1. Adrenergic Antagonists

2. 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

3. 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

4. 4

5. 5

6. 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

7. 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

8. 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

9. 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

10. 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

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

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

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

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

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

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

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

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

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

20. 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

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

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

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

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

25. 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

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

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

28. 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

29. Questions