part 3 cholinoceptor antagonists. a muscarinic receptor antagonists

Part 3Part 3

Cholinoceptor AntaCholinoceptor Antagonistsgonists

AAMuscarinic receptor antagonistsMuscarinic receptor antagonists

Action sites of Action sites of cholinoceptor acholinoceptor antagonistntagonist

Action sites of cholinoceptor antagonistAction sites of cholinoceptor antagonist

NN MM

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

AtropineAtropine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

AA 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

Durations of the action atropine-like drugs on eyeDurations of the action atropine-like drugs on eye

(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 remarkable effect no remarkable 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 medication, over-secretionPreanesthetic medication, over-secretion

(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) but not including the case of treating but not including the case of treating organophosphate toxicationorganophosphate toxication


(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 ( 毛果芸香毛果芸香

碱碱 ))

(4) Contraindications(4) Contraindications glaucoma, prostatauxe, glaucoma, prostatauxe, feverfever


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


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 da1/4 dayy ））

Synthetic Substitutes for atropineSynthetic Substitutes for atropine


Synthetic AntispasmadicsSynthetic Antispasmadics

AirwayAirwayIpratropine bromide Ipratropine bromide 异丙托溴铵异丙托溴铵 (( 溴化异丙托品溴化异丙托品 ))

poor absorption and BBB penetration; antispaspoor absorption and BBB penetration; antispasmodic effects in bronchial smooth musclemodic effects in bronchial smooth muscle

treatment of bronchial asthma and chronic brotreatment of bronchial asthma and chronic bronchitis; injection or aerosolnchitis; injection or aerosol


G.I.G.I.Propantheline bromide Propantheline bromide 溴化丙胺太林溴化丙胺太林 (( 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 ulcantispasmodic effects in GI, treatment of peptic ulc

er diseaseer disease

Benactyzine Benactyzine 贝那替秦贝那替秦 (( 胃复康胃复康 ))

peptic ulcer disease with anxiety, GI and urinary bpeptic ulcer disease with anxiety, GI and urinary bladder spasmsladder spasms


MM11 receptor antagonists receptor antagonists

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


BB

Nicotinic receptor antagonistsNicotinic receptor antagonists

Ganglion Blockers (NGanglion Blockers (NNN receptor antagonists) receptor antagonists)

Acting on sympathetic and parasympathetic Acting on sympathetic and parasympathetic ganglionic cells; ganglionic cells; reducing blood pressure by reducing blood pressure by inhibiting sympathetic gangliainhibiting sympathetic ganglia

Short-acting; tachyphylaxisShort-acting; tachyphylaxis

Used for Used for controlled hypotensioncontrolled hypotension

BB Nicotinic receptor antagonistsNicotinic receptor antagonists

BB Nicotinic receptor antagonists Nicotinic receptor antagonists neuromuscular blockersneuromuscular blockers

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

Binding to NBinding to NM M receptors, initial excitation action, thereceptors, initial excitation action, the

n persisting depolarization and resistance to AChn persisting 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, etc.etc. Prevention of trauma during electroshock theraPrevention of trauma during electroshock thera

pypy

Contraindicated in awake patients, should Contraindicated in awake patients, should be used under anesthesiabe used under anesthesia

B B Nicotinic receptor antagonistsNicotinic receptor antagonists

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, polymyxins, kanamycin, polymyxins, etc.etc. (synergism in (synergism in

neuromuscular blocking) neuromuscular blocking)


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

2.1 Effects: 2.1 Effects: competitive blockade of competitive blockade of NNM M

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 neostican be reversed by neostigminegmine

Enhancing histamine release:Enhancing histamine release: BP BP , bronchoco, bronchoconstriction, salivery secretionnstriction, salivery secretion

Blocking ganglion:Blocking ganglion: BP BP

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


part 3 cholinoceptor antagonists. a muscarinic receptor antagonists

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