AnticholinergicAnticholinergic drugsdrugs

WhatWhat studentsstudents shouldshould know:know: Student should be able to describe:

• Kinetics of muscarinic antagonists • The effects of on the major organ systems. • To list the clinical uses of muscarinic antagonists. • To know adverse effects & contraindications. • To identify one antimuscarinic agent for each of the following special uses: mydriasis, cycloplegia, peptic ulcer & parkinsonism. AnticholinergicAnticholinergic DrugsDrugs (Cholinoreceptor(Cholinoreceptor blockers)blockers)

NicotinicNicotinic blockers.blockers. GanglionicGanglionic blockers.blockers. NeuromuscularNeuromuscular blockers.blockers.

MuscarinicMuscarinic blockersblockers (Parasympatholytics)(Parasympatholytics) ClassificationClassification ofof AntimuscarinicsAntimuscarinics

1.1. NaturallyNaturally occurringoccurring alkaloids.alkaloids. AtropineAtropine –– HyoscineHyoscine

2.2. SyntheticSynthetic atropineatropine substitutes.substitutes. NaturallyNaturally occurringoccurring alkaloidsalkaloids AtropineAtropine

PharmacokineticsPharmacokinetics „ TertiaryTertiary amineamine ?? „ OrallyOrally absorbedabsorbed -- CrossCross BBBBBB „ MetabolizedMetabolized inin thethe liver,liver, excretedexcreted inin urine.urine. „ HasHas shortshort durationduration ofof actionaction onon mostmost organsorgans exceptexcept eyeeye.. MechanismMechanism ofof actionaction

„ ReversibleReversible competitivecompetitive blockadeblockade ofof allall muscarinicmuscarinic receptorsreceptors (NOT(NOT SELECTIVE).SELECTIVE).

„ BlockBlock muscarinicmuscarinic actionsactions ofof AchAch andand otherother parasympathomimeticsparasympathomimetics..

„ CanCan atropineatropine reversereverse thethe actionaction ofof AchAch onon skeletalskeletal musclesmuscles?? PharmacologicalPharmacological EffectsEffects CNSCNS „ CNSCNS sedativesedative actionaction

„ VagalVagal nucleusnucleus (CIC):(CIC): InitialInitial bradycardiabradycardia && Tachycardia.Tachycardia.

„ AntiemeticAntiemetic effecteffect (block(block vomitingvomiting center).center).

„ antiparkinsonianantiparkinsonian effecteffect (block(block basalbasal ganglia).ganglia).

„ ToxicToxic dose:dose: HyperthermiaHyperthermia -- excitementexcitement--hallucination.hallucination. CVSCVS 1.1. HeartHeart –– InitialInitial bradycardiabradycardia ((centralcentral)) followedfollowed byby tachycardiatachycardia ((peripheralperipheral).). –– ↑↑ AVAV conductionconduction (( ++ veve dromotropicdromotropic effecteffect).). 2.2. BloodBlood vesselsvessels –– TherapeuticTherapeutic dosedose:: ↓↓ VasodilatationVasodilatation inducedinduced byby cholinomimetics.cholinomimetics. –– ToxicToxic dose:dose: CutaneousCutaneous vasodilatationvasodilatation →→ (atropine(atropine flush).flush). EyeEye –– PassivePassive mydriasismydriasis duedue toto paralysisparalysis ofof circularcircular musclemuscle.. –– CycloplegiaCycloplegia (loss(loss ofof accommodation)accommodation) duedue toto paralysisparalysis ofof ciliaryciliary muscle.muscle. –– LossLoss ofof lightlight reflex.reflex. –– ↑↑ I.O.PI.O.P ## glaucoma.glaucoma. –– ↓↓ LacrimalLacrimal secretionsecretion →→ sandysandy eye.eye. SecretionsSecretions –– ↓↓ SalivarySalivary secretionsecretion →→ (( DryDry mouthmouth ).). –– ↓↓ SweatingSweating →→ DryDry skinskin →→ FeverFever inin infantsinfants andand children.children. –– ↓↓ BronchialBronchial secretionsecretion →→ ↑↑ Viscosity.Viscosity. –– ↓↓ LacrimalLacrimal secretionsecretion →→ SandySandy eye.eye. –– ↓↓ GastricGastric secretionsecretion →→ ↓↓ GastricGastric motilitymotility GITGIT –Relaxation of smooth muscles (constipation). –↓ GIT motility → Antispasmodic effect. –↑ Sphincter contractions.

UrinaryUrinary TractTract –Relaxation of the ureter smooth muscles. –Sphincter contraction. – Urinary retention. BronchialBronchial MusclesMuscles –Bronchial Relaxation

– ↓ Bronchial secretion → ↑↑ viscosity UsesUses

1. preanestheticpreanesthetic medicationmedication toto :: –– ↓↓ SalivarySalivary && bronchialbronchial secretion.secretion. –– ProtectProtect thethe heartheart fromfrom excessiveexcessive vagalvagal tone.tone. 2.2. AntispasmodicAntispasmodic inin renalrenal && intestinalintestinal colics.colics. 3.3. CholinomimeticCholinomimetic oror organophosphorousorganophosphorous poisoning.poisoning. 4.4. MyocardialMyocardial infarction(toinfarction(to preventprevent vagalvagal discharge).discharge). AdverseAdverse effectseffects && ToxicityToxicity –– BlurredBlurred visionvision –– MydriasisMydriasis –– TachycardiaTachycardia -- AtropineAtropine flushflush –– UrinaryUrinary retentionretention -- Constipation.Constipation. –– DrynessDryness ofof mouthmouth ,, SandySandy eyeeye –– MalignantMalignant hyperthermia.hyperthermia. –– Hallucination,Hallucination, ExcitationaExcitationa (Toxic(Toxic dose).dose). TreatmentTreatment –– GastricGastric lavage.lavage. –– Anticonvulsant.Anticonvulsant. –– CoolingCooling blanket.blanket. –– Antidote:Antidote: PhysostigminePhysostigmine (( IVIV slowly).slowly). HyoscineHyoscine ()(SCOPOLAMINE)

What is difference between atropine and hyoscine? Hyoscine „ MoreMore rapidrapid onsetonset ofof actionaction „ ShorterShorter durationduration ofof actionaction „ LessLess mydriaticmydriatic actionaction (2(2--44 days).days). „ MoreMore CNSCNS depressantdepressant actionaction Sedation – Inhibition of center. „ HasHas amnesicamnesic action.action. „ LessLess CVSCVS effecteffect UsesUses – Preanesthetic medication – Antiemetic action (Motion sickness). ContraindicationsContraindications –– Glaucoma.Glaucoma. –– Tachycardia.Tachycardia. –– ProstateProstate hypertrophyhypertrophy inin oldold patients.patients. –– ConstipationConstipation && paralyticparalytic ileusileus.. –– ChildrenChildren SyntheticSynthetic AtropineAtropine SubstitutesSubstitutes

EyeEye ForFor FunduscopicFunduscopic ExaminationExamination ofof thethe eye.eye. AtropineAtropine 77 days.days. HomatropineHomatropine 2424 hours.hours. CyclopentolateCyclopentolate 1212 hours.hours. TropicamideTropicamide 66 hours.hours.

GITGIT

PepticPeptic ulcerulcer PirenzepinePirenzepine (Selective(Selective M1M1 blocker)blocker) AntispasmodicAntispasmodic HyoscineHyoscine butylbutyl bromidebromide Oxyphenonium.Oxyphenonium. DicyclomineDicyclomine PropanthelinePropantheline.. Glycopyrrolate.Glycopyrrolate. ParkinsonismParkinsonism –– Benztropine.Benztropine. –– Trihexphenidyl.Trihexphenidyl.

BronchialBronchial AsthmaAsthma IpratropiumIpratropium bromidebromide –– QuaternaryQuaternary compound.compound. –– TakenTaken byby inhalationinhalation asas aerosolaerosol (bronchodilator).(bronchodilator). –– LittleLittle effecteffect onon viscosity.viscosity. –– UsefulUseful inin COPDCOPD patients.patients. USESUSES ofof antimuscarinicsantimuscarinics –– ASAS mydriatics.mydriatics. –– BronchialBronchial asthma.asthma. –– AntispasmodicAntispasmodic forfor intestinalintestinal andand renalrenal colicscolics –– TravellerTraveller 's's diarrheadiarrhea –– PepticPeptic ulcerulcer –– Antiparkinsonian.Antiparkinsonian. –– AntiemeticAntiemetic,, motionmotion sicknesssickness (( Hyoscine).Hyoscine). –– PrePre--anestheticanesthetic medication.medication. –– CholinomimeticsCholinomimetics intoxicationintoxication –– UrinaryUrinary incontinenceincontinence inin adultsadults Direct cholinomimetic drugs ACh ___

Methacholine ___ Paralytic ileus Urinary retention Glaucoma

Bethanechol Paralytic ileus Urinary retention Glaucoma Cevimeline Sjogren's syndrome. Indirect cholinomimetic drugs (Anticholinesterases)

Edrophonium.- Diagnosis of Myasthenia gravis. Supraventricular tachycardia Neostigmine Myasthenia gravis treatment , Paralytic ileus Urinary retention Physostigmine Glaucoma atropine toxicity Ambenonium Myasthenia gravis treatment Pyridostigmine Ecothiophate Glaucoma. Isofluorophate Donepezil Alzheimer disease Tacrine Antimuscarinic drugs

Atropine Preanesthetic medication - Antispasmodic Hyoscine Motion sickness - Preanesthetic medication Antispasmodic

Pirenzepine Peptic ulcer Ipratropium Asthma Benztropine Parkinsonism

Dicyclomine Antispasmodics Oxyphenonium Fundus examination ThankThank youyou