part 5 adrenoceptor antagonists 1. receptor antagonists 2. receptor antagonists 3. , receptor...

Part 5Part 5

Adrenoceptor AntagonistsAdrenoceptor Antagonists

1. 1. receptor antagonists receptor antagonists


3. 3. , , receptor antagonists receptor antagonists

Epinephrine reversalEpinephrine reversal （（肾上腺素作用的翻转肾上腺素作用的翻转））


1-1 1-1 11, , 2 2 receptor antagonistsreceptor antagonists

Short-actingShort-acting

Phentolamine Phentolamine 酚妥拉明酚妥拉明

N

NCH3

HO

N CH2

H

1.1 1.1 PharmacologyPharmacology

(1) Vasodilatation(1) Vasodilatation Blocking Blocking 1 1 receptor; direct actionreceptor; direct action

(2) Stimulating heart(2) Stimulating heart ReflexReflex ；； blocking blocking 2 2 receptor receptor ～～ NE release NE release

(3) Cholinergic and histamine-like effects(3) Cholinergic and histamine-like effects Contraction of GI smooth muscles,Contraction of GI smooth muscles, Gastric acid secretion Gastric acid secretion


1.2 1.2 Clinical usesClinical uses

(1) Peripheral vascular diseases(1) Peripheral vascular diseases Acrocyanosis, Raynaud’s diseaseAcrocyanosis, Raynaud’s disease

(2) Local vasoconstrictor extravasation(2) Local vasoconstrictor extravasation


(3) Shock(3) Shock cardiac output cardiac output ; ; redistribution of blood flow; redistribution of blood flow; shift of fluid from interstitial compartment shift of fluid from interstitial compartment

to vascular compartment; to vascular compartment; pulmonary pressure pulmonary pressure ;; should be used after fully adequate should be used after fully adequate

replacement of intravascular fluidreplacement of intravascular fluid


(4) Acute myocardial infarction and conges(4) Acute myocardial infarction and congestive heart failuretive heart failure

after-load after-load ；； cardiac output cardiac output


(5) Pheochromocytoma(5) Pheochromocytoma pre- and post-operation usespre- and post-operation uses diagnosisdiagnosis

(6) Others:(6) Others: impotency ( impotency ( 阳痿阳痿 ))


1.3 1.3 Adverse effectsAdverse effects

(1) Postural hypotension(1) Postural hypotension

(2) Reflex heart stimulation(2) Reflex heart stimulation tachycardia, arrhythmia, angina pectoristachycardia, arrhythmia, angina pectoris

(3) G.I. reactions(3) G.I. reactions

(4) Other(4) Other central depressioncentral depression


TolazolineTolazoline 妥拉唑啉妥拉唑啉

weak effectsweak effects more severe adverse effectsmore severe adverse effects


Long-actingLong-acting

Longer action durationLonger action durationused for peripheral vasculardiseasesperipheral vasculardiseases anti-shockanti-shock pheochromocytomapheochromocytoma improving urinary flow in patients with bimproving urinary flow in patients with b

enign prostatic hypertrophyenign prostatic hypertrophy

Phenoxybenzamine Phenoxybenzamine 酚苄明酚苄明


1-2 1-2 1 1 receptor antagonistsreceptor antagonists

prazosinprazosin （（哌唑嗪哌唑嗪）） , for hypertension , for hypertension treatmenttreatment

tamsulosintamsulosin （（坦洛新坦洛新）） , for benign pros, for benign prostatic hypertrophytatic hypertrophy

1-3 1-3 22 receptor antagonists receptor antagonists

yohimbineyohimbine （（育亨宾育亨宾））


2.1 2.1 ADMEADME

First-pass elimination,First-pass elimination, lower bioavailability: propranolollower bioavailability: propranolol

Hepatic metabolism and renal excretion, Hepatic metabolism and renal excretion, hepatic and renal functions alter the effects of hepatic and renal functions alter the effects of the drugs and result in large individual the drugs and result in large individual variationvariation

Thus, Thus, dose individualizationdose individualization is necessary. is necessary.


2.2 2.2 Pharmacological effectsPharmacological effects

(1) (1) receptor blockade receptor blockade

A. Cardiovascular effectsA. Cardiovascular effects ：： Depressing heart: Depressing heart: reduction in HR, A-V conduction,reduction in HR, A-V conduction,

automaticity, cardiac output, oxygen consumption automaticity, cardiac output, oxygen consumption Hypotension:Hypotension: hypotensive effects only in hypotensive effects only in hypertensihypertensi

ve patientsve patients; ; peripheral blood flow peripheral blood flow , BP , BP in in normal subjectsnormal subjects..


Blockade of Blockade of –adrenoceptor cardial responses –adrenoceptor cardial responses by propranololby propranolol

B. Bronchial smooth musclesB. Bronchial smooth muscles inducing bronchial smooth muscle contraction in inducing bronchial smooth muscle contraction in

asthmatic patientsasthmatic patients

C. MetabolismC. Metabolism lipolysis lipolysis , glycogenolysis , glycogenolysis , potentiating insulin e, potentiating insulin e

ffects ~ hypoglycemiaffects ~ hypoglycemia

D. Renin secretionD. Renin secretion decreasing secretion of renindecreasing secretion of renin


(2) Intrinsic sympathomimetic effects(2) Intrinsic sympathomimetic effects Some drugs: HR Some drugs: HR , output , output

(3) Membrane-stabilizing effects(3) Membrane-stabilizing effectsLarger doses of some drugs: quinidine-like effeLarger doses of some drugs: quinidine-like effe

cts due to Nacts due to Na++ channel block channel block

(4) Others(4) OthersLowering intraocular pressure;Lowering intraocular pressure; Inhibiting platelet aggregationInhibiting platelet aggregation


2.3 2.3 Clinical usesClinical uses

(1) Arrhythmia(1) Arrhythmia ：： supraventricular, sympathetisupraventricular, sympathetic activity c activity

(2) Hypertension(2) Hypertension

(3) Angina pectoris and myocardial infarction(3) Angina pectoris and myocardial infarction

(4) Chronic heart failure(4) Chronic heart failure

(5) Others: (5) Others: hyperthyroidism, migraine headachhyperthyroidism, migraine headache, glaucomae, glaucoma （（ timololtimolol ）） , , etcetc..


Effect of a Effect of a receptor antagonist on the mortality of ch receptor antagonist on the mortality of chronic heart failureronic heart failure

2.4 2.4 Adverse effectsAdverse effects

(1) Worsening of asthma: (1) Worsening of asthma: contraindicated in bronccontraindicated in bronchial asthmatic patientshial asthmatic patients

(2) Heart depression: (2) Heart depression: contraindicated in heart failcontraindicated in heart failure, severe A-V block, sinus bradycardiaure, severe A-V block, sinus bradycardia

(3) Worsening of peripheral vascular constriction(3) Worsening of peripheral vascular constriction (4) Withdrawal syndrome(4) Withdrawal syndrome ：： up-regulation of up-regulation of re re

ceptorsceptors (5) Others(5) Others ：： central depression, hypoglycemia, central depression, hypoglycemia, etcetc..



2.5 2.5 Representative drugsRepresentative drugs

Propranolol Propranolol 普萘洛尔普萘洛尔

O CH2CHCH2NHCH

OHCH3

CH3

11, , 2 2 receptor blocking receptor blocking

no intrinsic activityno intrinsic activity first-elimination after oral administration, first-elimination after oral administration,

individual variation of bioavailabilityindividual variation of bioavailability

Propranolol Propranolol 普萘洛尔普萘洛尔


For treatment of glaucoma (wide-angle)For treatment of glaucoma (wide-angle)

Timolol Timolol 噻马洛尔噻马洛尔


1 1 receptor antagonists, no intrinsic activityreceptor antagonists, no intrinsic activity

atenolol :atenolol : longer t longer t1/21/2, once daily, once daily

usually used for treatment of hypertensionusually used for treatment of hypertension

Atenolol Atenolol 阿替洛尔阿替洛尔

Metoprolol Metoprolol 美托洛尔美托洛尔


3. α, 3. α, receptor antagonists receptor antagonists

blockingblocking α, β receptors, β> αα, β receptors, β> α usually used for treatment of hyperusually used for treatment of hyper

tensiontension

Labetolol Labetolol 拉贝洛尔拉贝洛尔

3. α, 3. α, receptor antagonists receptor antagonists

α, β receptor blocking, β> αα, β receptor blocking, β> α

SS(-) isomer: βand α receptor blocking(-) isomer: βand α receptor blocking RR(+) isomer: α receptor blocking(+) isomer: α receptor blocking

usually used for treatment of hypertensiousually used for treatment of hypertension and n and chronic heart failurechronic heart failure

Carvedilol Carvedilol 卡维地洛卡维地洛

Part 6Part 6

Local AnestheticsLocal Anesthetics

COCH2CH2N

OC2H5

H2N

C2H5

NHCCH2N

OC2H5

C2H5

CH3

CH3

COCH2CH2N

OCH3

CH3

HN

H9C4

procaineprocaine

普鲁卡因普鲁卡因

lidocainelidocaine

利多卡因利多卡因

tetracainetetracaine

丁卡因丁卡因

Local anestheticsLocal anesthetics

1. 1. Pharmacological effectsPharmacological effects

(1) Local anesthetic effects(1) Local anesthetic effects

inhibiting Nainhibiting Na++ inward flow and the conduction of nerve inward flow and the conduction of nerve fibersfibers

sensory (fine – thick) sensory (fine – thick) CNS CNS (inhibiting - excitatory) (inhibiting - excitatory) ANS ANS motor nerves motor nerves muscles muscles

The The mechanism of mechanism of local local anestheticsanesthetics

Blocking NaBlocking Na+ +

channels on channels on the nerve the nerve fibersfibers

The mechanism of The mechanism of local anestheticslocal anesthetics

Intracellular blockade Intracellular blockade of Naof Na+ + channelchannel


(2) Systemic effects(2) Systemic effects （（ Adverse effectsAdverse effects ））

Depressing CNSDepressing CNS ：： excitation - depressionexcitation - depression

Cardiovascular effectsCardiovascular effects ：： heart depression; vaheart depression; vasodilatation; lowering BPsodilatation; lowering BP

combined with epinephrine:combined with epinephrine: reducing absorption areducing absorption and systemic effectsnd systemic effects

( but contraindicated in: ( but contraindicated in: terminal tissues; epinephrine contraiterminal tissues; epinephrine contraindications )ndications )

2. 2. Clinical usesClinical uses

(1) Surface anesthesia ((1) Surface anesthesia ( 表面麻醉表面麻醉）） penetrationpenetration

(2) Infiltration anesthesia (2) Infiltration anesthesia （（浸润麻醉浸润麻醉））

(3) Conduction anesthesia (3) Conduction anesthesia （（传导麻醉传导麻醉））


(4) Epidural anesthesia ((4) Epidural anesthesia ( 硬脊膜外麻醉硬脊膜外麻醉 )) Avoiding misdirection into cerebrospinal fluidAvoiding misdirection into cerebrospinal fluid

(5) Subarachnoid anesthesia ((5) Subarachnoid anesthesia ( 蛛网膜下腔麻蛛网膜下腔麻

醉醉 , , 腰麻腰麻）） head-up position;head-up position; hyperbaric solution;hyperbaric solution; hypotension: hypotension: prevention with ephedrineprevention with ephedrine


3. 3. Adverse effectsAdverse effects

(1) Systemic effects(1) Systemic effects depression of CNS:depression of CNS: excitation – depression – respi excitation – depression – respi

ratory depressionratory depression cardiovascular effects:cardiovascular effects: hypotension; arrhythmia hypotension; arrhythmia

(2) Allergic reactions(2) Allergic reactions urticaria, bronchoconstriction; anaphylactic shockurticaria, bronchoconstriction; anaphylactic shock


4. 4. Special agentsSpecial agents

Efffect Toxicity Pene-Efffect Toxicity Pene- UsesUses trationtration

procaineprocaine weak weak weak can not be used weak weak weak can not be used 普鲁卡因普鲁卡因 (allergic) for sur(allergic) for surfaceface skin allergic testskin allergic test

lidocainelidocaine stronger lower strongerstronger lower stronger for various uses for various uses ；；利多卡因利多卡因 anti-arrhythmiaanti-arrhythmia

tetracainetetracaine stronger stronger strongerstronger stronger stronger mainly for surface mainly for surface丁卡因丁卡因


part 5 adrenoceptor antagonists 1. receptor antagonists 2. receptor antagonists 3. , receptor...

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