Physostigmine: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Protected "Physostigmine": Protecting pages from unwanted edits ([edit=sysop] (indefinite) [move=sysop] (indefinite)))
No edit summary
 
(13 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = 1,2,3,3a,8,8a-hexahydro-1,3a, 8-trimethyl-, methylcarbamate (ester), (3aS,8aR)-pyrrolo(2,3-b)indol-5-ol
|authorTag={{AP}}
| CAS_number = 57-47-6
|genericName=Physostigmine
| ATC_prefix = S01
|aOrAn=a
| ATC_suffix = EB05
|drugClass=central nervous system agent, [[cholinesterase inhibitor]] and anti [[glaucoma]]
| ATC_supplemental = {{ATC|V03|AB19}}
|indicationType=treatment
| PubChem = 5983
|indication=clinical or toxic dosages of drugs capable of producing the [[anticholinergic syndrome]]
| DrugBank = APRD00406
|adverseReactions=[[diaphoresis]], abnormal defecation ([[diarrhea]]), excessive [[salivation]] and [[nausea]] and [[vomiting]]
| C=15 | H=21 | N=3 | O=2
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
| molecular_weight = 275.346 g/mol
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
| melting point = 105-107
|fdaLIADAdult======Past Anesthesia Care=====
| bioavailability =  
*Dosage: 0.5 to 1.0 mg intramuscularly or intravenously. IV administration should be at allow controlled rate of no more than 1 mg per minute. Dosage may be repeated at intervals of 10 to 30 minutes if desired patient response is not obtained.
| protein_bound =  
 
| metabolism =  
=====Clinical or Toxic Dosages of Drugs Capable of Producing the Anticholinergic Syndrome=====
| elimination_half-life =  
*Case report of a 68-year-old male patient admitted to the ICU for treatment of a severe thioridazine intoxication<ref name="pmid9366781">{{cite journal| author=Schmidt W, Lang K| title=Life-threatening dysrhythmias in severe thioridazine poisoning treated with physostigmine and transient atrial pacing. | journal=Crit Care Med | year= 1997 | volume= 25 | issue= 11 | pages= 1925-30 | pmid=9366781 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9366781  }} </ref>.
| pregnancy_category =  
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Physostigmine in adult patients.
| legal_status =  
|offLabelAdultNoGuideSupport======Reversal of Postoperative Reactions to Scopolamine=====
| routes_of_administration =  
*Dosage: 1.0-1.2 milligrams IV<ref name="pmid4796567">{{cite journal| author=Holzgrafe RE, Vondrell JJ, Mintz SM| title=Reversal of postoperative reactions to scopolamine with physostigmine. | journal=Anesth Analg | year= 1973 | volume= 52 | issue= 6 | pages= 921-5 | pmid=4796567 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4796567  }} </ref>. Unique dose.
}}
 
=====Reversal of Postoperative Reactions to Scopolamine in Post-Partum=====
*Clinical trial of 5 postpartum patients<ref name="pmid4707533">{{cite journal| author=Smiler BG, Bartholomew EG, Sivak BJ, Alexander GD, Brown EM| title=Physostigmine reversal of scopolamine delirium in obstetric patients. | journal=Am J Obstet Gynecol | year= 1973 | volume= 116 | issue= 3 | pages= 326-9 | pmid=4707533 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4707533  }} </ref>.
|fdaLIADPed======Clinical or Toxic Dosages of Drugs Capable of Producing the Anticholinergic Syndrome=====
*Case report of a 27 month-old patient with amitriptyline overdose<ref name="pmid9366781">{{cite journal| author=Schmidt W, Lang K| title=Life-threatening dysrhythmias in severe thioridazine poisoning treated with physostigmine and transient atrial pacing. | journal=Crit Care Med | year= 1997 | volume= 25 | issue= 11 | pages= 1925-30 | pmid=9366781 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9366781  }} </ref>.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Physostigmine in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Physostigmine in pediatric patients.
|contraindications=*Physostigmine Salicylate Injection should not be used in the presence of [[asthma]], [[gangrene]], [[diabetes]], [[cardiovascular disease]], [[mechanical obstruction]] of the intestine or urogenital tract or any [[vagotonic]] state, and in patients receiving [[choline esters]] and depolarizing neuromuscular blocking agents ([[decamethonium]], [[succinylcholine]]).
*For post-anesthesia, the concomitant use of [[atropine]] with physostigmine salicylate is not recommended, since the atropine antagonizes the action of physostigmine.
|warnings=*Contains [[sodium bisulfite]], a sulfite that may cause allergic-type reactions including [[anaphylactic symptoms]] and life-threatening or less severe [[asthmatic episodes]] in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.
*If excessive symptoms of [[salivation]], [[emesis]], urination and defecation occur, the use of Physostigmine Salicylate Injection should be terminated. If excessive sweating or [[nausea]] occur, the dosage should be reduced.
*Intravenous administration should be at a slow, controlled rate, no more than 1 mg per minute. Rapid administration can cause [[bradycardia]], [[hypersalivation]] leading to a respiratory difficulties and possible [[convulsions]]. An overdosage of Physostigmine Salicylate Injection can cause a [[cholinergic crisis]].
|clinicalTrials======Cardiovascular Effects=====
*[[Asystole]]
*[[Bradyarrhythmia]]
**Case Report of [[Alzheimer]] patients being treated with Physostigmine<ref name="pmid8422658">{{cite journal| author=Sano M, Bell K, Marder K, Stricks L, Stern Y, Mayeux R| title=Safety and efficacy of oral physostigmine in the treatment of Alzheimer disease. | journal=Clin Neuropharmacol | year= 1993 | volume= 16 | issue= 1 | pages= 61-9 | pmid=8422658 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8422658  }} </ref>
**Case Report of a patient treated with physostigmine for post-operative anesthesia with [[Scopolamine]]<ref name="pmid4796567">{{cite journal| author=Holzgrafe RE, Vondrell JJ, Mintz SM| title=Reversal of postoperative reactions to scopolamine with physostigmine. | journal=Anesth Analg | year= 1973 | volume= 52 | issue= 6 | pages= 921-5 | pmid=4796567 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4796567  }} </ref>.
*[[Cardiac dysrhythmia]]
*[[Hypertension]]
**Case report of a 72 year-old patient treated with 0.5 mg q2h for [[Alzheimer's disease]]<ref name="pmid3717434">{{cite journal| author=Cain JW| title=Hypertension associated with oral administration of physostigmine in a patient with Alzheimer's disease. | journal=Am J Psychiatry | year= 1986 | volume= 143 | issue= 7 | pages= 910-2 | pmid=3717434 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3717434  }} </ref>.
*Increased [[cardiac output]]<ref name="pmid6614520">{{cite journal| author=Nilsson E, Meretoja OA, Neuvonen P| title=Hemodynamic responses to physostigmine in patients with a drug overdose. | journal=Anesth Analg | year= 1983 | volume= 62 | issue= 10 | pages= 885-8 | pmid=6614520 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6614520  }} </ref>
*Increased [[pulmonary arterial wedge pressure]]<ref name="pmid6614520">{{cite journal| author=Nilsson E, Meretoja OA, Neuvonen P| title=Hemodynamic responses to physostigmine in patients with a drug overdose. | journal=Anesth Analg | year= 1983 | volume= 62 | issue= 10 | pages= 885-8 | pmid=6614520 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6614520  }} </ref>
*[[Tachycardia]]
**Dosage: 2mg may cause tachycardia<ref name="pmid3080707">{{cite journal| author=Janowsky DS, Risch SC, Kennedy B, Ziegler MG, Huey LY| title=Acute effects of physostigmine and neostigmine in man. | journal=Mil Med | year= 1986 | volume= 151 | issue= 1 | pages= 48-51 | pmid=3080707 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3080707  }} </ref>


{{SI}}
=====Endocrine/Metabolic Effects=====
*Increased leves of [[growth hormone]]
**Dosage: 12.5 mg/kg<ref name="pmid8206111">{{cite journal| author=Mazza E, Ghigo E, Boffano G, Valetto M, Maccario M, Arvat E et al.| title=Effects of direct and indirect acetylcholine receptor agonists on growth hormone secretion in humans. | journal=Eur J Pharmacol | year= 1994 | volume= 254 | issue= 1-2 | pages= 17-20 | pmid=8206111 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8206111  }} </ref>.


{{EH}}
=====Gastrointestinal Effects=====
==Overview==
*Abnormal [[defecation]]: [[diarrhea]]  
'''Physostigmine''' (also known as '''eserine''') is a [[parasympathomimetic]], specifically, a reversible [[cholinesterase inhibitor]] obtained from the [[Calabar bean]]. By interfering with the metabolism of [[acetylcholine]], physostigmine indirectly [[agonist|stimulates]] both [[nicotinic acetylcholine receptor|nicotinic]] and [[muscarinic acetylcholine receptor|muscarinic]] receptors. The chemical was synthesized for the first time in 1935 by the chemists Percy Lavon Julian and Josef Pikl.
*Excessive [[salivation]]
*[[Hyperperistalsis]]
*[[Nausea and vomiting]]


==Clinical uses==
=====Immunological Effects=====
Physostigmine is used to treat [[glaucoma]] and delayed gastric emptying. Because it is a tertiary amine, it can cross the [[blood-brain barrier]] and so it is also used to treat the [[central nervous system]] effects of [[atropine]], [[scopolamine]] and other [[anticholinergic]] drug overdoses.  Intravenous injection of physostigmine (0.5mg-2mg) can be used to reverse [[GHB]] overdose, although careful control of dose is needed to avoid convulsions; often a small dose of an anticonvulsant such as [[diazepam]] is administered first to counteract the lowering of seizure threshold from the physostigmine. 
*[[Hypersensitivity reactions]]
Possible side effects include depression, and overdose can cause a cholinergic syndrome.  It is available in the U.S. under the trade names Antilirium, Eserine Salicylate, Isopto Eserine, and Eserine Sulfate.


==Historical information==
=====Musculoeskeletal Effects=====
''The following historical information is from the 1911 edition of the Encyclopedia Britannica:''
*Muscle [[fasciculation]]
*[[Muscle weakness]]


The British pharmacopoeia contains an alcoholic extract of the bean, intended for internal administration; but the alkaloid is now always employed. This is used as the [[sulphate]], which has the empirical formula of (C<sub>15</sub>H<sub>21</sub>N<sub>3</sub>O<sub>2</sub>)<sub>2</sub>, H<sub>2</sub>SO<sub>4</sub>, plus an unknown number of molecules of water. It occurs in small yellowish crystals, which are turned red by exposure to light or air. They are readily soluble in water or alcohol and possess a bitter taste. The dose should invariably be administered by hypodermic injection. For the use of the oculist, who constantly employs this drug, it is also prepared in lamellae for insertion within the conjunctival sac. Each of these contains one-thousandth part of a grain of physostigmine sulphate, a quantity which is perfectly efficient. Physostigmine has no action on the unbroken skin. When swallowed it rapidly causes a great increase in the salivary secretion, being one of the most powerful [[sialogogue]]s known. It has been shown that the action is due to a direct influence on the secreting gland-cells themselves. After a few minutes the salivation is arrested owing to the constricting influence of the drug upon the blood vessels that supply the glands. There is also felt a sense of constriction in the [[pharynx]], due to the action of the drug on its [[muscle fiber|muscular fibers]].
=====Neurological Effects=====
*[[Seizures]]  
*Dosage: May appear if doses surpass1 mg/min in adults or 0.5 mg/min in children<ref name="pmid1173100">{{cite journal| author=Newton RW| title=Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage. | journal=JAMA | year= 1975 | volume= 231 | issue= 9 | pages= 941-3 | pmid=1173100 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1173100  }} </ref>.  


A similar stimulation of the non-striped muscle in the alimentary canal results in violent vomiting and purging, if a large dose has been taken. Physostigmine, indeed, stimulates nearly all the non-striped muscles in the body, and this action upon the muscular coats of the arteries, and especially of the arterioles, causes a great rise in blood-pressure shortly after its absorption, which is very rapid. The terminals of the [[vagus nerve]] are also stimulated, causing the heart to beat more slowly. Later in its action, the drug depresses the intra-[[cardiac]] motor [[ganglia]], causing prolongation of [[diastole]] and finally arrest of the heart in dilatation. A large lethal dose kills by this action, but the minimum lethal dose by its combined action on the respiration and the heart. The respiration is at first accelerated by a dose of physostigmine, but is afterwards slowed and ultimately arrested. The initial hastening is due to a stimulation of the vagus terminals in the lung, as it does not occur if these nerves are previously divided. The final arrest is due to paralysis of the respiratory centre in the [[medulla oblongata]], hastened by a quasi-asthmatic contraction of the non-striped muscular tissue in the [[bronchial tube]]s, and by a "water-logging" of the [[lung]]s due to an increase in the amount of bronchial secretion. It may here be stated that the non-striped muscular tissue of the [[Urinary bladder|bladder]], the [[uterus]] and the [[spleen]] is also stimulated, as well as that of the [[Iris (anatomy)|iris]]. It is only in very large doses that the voluntary muscles are poisoned, there being induced in them a tremor which may simulate ordinary convulsions. The action is a direct one upon the muscular tissue (cf. the case of the gland-cells), since it occurs in an animal whose motor nerves have been paralyzed by [[Curare#Pharmacological Properties|curare]]. Consciousness is entirely unaffected by physostigmine, there being apparently no action on any part of the brain above the medulla oblongata.
=====Psychiatric Depression=====
*[[Depression]]  


But the influence of the alkaloid upon the [[spinal cord]] is very marked and characteristic. The reflex functions of the cord are entirely abolished, and it has been experimentally shown that this is due to a direct influence upon the cells in the anterior cornua. It is precisely the reverse of the typical action of [[strychnine]]. Near the termination of a fatal case there is a paralysis of the sensory columns of the cord, so that general sensibility is lowered. The alkaloid calabarine is, on the other hand, a stimulant of the motor and reflex functions of the cord, so that only the pure alkaloid physostigmine and not any preparation of Calabar bean itself should be used when it is desired to obtain this action. Besides the secretions already mentioned as being stimulated, the bile, the tears and the perspiration are increased by the exhibition of this drug. 
=====Renal Effects=====
*[[Polyuria]]
*[[Urinary incontinence]]


Whether administered in the form of the official lamella or by subcutaneous injection, physostigmine causes a contraction of the pupil more marked than in the case of any other known drug. That this action is a direct and not a nervous one is shown by the fact that if the eye be suddenly shaded the pupil will dilate a little, showing that the nerves which cause dilatation are still competent after the administration of physostigmine. Besides the sphincter pupillae, the fibers of the [[ciliary muscle]] are stimulated. There is consequently spasm of accommodation, so that clear vision of distant objects becomes impossible. The intra-ocular tension is markedly lowered.This action, at first sight somewhat obscure, is due to the extreme pupillary contraction which removes the mass of the iris from pressing upon the spaces of Fontana, through which the intraocular fluids normally make a very slow escape from the eye into its efferent [[lymphatic]]s.
=====Respiratory Effects=====
*[[Bronchospasm]]
*Excessive [[bronchial secretion]]<ref name="pmid363335">{{cite journal| author=Nattel S, Bayne L, Ruedy J| title=Physostigmine in coma due to drug overdose. | journal=Clin Pharmacol Ther | year= 1979 | volume= 25 | issue= 1 | pages= 96-102 | pmid=363335 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=363335  }} </ref>
|useInPregnancyFDA=*Safe use in pregnancy and lactation has not been established; therefore, use in pregnant women, nursing mothers or women who may become pregnant requires that possible benefits be weighed against possible hazards to mother and child.
|AUSPregCat=C
|useInPregnancyAUS=*Safe use in pregnancy and lactation has not been established; therefore, use in pregnant women, nursing mothers or women who may become pregnant requires that possible benefits be weighed against possible hazards to mother and child.
|useInPed=*Recommended dosage is 0.02 mg/kg; intramuscularly or by slow intravenous injection, no more than 0.5 mg per minute. If the toxic effects persist, and there is no sign of cholinergic effects, the dosage may be repeated at 5 to 10 minute intervals until a therapeutic effect is obtained or a maximum of 2 mg dosage is attained.
|administration=*IV administration should be at allow controlled rate of no more than 1 mg per minute. Dosage may be repeated at intervals of 10 to 30 minutes if desired patient response is not obtained.
|overdose=Can cause a cholinergic crisis. Appropriate antidote is atropine sulfate.
|drugBox={{Drugbox2
| Watchedfields = changed
| verifiedrevid = 464206065
| IUPAC_name = (3a''R'',8a''S'')-1,3a,8-Trimethyl-1''H'',2''H'',3''H'',3a''H'',8''H'',8a''H''-pyrrolo[2,3-''b'']indol-5-yl ''N''-methylcarbamate
| image = Physostigmine Molecular Structure.png


There is a marked antagonism in nearly all important particulars between the actions of physostigmine and of [[atropine]]. The details of this antagonism, as well as nearly all our knowledge of this valuable drug, we owe to Sir Thomas Fraser, who introduced it into therapeutics. The clinical uses of physostigmine are based upon the facts of its pharmacology, as above detailed. It has been recommended in cases of chronic [[constipation]], and of want of tone in the muscular wall of the urinary bladder. It has undoubtedly been of value in many cases of [[tetanus]], in which it must be given in maximal doses. (The tetanus [[antitoxin]] should invariably be employed as well.) Sir Thomas Fraser differs from nearly all other authorities in regarding the drug as useless in cases of strychnine poisoning, and the question must be left open. There is some doubtful evidence of the value of the alkaloid in [[chorea]]. The oculist uses it for at least six purposes. Its stimulant action on the iris and ciliary muscle is employed when they are weak or paralyzed. It is used in all cases where one needs to reduce the intra-ocular tension, and for this and other reasons in [[glaucoma]]. It is naturally the most efficient agent in relieving the discomfort or intolerable pain of photophobia; and it is the best means of breaking down adhesions of the iris, and of preventing prolapse of the iris after injuries to the cornea.
<!--Clinical data-->
| tradename = Antilirium
| Drugs.com = {{drugs.com|monograph|antilirium}}
| pregnancy_AU = C
| pregnancy_US = C
| pregnancy_category = 
| legal_US = Rx-only
| legal_status = 
| routes_of_administration = intravenous, intramuscular, ophthalmic


In fact it is hardly possible to over-estimate its value in [[ophthalmology]]. The drug has been highly and widely recommended in general paralysis, but there remains grave doubt as to its utility in this disease. Physostigimine has also been advocated for treatment of [[Datura]] poisoning, but clinical studies have not found any discernable benefit.
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = Major metabolite: [[Eseroline]]
| elimination_half-life =


==References==
<!--Identifiers-->
*Brenner, G. M. (2000). ''Pharmacology.'' Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
| CASNo_Ref = {{cascite|changed|??}}
*Canadian Pharmacists Association (2000). ''Compendium of Pharmaceuticals and Specialties'' (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
| CAS_number_Ref = {{cascite|correct|??}}
* {{1911}}
| CAS_number = 57-47-6
*Yates SW, Viera AJ. Physostigmine in the treatment of gamma-hydroxybutyric acid overdose. Mayo clinic proceedings. 2000 Apr;75(4):401-2.
| ATC_prefix = S01
| ATC_suffix = EB05
| ATC_supplemental =  {{ATC|V03|AB19}}
| PubChem = 5983
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00981
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5763
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9U1VM840SP
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00196
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 27953
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 94


{{Anticholinesterases}}
<!--Chemical data-->
{{Antiglaucoma preparations and miotics}}
| C=15 | H=21 | N=3 | O=2
{{Antidotes}}
| molecular_weight = 275.346 g/mol
[[Category:Anticholinesterases]]
| smiles = O=C(Oc1cc2c(cc1)N([C@H]3N(CC[C@@]23C)C)C)NC
[[Category:Antidotes]]
| InChI = 1/C15H21N3O2/c1-15-7-8-17(3)13(15)18(4)12-6-5-10(9-11(12)15)20-14(19)16-2/h5-6,9,13H,7-8H2,1-4H3,(H,16,19)/t13-,15+/m1/s1
{{SIB}}
| InChIKey = PIJVFDBKTWXHHD-HIFRSBDPBN
[[de:Physostigmin]]
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
[[es:Fisostigmina]]
| StdInChI = 1S/C15H21N3O2/c1-15-7-8-17(3)13(15)18(4)12-6-5-10(9-11(12)15)20-14(19)16-2/h5-6,9,13H,7-8H2,1-4H3,(H,16,19)/t13-,15+/m1/s1
[[ru:Физостигмин]]
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = PIJVFDBKTWXHHD-HIFRSBDPSA-N
}}
|mechAction=Physostigmine Salicylate Injection is a reversible [[anticholinesterase]] which effectively increases the concentration of [[acetylcholine]] at the sites of [[cholinergic transmission]]. The action of [[acetylcholine]] is normally very transient because of its hydrolysis by the enzyme, [[acetylcholinesterase]]. Physostigmine Salicylate Injection inhibits the destructive action of [[acetylcholinesterase]] and thereby prolongs and exaggerates the effect of the [[acetylcholine]].
|PK=*Physostigmine Salicylate Injection contains a tertiary amine and easily penetrates the [[blood brain barrier]], while an [[anticholinesterase]], such as [[neostigmine]], which has a quaternary ammonium ion is not capable of crossing the barrier. Physostigmine Salicylate Injection can reverse both central and [[peripheral anticholinergia]]. The [[anticholinergic syndrome]] has both central and peripheral signs and symptoms. Central toxic effects include anxiety, [[delirium]], [[disorientation]], [[hallucinations]], [[hyperactivity]] and [[seizures]]. Severe poisoning may produce [[coma]], [[medullary paralysis]] and [[death]]. Peripheral toxicity is characterized by [[tachycardia]], [[hyperpyrexia]], [[mydriasis]], [[vasodilation]], [[urinary retention]], diminution of gastrointestinal motility, decrease of secretion in salivary and sweat glands, and loss of secretions in the pharynx, bronchi, and nasal passages.
*Dramatic reversal of the effects of anticholinergic symptoms can be expected in minutes after the intravenous administration of Physostigmine Salicylate Injection, if the diagnosis is correct and the patient has not suffered anoxia or other insult. The duration of action of Physostigmine Salicylate Injection is relatively short, approximately 45 to 60 minutes.
|howSupplied=*2 mL Ampules packed 10 per box, 1 mg per mL.
|storage=*Store at 20° to 25°C (68° to 77°F)
|packLabel=[[file:FDA label.png|none|600px]]
[[file:Physost Package3.png|none|400px]]
[[file:Physos Package4.png|none|400px]]
|alcohol=Alcohol-Physostigmine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|brandNames=*[[Antilirium]]
*[[Isopto Eserine]]
}}
{{LabelImage
|fileName=Packagejns.png
}}

Latest revision as of 17:14, 24 February 2015

Physostigmine
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: Alberto Plate [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

Physostigmine is a central nervous system agent, cholinesterase inhibitor and anti glaucoma that is FDA approved for the treatment of clinical or toxic dosages of drugs capable of producing the anticholinergic syndrome. Common adverse reactions include diaphoresis, abnormal defecation (diarrhea), excessive salivation and nausea and vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Past Anesthesia Care
  • Dosage: 0.5 to 1.0 mg intramuscularly or intravenously. IV administration should be at allow controlled rate of no more than 1 mg per minute. Dosage may be repeated at intervals of 10 to 30 minutes if desired patient response is not obtained.
Clinical or Toxic Dosages of Drugs Capable of Producing the Anticholinergic Syndrome
  • Case report of a 68-year-old male patient admitted to the ICU for treatment of a severe thioridazine intoxication[1].

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

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

Non–Guideline-Supported Use

Reversal of Postoperative Reactions to Scopolamine
  • Dosage: 1.0-1.2 milligrams IV[2]. Unique dose.
Reversal of Postoperative Reactions to Scopolamine in Post-Partum
  • Clinical trial of 5 postpartum patients[3].

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Clinical or Toxic Dosages of Drugs Capable of Producing the Anticholinergic Syndrome
  • Case report of a 27 month-old patient with amitriptyline overdose[1].

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

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

Non–Guideline-Supported Use

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

Contraindications

Warnings

  • Contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.
  • If excessive symptoms of salivation, emesis, urination and defecation occur, the use of Physostigmine Salicylate Injection should be terminated. If excessive sweating or nausea occur, the dosage should be reduced.
  • Intravenous administration should be at a slow, controlled rate, no more than 1 mg per minute. Rapid administration can cause bradycardia, hypersalivation leading to a respiratory difficulties and possible convulsions. An overdosage of Physostigmine Salicylate Injection can cause a cholinergic crisis.

Adverse Reactions

Clinical Trials Experience

Cardiovascular Effects
Endocrine/Metabolic Effects
Gastrointestinal Effects
Immunological Effects
Musculoeskeletal Effects
Neurological Effects
  • Seizures
  • Dosage: May appear if doses surpass1 mg/min in adults or 0.5 mg/min in children[9].
Psychiatric Depression
Renal Effects
Respiratory Effects

Postmarketing Experience

There is limited information regarding Physostigmine Postmarketing Experience in the drug label.

Drug Interactions

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

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Safe use in pregnancy and lactation has not been established; therefore, use in pregnant women, nursing mothers or women who may become pregnant requires that possible benefits be weighed against possible hazards to mother and child.


Pregnancy Category (AUS): C

  • Safe use in pregnancy and lactation has not been established; therefore, use in pregnant women, nursing mothers or women who may become pregnant requires that possible benefits be weighed against possible hazards to mother and child.

Labor and Delivery

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

Nursing Mothers

There is no FDA guidance on the use of Physostigmine in women who are nursing.

Pediatric Use

  • Recommended dosage is 0.02 mg/kg; intramuscularly or by slow intravenous injection, no more than 0.5 mg per minute. If the toxic effects persist, and there is no sign of cholinergic effects, the dosage may be repeated at 5 to 10 minute intervals until a therapeutic effect is obtained or a maximum of 2 mg dosage is attained.

Geriatic Use

There is no FDA guidance on the use of Physostigmine in geriatric settings.

Gender

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

Race

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

Renal Impairment

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

Hepatic Impairment

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

Females of Reproductive Potential and Males

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

Immunocompromised Patients

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

Administration and Monitoring

Administration

  • IV administration should be at allow controlled rate of no more than 1 mg per minute. Dosage may be repeated at intervals of 10 to 30 minutes if desired patient response is not obtained.

Monitoring

There is limited information regarding Physostigmine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Physostigmine and IV administrations.

Overdosage

Can cause a cholinergic crisis. Appropriate antidote is atropine sulfate.

Pharmacology

Template:Px
Physostigmine
Systematic (IUPAC) name
(3aR,8aS)-1,3a,8-Trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-methylcarbamate
Identifiers
CAS number 57-47-6
ATC code S01EB05 V03AB19 (WHO)
PubChem 5983
DrugBank DB00981
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 275.346 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Metabolism Major metabolite: Eseroline
Half life ?
Excretion ?
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)

Legal status

[[Prescription drug|Template:Unicode-only]](US)

Routes intravenous, intramuscular, ophthalmic

Mechanism of Action

Physostigmine Salicylate Injection is a reversible anticholinesterase which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. The action of acetylcholine is normally very transient because of its hydrolysis by the enzyme, acetylcholinesterase. Physostigmine Salicylate Injection inhibits the destructive action of acetylcholinesterase and thereby prolongs and exaggerates the effect of the acetylcholine.

Structure

There is limited information regarding Physostigmine Structure in the drug label.

Pharmacodynamics

There is limited information regarding Physostigmine Pharmacodynamics in the drug label.

Pharmacokinetics

Nonclinical Toxicology

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

Clinical Studies

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

How Supplied

  • 2 mL Ampules packed 10 per box, 1 mg per mL.

Storage

  • Store at 20° to 25°C (68° to 77°F)

Images

Drug Images

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

Patient Counseling Information

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

Precautions with Alcohol

Alcohol-Physostigmine 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 Physostigmine 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. ↑ 1.0 1.1 Schmidt W, Lang K (1997). "Life-threatening dysrhythmias in severe thioridazine poisoning treated with physostigmine and transient atrial pacing". Crit Care Med. 25 (11): 1925–30. PMID 9366781.
  2. ↑ 2.0 2.1 Holzgrafe RE, Vondrell JJ, Mintz SM (1973). "Reversal of postoperative reactions to scopolamine with physostigmine". Anesth Analg. 52 (6): 921–5. PMID 4796567.
  3. ↑ Smiler BG, Bartholomew EG, Sivak BJ, Alexander GD, Brown EM (1973). "Physostigmine reversal of scopolamine delirium in obstetric patients". Am J Obstet Gynecol. 116 (3): 326–9. PMID 4707533.
  4. ↑ Sano M, Bell K, Marder K, Stricks L, Stern Y, Mayeux R (1993). "Safety and efficacy of oral physostigmine in the treatment of Alzheimer disease". Clin Neuropharmacol. 16 (1): 61–9. PMID 8422658.
  5. ↑ Cain JW (1986). "Hypertension associated with oral administration of physostigmine in a patient with Alzheimer's disease". Am J Psychiatry. 143 (7): 910–2. PMID 3717434.
  6. ↑ 6.0 6.1 Nilsson E, Meretoja OA, Neuvonen P (1983). "Hemodynamic responses to physostigmine in patients with a drug overdose". Anesth Analg. 62 (10): 885–8. PMID 6614520.
  7. ↑ Janowsky DS, Risch SC, Kennedy B, Ziegler MG, Huey LY (1986). "Acute effects of physostigmine and neostigmine in man". Mil Med. 151 (1): 48–51. PMID 3080707.
  8. ↑ Mazza E, Ghigo E, Boffano G, Valetto M, Maccario M, Arvat E; et al. (1994). "Effects of direct and indirect acetylcholine receptor agonists on growth hormone secretion in humans". Eur J Pharmacol. 254 (1–2): 17–20. PMID 8206111.
  9. ↑ Newton RW (1975). "Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage". JAMA. 231 (9): 941–3. PMID 1173100.
  10. ↑ Nattel S, Bayne L, Ruedy J (1979). "Physostigmine in coma due to drug overdose". Clin Pharmacol Ther. 25 (1): 96–102. PMID 363335.

{{#subobject: 

 |Label Page=Physostigmine
 |Label Name=Packagejns.png

}}

Retrieved from "https://www.wikidoc.org/index.php?title=Physostigmine&oldid=1072986"