renal perfusion. Adverse Effects- -Most common adverse effect is tachycardia, dysrhtymias, and anginal pain from activation of beta 1 receptors.

Albuterol

Receptor Specificity: Beta 2 Chemical Classification: NON-catecholamine Terapeutic Uses: Asthma: Albuterol can reduce airway resistance in asthma by causing beta 2 mediated bronchodilation.Albuterol is SELECTIVE beta2 receptor. Adverse Effects: Tremor is most common.If dosage is high can cause tachycardia by activating beta 1 receptors.

Epinephrine

Receptor Specificity: alpha 1, alpha 2, beta 1, beta 2 Chemical Classification: Catecholamine Prototype for Sympatomimeitc drugs Therapeutic Uses: Activates all 4 subtypes. A1-Vasoconstriciton (delay absorption of local anestheitics, control superficial bleeding, elevate BP) & cause mydriasis B1-overcome AV block and restore cardiac function B2-promotoes lung bronchodilation. Tx of choice for anaphylaxis shock Adverse Effects: Hypertensive crisis dysrhythmias angina necrosis hyperglycemia-only to diabetic pt.;s

Isoproterenol

Receptor specificity: Beta 1 & Beta 2 Chemical Classification: Catecholamine Acts ONLY on beta receptors. Beta-selective adrenergic agonist. Therapeutic Uses: -Cardivascular-activated beta 1 receptors in heart, overcome av heart block, restart heart following cardiac arrest, increase cardiac output. -Bronchospasms-Tx bronchospasms during anesthesia. Adverse Effect: Produces few adverse effects, but can cause tachycardia, angina and hyperglycemia in diabetic pt.'s


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