Transcript 3: α、β-R antagonists Labetalol（拉贝洛尔

Chapter 9
adrenoceptor blocking drugs
(Adrenoceptor antagonists)
α-R antagonists
β-R antagonists
α、β-R antagonists
Section 1 α-R antagonists
α1, α2-R antagonists
α1-R antagonists
α2-R antagonists
Basic actions of α-R antagonists
1.CVS effects
(1)α1-R antagonistic effects:
Endogenous CA blockage: BP↓
(Postural hypotension)
Exogenous CA blockage: “adrenaline reversal”
(2) α2-R antagonistic effects:
presynaptic 2 antagonism –NE release ↑
CNS 2 antagonism -sympathetic activity ↑
Basic actions of α-R antagonists
2.other effects
(1) Prostate and bladder sphincter α1-R
antagonism: dilation
(2) insular α2-R antagonism: insulin ↑
Classification
Ⅰ. α1, α2-R antagonists


1.short-term acting: phentolamine (酚妥拉明),
tolazoline (妥拉唑啉)
2. long-term acting: phenoxybenzamine(酚苄明)
Ⅱ. α1-R antagonists: prazosin(哌唑嗪)
Ⅲ. α2-R antagonists: yohimbine(育亨宾)
α1, α2-R antagonists
phentolamine (酚妥拉明, regitine,立其丁)
competitive α-R antagonists
pharmacological actions
1.vessels : dilation; BP ↓

Mechanism:
(1) direct action
(2) 1-R blockade: “adrenaline reversal”
pharmacological actions
2.heart: excitation, CO ↑ HR ↑
Mechanism:
(1) BP ↓excite heart
(2) 2-R blockade
3.other effects: cholinergic action
histamine-like action
clinical uses
1. peripheral vasospasmatic disorders:
 eg. Raynaud’s syndrome, 雷诺氏综合征
2. local vasoconstrictor excess (eg, NA)
3. shock :
a. dilate vessel  peripheral resistance↓ (肺血管)
b. excite heart  Co↑
c. pulse pressure↑ improve viscera hemoperfusion,
relief microcirculation disturbance
Phentolamine+ NE
4. CHF and AMI
Pathophysiology:
Cardia
insufficiency
contraction
Phentolamine:
Co↑
dilate

arteriovenous
reflex
vesselcardiac
load↓
5. diagnosis and treatment of pheochromocytoma
6. others: male sexual dysfuction
 甲磺酸酚妥拉明分散片（伟哥）
adverse reactions
1.cardiovascular reaction:

Postural hypotension, tachycardia,
angina, arrhythmia
2.gastrointestinal reaction:

stomachache, diarrhea, vomiting, ulceration
Tolazoline(妥拉唑啉)

Characteristics (compared with phentolamine )
weaker in  antagonism,
stronger in cholinergic and histamine-like effects.

Used to treat peripheral vasospasmatic disorders
and pheochromocytoma
phenoxybenzamine(酚苄明)

Noncompetitive antagonism

Pharmacokinetics:
Slow onset(1h), long duration(3-4d)
pharmacological actions
1.α1-R antagonistic effects :
slow, strong and long.
(Postural hypotension)
2. HA-R antagonistic effects
clinical uses
1. peripheral vasospasmatic disorders
2. pheochromocytoma
3. Shock
4. Urinary obstruction caused by benign
prostatic hyperplasia
adverse reactions
Postural hypotension,
tachycardia (palpitation),
nasal congestion
CNS inhibition
α1-R antagonists
Prazosin(哌唑嗪)
 Terazosin（特拉唑嗪）
 Doxazosin（多沙唑嗪）
Actions: decrease BP, but weak influence on HR
Clinical uses:
1. HBP
2. CHF
3. Urinary obstruction caused by benign
prostatic hyperplasia

Tamsulosin (坦洛新)
Block α1A-R (prostate) > α1B-R (blood vessel)
 High effect on prostatic hyperplasia
(compare with phenoxybenzamine and prazosin)

Phenoxybenzamine: ↓BP, palpitation
Prazosin: ↓BP
Tamsulosin: have no effect on BP and HR
α2-R antagonists
Yohimbine (育亨宾)
uses

1. tool agent for research
2. impotence (阳痿)：痿必治
Section 2 β-R antagonists
β 1,β2-R antagonist
β 1-R antagonist
α、 β -R antagonist
classification

1.β 1,β2-R antagonist
1A：Propranolol(普萘洛尔), Timolol（噻吗~）
1B：pindolol（吲哚~）

2.β 1-R antagonist
2A：atenolol（阿替~） , metoprolol（美托~）
2B：Acebutolol(醋丁~)

3. α, , β -R antagonist
Labetalol（拉贝~）, carvedilol(卡维地洛)
Intrisic sympathomimetic activity (ISA)
partial agonistic activity (PAA)
Characteristics of Pharmacokinetics:
affected by liposolubility
1.absorption: first pass elimination
(propranolol is obvious, atenolol is not )
2.distribution:BBB (propranolol, atenolol)
3.elimination: hepatic metabolism and
Kidney excretion (propranolol, atenolol)
4. individual variation
basic actions of β-R antagonist
1. β-R blocking action:
1) cardiovascular effects:

heart : depression (β1)

vessels: contraction
a. blockβ2-R
b. Co↓vasoconstriction

BP↓
basic actions of β-R antagonist
2) bronchial smooth muscle :β2
3) metabolism:β2
a. Delay recovery of blood glucose after
insuline
(insulinehypoglycemia
increase CA releaseactivateα,β
 glycogenolysisblood glucose↑)
b. Inhibit lipoclasis
4) Renin release:β1(propranolol)
5) ↓intraocular pressure (timolol)
basic actions of β-R antagonist
2.intrinsic sympathominetic activity(ISA)
partial agonistic activity (PAA)

Characteristic of drugs with ISA
basic actions of β-R antagonist
3.membrane stabilizing action:
in large dose (local anesthetic action)
clinical uses





1.arrhythmias (tachyarrhythmia)
2. hypertension
3. angina pectoris, myocardial infarction
4.CHF
5.others: hyperthyroidism,
glaucoma
adverse actions





1. bronchial asthma
2. cardiovascular reaction
3. induce Raynaud’s syndrome
4. rebound phenomenon:
5. others: hypoglycemia,
depression
Some β-R antagonists
1A
 Propranolol(普萘洛尔), Timolol（噻吗洛尔）
1B
 Pindolol（吲哚洛尔）
2A
 Atenolol（阿替洛尔） Metoprolol（美托洛尔）
2B
 Acebutolol(醋丁洛尔)
3
 Labetalol（拉贝洛尔）
1A ：nonselective, no ISA
Propranolol(普萘洛尔),
1.pharmacokinetics: high liposolubility

2.uses: HBP, arrhythmia, CHF,
myocardial ischemia, hyperthyroidism
 Timolol（噻吗洛尔）
1.actions: strongest
2.uses: glaucoma (block β-R of ciliary body
aqueous humor↓)
1B:nonselective, ISA

Pindolol（吲哚洛尔）
Actions: stronger than propranolol
Uses: HBP
2A: selective, no ISA


Atenolol（阿替洛尔,氨酰心安）: long t1/2
Metoprolol（美托洛尔,美多心安）
3: α、β-R antagonists

Labetalol（拉贝洛尔,柳胺苄心定）
1.β-R blockage>α-R blockage
2. β-R blockage<propranlol
3.α-R blockage<phentolamine
4. ISA (β2-R)
5. used in HBP, angina pectoris
3: α、β-R antagonists



carvedilol (卡维地洛)
1.β-R blockage>α-R blockage
2. used in HBP, CHF