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