chapter 18 cholinoceptor antagonists. part a muscarinic receptor antagonists

Chapter 18Chapter 18

Cholinoceptor AntagonistsCholinoceptor Antagonists

Part APart AMuscarinic receptor antagonistsMuscarinic receptor antagonists

OH

CH

NCH3

CH

CH3

CH3

CH O CH C6H5

CH2CH2

CH2

C

O

OH

CH

NCH3

CH

CH3

CH3

CH O CH C6H5

CH2CH

CH

C

O

O

OH

CH

NCH3

CH

CH3

CH3

CH O CH C6H5

CH2

CH

C

O

CH2

HO

Atropine Atropine 阿托品阿托品ScopolamineScopolamine东莨菪碱东莨菪碱

AnisodamineAnisodamine山莨菪碱山莨菪碱

Atropine-like alkaloidsAtropine-like alkaloids

A A Muscarinic receptor antagonistsMuscarinic receptor antagonists

1. 1. Pharmacological effectsPharmacological effects(1) Inhibition of exocrine gland secretion (1) Inhibition of exocrine gland secretion salivary, sweat glandssalivary, sweat glands tear, respiratory tract glandstear, respiratory tract glands relatively ineffective: GI tractrelatively ineffective: GI tract(2) Eye (2) Eye mydriasismydriasis rise in intraocular pressurerise in intraocular pressure paralysis of accommodationparalysis of accommodation

Atropine Atropine 阿托品阿托品

pilocarpinepilocarpine

atropineatropine

(3) Antispamodic action on smooth muscle (3) Antispamodic action on smooth muscle

sensitive:sensitive: GI, urinary bladder (spasmodic state) GI, urinary bladder (spasmodic state) relatively insensitive:relatively insensitive: bile duct, urinary tract, br bile duct, urinary tract, br

onchial tractonchial tract insensitive:insensitive: uterus uterus

(4) Heat (4) Heat HRHR↓:↓: because of M because of M11 blockade; blockade; HRHR↑:↑: if if vagal tone ↑ vagal tone ↑ A-V conduction:A-V conduction: if if vagal tone ↑vagal tone ↑


(5) Blood vessels and blood pressure(5) Blood vessels and blood pressure

Therapeutic doses:Therapeutic doses: no effect no effect Larger doses:Larger doses: vasodilatation vasodilatation in the skin (indirect) in the skin (indirect) and in septic shockand in septic shock (6) Central stimulation(6) Central stimulation

Larger dosesLarger doses


2. 2. Clinical usesClinical uses

(1) Spasms of smooth muscles(1) Spasms of smooth muscles GI, biliary or renal colic, enuresisGI, biliary or renal colic, enuresis

(2) Inhibiting exocrine gland secretion(2) Inhibiting exocrine gland secretion Preanesthetic medicationPreanesthetic medication

(3) Ophthalmology(3) Ophthalmology Acute iritis or iridocyclitis:Acute iritis or iridocyclitis: mydriatics/miotics mydriatics/miotics Measurement of the refraction:Measurement of the refraction: children children


(4) Bradyarrhythmia(4) Bradyarrhythmia sinus or nodal bradycardia, A-V blocksinus or nodal bradycardia, A-V block

(5) Septic shock(5) Septic shock

(6) Antidote for organophosphate poisoning(6) Antidote for organophosphate poisoning


3. 3. Adverse effectsAdverse effects

(1) Side effects(1) Side effects

(2) Central toxicity(2) Central toxicity Lethal dose: 80~130 mg (adults), 10 mg (child)Lethal dose: 80~130 mg (adults), 10 mg (child)


(3) Detoxication (3) Detoxication Symptomatic treatment: diazepam, Symptomatic treatment: diazepam, etcetc.. Physostigmine (Physostigmine ( 毒扁豆碱毒扁豆碱 ) or pilocarpine () or pilocarpine ( 毛果毛果芸香碱芸香碱 ))

(4) Contraindications(4) Contraindications glaucoma, prostatauxe, feverglaucoma, prostatauxe, fever


Actions and clinical usesActions and clinical uses

Peripheral effects are similar to atropine; Peripheral effects are similar to atropine; but has stronger central effects (depression)but has stronger central effects (depression)

Pre-anesthetic medication, prevention of Pre-anesthetic medication, prevention of motion sickness, Parkinson’s disease motion sickness, Parkinson’s disease

Scopolamine Scopolamine 东莨菪碱东莨菪碱A A Muscarinic receptor antagonistsMuscarinic receptor antagonists

Actions and clinical usesActions and clinical uses

Primarily acts on the smooth muscles of Primarily acts on the smooth muscles of peripheral organs; weak in CNS, glands, peripheral organs; weak in CNS, glands, eyeeye

Septic shock, spasms of smooth muscles Septic shock, spasms of smooth muscles of GI and biliary ductof GI and biliary duct

Anisodamine Anisodamine 山莨菪碱山莨菪碱 , 654-2, 654-2


Synthetic mydriaticsSynthetic mydriatics

Homatropine Homatropine 后马托品后马托品shorter duration (1~2 days)shorter duration (1~2 days)Examination of eyes generallyExamination of eyes generally

TropicamideTropicamide 托吡卡胺托吡卡胺（（ 1/4 day1/4 day ））

Synthetic Substitutes for atropineSynthetic Substitutes for atropine


Propantheline bromide Propantheline bromide 丙胺太林丙胺太林 (( 普鲁本辛普鲁本辛 )) poor absorption (po) and BBB penetrationpoor absorption (po) and BBB penetration antispasmodic effects in GI, treatment of peptic ulcer antispasmodic effects in GI, treatment of peptic ulcer

diseasedisease

Benactyzine Benactyzine 贝那替秦贝那替秦 (( 胃复康胃复康 )) peptic ulcer disease with anxiety, GI and urinary blapeptic ulcer disease with anxiety, GI and urinary bla

dder spasmsdder spasms

Synthetic AntispasmadicsSynthetic Antispasmadics


Pirenzepine Pirenzepine 哌仑西平哌仑西平 inhibition of gastric acid and pepsin secretinhibition of gastric acid and pepsin secret

ionion

weak in salivary glands and eye, poor penweak in salivary glands and eye, poor penetration into CNSetration into CNS

used in treatment of peptic ulcer diseaseused in treatment of peptic ulcer disease

MM1 1 receptor antagonistsreceptor antagonists


Part BPart B Nicotinic receptor antagonistsNicotinic receptor antagonists

Acting on sympathetic and parasympatheActing on sympathetic and parasympathetic ganglionic cells; reducing blood presstic ganglionic cells; reducing blood pressure by inhibiting sympathetic gangliaure by inhibiting sympathetic ganglia

Short-acting; tachyphylaxisShort-acting; tachyphylaxis

Used for controlled hypotensionUsed for controlled hypotension

B B Nicotinic receptor antagonistsNicotinic receptor antagonists

1. 1. Depolarizing neuromuscular blockersDepolarizing neuromuscular blockers (depolarizing skeletal muscle relaxants)(depolarizing skeletal muscle relaxants)

Binding to NBinding to NN N receptors, initial excitation action, then receptors, initial excitation action, then persisting depolarization and resistance to AChpersisting depolarization and resistance to ACh

initially transient fasciculationsinitially transient fasciculations tachyphylaxis after repeated usestachyphylaxis after repeated uses anti-AChE potentiates their effectsanti-AChE potentiates their effects no ganglion-blocking effects at therapeutic dosesno ganglion-blocking effects at therapeutic doses


Succinylcholine Succinylcholine 琥珀胆碱琥珀胆碱 , , ScolineScoline

NCH2CH2OCCH2CH2COCH2CH2NH3C

CH3

O

++

H3C

H3C

CH3

CH3

O


1.1 1.1 Pharmacological effectsPharmacological effects

Transient excitation (fasciculations), and theTransient excitation (fasciculations), and then inhibition (relaxation)n inhibition (relaxation)

neck, limbs > face, tongue, throat; less effectivneck, limbs > face, tongue, throat; less effective on breath muscles at therapeutic dosese on breath muscles at therapeutic doses

Short-acting (5 min), degradation by Short-acting (5 min), degradation by plasma plasma pseudocholinesterasespseudocholinesterases


1.2 1.2 Clinical usesClinical uses

An adjuvant in anesthesia or operationAn adjuvant in anesthesia or operation Intubation of Intubation of trachea, esophagus, trachea, esophagus, ect.ect. Prevention of trauma during electroshock theraPrevention of trauma during electroshock thera

pypy

Contraindicated in awake patients, should Contraindicated in awake patients, should use under anesthesiause under anesthesia


1.3 1.3 Adverse effectsAdverse effects

(1)Apnea (respiratory paralysis)(1)Apnea (respiratory paralysis) overdose or hypersensitive patients;overdose or hypersensitive patients; neostigmine potentiates the toxic effectsneostigmine potentiates the toxic effects

(2) Muscle spasm (2) Muscle spasm muscular pain after operationmuscular pain after operation


(3) Elevation of K(3) Elevation of K++ in plasma in plasma contraindicated in patients with a tendency of contraindicated in patients with a tendency of

hyperkalemia hyperkalemia

(4) Malignant hyperthermia(4) Malignant hyperthermia genetic abnormalitygenetic abnormality

(5) Others(5) Others rise in intraocular pressure (glaucoma);rise in intraocular pressure (glaucoma); histamine release; histamine release;


1.4 1.4 Drug interactionsDrug interactions

ThiopentalThiopental

ChE inhibitors: ChE inhibitors: AChE inhibitors, cyclophosphamide, procaAChE inhibitors, cyclophosphamide, proca

ine, ine, etcetc..

Some antibiotics:Some antibiotics: kanamycin, polimyxins, kanamycin, polimyxins, etc.etc. (synergism in n (synergism in n

euromuscular blocking) euromuscular blocking)


2. 2. Nondepolarizing neuromuscular blockersNondepolarizing neuromuscular blockers(nondepolarizing skeletal muscle relaxants)(nondepolarizing skeletal muscle relaxants)

2.1 Effects: 2.1 Effects: competitive blockade of competitive blockade of NNN N

receptorsreceptors2.2 Uses: 2.2 Uses: adjuvant treatment of anesthesia oadjuvant treatment of anesthesia o

r operationsr operations

Tubocurarine Tubocurarine 筒箭毒碱筒箭毒碱


2.3 Adverse effects2.3 Adverse effects

Respiratory paralysis: Respiratory paralysis: can be reversed by neostigmcan be reversed by neostigmineine

Enhancing histamine release: Enhancing histamine release: BP BP , hypotension, b, hypotension, bronchoconstriction, salivery secretionronchoconstriction, salivery secretion

Blocking ganglion: Blocking ganglion: BP BP

Contraindications: Contraindications: myasthenia gravis, bronchial astmyasthenia gravis, bronchial asthma, shock, child (< 10 y)hma, shock, child (< 10 y)


Benzylisoquinolines Benzylisoquinolines （苄基异喹啉类）（苄基异喹啉类） atracurium atracurium 阿曲库铵阿曲库铵 ; doxacurium ; doxacurium 多库铵多库铵 mivacurium mivacurium 米库铵米库铵Ammonio steroidsAmmonio steroids （类固醇铵类）（类固醇铵类） pancuronium pancuronium 泮库铵泮库铵 ;; vecuronium vecuronium 维库铵维库铵 ; ; pipecuronium pipecuronium 哌库铵哌库铵 ; rocuronium ; rocuronium 罗库铵罗库铵

Other nondepolarizing neuromOther nondepolarizing neuromuscular blockersuscular blockers


chapter 18 cholinoceptor antagonists. part a muscarinic receptor antagonists

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