l8: b-adrenergic blockers
Post on 23-Jan-2015
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β-Adrenergic Blockers
Dr. Hiwa K. SaaedPh.D. Pharmacology
& Toxicology
β-Adrenergic Blockersβ-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.
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.
A. Classification and MechanismsSelectivity (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)
A. Classification: Selectivity (β1>β2)
• β1 selective (cardioselective)• Atenolol• Acebutolol• Bisoprolol• Esmolol (short t1/2)• MetoplrololAdvantage: HTN with asthma,
peripheral vascular disease (coldness of extremities), NIDDM
A. Classification and Mechanisms
Selective β2 • Butoxamine (experimental)Nonselective (β1 & β2)• Nadolol• Propranolol• Timolol
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)
Partial agonist activity ISA• Pindolol• Acebutolol• Labetalolless bradycardia & diminished effect on
COP, less disturbances of lipid and carbohydrate
metabolismAdvantages: • HTN with asthma, • HTN with moderate bradycardia • HTN+DM
A. Classification and Mechanisms3. 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
4. Lipid solubility–responsible for CNS adverse effects: propranolol
Lipid soluble
Pharmacokinetic properties
Water soluble
Pharmacokinetic properties
Propranolol
Highly metabolizedLarge VdCNS penetration Shorter t1/2
Acebutolol
Excreted unchanged by kidneyLess 1st pass effectSmall VdLonger t1/2 except esmolol
Timolol
Atenolol
Pindolol
Esmolol
Metoprolol
Nadolol
Labetalol
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
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
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
2. Respiratory: bronchoconstriction; contraindicated in asthma
3. Eye: reduce IOP especially in Glaucomatous eyes decrease aqueous humor production
B. Pharmacological Effects and Clinical Uses
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
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
B. Clinical UsesCardiovascular and ophthalmic
applications are extremly importantA. CVS:
-angina pectoris ↓cardiac work & O2
demand, -Chronic hypertension, ↓CO, ↓ TPR,
inhibition of renin releaseNB: β blockers are not used for acute or emergency Rx of HTN,? ma y
increase diastolic pressure
Labetalol is effective in emergency
-Arrhythmia (supraventricular tachycardias),
-prophylaxis after MI: 1) early use within 6-12 hrs for
3-4 wks2) 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
B. Eye: Glaucoma: reduce aqueous humor secretion (timolol)
C. Endocrine use: Thyroid storm, thyrotoxicosis: propranolol
D. CNS: propranolol 1. Anxiety with somatic symptoms2. Migraine headache prophylaxis:3. Famillial tremor, other types of
tremor, “stage fright”:
4. Alcohol, opioids acute withdrawal symptoms
B. Clinical Uses
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
Thank You
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