Guanethidine: Difference between revisions

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__NOTOC__
{{Drugbox
{{drugbox
| Verifiedfields = changed
| IUPAC_name = 2-(2-azocan-1-ylethyl)guanidine
| verifiedrevid = 461124124
| image = Guanethidine_svg.png
| IUPAC_name = 2-[2-(azocan-1-yl)ethyl]guanidine
| image = Guanethidine Wiki Str.png
| alt = Skeletal formula of guanethidine
| width = 250
| image2 = Guanethidine BnS.png
| alt2 = Ball-and-stick model of the guanethidine molecule
 
<!--Clinical data-->
| tradename = 
| Drugs.com = {{drugs.com|CONS|guanethidine}}
| MedlinePlus = a600027
| pregnancy_category = 
| legal_status = 
| routes_of_administration = 
 
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 1.5 days
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 645-43-2
| CAS_number = 645-43-2
| ATC_prefix = C02
| ATC_prefix = C02
| ATC_suffix = CC02
| ATC_suffix = CC02
| ATC_supplemental = {{ATC|S01|EX01}}
| ATC_supplemental = {{ATC|S01|EX01}}
| PubChem = 3518
| PubChem = 3518
| DrugBank = APRD01007
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| C=10 | H=22 | N=4
| DrugBank = DB01170
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3398
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5UBY8Y002G
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D08030
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 5557
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 765
 
<!--Chemical data-->
| C=10 | H=22 | N=4  
| molecular_weight = 198.309 g/mol
| molecular_weight = 198.309 g/mol
| bioavailability =  
| smiles = N(=C(\N)N)\CCN1CCCCCCC1
| protein_bound =  
| InChI = 1/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13)
| metabolism =  
| InChIKey = ACGDKVXYNVEAGU-UHFFFAOYAQ
| elimination_half-life = 1.5 days
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category =  
| StdInChI = 1S/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13)
| legal_status =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration =  
| StdInChIKey = ACGDKVXYNVEAGU-UHFFFAOYSA-N
}}
}}
__NOTOC__
{{SI}}
{{CMG}}
{{CMG}}
==Overview==
'''Guanethidine''' is an [[antihypertensive]] drug that reduces the release of [[catecholamines]], such as [[norepinephrine]]. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself (NET, uptake 1), and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine.It may also inhibit the release of granules by decreasing norepinephrine.
==Side effects==
Side effects include orthostatic and exercise [[hypotension]], [[sexual dysfunction]] (delayed or [[retrograde ejaculation]]), and [[diarrhea]].


{{Editor Join}}
==Pharmacology==
Guanethidine is transported by uptake 1 into the [[presynaptic terminal]] transported by Norepinephrine transporter (NET). (In this it competes with norepinephrine so can potentiate exogenously applied norepinephrine.) It becomes concentrated in norepinephrine transmitter vesicles, replacing norepinephrine in these vesicles. This leads to a gradual depletion of norepinephrine stores in the nerve endings.
Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential. Spontaneous release is not affected.


==[[Guanethidine (patient information)|For patient information, click here]]==
==Uses==
Guanethidine was once a mainstay for hypertension resistant to other agents, and was often used safely during pregnancy, but it is no longer used in the US due to lack of availability. It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a [[hypertensive emergency]].


'''Guanethidine''' is an [[antihypertensive]] drug that reduces the release of [[catecholamines]], such as noradrenaline. Its mechanism is inhibition of the [[Mg++ATPase dependent pump]]. Side effects include orthostatic and exercise hypotension, sexual dysfunction, and diarrhea.
Intravenous nerve block ([[Intravenous regional anesthesia|Bier block]]) using guanethidine has been used to treat [[chronic pain]] caused by [[complex regional pain syndrome]].<ref name="pmid12401623">{{cite journal |author=Joyce PI, Rizzi D, Caló G, Rowbotham DJ, Lambert DG |title=The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens |journal=Anesth. Analg. |volume=95 |issue=5 |pages=1339–43, table of contents |date=November 2002 |pmid=12401623 |doi= 10.1097/00000539-200211000-00045|url=http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=12401623}}</ref>


It is no longer available in the US due to side effects and because substantially better drugs are available. It is still licensed in some countries, e.g. UK, for the rapid control of blood pressure in a [[hypertensive emergency]].
==Chemical synthesis==
Guanethidine is [[organic synthesis|synthesized]] beginning with the alkylation of [[azocine]] with [[chloroacetonitrile]].  This reaction which forms 1-azocinylacetonitrile, which can be reduced into 1-(2-aminoethyl)azocine by using [[lithium aluminium hydride]] as a [[reductant]].  This compound reacts with ''S''-methylthiourea forming guanethidine.<ref>R.P. Mull, {{US Patent|2928829}} (1960)</ref><ref>R.P. Mull, {{US Patent|3006913}} (1961)</ref><ref>R.P. Mull, {{US Patent|3055882}} (1962)</ref>
:[[File:Guanethidine Syn.png|none|800px]]


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


{{Adrenergics}}
{{Antihypertensives and diuretics}}
{{Antihypertensives and diuretics}}
{{Antiglaucoma preparations and miotics}}
{{Antiglaucoma preparations and miotics}}


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[[de:Guanethidin]]
{{antihypertensive-stub}}
[[hu:Guanethidin]]
[[pl:Guanetydyna]]

Latest revision as of 12:45, 8 April 2015

Guanethidine
Skeletal formula of guanethidine
Ball-and-stick model of the guanethidine molecule
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa600027
ATC code
Pharmacokinetic data
Elimination half-life1.5 days
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC10H22N4
Molar mass198.309 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself (NET, uptake 1), and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine.It may also inhibit the release of granules by decreasing norepinephrine.

Side effects

Side effects include orthostatic and exercise hypotension, sexual dysfunction (delayed or retrograde ejaculation), and diarrhea.

Pharmacology

Guanethidine is transported by uptake 1 into the presynaptic terminal transported by Norepinephrine transporter (NET). (In this it competes with norepinephrine so can potentiate exogenously applied norepinephrine.) It becomes concentrated in norepinephrine transmitter vesicles, replacing norepinephrine in these vesicles. This leads to a gradual depletion of norepinephrine stores in the nerve endings. Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential. Spontaneous release is not affected.

Uses

Guanethidine was once a mainstay for hypertension resistant to other agents, and was often used safely during pregnancy, but it is no longer used in the US due to lack of availability. It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a hypertensive emergency.

Intravenous nerve block (Bier block) using guanethidine has been used to treat chronic pain caused by complex regional pain syndrome.[1]

Chemical synthesis

Guanethidine is synthesized beginning with the alkylation of azocine with chloroacetonitrile. This reaction which forms 1-azocinylacetonitrile, which can be reduced into 1-(2-aminoethyl)azocine by using lithium aluminium hydride as a reductant. This compound reacts with S-methylthiourea forming guanethidine.[2][3][4]

References

  1. Joyce PI, Rizzi D, Caló G, Rowbotham DJ, Lambert DG (November 2002). "The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens". Anesth. Analg. 95 (5): 1339–43, table of contents. doi:10.1097/00000539-200211000-00045. PMID 12401623.
  2. R.P. Mull, Template:US Patent (1960)
  3. R.P. Mull, Template:US Patent (1961)
  4. R.P. Mull, Template:US Patent (1962)

Template:Antiglaucoma preparations and miotics

Template:Antihypertensive-stub