BENZODIAZEPINES

They were discovered accidentally .the first to be synthesized was diazea! in "#$# followed by
!idazola! in "#%& which was water sol'ble.the ter! benzodiazeine refers to the ortion of the
str'ct're co!osed of abenzene rin( f'sed to a seven !e!ber diazeine rin(. however since all of
the i!ortant !e!bers of the (ro' contain a $)aryl s'bstit'ent and a ".*)diazeine rin( + the ter!
has co!e to refer to the $)aryl)"+*)benzodiazeines. the $)aryl rin( (reatly enhances otency. fro!
the standoint of anaesthesia diazea!+lorazea! and !idazola! are of artic'lar interest.
diazea! and lorazea! have ,'ite si!ilar str'ct'resb+ while !idazola! contains an i!idazole
rin( hence water sol'ble while the for!er two need sol'bilizin( a(ents .
The benzodiazeines alter the confor!ation of the recetor s'ch that the affinity for -aba is
inreased with res'ltant increase in chloride channel activation. anta(onists occ'y the recetor b't
have no intrinsic activity+ therefore they revent the effects of both a(onists and inverse a(onists
thatbis do not affect the bindin( of -aba.
The har!acolo(ical effects of the benzodiazeines in the central nervo's syste! are an.iolysis+
sedation+hynosis+!'scle rela.ation+a!nesia and anticonv'lsant.in h'!an bein(s as the dose
increases sedation ro(resses to hynosis then st'or.
The benzodiazeines have little effect on the resiration+ hynotic doses are witho't effect in
nor!al s'b/ects. the effects o !idazola! are (reater in this area . re)anaesthetic doses ca'se a
decrease in alveolar ventilation and resiratory acidosis. iIn atients with obstr'ctive 'l!onary
disease they !ay res'0t in si(nificant resiratory deression + carbon dio.ide retention and
narcosis. diazea! !ay ca'se anoea d'rin( anaesthesia or when (iven in con/'ction with the
oiods.other factirs li0ely to increase the incidence of si(nificantbresiratory deression or anoea
incl'de old a(e+ debilitatin( disease+ other resiratory deressantbdr'(s.
D'e to the slow onset of hynosis + benzodiazeines are not (enerally (ood ind'ction a(ents for
ro'tine anaesthesia with ossible e.cetion of !idazola!. They are 'sef'l when cardiovasc'lar
stability is i!ortant and slow ind'ction er!issible.
The vol'!e of distrib'tion are lar(e and !any be increased in the elderly. These dr'(s readily
cross the lacenta and e.creted in the breast !il0. The lon(er actin( a(ents are !etabolised in the
liver to active !etabolites which are har!acolo(ically active + contrib'tin( to the clinical effect
of the dr'(s and e.tendin( the effective half)life . These a(ents ca'se !ini!al enzy!e ind'ction .
Inter!ediate and short actin( a(ents arebinactivated by (l'c'ronidation and then eli!inated by
renal e.cretion therefore + for t(e elderly and atients with heatic disease + the inter!ediate and
shorter actin( a(ents are referable. 1i!etidine rolon(s the effects of benzodiazeines.
DIAZEPA2
Insol'ble in water and therefore reared co!!ercially in an or(anic solvent containin(
roylene (lycol. Now available also as an intraliid 3water e!'lsion.desite its hi(h liid
sol'bility +the central nervo's syste! effects after intraveno's ad!inistration have a slow or
irre('lar onset and th's not very 'sef'l as an ind'ction a(ent.2ore co!!only 'sed as asedative in
re!edication and d'rin( re(ional roced'res. The clearance of diazea! is deendent on hase "
heatic !etabolis! + bein( o.idised and red'ced to for! active !etabolites and these rolon( the
d'ration of central
nervo's syste! effects.
AD4E5SE 5EA1TIONS
6sef'lly described 'nder fo'r headin(s which are reactions on ind'ction which incl'de ain on
in/ection+ !'scle !ove!ent+ co'(h and hicc's and cardioresiratory deression.The other will
be reactions on recovery which cover sychic roble!s+ !otor dist'rbances +ain . na'sea and
vo!ittin(+rolon(ed so!nolescence and resiratory deression.
Tiss'e co!lications which cover local tiss'e da!a(e and thro!bohlebitis at the site of
in/ection. And lastly hyersensitivity which enco!ass anahylactic reactions+anahylactoid
reactions+ hista!ine release+ s0in rashes and bronchosas!.
OPIODS
Oiods can be ad!inistered as the ri!ary or sole anaesthetic in oiod based anaesthetic
techni,'es. Several factors have di!inished the o'larity of hi(h dose oiod anaesthesia even in
cardiac anaesthesia in which it was co!!only e!loyed.oiods + artic'larly when ad!inistered
by contino's inf'sion+ are still a!on( the !ost effective anesthetics for atients 'nder(oin(
cardiac or other e.tensive oerations.in addition + the efficacy of oiod based anesthesia can be
oti!ized intraoeratively with the ad!inistration of !oderate dr'( doses and not res'lt in
rolon(ed ostoerative resiratory deression.
7ENTAN89
The o'larity of hi(h dose oiod anaesthesia was first established with !orhine. Proble!s with
intraoerative he!odyna!ic instability+ the need to intevene with vasoactive a(ents + e.cessive
ostoerative resiratory deression and rolon(ed e!er(ence have been noted to be !ore
fre,'ent with !orhine than with fentanyl or s'fentanil. 2orhine is no lon(er reco!!ended for
hi(h oiod anaesthesia.
:i(h dose fentanyl anaesthesia has roved effective and safe in re!at're infants for reair of
atent d'ct's arterios's and for adiatric heart s'r(ery.
Eto!idate has been reco!!ended for the ind'ction of anaesthesia in atients with si(nificant
cardiovasc'lar disease. Eto!idate co!bined with an oiod can rovide e.cellent anaesthetic
conditions with !ini!al he!odyna!ic ert'bation. 2aintanence of anasethesia with an oiod li0e
s'fentanil achieves the advanta(es of an oiod based anaesthetic and avoids rolon(ed oiod
action into the ostoerative eriod.
A(ents of historical i!ortance
Althesin
This dr'(+ a !i.t're of two steroids was very si!ilar to roofol in its anaesthetic rofile b't was
!etabolised even !ore reidly. It was introd'ced in "#%; . In co!!on with roanidid+ it was
sol'bilized in 1re!ohor E9 and an 'naccetable n'!ber of adverse reactions were reorted.
y):ydro.yb'tyric acid
Anaesthesia of slow onset and recovery was rod'ced by this a(ent+ which is related che!ically to
the ne'rotrans!itter y)a!inib'tyric acid. It was intrid'ced in "#&;. It is still 'sed for basal
sedation in so!e E'roean co'ntries.