Acetylcholine: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
m (Protected "Acetylcholine": Bot: Protecting all pages from category Drug ([Edit=Allow only administrators] (indefinite) [Move=Allow only administrators] (indefinite)))
 
(18 intermediate revisions by one other user not shown)
Line 1: Line 1:
{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = 2-acetoxy-N,N,N-trimethylethanaminium
|authorTag={{Ammu}}
| image = ACh.png
|genericName=acetylcholine
| image2 = ACh-stick.png
|aOrAn=a
| CAS_number = 51-84-3
|drugClass=neurotransmitter
| ATC_prefix = S01
|indicationType=treatment
| ATC_suffix = EB09
|indication=for temporary relief of [[chest congestion]] with mild constriction, indigestion, [[drowsiness]], [[headache]], [[forgetfulness]], and general [[fatigue]]
| ATC_supplemental =  
|adverseReactions=[[corneal edema]], [[corneal clouding]], and [[corneal decompensation]] have been reported with the use of intraocular acetylcholine
| PubChem = 187
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| DrugBank = EXPT00412
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| chemical_formula =  
| C=7 | H=16 | N=1 | O=2
| molecular_weight = 146.21 g/mol
| smiles = CC(OCC[N<sup>+</sup>](C)(C)C)=O
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = approximately 2 minutes
| pregnancy_category =
| legal_status = legal with license
| routes_of_administration =
}}
{{CMG}}


* Content


<!--Adult Indications and Dosage-->


==Overview==
<!--FDA-Labeled Indications and Dosage (Adult)-->
The [[chemical compound]] '''acetylcholine''' (often abbreviated '''ACh''') is a [[neurotransmitter]] in both the [[peripheral nervous system]] (PNS) and [[central nervous system]] (CNS) in many organisms including [[homo sapiens|humans]]. Acetylcholine is one of many neurotransmitters in the [[autonomic nervous system]] (ANS) and the only neurotransmitter used in the [[somatic nervous system]]. It is also the neurotransmitter in all [[autonomic ganglia]].
|fdaLIADAdult=* For temporary relief of chest congestion with mild constriction, indigestion, drowsiness, [[headache]], forgetfulness, and general [[fatigue]].
* To obtain miosis of the iris in seconds after delivery of the [[lens]] in [[cataract]] surgery, in penetrating [[keratoplasty]], [[iridectomy]] and other anterior segment surgery where rapid [[miosis]] may be required
==Chemistry==
* 10 drops  orally, 3 times a day.  Consult a physician for use in children under 12 years of age.
Acetylcholine is an [[ester]] of [[acetic acid]] and [[choline]] with [[chemical formula]] [[acetyl|CH<sub><small>3</small></sub>CO]][[oxygen|O]][[methylene|CH<sub><small>2</small></sub>]][[methylene|CH<sub><small>2</small></sub>]][[Nitrogen|N]]<sup><small>+</small></sup>([[methyl|CH<sub><small>3</small></sub>]])<sub><small>3</small></sub>. This structure is reflected in the systematic name, ''2-acetoxy-N,N,N-trimethylethanaminium''.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.


==Function==
<!--Pediatric Indications and Dosage-->
Acetylcholine has functions both in the [[peripheral nervous system]] (PNS) and in the [[central nervous system]] (CNS) as a [[neuromodulator]].


In the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system.
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.


In the CNS, acetylcholine and the associated neurons form a [[neurotransmitter system]], the cholinergic system, which tends to cause excitatory actions.  
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.


===In PNS===
<!--Contraindications-->
In the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system.
|contraindications=* It is contraindicated in persons with a known hypersensitivity to any component of this product.
|warnings=* If pregnant or breast-feeding, ask a health care professional before use.
* Keep out of reach of children.  In case of overdose, get medical help or contact a Poison Control Center right away.
* Do not use if tamper evident seal is broken or missing.  Store in a cool, dry place.
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=* Infrequent cases of corneal edema, corneal clouding, and corneal decompensation have been reported with the use of intraocular acetylcholine.
* Adverse reactions have been reported rarely which are indicative of systemic absorption. These include bradycardia, hypotension, flushing, breathing difficulties and sweating.
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''


When acetylcholine binds to [[acetylcholine receptor]]s on [[skeletal muscle]] fibers, it opens [[ligand gated sodium channels]] in the [[cell membrane]]. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine, while inducing contraction of skeletal muscles, instead induces decreased contraction in [[cardiac muscle]] fibers. This distinction is attributed to differences in receptor structure between skeletal and cardiac fibers.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.


In the [[autonomic nervous system]], acetylcholine is released in the following sites:
<!--Administration and Monitoring-->
*all pre and post-ganglionic [[parasympathetic nervous system|parasympathetic]] neurons
|administration=* [[Oral]]
*all preganglionic [[sympathetic nervous system|sympathetic]] neurons
* [[Anterior chamber instillation]]
**preganglionic sympathetic fibers to suprarenal medulla, the modified sympathetic ganglion. On stimulation by acetylcholine, it releases [[adrenaline]] and [[noradrenaline]].
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
*some postganglionic sympathetic fibers : )
**sudomotor neurons to [[sweat gland]]s


===In CNS===
In the central nervous system, ACh has a variety of effects as a [[neuromodulator]], e.g. for plasticity and excitability. Other effects are arousal and [[reward system|reward]].


====Structure====
Acetylcholine and the associated neurons form a [[neurotransmitter system]], the cholinergic system. It originates mainly in ''pontomesencephalotegmental complex'', [[basal optic nucleus of Meynert]] and medial [[septal nucleus]], and projects axons to vast areas of the brain:
* The ''pontomesencephalotegmental complex'' acts mainly on [[M1 receptor]]s in the [[brainstem]] .
*[[basal optic nucleus of Meynert]] acts mainly on [[M1 receptor]]s in the [[neocortex]].
*medial [[septal nucleus]] acts mainly on [[M1 receptor]]s in the [[hippocampus]] and [[neocortex]].


====Plasticity====
<!--IV Compatibility-->
ACh is involved with [[synaptic plasticity]], specifically in [[learning]] and [[Memory#Short-term|short-term memory]]
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.


It has been shown to enhance the amplitude of synaptic potentials following [[long-term potentiation]] in many regions, including the [[dentate gyrus]], [[CA1]], [[piriform cortex]], and [[neocortex]]. This effect most likely occurs either through enhancing currents through [[NMDA]] receptors or indirectly by suppressing [[neural adaptation|adaptation]]. The suppression of adaptation has been shown in brain slices of regions CA1, [[cingulate cortex]], and piriform cortex as well as [[in vivo]] in cat [[somatosensory cortex|somatosensory]] and [[motor cortex]] by decreasing the conductance of voltage-dependent [[M current]]s and [[calcium|Ca<sup>2+</sup>]]-dependent [[potassium|K<sup>+</sup>]] currents.
<!--Overdosage-->
|overdose=* Atropine sulfate (0.5 to 1 mg) should be given intramuscularly or intravenously and should be readily available to counteract possible overdosage. [[Epinephrine]] (0.1 to 1 mg subcutaneously) is also of value in overcoming severe cardiovascular or bronchoconstrictor responses.
|drugBox={{Ionbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 401028016
| ImageFile = Acetylcholine.svg
| ImageFile_Ref = {{chemboximage| Verifiedfields = changed| Watchedfields = changed| verifiedrevid = 401028016|correct|??}}
| ImageSize = 181
| ImageName = Skeletal formula of acetylcholine
| ImageFile1 = Acetylcholine-cation-3D-balls.png
| ImageFile1_Ref = {{chemboximage|correct|??}}
| ImageSize1 = 181
| ImageName1 = Stick model of acetylcholine
| IUPACName = 2-Acetoxy-''N'',''N'',''N''-trimethylethanaminium
| Section1 = {{Chembox Identifiers
|  Abbreviations = ACh
|  CASNo =  51-84-3
|  CASNo_Ref = {{cascite|correct|CAS}}
|  PubChem = 187
|  PubChem_Ref = {{Pubchemcite|correct|pubchem}}
|  ChemSpiderID = 182
|  ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|  UNII = N9YNS0M02X
|  UNII_Ref = {{fdacite|correct|FDA}}
|  EINECS = 200-128-9
|  DrugBank = EXPT00412
|  KEGG = C01996
|  KEGG_Ref = {{keggcite|changed|kegg}}
|  MeSHName = Acetylcholine
|  ChEBI = 15355
|  ChEMBL = 667
|  ChEMBL_Ref = {{ebicite|changed|EBI}}
|  IUPHAR_ligand = 294
|  Beilstein = 1764436
|  Gmelin = 326108
|  3DMet = B00379
|  ATCCode_prefix = S01
|  ATCCode_suffix = EB09
|  SMILES = CC(=O)OCC[N+](C)(C)C
|  StdInChI = 1S/C7H16NO2/c1-7(9)10-6-5-8(2,3)4/h5-6H2,1-4H3/q+1
|  StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|  InChI = 1/C7H16NO2/c1-7(9)10-6-5-8(2,3)4/h5-6H2,1-4H3/q+1
|  StdInChIKey = OIPILFWXSMYKGL-UHFFFAOYSA-N
|  StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|  InChIKey = OIPILFWXSMYKGL-UHFFFAOYAY
}}
| Section2 = {{Chembox Properties
|  Formula = {{Chem|C|7|H|16|N|O|2|+}}
|  MolarMass = 146.2074 g mol<sup>-1</sup>
|  ExactMass = 146.118103761 g mol<sup>-1</sup>
}}
| Section3 = {{Chembox Pharmacology
|  HalfLife = 2 min
}}
}}
|mechAction=* Acetylcholine is a naturally occurring neurohormone which mediates nerve impulse transmission at all cholinergic sites involving somatic and autonomic nerves. After release from the nerve ending, acetylcholine is rapidly inactivated by the enzyme acetylcholinesterase by hydrolysis to acetic acid and choline.
|structure=* Acetylcholine chloride  is a parasympathomimetic preparation for intraocular use. It is packaged in a blister pack containing one vial and one ampule. The vial contains 20 mg acetylcholine chloride and 56 mg mannitol. The accompanying ampule contains 2 mL of a modified diluent of sodium acetate trihydrate, potassium chloride, magnesium chloride hexa-hydrate, calcium chloride dihydrate and sterile water for injection.
* The reconstituted liquid will be a sterile isotonic solution (275–330 milliosmoles/Kg) containing 20 mg acetylcholine chloride (1:100 solution) and 2.8% mannitol. The pH range is 5.0–8.2. [[Mannitol]] is used in the process of lyophilizing acetylcholine chloride, and is not considered an active ingredient.
* The chemical name for acetylcholine chloride, C7H16ClNO2, is Ethanaminium, 2-(acetyloxy)-N,N,N-trimethyl-, chloride and is represented by the following chemical structure:
<!--: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]-->
|PD=* Direct application of acetylcholine to the iris will cause rapid [[miosis]] of short duration. Topical ocular instillation of acetylcholine to the intact eye causes no discernible response as cholinesterase destroys the molecule more rapidly than it can penetrate the cornea.
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.


====Excitability====
<!--Nonclinical Toxicology-->
Acetylcholine also has other effects on excitability of neurons. Its presence causes a slow [[depolarization]] by blocking a tonically active K<sup>+</sup> current, which increases neuronal excitability. Paradoxically, it increases spiking activity in [[inhibitory interneuron]]s while decreasing strength of synaptic transmission from those cells. This decrease in synaptic transmission also occurs selectively at some excitatory cells: for instance, it has an effect on intrinsic and associational fibers in layer Ib of piriform cortex, but has no effect on afferent fibers in layer Ia. Similar laminar selectivity has been shown in dentate gyrus and region CA1 of the hippocampus. One theory to explain this paradox interprets acetylcholine neuromodulation in the neocortex as modulating the estimate of expected uncertainty, acting counter to [[norepinephrine]] (NE) signals for unexpected uncertainty. Both would then decrease synaptic transition strength, but ACh would then be needed to counter the effects of NE in learning a signal understood to be noisy.
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.


==Synthesis and Degradation==
<!--Clinical Studies-->
Acetylcholine is synthesized in certain [[neuron]]s by the [[enzyme]] [[choline acetyltransferase]] from the compounds [[choline]] and [[acetyl-CoA]].
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.


Normally, the enzyme [[acetylcholinesterase]] converts acetylcholine into the inactive [[metabolites]] [[choline]] and [[acetate]]. This enzyme is abundant in the synaptic cleft, and its role in rapidly clearing free acetylcholine from the synapse is essential for proper muscle function.
<!--How Supplied-->
|howSupplied=* Miochol®-E (acetylcholine chloride intraocular solution)
:* NDC 24208-539-20


==Receptors==
One blister pack containing the following components:
{{Main|Acetylcholine receptor}}
* Vial of 20 mg acetylcholine chloride powder for intraocular solution
There are two main classes of acetylcholine receptor (AChR), [[nicotinic acetylcholine receptor]]s (nAChR) and [[muscarinic acetylcholine receptor]]s (mAChR). They are named for the [[ligands]] used to discover the receptors.  
* Ampoule of 2 mL diluent
* One 0.2 micron sterile filter
* Priming volume 0.6 mL (approximately)
|storage=* Store at 4°–25°C (39°–77°F).
* KEEP FROM FREEZING.
|packLabel=<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.


===Nicotinic===
<!--Precautions with Alcohol-->
Nicotinic AChRs are [[Ligand-gated ion channel|ionotropic receptors]] permeable to [[sodium]], [[potassium]], and [[chloride]] ions. They are stimulated by [[nicotine]] and acetylcholine. They are of two main types, muscle type and neuronal type. The former can be selectively blocked by [[curare]] and the latter by [[hexamethonium]]. The main location of nicotinic AChRs are on [[muscle]] end plates, autonomic ganglia (both sympathetic and parasympathetic), and in the CNS.<ref> Katzung, B.G. (2003). ''Basic and Clinical Pharmacology (9th ed.).'' McGraw-Hill Medical. ISBN 0-07-141092-9</ref>
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


===Muscarinic===
<!--Brand Names-->
Muscarinic receptors are [[metabotropic]] and affect neurons over a longer time frame. They are stimulated by [[muscarine]] and acetylcholine, and blocked by [[atropine]]. Muscarinic receptors are found in both the central nervous system and the peripheral nervous system, in heart, lungs, upper GI tract and sweat glands. Extracts from the plant [[Deadly nightshade]] included this compound, and its action on muscarinic AChRs that increased pupil size was used for attractiveness in many European cultures in the past. Now, ACh is sometimes used during [[cataract]] surgery to produce rapid constriction of the pupil. It must be administered intraocularly because [[cornea|corneal]] [[cholinesterase]] metabolizes topically administered ACh before it can diffuse into the eye. It is sold by the trade name Miochol-E (CIBA Vision). Similar drugs are used to induce [[mydriasis]] (dilation of the pupil) in [[cardiopulmonary resuscitation]] and many other situations.
|brandNames=* MIOCHOL E®<ref>{{Cite web | title = MIOCHOL E- acetylcholine chloride  | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e701ef07-9499-4b56-931f-f4eb3eedbe24 }}</ref>


==Drugs Acting on the ACh System==
<!--Look-Alike Drug Names-->
Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Drugs acting on the acetylcholine system are either agonists to the receptors, stimulating the system, or antagonists, inhibiting it.
|drugShortage=
 
}}
=== ACh Receptor Agonists ===
{{LabelImage
Acetylcholine receptor agonists can either have an effect directly on the receptors, or exert their effects indirectly, e.g. by affecting the enzyme [[acetylcholinesterase]], which degrades the receptor ligand.
|fileName=Acetylcholine 1.png
 
}}
====Associated disorders====
{{LabelImage
ACh Receptor Agonists are used to treat [[myasthenia gravis]] and [[Alzheimer's disease]].
|fileName=DailyMed - MIOCHOL E- acetylcholine chloride    .png
 
}}
=====Myasthenia gravis=====
<!--Pill Image-->
The disease [[myasthenia gravis]], characterized by muscle weakness and fatigue, occurs when the body inappropriately produces [[antibody|antibodies]] against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission. Over time the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine or physostigmine) are effective in treating this disorder. They allow endogenously released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in the gap junction.
 
=====Alzheimer's disease=====
Since a shortage of acetylcholine in the [[brain]] has been associated with [[Alzheimer's disease]], some drugs that inhibit acetylcholinesterase are used in the treatment of that disease. A recent study has shown that [[THC]] is one such drug, effective at reducing the formation of characteristic [[neurofibrillary tangle]]s and [[amyloid beta]] plaques<ref name="eubanks 2006">Eubanks LM, Rogers CJ, Beuscher AE 4th, Koob GF, Olson AJ, Dickerson TJ, Janda KD. "A molecular link between the active component of marijuana and Alzheimer's disease pathology." ''Molecular Pharmaceutics''. 2006 Nov-Dec; 3(6):773-7. PMID 17140265</ref>.
 
====Direct Acting====
* Acetylcholine
* [[Bethanechol]]
* [[Carbachol]]
* [[Cevimeline]]
* [[Pilocarpine]]
* [[Suberylcholine]]
* [[Nicotine]] (in small doses)
 
====Cholinesterase inhibitors====
Most indirect acting ACh receptor agonists work by inhibiting the enzyme [[acetylcholinesterase]]. The resulting accumulation of acetylcholine causes continuous stimulation of the muscles, glands and central nervous system.
 
They are examples of [[enzyme inhibitors]], and increase the action of acetylcholine by delaying its degradation; some have been used as [[nerve agent]]s ([[Sarin]] and [[VX (nerve agent)|VX]] nerve gas) or [[pesticide]]s ([[organophosphates]] and the [[carbamates]]). Clinically they are used to reverse the action of [[muscle relaxant]]s, to treat [[myasthenia gravis]] and in [[Alzheimer's disease]] ([[rivastigmine]], which increases cholinergic activity in the brain).
 
=====Reversible=====
The following substances reversibly inhibit the enzyme [[acetylcholinesterase]] (which breaks down acetylcholine), thereby increasing acetylcholine levels.
* Many medications in [[Alzheimer's disease]]
** [[Donepezil]]
** [[Galantamine]]
** [[Rivastigmine]]
** [[Tacrine]]
** [[THC]]
* [[Edrophonium]] (differs [[myasthenic crisis|myasthenic]] and [[cholinergic crisis]])
* [[Neostigmine]] (in [[myasthenia gravis]])
* [[Physostigmine]] (in [[glaucoma]] and [[anticholinergic]] drug overdoses)
* [[Pyridostigmine]] (in [[myasthenia gravis]]
* [[Carbamate]] [[insecticides]] (e.g. [[Aldicarb]])
 
=====Irreversible=====
Semi-permanently inhibit the enzyme acetylcholinesterase.
* [[Echothiophate]]
* [[Isoflurophate]]
* [[Organophosphate]] [[Insecticides]] ([[Malathion]], [[Parathion]], [[Azinphos Methyl]], [[Chlorpyrifos]], among others)
* Organophosphate-containing [[nerve agents]] (e.g. [[Sarin gas]])
 
Victims of [[sarin gas]], commonly die of suffocation as they cannot relax their [[Thoracic diaphragm|diaphragm]].
 
====Reactivation of Acetylcholine Esterase====
* [[Pralidoxime]]
 
=== ACh Receptor Antagonists ===
====Antimuscarinic Agents====
* [[Atropine]]
* [[Ipratropium]]
* [[Scopolamine]]
* [[Tiotropium]]
 
====Ganglionic Blockers====
* [[Mecamylamine]]
* [[Hexamethonium]]
* [[Nicotine]] (in high doses)
* [[Trimethaphan]]
 
====Neuromuscular Blockers====
* [[Atracurium]]
* [[Cisatracurium]]
* [[Doxacurium]]
* [[Metocurine]]
* [[Mivacurium]]
* [[Pancuronium]]
* [[Rocuronium]]
* [[Succinylcholine]]
* [[Tubocurarine]]
* [[Vecuronium]]
* [[HemiCholine]]


====Synthesis inhibitors====
Organic [[mercurial]] compounds have a high affinity for [[thiol|sulfhydryl groups]], which causes dysfunction of the enzyme choline acetyl transferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function.


====Release inhibitors====
[[Botulism toxin|Botulin]] acts by suppressing the release of acetylcholine; where the venom from a [[black widow spider]] has the reverse effect.


====Other / Uncategorized / Unknown====
<!--Label Display Image-->
* [[surugatoxin]]


==History==
Acetylcholine (ACh) was first identified in 1914 by [[Henry Hallett Dale]] for its actions on heart tissue. It was confirmed as a neurotransmitter by [[Otto Loewi]] who initially gave it the name [[vagusstoff]] because it was released from the [[vagus nerve]]. Both received the 1936 [[Nobel Prize in Physiology or Medicine]] for their work.


Acetylcholine was the first [[neurotransmitter]] to be identified.


==References==
{{reflist|2}}


{{refbegin}}
*Brenner, G. M. and Stevens, C. W. (2006). ''Pharmacology (2nd ed.).'' Philadelphia, PA: W.B. Saunders Company (Elsevier). ISBN 1-4160-2984-2
*Canadian Pharmacists Association (2000). ''Compendium of Pharmaceuticals and Specialties (25th ed.)''. Toronto, ON: Webcom. ISBN 0-919115-76-4
*Carlson, NR (2001). ''Physiology of Behavior (7th ed.)''. Needham Heights, MA: Allyn and Bacon. ISBN 0-205-30840-6
*Gershon, Michael D. (1998). ''The Second Brain''.  New York, NY: HarperCollins. ISBN 0-06-018252-0
*Hasselmo, ME. [http://people.bu.edu/hasselmo/HasselmoBBR1995.pdf "Neuromodulation and cortical function: Modeling the physiological basis of behavior."] ''Behavioral Brain Research''. 1995 Feb; 67(1):1-27. PMID 7748496
*Yu, AJ & [[Peter Dayan|Dayan, P]]. [http://www.gatsby.ucl.ac.uk/~dayan/papers/yud2005.pdf "Uncertainty, neuromodulation, and attention."] ''Neuron''. 2005 May 19; 46(4):681-92. PMID 15944135
{{refend}}


==External links==
<!--Category-->
* [http://www.neuro.wustl.edu/neuromuscular/mother/acetylcholine.htm Washington University (St. Louis) writeup]
 
<br>


[[Category:Drug]]
[[Category:Acetylcholine| ]]
[[Category:Choline esters]]
[[Category:Choline esters]]
[[Category:Acetates]]
[[Category:Neurotransmitters]]
[[Category:Quaternary ammonium compounds]]
[[Category:Quaternary ammonium compounds]]
[[ar:أستيل كولين]]
[[ceb:Acetylcholine]]
[[de:Acetylcholin]]
[[es:Acetilcolina]]
[[fr:Acétylcholine]]
[[hr:Acetilkolin]]
[[it:Acetilcolina]]
[[he:אצטילכולין]]
[[lt:Acetilcholinas]]
[[hu:Acetilkolin]]
[[nl:Acetylcholine]]
[[ja:アセチルコリン]]
[[no:Acetylkolin]]
[[pl:Acetylocholina]]
[[pt:Acetilcolina]]
[[ru:Ацетилхолин]]
[[sl:Acetilholin]]
[[sr:Ацетилхолин]]
[[fi:Asetyylikoliini]]
[[sv:Acetylkolin]]
[[tl:Acetylcholine]]
[[tr:Asetilkolin]]
[[uk:Ацетилхолін]]
[[ur:اسی ٹائل کولین]]
[[zh:乙酰胆碱]]
{{jb1}}
{{WH}}
{{WS}}

Latest revision as of 17:10, 18 August 2015

Acetylcholine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Acetylcholine is a neurotransmitter that is FDA approved for the treatment of for temporary relief of chest congestion with mild constriction, indigestion, drowsiness, headache, forgetfulness, and general fatigue. Common adverse reactions include corneal edema, corneal clouding, and corneal decompensation have been reported with the use of intraocular acetylcholine.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • For temporary relief of chest congestion with mild constriction, indigestion, drowsiness, headache, forgetfulness, and general fatigue.
  • To obtain miosis of the iris in seconds after delivery of the lens in cataract surgery, in penetrating keratoplasty, iridectomy and other anterior segment surgery where rapid miosis may be required
  • 10 drops orally, 3 times a day. Consult a physician for use in children under 12 years of age.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Acetylcholine in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Acetylcholine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Acetylcholine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Acetylcholine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Acetylcholine in pediatric patients.

Contraindications

  • It is contraindicated in persons with a known hypersensitivity to any component of this product.

Warnings

  • If pregnant or breast-feeding, ask a health care professional before use.
  • Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.
  • Do not use if tamper evident seal is broken or missing. Store in a cool, dry place.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Acetylcholine in the drug label.

Postmarketing Experience

  • Infrequent cases of corneal edema, corneal clouding, and corneal decompensation have been reported with the use of intraocular acetylcholine.
  • Adverse reactions have been reported rarely which are indicative of systemic absorption. These include bradycardia, hypotension, flushing, breathing difficulties and sweating.

Drug Interactions

There is limited information regarding Acetylcholine Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Acetylcholine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Acetylcholine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Acetylcholine with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Acetylcholine with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Acetylcholine with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Acetylcholine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Acetylcholine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Acetylcholine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Acetylcholine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Acetylcholine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Acetylcholine in patients who are immunocompromised.

Administration and Monitoring

Administration

Monitoring

There is limited information regarding Monitoring of Acetylcholine in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Acetylcholine in the drug label.

Overdosage

  • Atropine sulfate (0.5 to 1 mg) should be given intramuscularly or intravenously and should be readily available to counteract possible overdosage. Epinephrine (0.1 to 1 mg subcutaneously) is also of value in overcoming severe cardiovascular or bronchoconstrictor responses.

Pharmacology

Template:Ionbox

Mechanism of Action

  • Acetylcholine is a naturally occurring neurohormone which mediates nerve impulse transmission at all cholinergic sites involving somatic and autonomic nerves. After release from the nerve ending, acetylcholine is rapidly inactivated by the enzyme acetylcholinesterase by hydrolysis to acetic acid and choline.

Structure

  • Acetylcholine chloride is a parasympathomimetic preparation for intraocular use. It is packaged in a blister pack containing one vial and one ampule. The vial contains 20 mg acetylcholine chloride and 56 mg mannitol. The accompanying ampule contains 2 mL of a modified diluent of sodium acetate trihydrate, potassium chloride, magnesium chloride hexa-hydrate, calcium chloride dihydrate and sterile water for injection.
  • The reconstituted liquid will be a sterile isotonic solution (275–330 milliosmoles/Kg) containing 20 mg acetylcholine chloride (1:100 solution) and 2.8% mannitol. The pH range is 5.0–8.2. Mannitol is used in the process of lyophilizing acetylcholine chloride, and is not considered an active ingredient.
  • The chemical name for acetylcholine chloride, C7H16ClNO2, is Ethanaminium, 2-(acetyloxy)-N,N,N-trimethyl-, chloride and is represented by the following chemical structure:

Pharmacodynamics

  • Direct application of acetylcholine to the iris will cause rapid miosis of short duration. Topical ocular instillation of acetylcholine to the intact eye causes no discernible response as cholinesterase destroys the molecule more rapidly than it can penetrate the cornea.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Acetylcholine in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Acetylcholine in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Acetylcholine in the drug label.

How Supplied

  • Miochol®-E (acetylcholine chloride intraocular solution)
  • NDC 24208-539-20

One blister pack containing the following components:

  • Vial of 20 mg acetylcholine chloride powder for intraocular solution
  • Ampoule of 2 mL diluent
  • One 0.2 micron sterile filter
  • Priming volume 0.6 mL (approximately)

Storage

  • Store at 4°–25°C (39°–77°F).
  • KEEP FROM FREEZING.

Images

Drug Images

{{#ask: Page Name::Acetylcholine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Acetylcholine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Acetylcholine in the drug label.

Precautions with Alcohol

  • Alcohol-Acetylcholine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

There is limited information regarding Acetylcholine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ "MIOCHOL E- acetylcholine chloride".

{{#subobject: 

 |Label Page=Acetylcholine
 |Label Name=Acetylcholine 1.png

}}

{{#subobject: 

 |Label Page=Acetylcholine
 |Label Name=DailyMed - MIOCHOL E- acetylcholine chloride    .png

}}

Retrieved from "https://www.wikidoc.org/index.php?title=Acetylcholine&oldid=1134628"