Adrenoceptor blocking drugs

Classification:depend on the affinity for different groups of receptor α-adrenoceptor antagonists β-adrenoceptor antagonists α, β-adrenoceptor antagonists

Adrenaline reversal

α-R blocking agents

reversible α-R blocking agents Phentolamine Tolazoline

irreversible α-R blocking agents phenoxybenzamine

Phentolamine and Tolazoline

Binds to α-R, producing an reversible blockage

competitive antagonists

Pharmacological Effects

produces vasodialation, decrease peripheral resistance and increase venous capacity

reflex cardiac stimulation stimulates salivary, lacrimal, pancr

eatic , respiratory tract and gastric secretion

Therapeutic Uses

Peripheral vascular disease control acute hypertension episodes c

aused by use of sympathemimetics diagnostic test for pheochromocytom

a Antishock heart failure with pulmonary edema

Adverse reactions

Hypotension Gastrointestinal reactions arrhythmia

Phenoxybenzamine

binds to the α-R, producing an irreversible blockage, more potent in blocking α-R

a little effects on His-R and 5-HT-R

Pharmacological Effects

produce vasodialation, decrease peripheral resistance

diastolic pressure decrease reflex cardiac stimulation a little effects on His-R and 5-H

T-R

Therapeutic Uses

Peripheral vascular disease Antishock pheochromocytoma BPH

α1-R blocking agents

Selectively block α1-R Prazosin, terazosin, tamsulosin,

doxazosin Therapeutic Uses: hypertension,

BPH

α2-R blocking agents

Selectively block Presynaptic α2-R, regulation in Periphery and CNS NA

Yohimbine

β-R blocking agents block the neurotransmitter and adrenom

imetic drugs from adrenergic nerve ending to bind with β-R

competitive antagonists nonselective β-R antagonist:competes fo

r both β1-R and β2-R β1-R antagonist

Pharmacological Effects

Cardiovascular system decrease the heart rate and

cardiac output and prolongs systole

decrease the blood flow to most tissue

decrease the total coronary blood flow and oxygen consumption

Pharmacological Effects

Bronchial smooth muscleincrease airway resistance by β-R blockade

Metabolism: carbohydrate and fat metabolism are mediated by β-R

交感神经兴奋 β1 受体激动 脂肪分解普萘洛尔抑制

α 、 β 受体兴奋

肝糖原、肌糖原分解

糖原分解 肾上腺素增强 普萘洛尔抑制

血糖水平升高

胰 岛 素 增 强普萘洛尔无作用

血糖水平降低

普萘洛尔抑制儿茶酚胺反馈性释放增加

增强

Pharmacological Effects

membrane-stabilization action : quinidine like action and local anesthesia action

intrinsic sympathomimetic activity(ISA)

Antiplatelet, ocular pressure reduction

Therapeutic Uses

tachycardia supraventricular and ventricular arrythmias, especially for sinus tachycardia

angina pectoris, myocardial infarction

Hypertension BHF Others: Hyperthyroidium

Adverse reactions

Cardiovascular system Asthma Withdrawal reaction Others: Contraindication: Bradycardia, card

iac function insufficiency, severe A-V blocking, asthma

Propranolol Bioavailability: 30% Interindividual variation HR , cardiac output ,BP Therapeutic Uses: arrythmias, hyperte

nsion, angina pectoris, hyperthyroidism

otherβ-R antagents Nadolol: more potent than propranol

ol, and half life are longer Timolol: most potent, glaucoma Pindolol ： more potent than propran

olol ， ISA(β2-R)

β1-R blocking agents

Atenolol, metoprolol Little effect on β2-R hypertension

α 、 β-R blocking agents

Labetalol, bucindolol, arotinolol, amosulalol

More potent in blocking β-R Major use in hypertension

Labetalol

Bioavailability: 20-40% ISA to β2-R Therapeutic Uses: hypertension,

angina pectoris

arotinilol α:β=1:8 contractility decrease, HR BP Therapeutic Uses: hypertension,

Supraventricular tachycardia, angina

传出神经系统药物对狗血压的影响 （实验记录）

结 果 解 释 静注肾上腺素可以兴奋 α 、 β1 受体。 β 受体兴奋可使心脏兴奋，心输出量增加， s

p 升高， dp 不变或下降。 β 受体对肾上腺素更敏感，所以肾上腺素浓度

低时可出现后继性降压。 较大剂量静注时，由于血管 α 受体占优势，导

致血管收缩，血压 sp 、 dp 均升高。

去甲肾上腺素可以兴奋血管的 α 受体，使外周血管收缩，血压增高，但作用时间短。

麻黄碱的作用发生慢而温和，且比较持久，他可以直接作用于 α 、 β 受体，使心率加快，血管收缩，血压上升，也可以通过促使肾上腺素能神经末梢释放递质（主要是去甲肾上腺素），使血管 α 受体兴奋，血压上升。

大剂量乙酰胆碱静注可致 N 样作用，使心收缩

力加强，小血管收缩而出现血压升高。 烟碱是 N 受体兴奋剂，小剂量兴奋 N2 受体和

中枢神经系统，也兴奋 N1 受体。预先使用阿托品仅仅阻断了 M 受体，故出现血压的迅速升高。

静注酚妥拉明后，阻断了 α 受体，使外周 β 兴奋占优势，血管扩张，同时酚妥拉明还可以直接舒张小动脉平滑肌，这两者均导致血压迅速下降。