muscarinic receptors and directly acting cholinomimetics when your eyes hurt, you cant pee, and your...

Muscarinic Receptors Muscarinic Receptors and Directly Acting and Directly Acting CholinomimeticsCholinomimetics

When your eyes hurt, you When your eyes hurt, you can’t pee, and your GI tract can’t pee, and your GI tract

turns offturns off

Drug ListDrug List AcetylcholineAcetylcholine

– Has lots of muscarinic activity but also nicotinic activity (of course, as Has lots of muscarinic activity but also nicotinic activity (of course, as it is the physiologic nicotinic and muscarinic agonist). Very suceptible it is the physiologic nicotinic and muscarinic agonist). Very suceptible to acetylcholinesterase.to acetylcholinesterase.

MethacolineMethacoline– Choline ester with effects similar to acetylcholine and no nicotinic Choline ester with effects similar to acetylcholine and no nicotinic

activity. Not used due to CV effects. Somewhat resistant to activity. Not used due to CV effects. Somewhat resistant to acetylcholinesterase.acetylcholinesterase.

CarbacholCarbachol– Choline eseter with some nicotinic activity, used for glaucoma.Choline eseter with some nicotinic activity, used for glaucoma.

BethanecolBethanecol– Choline ester with Muscarinic effects with less CV effects and no Choline ester with Muscarinic effects with less CV effects and no

nicotinic activity, totally resistant to AChEsterase, used for GI and nicotinic activity, totally resistant to AChEsterase, used for GI and bladder problems and antimuscarinic poisoningbladder problems and antimuscarinic poisoning

PilocarpinePilocarpine– Alkaloid used to reduce intraocular pressure. Has some nicotinic Alkaloid used to reduce intraocular pressure. Has some nicotinic

activityactivity MuscarineMuscarine

– Pure muscarinic agonist, clinically useless.Pure muscarinic agonist, clinically useless. More on these drugs later…More on these drugs later…

By the end of this lecture you By the end of this lecture you should be able to…should be able to…

Describe in detail the physiologic effects Describe in detail the physiologic effects of muscarinic receptor activation in both of muscarinic receptor activation in both the ANS and the CNS.the ANS and the CNS.

Describe the pharmacologic properties Describe the pharmacologic properties of the two classes of directly acting of the two classes of directly acting muscarinic cholinomimetics.muscarinic cholinomimetics.

List the therapeutic uses and adverse List the therapeutic uses and adverse side effects of cholinomimeticsside effects of cholinomimetics

M-1 ReceptorM-1 Receptor LocationLocation

– NervesNerves G ProteinG Protein

– GPCR GGPCR Gq/11-q/11-linkedlinked

Second Messenger Second Messenger – PLC, IP3, DAGPLC, IP3, DAG– Blocks voltage gated M-type K+ channels.Blocks voltage gated M-type K+ channels.

Primary ANS EffectsPrimary ANS Effects– Critical for muscarinic effect in the sympathetic Critical for muscarinic effect in the sympathetic

ganglion and the parasympathetic myenteric plexus ganglion and the parasympathetic myenteric plexus innervation. innervation.

CNS EffectsCNS Effects– Highly expressed in the CNS and may be involved in Highly expressed in the CNS and may be involved in

epilepsy.epilepsy.


– Heart, nerves, smooth muscleHeart, nerves, smooth muscle G ProteinG Protein

– GPCR GGPCR Gi/o-i/o-linkedlinked Second Messenger Second Messenger

– Decreases cAMP and activates K+ channelsDecreases cAMP and activates K+ channels Primary ANS EffectsPrimary ANS Effects

– Heart- decreases pacemaker current velocity and decreases heart Heart- decreases pacemaker current velocity and decreases heart rate by activating K+ channels (GIRKs) (aka is a negative rate by activating K+ channels (GIRKs) (aka is a negative chronotrope)chronotrope)

– Smooth muscle- works with M3 to contractSmooth muscle- works with M3 to contract– Autoreceptors- presynaptic receptors inhibit the release of Ach Autoreceptors- presynaptic receptors inhibit the release of Ach

Dysfunction of M2 autoreceptors may cause airway problems.Dysfunction of M2 autoreceptors may cause airway problems.– Heteroreceptors-a mixture of M2 and “non-M2” receptors, these Heteroreceptors-a mixture of M2 and “non-M2” receptors, these

receptors lie on sympathetic nerve terminals and inhibit NE release.receptors lie on sympathetic nerve terminals and inhibit NE release. CNS EffectsCNS Effects

– Is the prominent receptor in the spinal chord and thusly is critical in Is the prominent receptor in the spinal chord and thusly is critical in muscarinic agonist-induced analgesia, whatever that means.muscarinic agonist-induced analgesia, whatever that means.

– Serves as an autoreceptor in the brain, which might make it Serves as an autoreceptor in the brain, which might make it important for learning and memory.important for learning and memory.


– Glands, smooth muschle, endotheliumGlands, smooth muschle, endothelium G ProteinG Protein

– GPCR GGPCR Gq/11-q/11-linkedlinked Second MessengerSecond Messenger

– PLC, IP3, DAG PLC, IP3, DAG Primary ANS EffectsPrimary ANS Effects

– Sweat glands- secretion through the sympathetic pathwaySweat glands- secretion through the sympathetic pathway Designed to make your life difficult and be an exceptionDesigned to make your life difficult and be an exception

– Smooth muscle- most important receptor for contraction (GI Smooth muscle- most important receptor for contraction (GI tract, airway, bladder, uterus, and eye smooth muscle)tract, airway, bladder, uterus, and eye smooth muscle)

– Salivary Glands- “M3 receptors play a major role in mACHRs-Salivary Glands- “M3 receptors play a major role in mACHRs-mediated stimulation of salivary secretion”mediated stimulation of salivary secretion”

CNS EffectsCNS Effects– Poorly understood. M3 knockout mice are lean due to reduced Poorly understood. M3 knockout mice are lean due to reduced

food intake. So maybe hypothalamic M3s are important for food intake. So maybe hypothalamic M3s are important for eating behavior.eating behavior.


– CNSCNS– Elsewhere (see effects below)Elsewhere (see effects below)

G ProteinG Protein– GPCR GGPCR Gi/o-i/o-linkedlinked

Second MessengerSecond Messenger– Decreased cAMP Decreased cAMP

Primary EffectsPrimary Effects– Similar to M2 in the CNS as autoreceptorsSimilar to M2 in the CNS as autoreceptors– Autoreceptor in atrial and bladder Autoreceptor in atrial and bladder

parasympathetic nerve terminals (works with M2)parasympathetic nerve terminals (works with M2)– May also play a role as heteroreceptors (NE May also play a role as heteroreceptors (NE

release blockers) in sympathetic nerve terminals.release blockers) in sympathetic nerve terminals.


– CNSCNS G ProteinG Protein

– GPCR GGPCR Gq/11-q/11-linkedlinked Second MessengerSecond Messenger

– PLC, IP3, DAG PLC, IP3, DAG Primary EffectsPrimary Effects

– May be involved in reward circuitry of the brainMay be involved in reward circuitry of the brain– Mediate ACh-induced dilation of cerebral Mediate ACh-induced dilation of cerebral

arteries/arteriolesarteries/arterioles– Effects outside CNS are unknownEffects outside CNS are unknown

Muscarinic Agonists: Choline Muscarinic Agonists: Choline EstersEsters

ChemistryChemistry– Are structural modifications of Acetylcholine. Are structural modifications of Acetylcholine.

1) addition of a carbon-methacholine 1) addition of a carbon-methacholine 2) change a C to an N -Carbamoylcholine/carbachol 2) change a C to an N -Carbamoylcholine/carbachol 3) or do both- Bethanechol3) or do both- Bethanechol

– Are less susciptible than ACh to acetylcholinesterase, Are less susciptible than ACh to acetylcholinesterase, thus have a longer duration of action.thus have a longer duration of action.

– Work by stimulating ACh receptors (of course)Work by stimulating ACh receptors (of course) Absorption, Distribution, and MetabolismAbsorption, Distribution, and Metabolism

– HydrophilicHydrophilic– Poorly absorbed in GI tractPoorly absorbed in GI tract– Do not cross the blood brain barrier readilyDo not cross the blood brain barrier readily– Metabolized by acetylcholinesteraseMetabolized by acetylcholinesterase

Muscarinic Agonists: Muscarinic Agonists: Natural AlkaloidsNatural Alkaloids

ChemistryChemistry– Muscarine- Quaternary ammonium compoundMuscarine- Quaternary ammonium compound– Pilocarpin- Tertiary aminePilocarpin- Tertiary amine– Produce effects by binding to and stimulating ACh Produce effects by binding to and stimulating ACh

receptorsreceptors Absorption, Distribution, and MetabolismAbsorption, Distribution, and Metabolism

– Tertiary amines are well absorbed, while Tertiary amines are well absorbed, while quaternary amines are less well absorbed in the GI quaternary amines are less well absorbed in the GI tracttract

– Both cross the blood brain barrier wellBoth cross the blood brain barrier well– Eliminated by kidneysEliminated by kidneys

Excretion can be accelarated by acidification of urineExcretion can be accelarated by acidification of urine(Testable and emphasized Concept)(Testable and emphasized Concept)

Strange Muscarinic EffectsStrange Muscarinic Effects What effect does stimulation of M3 receptors on arteries and veins have What effect does stimulation of M3 receptors on arteries and veins have

under normal conditions and at low concentrations of agonist?under normal conditions and at low concentrations of agonist?– VasodilationVasodilation

What effect does stimulation of M3 receptors on vascular smooth muscle What effect does stimulation of M3 receptors on vascular smooth muscle cells have at high concentrations of agonist, primarily during injury or cells have at high concentrations of agonist, primarily during injury or disease?disease?– VasoconstrictionVasoconstriction

What effect do the various Muscarinic receptors have on airways?What effect do the various Muscarinic receptors have on airways?– M1- bronchoconstriction and secretionM1- bronchoconstriction and secretion– M2- bronchoconstriction by antagonizing Beta adrenergicsM2- bronchoconstriction by antagonizing Beta adrenergics– M3- increases secretion of bronchial glandsM3- increases secretion of bronchial glands

What muscarinic receptors are most prominent in the myenteric plexus?What muscarinic receptors are most prominent in the myenteric plexus?– M1M1

What 3 effects do muscarinics have on the eyes?What 3 effects do muscarinics have on the eyes?– Contraction of the iris sphincter causing miosisContraction of the iris sphincter causing miosis– Contraction of the ciliary muscle for accomodationContraction of the ciliary muscle for accomodation– Draining of the anterior chamberDraining of the anterior chamber

Which muscarinic drugs cause cortical arousal?Which muscarinic drugs cause cortical arousal?– Muscarine and pilocarpineMuscarine and pilocarpine

Which muscarinic receptor is must important in: A) epileptogenesis? B) Which muscarinic receptor is must important in: A) epileptogenesis? B) spinal chord? C) food intake (hypothalamus)spinal chord? C) food intake (hypothalamus)– A) M1, B) M2 C)M3A) M1, B) M2 C)M3

MethacholineMethacholine

Pharmacologic actionPharmacologic action– Similar to Ach given IV; no nicotinic effectsSimilar to Ach given IV; no nicotinic effects– Longer duration with some resistance to Longer duration with some resistance to

acetylcholinesteraseacetylcholinesterase Clinical useClinical use

– No longer used due to side effects, No longer used due to side effects, particularly cardiovascularparticularly cardiovascular

– Historically used to diagnose atropine Historically used to diagnose atropine poisoning and to treat peripheral vascular poisoning and to treat peripheral vascular diseasedisease

Carbachol Carbachol (Carbamoylcholine)(Carbamoylcholine)

Pharmacologic ActionPharmacologic Action– Some nicotinic effectSome nicotinic effect– More pronounced muscarinic effect in the GI tract, More pronounced muscarinic effect in the GI tract,

urinary bladder, and iris.urinary bladder, and iris.– Less effective on cardiovascular systemLess effective on cardiovascular system– Resistant to acetylcholinesteraseResistant to acetylcholinesterase

Clinical UseClinical Use– Used only as opthalmic solution, primarily because of Used only as opthalmic solution, primarily because of

nicotinic effects of systemic administrationnicotinic effects of systemic administration– Used for wide angle glaucoma and to produce miosis Used for wide angle glaucoma and to produce miosis

during eye surgeryduring eye surgery– Side effects include pupillary constriction, accomodative Side effects include pupillary constriction, accomodative

spasm, headache, and conjunctival hyperemiaspasm, headache, and conjunctival hyperemia

BethanecholBethanechol Pharmacologic ActionPharmacologic Action

– Similar muscarinic effect to carbachol, but without the nicotinic effectSimilar muscarinic effect to carbachol, but without the nicotinic effect– Completely resistant to acetylcholinesteraseCompletely resistant to acetylcholinesterase

Clinical UseClinical Use– Primarily used as a treatment for urinary retention (postoperative or Primarily used as a treatment for urinary retention (postoperative or

neurogenic)neurogenic)– Also used for postoperative abdominal distension and (rarely) for Also used for postoperative abdominal distension and (rarely) for

antimuscarinic intoxicationantimuscarinic intoxication– Given orally or subcutaneouslyGiven orally or subcutaneously– Contraindicated in peptic ulcer, asthma, coronary insufficiency, Contraindicated in peptic ulcer, asthma, coronary insufficiency,

bradycardia, hypotensionbradycardia, hypotension– While cardiovascular side effects are not common, overdose can cause While cardiovascular side effects are not common, overdose can cause

cardiac arrest.cardiac arrest.– other side effects are consistent with muscarinic activationother side effects are consistent with muscarinic activation

Drug interactionsDrug interactions– Quinidine and procainamide antagonize itQuinidine and procainamide antagonize it– Serotonin reducing drugs (e.g. reserpine) with Bethanechol cause Serotonin reducing drugs (e.g. reserpine) with Bethanechol cause

profound hypothermiaprofound hypothermia

MuscarineMuscarine

Pharmacologic actionPharmacologic action– No nicotinic activity. The reason muscarinic No nicotinic activity. The reason muscarinic

receptors are called muscarinicreceptors are called muscarinic– Absorbed from GI tract, crosses BBB.Absorbed from GI tract, crosses BBB.– Resistant to acetylcholinesterase, long actingResistant to acetylcholinesterase, long acting

Clinical RelevanceClinical Relevance– Not usedNot used– Is the alkaloid responsible for Inocybe type Is the alkaloid responsible for Inocybe type

mushroom poisoningmushroom poisoning Treatment for muscarine poisoning is AtropineTreatment for muscarine poisoning is Atropine

PilocarpinePilocarpine

Pharmacologic ActionPharmacologic Action– Mostly muscarinic but some nicotinic activityMostly muscarinic but some nicotinic activity– Few cardiovascular effectsFew cardiovascular effects

Clinical UseClinical Use– Only as opthalmic solution or Ocusert, to Only as opthalmic solution or Ocusert, to

reduce intraocular pressurereduce intraocular pressure Side EffectsSide Effects

– Ciliary spasm, conjunctival vascular Ciliary spasm, conjunctival vascular congestion, headache, and reduced visual congestion, headache, and reduced visual acuityacuity

Muscarinic BlockersMuscarinic BlockersWhen you can’t breathe, your When you can’t breathe, your

stomach is bleeding, you wet the stomach is bleeding, you wet the bed, and you have tremors and bed, and you have tremors and

motion sicknessmotion sickness9/26/079/26/07

Drug ListDrug List Atropine, ScopolamineAtropine, Scopolamine

– Belladonna alkaloids, oldest antimuscarinicsBelladonna alkaloids, oldest antimuscarinics TropicamideTropicamide

– Used opthalmically to produce mydriasis and cycloplegiaUsed opthalmically to produce mydriasis and cycloplegia DicyclomineDicyclomine

– Historically used to decrease spasm in GI tract, replacedby Historically used to decrease spasm in GI tract, replacedby Oxybutynin and othersOxybutynin and others

GlycopyrrolateGlycopyrrolate– Decreases GI motility. Used parenterally in surgery.Decreases GI motility. Used parenterally in surgery.

PropanthelinePropantheline– Ganglionic and NMJ blocker, widely used for ulcersGanglionic and NMJ blocker, widely used for ulcers

Oxybutynin, Tolterodine, SolifenacinOxybutynin, Tolterodine, Solifenacin– Used Urologically (for bladder spasm etc.), Solifenacin is a Used Urologically (for bladder spasm etc.), Solifenacin is a

selective M3 blocker and is the best and newest treatmentselective M3 blocker and is the best and newest treatment Ipratropium, TriatropiumIpratropium, Triatropium

– Quaternary amines used in aerisolized form to treat COPD. Quaternary amines used in aerisolized form to treat COPD. Triatropium preferentially blocks M1 and M3 and has a longer Triatropium preferentially blocks M1 and M3 and has a longer duration, making it slightly betterduration, making it slightly better

By the end of this session, you By the end of this session, you should be able to:should be able to:

Describe the pharmacologic activities Describe the pharmacologic activities of the prototype muscarinic blocker, of the prototype muscarinic blocker, atropineatropine

Describe the pharmacological Describe the pharmacological properties of muscarinic blockers that properties of muscarinic blockers that are used clinicallyare used clinically

List the therapeutic uses for and List the therapeutic uses for and adverse side effects of muscarinic adverse side effects of muscarinic blockersblockers

Atropine and Scopolamine: Atropine and Scopolamine: Chemo-pharmacologyChemo-pharmacology

ChemistryChemistry– Tertiary amines, levos are activeTertiary amines, levos are active

Pharmacologic actionPharmacologic action– Competitive antagonists of muscarinic Competitive antagonists of muscarinic

receptors (bind to receptors but elicit no receptors (bind to receptors but elicit no response)response)

– Do not effect nicotinic receptorsDo not effect nicotinic receptors

Atropine and Scopolamine: Atropine and Scopolamine: EffectsEffects CNSCNS

– Atropine at therapeutic doses produces few effectsAtropine at therapeutic doses produces few effects– Scopolamine at therapeutic dose and atropine at high dose causes: drowsiness, amnesia, Scopolamine at therapeutic dose and atropine at high dose causes: drowsiness, amnesia,

fatigue, REM disturbancesfatigue, REM disturbances– Higher and higher doses make confusion, hallucination, convulsion, paralysis, coma, Higher and higher doses make confusion, hallucination, convulsion, paralysis, coma,

respiratory failure, and ciruculatory collapserespiratory failure, and ciruculatory collapse EyeEye

– Mydriasis (pupil dilation)Mydriasis (pupil dilation)– Cycloplegia, photophobia, blurred visionCycloplegia, photophobia, blurred vision– Reduced aqueous outflowReduced aqueous outflow

CardiovascularCardiovascular– Transient decrease in HRTransient decrease in HR– High dose produces tachycardia (M2 at SA node), no change in BPHigh dose produces tachycardia (M2 at SA node), no change in BP– No vascular effect at therapeutic level, flushing at toxic doseNo vascular effect at therapeutic level, flushing at toxic dose

Respiratory systemRespiratory system– Bronchodilation and reduced secretions (M3)Bronchodilation and reduced secretions (M3)– Blocking M2 autoreceptors increases Ach releaseBlocking M2 autoreceptors increases Ach release– Better bronchodilation in patients with COPDBetter bronchodilation in patients with COPD

Digestive systemDigestive system– Inhibits salivation (strongly), causes dry mouth at very low doseInhibits salivation (strongly), causes dry mouth at very low dose– Reduces gastric, pancreatic,intestinal and biliary secretions at higher dosesReduces gastric, pancreatic,intestinal and biliary secretions at higher doses

Urinary Urinary – Reduced tone and amplitude of contractionsReduced tone and amplitude of contractions

Sweat GlandsSweat Glands– Inhibits sweating at low doses, increases body temp at higher doses (especially in children)Inhibits sweating at low doses, increases body temp at higher doses (especially in children)

Atropine dose dependencyAtropine dose dependency 0.5 mg0.5 mg

– Slight cardiac slowing, some dry mouth, inhibition of sweatingSlight cardiac slowing, some dry mouth, inhibition of sweating 1 mg1 mg

– Dry mouth, thirst, accelerated heart rate sometimes preceded Dry mouth, thirst, accelerated heart rate sometimes preceded by slowing, mild pupillary dilationby slowing, mild pupillary dilation

2 mg2 mg– Rapid heart rate, palpitation, marked dryness of mouth, dilated Rapid heart rate, palpitation, marked dryness of mouth, dilated

pupils, blurring of near visionpupils, blurring of near vision 5 mg5 mg

– All above and difficulty speaking and swallowing, reslessness All above and difficulty speaking and swallowing, reslessness and fatigue; headache; dry hot skin; difficulty in micturition; and fatigue; headache; dry hot skin; difficulty in micturition; reduced intestinal peristalsisreduced intestinal peristalsis

10 mg or more10 mg or more– Ave symptoms more marked, pulse rapid and weak, iris Ave symptoms more marked, pulse rapid and weak, iris

practically obliterated, vision very blurred, skin flushed, hot dry practically obliterated, vision very blurred, skin flushed, hot dry and scarlet skin; ataxia, restlessness, excitement, and scarlet skin; ataxia, restlessness, excitement, hallucinations, delerium, comahallucinations, delerium, coma

Muscarinic antagonist Muscarinic antagonist chemo-pharmacologychemo-pharmacology

Tertiary AminesTertiary Amines– Well absorbed through the GI tractWell absorbed through the GI tract– Readily cross the blood brain barrier (BBB)Readily cross the blood brain barrier (BBB)

Quaternary AminesQuaternary Amines– Poorly absorbed (10-30%)Poorly absorbed (10-30%)– Do not cross the BBB, so no CNS effectsDo not cross the BBB, so no CNS effects

ExcretionExcretion– Both are mostly excreted in the urineBoth are mostly excreted in the urine– Some are metabolized by liver P450 (not Some are metabolized by liver P450 (not

specified which)specified which)

Clinical Uses: OpthalmologyClinical Uses: Opthalmology

Opthalmologic UseOpthalmologic Use– Muscarinic blockers are useful to Muscarinic blockers are useful to

produce cycloplegia to study disorders produce cycloplegia to study disorders of accomodationof accomodation

– Produce mydriasis which enables easy Produce mydriasis which enables easy examination of retina and optic discexamination of retina and optic disc

Specific Drug usedSpecific Drug used– Tropicamide is used because it is the Tropicamide is used because it is the

only one listed with a short enough only one listed with a short enough duration of effect to be practicalduration of effect to be practical

Respiratory UsesRespiratory Uses LimitationsLimitations

– Usefulness is somewhat limited because of systemic side Usefulness is somewhat limited because of systemic side effects and the reduced production of respiratory mucouseffects and the reduced production of respiratory mucous

IpratropiumIpratropium– Non selective quaternary amine used as an aerosol for Non selective quaternary amine used as an aerosol for

COPDCOPD– Few systemic effects due to poor absorptionFew systemic effects due to poor absorption– Does not impede mucociliary transportDoes not impede mucociliary transport

TiotropiumTiotropium– Quaternary amine preferentially inhibits M1 and M3 over Quaternary amine preferentially inhibits M1 and M3 over

M2M2– Few systemic effects due to poor absorptionFew systemic effects due to poor absorption– Does not impede mucociliary transportDoes not impede mucociliary transport– Longer duration of action than ipratropiumLonger duration of action than ipratropium– Also used for COPDAlso used for COPD

Urologic UsesUrologic Uses ClinicologyClinicology

– Used in uninhibited bladder syndrome, bladder spasm, Used in uninhibited bladder syndrome, bladder spasm, enuresis, and urge incontinenceenuresis, and urge incontinence

– Increase functional bladder capacity, reduce pressure Increase functional bladder capacity, reduce pressure and frequency of contractionsand frequency of contractions

– Side effects include dry mouth and dry eyeSide effects include dry mouth and dry eye OxybutyninOxybutynin

– Tertiary amine, non-selective antagonistTertiary amine, non-selective antagonist TolterodineTolterodine

– Tertiary amine with slight preference for M2Tertiary amine with slight preference for M2 SolifenacinSolifenacin

– Tertiary amine with preference for M3, newest and most Tertiary amine with preference for M3, newest and most usefuluseful

Digestive Tract Uses: adjunct Digestive Tract Uses: adjunct onyony

Muscarinic antagonists are used as an Muscarinic antagonists are used as an adjunctadjunct therapy for therapy for– Peptic Ulcer- effective at reucing basal and Peptic Ulcer- effective at reucing basal and

nocturnal acid secretion (not postprandial)nocturnal acid secretion (not postprandial)– Duodenal ulcer- used when initial H2 antagonists Duodenal ulcer- used when initial H2 antagonists

and antacids are inadequateand antacids are inadequate– Irritable bowel syndromeIrritable bowel syndrome– Acute pancreatitis- if pancreatic ducts are Acute pancreatitis- if pancreatic ducts are

obstructedobstructed PirenzepinePirenzepine

– M1 preferring (and M4) antagonist used in EuropeM1 preferring (and M4) antagonist used in Europe

CNS UsesCNS Uses

Used in two CNS conditions:Used in two CNS conditions:– ParkinsonismParkinsonism

Tertiary amines are used as an adjunct to L-Tertiary amines are used as an adjunct to L-dopa or in patients for whom L-dopa is dopa or in patients for whom L-dopa is contraindicatedcontraindicated

– Motion SicknessMotion Sickness May block cholinergic sites investibular May block cholinergic sites investibular

nuclei and the reticular formationnuclei and the reticular formation Scopalamine is used; available in dermal Scopalamine is used; available in dermal

patch to be placed behind the earpatch to be placed behind the ear

Cardiovascular Use: limitedCardiovascular Use: limited

Therapeutic IndexTherapeutic Index– Very lowVery low

Myocardial InfarctionMyocardial Infarction– Atropine used in patients with severe Atropine used in patients with severe

bradycardia and hypotension to increase bradycardia and hypotension to increase heart rate, BP, and COheart rate, BP, and CO

Other UseOther Use– Bradycardia caused by excessive carotid Bradycardia caused by excessive carotid

sinus reflexsinus reflex

Anesthesiology usesAnesthesiology uses

As PremedicationAs Premedication– Historically used with diethyl ether to Historically used with diethyl ether to

reduce salivary and respiratory secretionsreduce salivary and respiratory secretions– Currently used to block bradycardia and Currently used to block bradycardia and

hypotension from reduced vagal activity hypotension from reduced vagal activity during surgeryduring surgery

With AChEWith AChE– Also used to prevent excess muscarinic Also used to prevent excess muscarinic

effects when acetylcholinesterase agents effects when acetylcholinesterase agents are used to treat competitive are used to treat competitive neuromuscular blockadeneuromuscular blockade

As AntidoteAs Antidote

Antidote for 2 poisoningsAntidote for 2 poisonings– Anticholinesterase poisoningAnticholinesterase poisoning– Amanita muscaria mushroom poisoningAmanita muscaria mushroom poisoning

Random clinical uses of Random Random clinical uses of Random drugsdrugs

(from the last page of the lecture)(from the last page of the lecture) DicyclomineDicyclomine

– Decrease spasm in the gi tractDecrease spasm in the gi tract– Replaced by oxybutyninReplaced by oxybutynin

GlycopyrrolateGlycopyrrolate– oral use decreases GI motilityoral use decreases GI motility– Parenterally used during surgeryParenterally used during surgery

PropanthelinePropantheline– Widely used for ulcerWidely used for ulcer– Ganglionic blockerGanglionic blocker– NMJ blockadeNMJ blockade

Anticholinesterase Anticholinesterase poisoningpoisoning

Natural causesNatural causes– Ingestion of plants in Solanacae family: deadly nightshade, Ingestion of plants in Solanacae family: deadly nightshade,

jimson weed, stinkweed (with names like that who wouldn’t jimson weed, stinkweed (with names like that who wouldn’t eat them)eat them)

Most sensitive patientsMost sensitive patients– ChildrenChildren

PresentationPresentation– Peripheral effects seen at lower doses, CNS effects at high Peripheral effects seen at lower doses, CNS effects at high

doses (emphasized in class)doses (emphasized in class) DiagnosisDiagnosis

– Based on symptoms; can use methacholine injectionBased on symptoms; can use methacholine injection TreatmentTreatment

– Gastric lavae, respiratory assistance, physostigmine, Gastric lavae, respiratory assistance, physostigmine, benzodiazepines (if delirious or convulsive), and monitor benzodiazepines (if delirious or convulsive), and monitor body tempbody temp

The EndThe End

What is a gastric lavage?What is a gastric lavage?– According to Wikipedia:– Gastric lavage, also commonly called Stomach

pump or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or overdosed on a drug. They may also be used prior to surgery, to clear the contents of the digestive tract before it is opened.

muscarinic receptors and directly acting cholinomimetics when your eyes hurt, you cant pee, and your...

Documents

muscarinic effects

effects of cholinomimetics

cv effects

muscarinic cholinomimetics

muscarinic receptors

muscarinic agonists

lots of muscarinic activity

important receptor