Adrenoceptor antagonist drugsAdrenoceptor antagonist drugs

Department of pharmacology

Zhu ling (朱玲 )

2010.3

Adrenoceptor antagonist drugsAdrenoceptor 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 drugsAdrenoceptor antagonist drugs groups drugs

αreceptor antagonist

α1 α2 R antagonist phentolamine phenoxybenzamine

α1 R antagonist Prazosin, terazosin

α2 R antagonist yohimbine

β receptor antagonist

β1 β2 R antagonist Propranolol, timolol, pindolol

β1 R antagonist Atenolol, metoprolol

β2 R antagonist butoxamine

αβ receptor antagonist labetalol

αreceptor antagonistαreceptor 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 antagonistαreceptor antagonisteffect

1 blood vessels and blood pressure

block α receptor

direct relaxes blood vessels muscle

vasodilation blood pressure

epinephrine reversal

2 heart reflex cardiac stimulation

presynapseα2 R blocking ， negative feedback

αreceptor antagonistαreceptor antagonist

3 others cholinomimetic and histamine-like effect (short-duration agents)

blocking Ach, histamine and serotonin (5-HT) receptors （ phenoxybenzamine ）

αreceptor antagonistαreceptor antagonist

Therapeutic application ：① peripheral vascular disease (raynaud’s

disease)② inadvertent infiltration of NA into

subcutaneous during intravenous administration

③ shock cardiac stimulation④ prostate hyperplasia⑤ preoperative management of patients with

pheochromocytoma ⑥ hypertensive emergencies

αreceptor antagonistαreceptor antagonist

Adverse reaction ：① prostural hypotension

② reflex tachycardia, arrhythmia

③ diarrhea, gastrointestinal stimulation, etc

β β receptor antagonistreceptor 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 antagonistβ receptor antagonistthe process in the bodythe process in the body

high lipid-solubility low lipid-solubility

Propranolol metoprolol timolol

Atenolol pindolol nadolol acebutolol

Well absorption Limited absorption

Low bioavailability No obviously first-pass elimination

Half life short Half life long

Plasma concentrations: great individual variability

Plasma concentrations: relatively invariableness

hepatic metabolism Excreted unchanged in the urine

β β receptor antagonistreceptor antagonistPharmacodynamics1 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 drugsAdrenoceptor 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

β β receptor antagonistreceptor 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 antagonistβ 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 β receptor antagonistreceptor 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)