Part 3 Cholinoceptor Antagonists. A Muscarinic receptor antagonists

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  • Part 3Cholinoceptor Antagonists

  • AMuscarinic receptor antagonists

  • Action sites of cholinoceptor antagonist

  • Action sites of cholinoceptor antagonistNM

  • AtropineScopolamineAnisodamine

    Atropine-like alkaloids

  • A Muscarinic receptor antagonists1. Pharmacological effects(1) Inhibition of exocrine gland secretion salivary, sweat glands tear, respiratory tract glands relatively ineffective: GI tract(2) Eye mydriasis rise in intraocular pressure paralysis of accommodationAtropine

  • pilocarpineatropine

  • Durations of the action atropine-like drugs on eye

  • (3) Antispamodic action on smooth muscle

    sensitive: GI, urinary bladder (spasmodic state)relatively insensitive: bile duct, urinary tract, bronchial tractinsensitive: uterus

    (4) Heat HR: because of M1 blockade; HR: if vagal tone A-V conduction: if vagal tone A Muscarinic receptor antagonists

  • (5) Blood vessels and blood pressure

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

    Larger dosesA Muscarinic receptor antagonists

  • 2. Clinical uses

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

    (2) Inhibiting exocrine gland secretion Preanesthetic medication, over-secretion

    (3) Ophthalmology Acute iritis or iridocyclitis: mydriatics/miotics Measurement of the refraction: childrenA Muscarinic receptor antagonists

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

    (5) Septic shock

    (6) Antidote for organophosphate poisoningA Muscarinic receptor antagonists

  • 3. Adverse effects

    (1) Side effects

    (2) Central toxicity Lethal dose: 80~130 mg (adults), 10 mg (child) but not including the case of treating organophosphate toxicationA Muscarinic receptor antagonists

  • (3) Detoxication Symptomatic treatment: diazepam, etc. Physostigmine () or pilocarpine ()

    (4) Contraindications glaucoma, prostatauxe, feverA Muscarinic receptor antagonists

  • Actions and clinical uses

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

    Pre-anesthetic medication, prevention of motion sickness, Parkinsons disease Scopolamine A Muscarinic receptor antagonists

  • Actions and clinical uses

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

    Septic shock, spasms of smooth muscles of GI and biliary ductAnisodamine , 654-2A Muscarinic receptor antagonists

  • Synthetic mydriatics

    Homatropine shorter duration (1~2 days)Examination of eyes generally

    Tropicamide 1/4 daySynthetic Substitutes for atropineA Muscarinic receptor antagonists

  • Synthetic Antispasmadics

    AirwayIpratropine bromide ()

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

    treatment of bronchial asthma and chronic bronchitis; injection or aerosolA Muscarinic receptor antagonists

  • G.I.Propantheline bromide ()poor absorption (po) and BBB penetrationantispasmodic effects in GI, treatment of peptic ulcer disease

    Benactyzine ()peptic ulcer disease with anxiety, GI and urinary bladder spasmsA Muscarinic receptor antagonists

  • M1 receptor antagonists


    inhibition of gastric acid and pepsin secretion

    weak in salivary glands and eye, poor penetration into CNS

    used in treatment of peptic ulcer diseaseA Muscarinic receptor antagonists

  • B Nicotinic receptor antagonists

  • Ganglion Blockers (NN receptor antagonists)

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

    Short-acting; tachyphylaxis

    Used for controlled hypotensionB Nicotinic receptor antagonists

  • B Nicotinic receptor antagonists neuromuscular blockers

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

    Binding to NM receptors, initial excitation action, then persisting depolarization and resistance to ACh

    initially transient fasciculations tachyphylaxis after repeated uses anti-AChE potentiates their effects no ganglion-blocking effects at therapeutic dosesB Nicotinic receptor antagonists

  • Succinylcholine , ScolineB Nicotinic receptor antagonists

  • 1.1 Pharmacological effects

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

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

    Short-acting (5 min), degradation by plasma pseudocholinesterasesB Nicotinic receptor antagonists

  • 1.2 Clinical uses

    An adjuvant in anesthesia or operation Intubation of trachea, esophagus, etc. Prevention of trauma during electroshock therapy

    Contraindicated in awake patients, should be used under anesthesiaB Nicotinic receptor antagonists

  • 1.3 Adverse effects

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

    (2) Muscle spasm muscular pain after operationB Nicotinic receptor antagonists

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

    (4) Malignant hyperthermia genetic abnormality

    (5) Others rise in intraocular pressure (glaucoma) histamine release B Nicotinic receptor antagonists

  • 1.4 Drug interactions


    ChE inhibitors: AChE inhibitors, cyclophosphamide, procaine, etc.

    Some antibiotics: kanamycin, polymyxins, etc. (synergism in neuromuscular blocking) B Nicotinic receptor antagonists

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

    2.1 Effects: competitive blockade of NM receptors2.2 Uses: adjuvant treatment of anesthesia or operationsTubocurarine B Nicotinic receptor antagonists

  • 2.3 Adverse effects

    Respiratory paralysis: can be reversed by neostigmine

    Enhancing histamine release: BP , bronchoconstriction, salivery secretion

    Blocking ganglion: BP

    Contraindications: myasthenia gravis, bronchial asthma, shock, child (< 10 y)B Nicotinic receptor antagonists

  • Benzylisoquinolines atracurium doxacurium mivacurium Ammonio steroids pancuronium vecuronium pipecuronium rocuronium Other nondepolarizing neuromuscular blockersB Nicotinic receptor antagonists