β-Blockers are effective in treating several cardiovascular conditions such as angina, arrhythmias, myocardial infarction, and congestive heart failure. They are also used for hyperthyroidism, glaucoma, and migraine prevention. β-Blockers are competitive antagonists that lower blood pressure and heart rate by blocking β-adrenergic receptors. They have various mechanisms of action depending on their selectivity for β1 and β2 receptors, intrinsic sympathomimetic activity, lipid solubility, and ability to block alpha receptors or potassium channels. Common adverse effects include bradycardia, hypotension, bronchospasm, fatigue and sexual dysfunction.

1. β-Adrenergic
Blockers
Dr. Hiwa K. Saaed
Ph.D. Pharmacology
& Toxicology

3. β-Adrenergic Blockers
β-Blockers are effective in treating :
• angina,
• cardiac arrhythmias,
• myocardial infarction,
• congestive heart failure,
• hyperthyroidism,
• and glaucoma,
• prophylaxis of migraine headaches.
Note: The names of all β-blockers end in “olol” except for
labetalol and carvedilol.

4. β-Blockers
• 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.

5. 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)

6. A. Classification: 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

7. A. Classification and Mechanisms
Selective β2
• Butoxamine (experimental)
Nonselective (β1 & β2)
• Nadolol
• Propranolol
• Timolol

8. 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)

9. Partial agonist activity ISA
• Pindolol
• Acebutolol
• Labetalol
less bradycardia & diminished effect on COP,
less disturbances of lipid and carbohydrate
metabolism
Advantages:
• HTN with asthma,
• HTN with moderate bradycardia
• HTN+DM

10. A. Classification and Mechanisms
3. 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

11. 4. Lipid solubility
– responsible for CNS adverse effects: propranolol
Lipid soluble Pharmacokinetic properties Water soluble Pharmacokinetic properties
Propranolol Highly metabolized
Large Vd
CNS penetration
Shorter t1/2
Acebutolol Excreted unchanged by
kidney
Less 1st pass effect
Small Vd
Longer t1/2 except esmolol
Timolol Atenolol
Pindolol Esmolol
Metoprolol Nadolol
Labetalol

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

13. 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

14. Reflex peripheral vasoconstriction!?
B. Vascular system: prevent β2 mediated vasodilation→
reduction in COP (because of cardiac effect) → decrease
BP → reflex vasoconstriction.
• On balance there is gradual reduction of both systolic and
diastolic BP

15. 2. Respiratory: bronchoconstriction; contraindicated in asthma
3. Eye: reduce IOP especially in Glaucomatous eyes decrease
aqueous humor production
B. Pharmacological Effects and Clinical Uses

16. 4. metabolic and endocrine effects:
A. Increased Na+ retention, how?
– Reduced blood pressure causes a decrease in renal perfusion, resulting in
an increase in Na+ retention and ↑plasma volume→
– In some cases, ↑blood pressure.
– 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

17. 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..
B. Pharmacological Effects and Clinical Uses

18. B. 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,? ma y
increase diastolic pressure
Labetalol is effective in emergency

19. -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*
B. Clinical Uses

20. 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. Clinical Uses

21. 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?? Indep of β blockade
• CNS effects: sedation, fatigue, sleep
alterations

22. Thank You