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Curara reprezint extractul uscat obinut prin diferite procedee (macerare, percolare, fierbere cu ap) a scoarelor de la diferite specii

de Menispermiaceae (Chondodendron tomentosum, Chondodendron mycrophyllum, Chondodendron platyphyllum) i Loganiaceae (Strychnos toxifera,Strychnos letalis). Este cunsocut sub diferite nume: woorari, woorara, curari, cururu, ourari, wourali . Curara a fost utilizata ca si otrava paralizanta de catre indigenii amerindieni. Acestia otraveau sagetile cu care isi vanau prada, ce murea prin asfixiere. Ei foloseau o scala pentru a evalua nivelul de toxicitate care cuprindea 3 trepte: 1 curara, 2 curara sau 3 curara. O otrava puternica permitea maimutei sa se mai urce intr-un copac inainte de a-si face efectul , in timp ce dupa o solutie de 3 curara se mai putea urca in 3 copaci. Ei puteau manca apoi vanatul otravit in siguranta. Prima relatare a acestui fenomen apartine lui Sir Walter Raleigh in urma calatoriilor sale in Trinidad si Guayana. In urma cercetarilor de-a lungul timpului s-a dovedit ca toxina actioneaza asupra muschilor somatici si nu asupra miocardului sau nervilor. Asadar animalul murea prin blocarea muschilor respiratori, iar experimental, daca acesta beneficia de respiratie artificiala, era mentinut in viata, iar recuperarea era completa. Curara nu se absoarbe la nivel intestinal, ceea ce explica utilizarea ei pentru vanatoare. La jumatatea secolului al XIX lea Claude Bernard a descoperit ca locul actiunii curarei este la nivelul jonctiunii neuromusculare. Aici D-Tubocurarina ( cea mai importanta toxina din curara) actioneaza competitiv asupra receptorilor nicotinici musculari ai acetilcolinei si astfel blocheaza actiunea acetilcolinei. Acesti receptori, situati la poarta canalelor de Na si de K sunt fixati pe pozitie inchisa blocand influxul de Na si efluxul de K deci inhiba depolarizarea. Antidotul pentru intoxicatia cu D-Tubocurarina este un inhibitor de acetilcolinesteraza cum ar fi neostigmina sau fisostigmina. Blocand degradarea acetilcolinei , inhibitorii de acetilcolinesteraza cresc cantitatea de acetilcolina in jonctiunea neuromusculara , astfel crescand sansele ca moleculele de acetilcolina sa se cupleze cu receptorii in defavoarea curarei. Este un miorelaxant cu actiune sinaptica , facand parte din clasa curarizantelor nedepolarizante (de ordinul I , pahicurare )- derivati izochinolinici. Utilizare in medicina Din anii 1930 a fost folosit ca miorelaxant , iar in anii 1940 a fost considerat in mod eronat ca anestezic sau analgezic in timpul operatiilor. Postoperator pacientii au declarat ca au simtit durerea in timpul interventiei chirurgicale la intensitate maxima insa nu puteau reactiona nici macar prin mimica din cauza efectului paralizant al toxinei D-Tubocurarinei. In prezent se foloseste in domeniul anesteziei pentru a preveni contractura musculara reflexa si pentru a facilita intubatia oro-traheala . D-Tubocurarina se gaseste sub forma de clorura de tubocurarina, este solubila in apa. Aceasta se administreaza intravenous. Efectul se instaleaza dupa cea. 3 minute de la injectia iv si dureaza 30-40 de minute. La doze mici produce o relaxare a musculaturii striate prin blocarea receptorilor N de la nivelul fusurilor neuro-muscular (acestea mentin tonusul musculaturiI). La doze mai mari (10-15 mG) se produce paralizia musculaturii striate. Aceasta paralizie se produce prin urmatoarea succesiune de fenomene:

sunt paralizati initial muschii globilor oculari cu ptoza palpebrala, ai fetei, apoi musculatura bratelor, a gatului, a membrelor inferioare, a musculaturii trunchiului, a muschilor intercostali si in final, paralizia diafragmului cu imposibilitatea respiratiei fara aparatul de ventilatie artificiala. Efectul d-tubocurarinei este reversibil, iar revenirea se face in ordine inversa - primul muschi care isi reia activitatea fiind diafragmul. Alte efecte: hipotensiune, bronhospasm, hipersalivatie, hipersecretie gastrica si bronsica, urticarie, prin eliberare de histamina. La doze mari are si un efect ganglioplegic, mai intens asupra ganglionilor parasimpatici. Indicatii terapeutice: interventii chirurgicale pe abdomen, torace, operatii cezariene; tratamentul convulsiilor din tetanos, prevenirea rupturilor musculare in terapia prin electrosoc. Se mai poate folosi in cazurile incerte de myasthenia gravis (in scop diagnostic) - este riscanta aceasta utilizare. Efecte adverse: apneea prelungita (cel mai important accidenT), hipotensiune, urticarie, bronhospasm si alte fenomene alergice, mai ales la persoane cu stari alergice in antecedente. Este contraindicata in caz de astm bronsic, myasthenia gravis, se impune prudenta in folosirea la persoane in varsta. In concluzie desi exista efecte adverse , este des folosita in practica chirurgicala.
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Final comments
It might well be that apart from marginal and expensive improvements, as much as possible has already been achieved in the field of neuromuscular blocking drugs. Such is the prolonged development phase for new drugs that the molecules that might become clinically useful in say 10 years time are already known. Yet, who knows what advances in surgical techniques there might have been by then. Muscle relaxants as we know them today might rarely be required, and, when they are, the existing drugs should be adequate. Hence, it is my view that attempts at any further advance will be initially for academic research, rather than a commercial proposition. Go to:

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