Adrenoceptor antagonist drugs Department of pharmacology Zhu ling ( 朱玲 )

Adrenoceptor antagonist drugs Adrenoceptor antagonist drugs （ Adrenoceptor blocking drugs ） A kind of drugs that can combine to adrenoreceptor and have little or no mimic action of NA ， but prevent the receptor activation by adrenergic transmitter and related agonist. According to receptor selectivity, it can be classified to three groups.

Adrenoceptor antagonist drugs groups drugs αreceptor antagonist α 1 α 2 R antagonistphentolamine phenoxybenzamine α 1 R antagonistPrazosin, terazosin α 2 R antagonistyohimbine β receptor antagonist β 1 β 2 R antagonistPropranolol, timolol, pindolol β 1 R antagonistAtenolol, metoprolol β 2 R antagonistbutoxamine αβ receptor antagonistlabetalol

αreceptor antagonist αreceptor antagonist may be reversible or irreversible in their inter action with these receptor. classification ： short-duration group phentolamine 酚妥拉明 tolazoline 妥拉唑啉 Prazosin and analogs reversible antagonists long-duration group phenoxybenzamine 酚苄明 irreversible antagonist

αreceptor antagonist effect 1 blood vessels and blood pressure block α receptor direct relaxes blood vessels muscle vasodilation blood pressure epinephrine reversal 2 heart reflex cardiac stimulation presynapseα 2 R blocking ， negative feedback

αreceptor antagonist 3 others cholinomimetic and histamine-like effect (short-duration agents) blocking Ach, histamine and serotonin (5-HT) receptors （ phenoxybenzamine ）

αreceptor antagonist Therapeutic application ： ① peripheral vascular disease (raynaud’s disease) ② inadvertent infiltration of NA into subcutaneous during intravenous administration ③ shock cardiac stimulation ④ prostate hyperplasia ⑤ preoperative management of patients with pheochromocytoma ⑥ hypertensive emergencies

αreceptor antagonist Adverse reaction ：  prostural hypotension  reflex tachycardia, arrhythmia  diarrhea, gastrointestinal stimulation, etc

β receptor antagonist A kind of drugs share the common feature of antagonizing the effects of catecholamine at βadrenoceptors, high selectivity occupy β adrenoceptors and competitively reduce receptor occupancy by catecholamines and other βagonists. pure antagonist partial antagonist

β receptor antagonist the process in the body β receptor antagonist the process in the body high lipid-solubility low lipid-solubility Propranolol metoprolol timolol Atenolol pindolol nadolol acebutolol Well absorptionLimited absorption Low bioavailability No obviously first-pass elimination Half life shortHalf life long Plasma concentrations: great individual variability Plasma concentrations: relatively invariableness hepatic metabolism Excreted unchanged in the urine

β receptor antagonist Pharmacodynamics 1 β blockade effects 1) heart inhibition 2) blood vessels peripheral resistance↑ 3) blood pressure chronically lower β blockade – reduce cardiac output presynaptic membranes β blockade effects CNS β blockade effects antagonize the release of renin

Adrenoceptor antagonist drugs

4) bronchia smooth muscles contraction 5) metabolism inhibit sympathtic nervous system stimulation of lipolysis, partially inhibit glycogenolysis (impair recovery from hypoglycemia, great caution in insulin-dependent diabetic patients) anti-hyperthyroid renin release decrease β receptor antagonist

2 Intrinsic sympathomimetic activity(ISA) except blockade effect, it has partial agonistic action 3 else local anesthetic action (membrane- stabilizing action) anti-platelet congregate

β receptor antagonist Therapeutic application 1 cardiac arrhythmias (tachycardia) 2 hypertension 3 ischemic heart disease (angina,resulting in decreased cardiac work and reduction in oxygen demand, slowing and regularization of the heart rate) 4 myocardial infraction (increase stroke volume in some patients with obstructive cardiomyopathy) 5 else hyperthyroidism and crisis, glaucoma (timolol), splitting headache (brow ague), cardiomyopathy

β receptor antagonist Adverse reaction 1 alimentary tract and CNS effects 2 worsening of preexisting bronchial asthma 3 heart inhibition, peripheral blood vessels spasm 4 rebound phenomenon (rapid withdraw can lead to supersensitivity of receptor)