autonomic nervous system ii
DESCRIPTION
Autonomic nervous system II. MUDr. Martin Votava. Main functions. contraction and relaxation of smooth muscles function of all exocrine and some endocrine glands heart beat some metabolic pathways. Homotropic and heterotropic inhibition. Parasympatomimetics Parasympatolytics - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/1.jpg)
Autonomic nervous system II.
MUDr. Martin Votava
![Page 2: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/2.jpg)
Main functions
• contraction and relaxation of smooth muscles
• function of all exocrine and some endocrine glands
• heart beat
• some metabolic pathways
![Page 3: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/3.jpg)
![Page 4: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/4.jpg)
![Page 5: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/5.jpg)
Homotropic and heterotropic inhibition
![Page 6: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/6.jpg)
• Parasympatomimetics
• Parasympatolytics
• Drugs affecting autonomic ganglia
![Page 7: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/7.jpg)
Cholinomimetics
• Effect similar to stimulation of cholinergic nervous system
• Act on muscarinic (M) a nicotinic (N) receptors
![Page 8: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/8.jpg)
M1, M3, M5 receptors
muscarinic receptor
![Page 9: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/9.jpg)
M2, M4 receptors
muscarinic receptor
![Page 10: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/10.jpg)
Muscarinic and nicotinic (cholinergic) receptors
Receptor Localisation G protein Effector M1 Nerve fibres + IP3, DAG M2 Heart, nerve fibres,
smooth muscles + cAMP
M3 Glands, smooth muscles + IP3, DAG M4 CNS? + cAMP M5 CNS? + IP3, DAG NM Neuromuscular junction - Opening of Na+/K+ ion
channel NN Ganglial receptors - Opening of Na+/K+ ion
channel and depolarisation
![Page 11: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/11.jpg)
Stimulation of muscarinic receptorOrgan Effect
Eye m. sphincter pupillae Contraction –miosis
m.ciliaris Contraction- accommodation
Heart SA nodus frequency (neg. chronotropic)
Atriums contractility (neg. inotropnic)
AV nodus conduction speed (neg. dromotropic)
Ventricules contractility (neg. inotropic)
Vessels Dilatation (EDRF) – NO
Airways Bronchoconstriction
Glands Stimulation
GIT motility increases
Sfincters relaxation
Glands secretion increases
Vesica urinaria
Detrusor Contraction
Trigonum and sfinkter Relaxation
Glands sweat, salivary, lacrimal, nasopharyngeal
Secretion
![Page 12: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/12.jpg)
Nicotinic effects
Ganglial receptors
Depends on autonomic stimulation. When sympathetic nervous system outweighs (vessels), then their stimulation stimulates sympathetic neurons.
When parasympathetic system outweighs (heart, GIT), then their stimulation stimulates parasympathetic neurons.
Adrenal medula - adrenalin and noradrenalin release
Neuromuscular junction - spasms and convulsions of skeletal muscles
![Page 13: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/13.jpg)
Cholinomimetics
1. directM receptor agonistsN receptor agonists
(most of them are nonspecific)
2. indirect (AChE inhibitors) short acting-edrofoniumintermediate acting - carbamateslong acting (irreversible blockers) - organophosphates
![Page 14: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/14.jpg)
Direct cholinomimetics
Acetylcholine - direct endogenous cholinomimetics, which is released in:
• sympathetic and parasympathetic ganglias (N-effects)• postganglial parasympathetic neurons (M-effects)• neuromuscular junction (N-effects)• adrenal medula (N-effect, adrenaline secretion)• CNS (N-effect)
Very fast hydrolysis by acetylcholinesterase.
![Page 15: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/15.jpg)
![Page 16: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/16.jpg)
Acetylcholine
• poor absorption p.o. and s.c., does not cross HEB• rapid hydrolysis by AChE• BP decrease, bradycardia, heart arrest• sweating, salivation, lacrimation, glands secretion• nauzea, cough, dyspnoe• vessels dilatation EDRF (NO) release• effect
![Page 17: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/17.jpg)
Acetylcholine effect
![Page 18: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/18.jpg)
Pilocarpine
• tercial N atom - increased lipofility, cross HE barrier and enters cornea
• M and N effect • miosis and decreases intraocular pressure
![Page 19: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/19.jpg)
Carbachol
• quartery N atom, does not cross HEB, resistance to AChE
• secretion GIT glands• GIT muscles atonia• miosis and decreases intraocular pressure• CI - obstruction GIT
![Page 20: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/20.jpg)
Metacholine, betanechol
• quartery N atom, does not cross HEB, resistance to AChE
• GIT motility increasing, urinary retention after anesthesia or vagotomia
• examination of exocrine pancreas secretion• CI - obstruction GIT
![Page 21: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/21.jpg)
Intoxication
M receptors: CNS stimulation, miosis, accommodation, dyspnoe, (bronchoconstriction, hypersecretion of bronchial glands), diarrhoea (hypermotility and hypersecretion), hypotension (vazodilatation), bradycardia.
N receptors: convulsions, BP increase (adrenal and ganglia N receptor stimulation).
![Page 22: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/22.jpg)
Indication
• postoperative and neurogenic ileus, urinary retention.
• glaucoma (carbachol, pilokarpine).
![Page 23: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/23.jpg)
Reversible (competitive) AChE inhibitors
Drug Effect PharmacokineticsEdrofonium M, N Quartery amine, parenteral
administration, effect 5-15 minCarbamates
Physostigmine M, N Tercialy amine, per os admin., effect0.5-2 h.
Neostigmine M, N Quartery amine, effect 0.5-3 h.Pyridostigmine M, N Quartery amine, effect 4-8 h.
![Page 24: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/24.jpg)
Indications
• Postoperative and neurogenic ileus, urinary retention – neostigmine
• Glaucoma- physostigmine• Myastenia gravis – neostigmine,
pyridostigmine, edrophonium• Treatment of neuromuscular blocks• Alzheimer disease
– rivastigmine, donezepil
![Page 25: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/25.jpg)
Ireversible AChE inhibitors - organphosphates
• M and N effect– AChE activity 70% - mild intoxication– AChE activity 30% - severe intoxication
![Page 26: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/26.jpg)
Toxicology importance
• agriculture - herbicids and pesticids• chemical weapons: tabun, sarin, soman (cross skin
and mucos membranes)• Intoxication - nausea, vomitus, cephalea, weakness,
sweating, salivation, bradycardia, dyspnoe, breathing arrest
• Pharmacotherapy:• Very rare: glaucoma: echothiophtate
– scabies: malathione
![Page 27: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/27.jpg)
Therapy of intoxication
• avoid absorption• atropine - blocks muscarinic effects• ventilation• AChE reactivators- pralidoxime• short acting AChE inhibitors - save AChE,
which is not affected by poison
![Page 28: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/28.jpg)
Parasympatolytics
tercial amonium basis (tercial amonium atom):natural alkaloids. Atropin (Atropa belladonna) or
(Datura stramonium) and scopolamine (Hyosciamus niger).
synthetic analogs - esterification of natural basis with organic acids
Quartery amonium basis (quartery amonium atom)
![Page 29: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/29.jpg)
Pharmacokinetics
absorption:
tercial basis - good GIT and corneal absorption
Quartery basis - GIT absorption only 10-30%
distribution:
tercial basis - very wide distribution (HEB) after 1 hour - many CNS side effects
Quartery basis - dont cross HEB
![Page 30: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/30.jpg)
Atropine - competitive reversible inhibitor
dose(mg)
effect
0,5bradycardia, xerostomia, sweating decrease
1,0tachycardia, mydiasis
2,0tachycardia, mydriasis, accommodationdisorders
5,0worsening of previous effect, fatigue,headache, obstipation, hot and dry skin,swallowing problems
>10,0tachycaria, hot and red skin, ataxia,excitation, hallucinations, delirium, coma
![Page 31: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/31.jpg)
CNS effects
Antiemetic properties (scopolamine) - kinetosis, vestibular apparatus disorders
tremor attenuation in Parkinson disease (Acetylcholine increased release)
n. vagus center stimulation - bradycardia (after low doses of atropine), after high doses direct antimuscarinic effect - tachycardia
![Page 32: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/32.jpg)
Eye effect
m. sphincter pupillae - inhibition of m. sfincter pupillae, m. dilatator pupillae indirect activation - mydriasis
m. ciliaris paralysis - cycloplegia. accommodation attenuation
cave - acute glaucoma attack
lacrimation decrease
![Page 33: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/33.jpg)
GIT effect
Attenuation of GIT motility (M receptors), then gland secretion
Relaxation of GIT smooth muscles
Contraction of sphincters, GIT paralyis
Stomach secretion is attenuated after relatively high doses of parasympatolytics
![Page 34: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/34.jpg)
Termoregulation
atropine attenuated sweating, one of the most important termoregulatory mechanism. It causes body temperature increase, but only after high doses. Children can have atropine fewer after lower doses of artropine
![Page 35: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/35.jpg)
Indications I.
Parkinson disease, symptomatic therapy, (first line therapy are dopaminergic drugs)
Kinetosis - scopolamine, transcutal form, (24-48 h.), side effects
Bradycardia
Eyes
mydriasis for diagnostic examination
synechia prevention when inflammation is present (uveitis, iritis)
![Page 36: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/36.jpg)
Indications II.
Gastrointestinal disorders (Quartery bases)
peptic ulcer disease. (Antimuscarinic effect to the parietal cells - pirenzepine, poldine)
spasmolytics - GIT - urolithiasis, cholelythiasis
diarrhoea with cramps (combination with opiates) (e.g. atropine with diphenoxylate [REASEC])
bronchodilatation and inhibition of secretion
asthma bronchiale therapy: ipratropium (ATROVENT), or combination with fenoterole (BERODUAL)
sweating
![Page 37: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/37.jpg)
Indications III.
therapy of AChE irreversible inhibitors poisoning (organophaosphates). Atropinsulphate in high doses(1-2 mg) i.v. after 5-15 min. until atropine side effect are present (dry mouth, miosis)
Mushroom poisoning
Amanita muscarina - after 30 - 60 minutes - nausea, vomitus, diarrhoea, tachycardia, sweating, salivation, bronchoconstriction - atropine (1-2 mg parenteral)
![Page 38: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/38.jpg)
Side effects
peripheral - dry skin, tachycardia, mydriasis, cycloplegia
Stimulation, CNS excitation (hallucinations, delirium, convulsions, coma)
Warm and red, dry skin, increased body temperature
Quartery bases - mostly antimuscarinic affects, minimal central effects
Antinicotinic effects - hypotension
Therapy - neostigmine, sympatomimetics (fenylefrine)
![Page 39: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/39.jpg)
Contraindications
glaucoma, (closed angle)
prosthatic hypertrophy
![Page 40: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/40.jpg)
![Page 41: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/41.jpg)
Drugs affecting autonomic ganglia
• Ganglion stimulants– (acetylcholine)– Nicotine (drug of abuse)– Lobeline (found in tabacco leaves as well)
– Dimethylphenylpiperazinium (DMPP)– Tetramethylamonium
Used as experimental tools
![Page 42: Autonomic nervous system II](https://reader034.vdocuments.net/reader034/viewer/2022051517/56814e62550346895dbc00dd/html5/thumbnails/42.jpg)
Ganglion-blocking drugs
• Interference with acetylcholine release– Botulinum toxin, hemicholinium
• Prolonged depolarization– Nicotine
• Competitive antagonist– Hexamethonium, tetraethylamonium