Adrenergic Antagonists

Adrenergic Antagonists Cause direct blockade of adrenergic receptors With one exception, all produce reversible (competitive) blockade Most adrenergic antagonists are more selective than the adrenergic agonists Two major groups Alpha-adrenergic blocking agents Beta-adrenergic blocking agents 2

Adrenergic Antagonists Alpha-adrenergic antagonists I – therapeutic and adverse response to alpha blockade Alpha-adrenergic antagonists II – properties of individual alpha blockers Beta-adrenergic antagonists I – therapeutic and adverse responses to beta blockade Beta-adrenergic antagonists II – properties of individual beta blockers 3

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Therapeutic Applications of Alpha Blockade Essential hypertension Lower blood pressure by blocking alpha1 receptors on arterioles and veins, causing vasodilation Reversal of toxicity from alpha1 agonists Benign prostatic hyperplasia Reduced contraction of smooth muscle in the bladder neck and prostatic capsule 6

Therapeutic Applications of Alpha Blockade Pheochromocytoma Catecholamine-secreting tumor Usually located in adrenal medulla Principal cause of hypertension is usually activation of alpha1 receptors, but beta1 receptors can also contribute Treatment – best option is surgery - Inoperable tumor – alpha1 antagonists suppress hypertension - Surgery – before surgery, manipulation of tumor can cause massive catecholamine release 7

Therapeutic Applications of Alpha Blockade Raynaud’s disease Peripheral vascular disorder Vasospasms in the toes and fingers Suppress symptoms by preventing alpha-mediated vasoconstriction Ineffective against other peripheral vascular disorders that involve inappropriate vasoconstriction 8

Adverse Effects of Alpha1 Blockade Detrimental effects result from blockade of alpha1 receptors Effects from alpha2 receptors are minor Orthostatic hypotension Blockade of alpha receptors on veins Reduces muscle tone in the venous wall Upon standing, blood pools in the veins Return of blood to the heart reduced Cardiac output decreased – blood pressure drops 9

Adverse Effects of Alpha1 Blockade Reflex tachycardia Reflex to increase heart rate via the ANS Nasal congestion Dilate the blood vessels of the nasal mucosa Inhibition of ejaculation Alpha1 activation required for ejaculation Impotence is reversible; resolves when drug discontinued Sodium retention and increased blood volume Reduced BP promotes renal retention of sodium and water Usually combined with diuretic when used for hypertension 10

Adverse Effects of Alpha2 Blockade The most significant adverse effect associated with alpha2 blockade – potentiation of the reflex tachycardia 11

Alpha-Adrenergic Antagonists II Prazosin Terazosin Doxazosin Tamsulosin Alfuzosin Phentolamine Phenoxybenzamine 12

Prazosin Actions and uses Pharmacokinetics Adverse effects Preparations, dosage, and administration 13

Terazosin Actions and uses Pharmacokinetics Adverse effects Preparations, dosage, and administration 14

Doxazosin Actions and uses Pharmacokinetics Adverse effects Preparations, dosage, and administration 15

Tamsulosin Actions and uses Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration 16

Alfuzosin Actions and uses Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration 17

Phentolamine Actions and uses Adverse effects Preparations, dosage, and administration 18

Phenoxybenzamine Actions and uses Adverse effects Preparations, dosage, and administration 19

Beta-Adrenergic Antagonists I Therapeutic applications of beta blockade Angina pectoris Hypertension cardiac dysrhythmias Myocardial infarction Heart failure Hyperthyroidism Migraine Stage fright Pheochromocytoma Glaucoma 20

Beta-Adrenergic Antagonists I Adverse effects of beta blockade Adverse effects involve both beta1 and beta2 blockade 21

Beta-Adrenergic Antagonists I Adverse effects of beta1 blockade Bradycardia Reduced cardiac output Precipitation of heart failure AV heart block Rebound cardiac excitation 22

Beta-Adrenergic Antagonists I Adverse effects of beta2 blockade Bronchoconstriction Inhibition of glycogenolysis 23

Beta-Adrenergic Antagonists II: Propranolol Pharmacologic effects Pharmacokinetics Therapeutic uses Adverse effects Bradycardia AV heart block Heart failure Rebound cardiac excitation 24

Beta-Adrenergic Antagonists II: Propranolol Adverse effects (cont’d) Bronchoconstriction Inhibition of glycogenolysis CNS effects Precautions, warnings, & contraindications Severe allergy Diabetes Cardiac, respiratory, and psychiatric disorders 25

Beta-Adrenergic Antagonists II: Propranolol Drug interactions Calcium channel blockers Insulin Preparations, dosage, and administration General dosing considerations Preparations Dosage 26

Beta-Adrenergic Antagonists II: Metoprolol Pharmacologic effects Pharmacokinetics Therapeutic uses Adverse effects Precautions, warnings, and contraindications Preparations, dosage, and administration 27

Beta-Adrenergic Antagonists II: Other Beta-Adrenergic Blockers Receptor specificity Pharmacokinetics Therapeutic uses Adverse effects Intrinsic sympathomimetic activity (partial agonist activity) Dosage and administration 28

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