This document discusses β-adrenergic blockers (β-blockers), which are effective in treating several cardiovascular conditions like angina, arrhythmias, hypertension, and congestive heart failure. It covers the classification of β-blockers based on their selectivity, intrinsic sympathomimetic activity, lipid solubility, and ability to block alpha receptors. The main pharmacological effects and clinical uses of β-blockers are reducing heart rate and contractility, lowering blood pressure, and decreasing intraocular pressure for glaucoma. Adverse effects can include bradycardia, bronchospasm, fatigue, and sexual dysfunction.

1. Drugs Affecting
The Autonomic Nervous System(ANS)
β-Adrenergic Blockers
ANS Pharmacology
Lecture 7
Dr. Hiwa K. Saaed
College of Pharmacy/University of Sulaimani
2017-2018

3. β-Adrenergic Blockers
• β-Blockers are effective in treating:
• angina,
• cardiac arrhythmias,
• myocardial infarction,
• congestive heart failure,
• hyperthyroidism,
• and glaucoma,
• as well as serving in the prophylaxis of migraine headaches.
• Note: The names of all β-blockers end in “olol” except for labetalol and carvedilol.
• All are competitive antagonists
• Propranolol is prototype
• Although all β-blockers lower blood pressure in hypertension, they do not induce
postural hypotension!? because the α-adrenoceptors remain functional.

4. A. Classification and Mechanisms
• Selectivity (β1>β2)
• Partial agonist activity (Intrinsic Sympathomimetic Activity “ISA”)
• Lipid solubility (CNS effect)
• Membrane stabilizing activity (MSA)(local anesthetic action)
• Capacity to block alpha adrenoceptors.
• K+ channel blockade (sotalol)

5. 1. Selectivity (β1>β2)
β1 selective (cardioselective)
• Atenolol
• Acebutolol
• Bisoprolol
• Esmolol (short t1/2)
• Metoplrolol
Advantage: HTN with asthma,
peripheral vascular disease (coldness
of extremities), NIDDM
Selective β2
• Butoxamine (experimental)
Nonselective (β1 & β2)
• Nadolol
• Propranolol
• Timolol

6. 2, Combined (α & β): peripheral vasodilation
Labetalol & Carvedilol
• Useful in Rx HTN patients for whom increased Peripheral resistance is
undesirable (elderly or black)
• Labetalol in Rx preeclampsia, pheochromocytoma
• They do not alter serum lipid or blood glucose levels
• Carvedilol also decreasees lipid peroxidation and vascular wall thickening
(benefit in heart failure)

7. 3. Partial agonist activity ISA
Pindolol, Acebutolol & Labetalol
less bradycardia & diminished effect on CO,
less disturbances of lipid and carbohydrate metabolism
Advantages:
• HTN with asthma,
• HTN with moderate bradycardia
• HTN+DM
4. Local anesthetic activity (membrane-stabilizing activity):
Is a disadvantage when used topically in the eye because it decreases protective
reflexes and increases the risk of corneal ulceration
Timolol, atenolol, carvedilol & nadolol: no Local anesthetic activity

8. 5. Lipid solubility
Lipid soluble
• Propranolol. Timolol. Pindolol
Metoprolol. Labetalol
Pharmacokinetic properties
• Highly metabolized
• Large Vd
• CNS penetration
• Shorter t1/2
WATER SOLUBLE
• Acebutolol, Atenolol, Esmolol,
Nadolol
Pharmacokinetic properties
• Excreted unchanged by kidney
• Less 1st pass effect
• Small Vd
• Longer t1/2 except esmolol

9. 6. K+ channel blockade: sotalol
• Sotalol is a nonselective β receptor antagonists,
• that lack Local Anesthetic action
• but has marked class III antiarrhythmia effect reflecting k+ channel
blockade

10. B. Pharmacological Effects and Clinical Uses
1. CVS:
A. Heart: both
• decreased HR, force of contraction (–ve inotropic & chronotropic effect)
• decreased A-V conduction, ↑PR interval
• Decrease CO, work & O2 consumption
Rx: Angina and Supraventricular tachycardia
B. Vascular system: prevent β2 mediated vasodilation→ reduction in CO
(because of cardiac effect) → decrease BP → reflex vasoconstriction.
On balance there is gradual reduction of both systolic and diastolic BP

11. 2. Respiratory: bronchoconstriction; contraindicated in asthma
3. Eye: reduce IOP especially in Glaucomatous eyes decrease aqueous humor
production
4. metabolic and endocrine effects:
A. Increased Na+ retention, how?
• Reduced BP causes a decrease in renal perfusion, resulting in an increase in Na+
retention and ↑plasma volume → In some cases, ↑BP.
• For these patients, β-blockers are often combined with a diuretic to prevent Na+
retention.
• Also by inhibiting β receptors, renin production is also prevented, contributing to
Na+ retention.
B. Pharmacological Effects and Clinical Uses

12. B. inhibit lipolysis: ↑ plasma VLDL, ↓ HDL,─LDL
↓ HDL/LDL ratio→ coronary heart disease
C. partially inhibit glycogenolysis and decrease glucagon secretion
Great caution in IDDM (Type 1)?
Because pronounce hypoglycemia may occur after insulin injection, β blockers also
attenuate the normal physiologic response to hypoglycemia, furthermore they
mask signs of hypoglycemia; tremor, palpitation..
4. metabolic and endocrine effects:

13. B. Pharmacological Effects and Clinical Uses
Cardiovascular and ophthalmic applications are extremly important
A. CVS:
-angina pectoris ↓cardiac work & O2 demand,
-Chronic hypertension, ↓CO, ↓ TPR, inhibition of renin release
NB: β blockers are not used for acute or emergency Rx of HTN,? may increase diastolic pressure
Labetalol is effective in emergency HTN
-Arrhythmia (supraventricular tachycardias),
-prophylaxis after MI:
1) early use within 6-12 hrs for 3-4 wks
2) Late use within 4 days- 4 wks after onset of infarction and continued for at least 2 years useful for secondary
prevention from another MI
- congestive heart failure*

14. B. Eye: Glaucoma: reduce aqueous humor secretion (timolol)
C. Endocrine use: Thyroid storm, thyrotoxicosis: propranolol
D. CNS: propranolol
1. Anxiety with somatic symptoms
2. Migraine headache prophylaxis:
3. Famillial tremor, other types of tremor, “stage fright”:
4. Alcohol, opioids acute withdrawal symptoms
B. Pharmacological Effects and Clinical Uses

15. C. Adverse effects
• CVS: bradycardia, A-V blockade, CHF
• Arrhythmias: never stop Rx with β blockers suddenly
• Bronchoconstriction: Patients with airway disease: asthmatic attack
• Sexual dysfunction?? Independent of β blockade
• CNS effects: sedation, fatigue, sleep alterations