Jump to content

Trimetaphan camsilate: Difference between revisions

Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
No edit summary
 
(52 intermediate revisions by 31 users not shown)
Line 1: Line 1:
{{Short description|Chemical compound}}
{{Drugbox|
{{Drugbox
| IUPAC_name = decahydro-2-oxo-1,3-bis(phenylmethyl)-<br>thieno(1',2':1,2)thieno(3,4-d)imidazol-5-ium
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 408211184
| IUPAC_name = 3,5-dibenzyl-4-oxo-8λ<sup>4</sup>-thia-3,5-diazatricyclo[6.3.0.0<sup>2,6</sup>]undecan-8-ylium (7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate
| image = Trimetaphan camsilate.svg
| image = Trimetaphan camsilate.svg
| alt = Skeletal formulas of trimetaphan camsilate
| width = 280
| CAS_number = 7187-66-8
| =
| image2 = Trimetaphan camsilate 3D ball.png
⚫
| ATC_prefix = C02
| alt2 = Ball-and-stick models of the component ions of trimetaphan camsilate
⚫
| ATC_suffix = BA01
| ATC_supplemental =
| =

⚫
| PubChem = 23576
<!--Clinical data-->
⚫
| DrugBank = APRD00044
| tradename = Arfonad
⚫
| C = 22 | H = 25 | N = 2 | O = 1 | S = 1 <big>(free base)</big>
⚫
| pregnancy_AU =
| molecular_weight = 365.513 g/mol (free base)
| molar_refractivity =
⚫
| bioavailability =
⚫
| metabolism =
⚫
| elimination_half-life =
⚫
| excretion = [[Kidney|Renal]], mostly unchanged
⚫
| pregnancy_AU =
| pregnancy_US = D
| pregnancy_US = D
| legal_status =
| legal_status =
| routes_of_administration = Oral, [[Intramuscular injection|IM]], [[Intravenous therapy|IV]]
| routes_of_administration = Oral, [[Intramuscular injection|IM]], [[Intravenous therapy|IV]]

<!--Pharmacokinetic data-->
⚫
| bioavailability =
⚫
| metabolism =
⚫
| elimination_half-life =
⚫
| excretion = [[Kidney|Renal]], mostly unchanged

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 68-91-7
⚫
| ATC_prefix = C02
⚫
| ATC_suffix = BA01
| ATC_supplemental =
⚫
| PubChem = 23576
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
⚫
| DrugBank =
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 8W556014K9
| KEGG = D00612
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1245

<!--Chemical data-->
⚫
| C=22 | H=25 | N=2 | O=1 | S=1
| chemical_formula_comment = (free base)
}}
}}

⚫
'''Trimetaphan camsilate''' ([[International Nonproprietary Name|INN]]) or '''trimethaphan camsylate''' ([[United States Adopted Name|USAN]]), trade name '''Arfonad''', is a drug that counteracts [[cholinergic]] transmission at the [[ganglion type receptor|ganglion type]] of [[nicotinic receptor]]s of the [[autonomic ganglia]] and therefore blocks both the [[sympathetic nervous system]] and the [[parasympathetic nervous system]]. It acts as a non-depolarizing [[competitive antagonist]] at the nicotinic [[acetylcholine]] receptor, is short-acting, and is given intravenously.
'''Trimetaphan camsilate''' ([[International Nonproprietary Name|INN]]) or '''trimethaphan camsylate''' ([[United States Adopted Name|USAN]]), trade name '''Arfonad''', is a [[sympatholytic]] drug used in rare circumstances to lower [[blood pressure]].

⚫
Trimetaphan [[ ]] counteracts [[cholinergic]] transmission at [[ receptor| type]] of [[nicotinic receptor]]s the [[autonomic ganglia]] and therefore blocks both the [[sympathetic nervous system]] and the [[parasympathetic nervous system]]. It acts as a non-depolarizing [[competitive antagonist]] at the nicotinic receptor, is short-acting, and is given intravenously.

It was discovered by [[Leo Sternbach]].<ref>{{cite journal | author=Bause GS | journal=Anesthesiology | title=From Coenzyme R to “Arfonad” and from Vitamin H to Hypotension | volume=127 | issue=2 | pages=381–381 | date=1 August 2017 | issn=0003-3022 | doi=10.1097/ALN.0000000000001771}}</ref>


==Effects==
==Effects==
Trimetaphan is a [[sulfonium]] compound and therefore carries a positive charge. Being charged, it cannot cross [[lipid]] [[cell membrane]]s, such as those that comprise the [[blood-brain barrier]]. Due to this, trimethaphan does not have any effect on the [[central nervous system]].
Trimetaphan is a [[sulfonium]] compound and therefore carries a positive charge. Being charged, it cannot cross [[lipid]] [[cell membrane]]s, such as those that comprise the [[ barrier]]. Due to this, trimethaphan does not have any effect on the [[central nervous system]].


The [[ciliary muscle]] of the [[eye]] functions to round the [[Lens (anatomy)|lens]] for [[Accommodation (eye)|accommodation]] and is controlled mainly by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle cannot contract ([[cycloplegia]]) and the patient loses the ability to focus their eyes.
The [[ciliary muscle]] of the [[eye]] functions to round the [[Lens (anatomy)|lens]] for [[Accommodation (eye)|accommodation]] and is controlled mainly by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle cannot contract ([[cycloplegia]]) and the patient loses the ability to focus their eyes.


Trimetaphan has a strong effect on the [[cardiovascular system]]. The size of blood vessels is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the [[blood vessel]]s causes them to get larger ([[vasodilation]]) which has the effect of lowering [[blood pressure]]. [[Postural hypotension]] is a common side effect of such drugs. Trimethaphan causes a histamine release which further lowers blood pressure. Effects on the [[heart]] include a decreased force of contraction and an increase in heart rate ([[tachycardia]]). Reflexive tachycardia can be diminished or undetected because trimetaphan is also blocking the sympathetic ganglia innervating the heart.
Trimetaphan has a strong effect on the [[cardiovascular system]]. The size of blood vessels is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the [[blood vessel]]s causes them to get larger ([[vasodilation]]) which has the effect of lowering [[blood pressure]]. [[Postural hypotension]] is a common side effect of such drugs. Trimethaphan causes a histamine release which further lowers blood pressure. Effects on the [[heart]] include a decreased force of contraction and an increase in heart rate ([[tachycardia]]). Reflexive tachycardia can be diminished or undetected because trimetaphan is also blocking the sympathetic ganglia innervating the heart.


The motility of the [[gastrointestinal tract]] is regulated by the parasympathetic system, and blockage of this input results in diminished motility and [[constipation]].
The motility of the [[gastrointestinal tract]] is regulated by the parasympathetic system, and blockage of this input results in diminished motility and [[constipation]].

A rare side effect of trimethaphan administration is sudden [[respiratory arrest]]. The mechanism behind it is unknown, as trimethaphan does not appear to block [[neuromuscular junction|neuromuscular transmission]], and respiratory arrest is not an expected consequence of ganglionic blockage.<ref name=pmid938175>{{cite journal | vauthors = Dale RC, Schroeder ET | title = Respiratory paralysis during treatment of hypertension with trimethaphan camsylate | journal = Archives of Internal Medicine | volume = 136 | issue = 7 | pages = 816–8 | date = July 1976 | pmid = 938175 | doi = 10.1001/archinte.1976.03630070060018 }}</ref>


==Therapeutic uses==
==Therapeutic uses==
The therapeutic uses of trimetaphan are very limited due to the competition from newer drugs that are more selective in their actions and effects produced. It is occasionally used to treat a [[hypertensive crisis]] and [[dissecting aortic aneurysm]], to treat [[pulmonary edema]], and to reduce bleeding during [[neurosurgery]].
The therapeutic uses of trimetaphan are very limited due to the competition from newer drugs that are more selective in their actions and effects produced. It is occasionally used to treat a [[hypertensive crisis]] and [[dissecting aortic aneurysm]], to treat [[pulmonary edema]], and to reduce bleeding during [[neurosurgery]].


==Adverse effects==
== ==
{{Morefootnotes|article|date=September 2018}}{{reflist}}
The adverse effects are due to its nonselective ganglion block and are described in the "Effects" section above. The side effects are severe enough to limit this drugs use to emergency and acute situations.

==References==
* "Ganglion-blocking Drugs." ''Drug Benefits and Risks: International Textbook of Clinical Pharmacology.'' (2001). ISBN 0-471-89927-5
* Katzung, Bertram G. ''Basic and Clinical Pharmacology, 9th ed.'' (2004). ISBN 0-07-141092-9


== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Anderson SM | title = Controlled hypotension with arfonad in paediatric surgery | journal = British Medical Journal | volume = 2 | issue = 4931 | pages = 103–4 | date = July 1955 | pmid = 14378656 | pmc = 1980290 | doi = 10.1136/bmj.2.4931.103 }}
* {{cite journal | vauthors = Kling TF, Wilton N, Hensinger RN, Knight PR | title = The influence of trimethaphan (Arfonad)-induced hypotension with and without spine distraction on canine spinal cord blood flow | journal = Spine | volume = 11 | issue = 3 | pages = 219–24 | date = April 1986 | pmid = 3715622 | doi = 10.1097/00007632-198604000-00007 | s2cid = 24029902 }}
* {{cite journal | vauthors = Moyer JH, Handley CA | title = Renal and cardiovascular hemodynamic response to ganglionic blockade with pendiomide and a comparison with hexamethonium and arfonad | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 113 | issue = 4 | pages = 383–92 | date = April 1955 | pmid = 14368507 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14368507 }}
* {{cite journal | vauthors = Ulm AH | title = The treatment of primary priapism with arfonad | journal = The Journal of Urology | volume = 81 | issue = 2 | pages = 291–3 | date = February 1959 | pmid = 13631819 | doi = 10.1016/S0022-5347(17)66009-9 }}
* {{cite journal | vauthors = Petrides G, Maneksha F, Zervas I, Carasiti I, Francis A | title = Trimethaphan (Arfonad) control of hypertension and tachycardia during electroconvulsive therapy: a double-blind study | journal = Journal of Clinical Anesthesia | volume = 8 | issue = 2 | pages = 104–9 | date = March 1996 | pmid = 8695090 | doi = 10.1016/0952-8180(95)00192-1 }}
* {{cite journal | vauthors = Tewfik GI, Wells BG | title = The use of arfonad for the alleviation of cardio-vascular stress following electro-convulsive therapy | journal = The Journal of Mental Science | volume = 103 | issue = 432 | pages = 636–44 | date = July 1957 | pmid = 13449573 | doi = 10.1192/bjp.103.432.636 }}
* {{cite journal | vauthors = Rowe GG, Afonso S, Lugo JE, Boake WC | title = Systemic and Coronary Hemodynamic Effects of Trimethaphan Camphorsulfonate (Arfonad) in the Dog | journal = Anesthesiology | volume = 25 | issue = 2 | pages = 156–60 | year = 1964 | pmid = 14156542 | url = http://anesthesiology.pubs.asahq.org/article.aspx?volume=25&page=156 | doi = 10.1097/00000542-196403000-00008 | s2cid = 36791833 | doi-access = free }}
{{refend}}


{{Antihypertensives and diuretics}}
{{Antihypertensives and diuretics}}
{{Nicotinic acetylcholine receptor modulators}}
{{Cholinergics}}


[[Category:Nicotinic antagonists]]
[[Category:Imidazolidinones]]
[[Category:Imidazolidinones]]
[[Category:Ureas]]
[[Category:]]
[[Category:Peripherally selective drugs]]
[[Category:Sulfonium compounds]]
[[Category:Sulfonium compounds]]
[[Category:Ureas]]
[[Category:Drugs developed by Hoffmann-La Roche]]
Retrieved from "https://en.wikipedia.org/wiki/Special:ComparePages"