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Dipirona
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<p style="text-align: justify;"><span id="more-4682"></span>INTRODU&Ccedil;&Atilde;O<br>

Analgesia por AINEs &eacute; explicada pela a&ccedil;&atilde;o
inibit&oacute;ria da s&iacute;ntese local
de PGE2 (Vane, 1971). Essa a&ccedil;&atilde;o previne o desenvolvimento
da
hiperalgesia , isto &eacute;, a&nbsp; sensibiliza&ccedil;&atilde;o dos
receptores de dor para
est&iacute;mulos qu&iacute;micos e f&iacute;sicos.</p>

<p style="text-align: justify;">Dipirona &eacute; um analg&eacute;sico
e antipir&eacute;tico muito utilizado em diversos pa&iacute;ses onde
sua propaganda &eacute; permitida.</p>

<p style="text-align: justify;">Existe uma impress&atilde;o entre os
m&eacute;dicos
de que a dipirona tem um efeito cl&iacute;nico diferente dos AINEs.
Existem
muitos artigos e estudos na literatura mostrando que a dipirona tem
efeito analg&eacute;sico maior que aspirina, que &eacute; um
antiinflamat&oacute;rio
inibidor de COX cl&aacute;ssico (Mukherjee et Sudha, 1980; Petrova et
al.
1980) ou paracetamol (Daftary et al, 1980), um analg&eacute;sico do
grupo da
anilina, e por isso o perfil do efeito farmacol&oacute;gico da dipirona
&eacute;
certamente diferente do que dos AINEs e tamb&eacute;m dos
analg&eacute;sicos de a&ccedil;&atilde;o
central (Nikolova et al, 1980; Nikolov et al., 1980). No entanto, esse
s&iacute;tio de a&ccedil;&atilde;o analg&eacute;sica &eacute; um
mecanismo controverso. A a&ccedil;&atilde;o central foi
proposta por Von Tomek (1955) e n&atilde;o confirmada por Lorenzetti
(1999)
que, ao aplicar dipirona intra-cerebroventricular de rato, n&atilde;o
conseguiu inibir a hiperalgesia induzida por prostaglandina em pata
trazeira de rato.</p>

<p style="text-align: justify;">2 &ndash; O QUE &Eacute; DIPIRONA</p>

<p style="text-align: justify;">Dipirona &eacute; o nome
gen&eacute;rico de &aacute;cido
[(2,3-dihidro-1,5-dimetil-3-oxo-2-fenil-1H-pirazol-4-il)metilamino]metanossulf&ocirc;nico,
tamb&eacute;m chamado de
1-fenil-2,3-dimetil-5-pirazolona-4-metilaminometanossulfonato de
s&oacute;dio
(ou de magn&eacute;sio), e ainda denominado de metamizol, um segundo
nome
gen&eacute;rico e muito encontrado na literatura farmacol&oacute;gica
norte-americana
e europ&eacute;ia.</p>

<p style="text-align: justify;"><br>

</p>

<p style="text-align: center;"><img class="aligncenter size-full wp-image-12787" title="dipirona" src="http://antonini.med.br/portal/wp-content/uploads/2009/06/dipirona.jpg" alt="" height="151" width="367"></p>

<p style="text-align: justify;">Com peso molecular de 351,36 e uma
distribui&ccedil;&atilde;o relativa de 44,44% de carbono, 5,16% de
hidrog&ecirc;nio, 11,96%
de nitrog&ecirc;nio, 6,54% de s&oacute;dio (7,26% se for
magn&eacute;sio), 22,77% de
oxig&ecirc;nio e 9,13% de enxofre, apresenta f&oacute;rmula
emp&iacute;rica
C13H16N3NaO4S.H2O (ou C26H32MgN6O8S2. Na dipirona magnesiana ligam-se
duas mol&eacute;culas de dipirona ao c&aacute;tion magn&eacute;sio).
&Eacute; preparada a partir da
metila&ccedil;&atilde;o do grupo amino da sulfamipirina, tratada com
alde&iacute;do
metan&oacute;ico (formalde&iacute;do ou formol), em
solu&ccedil;&atilde;o de bissulfito de s&oacute;dio.
Muito sol&uacute;vel em &aacute;gua (1g/1,5ml), &eacute; pouco
sol&uacute;vel em etanol e
praticamente insol&uacute;vel em &eacute;ter, acetona, benzeno e
clorof&oacute;rmio, sendo
um complicador quando &eacute; necess&aacute;rio fazer uma
cromatografia de camada
delgada para diferencia&ccedil;&atilde;o da dipirona de outros
t&oacute;xicos e barbit&uacute;ricos
em processos jucidiais onde &eacute; pedido a
identifica&ccedil;&atilde;o toxicol&oacute;gica com
fins forenses, pois os melhores carreadores de mol&eacute;culas em
cromatografia de camada delgada s&atilde;o justamente o benzeno, o
&eacute;ter, o
etanol, o hexano e a acetona, sendo o metanol muito pouco utilizado
devido &agrave; sua toxicidade e a &aacute;gua n&atilde;o ser usada por
dissolver a camada
de s&iacute;lica da placa.</p>

<p style="text-align: justify;">Observando a mol&eacute;cula da
dipirona, &eacute;
poss&iacute;vel identificar duas estruturas ligantes que tem
pap&eacute;is
importantes no mecanismo de a&ccedil;&atilde;o deste f&aacute;rmaco. O
primeiro &eacute; o
grupamento benzoil, que tem atividade anest&eacute;sica comprovada,
tanto que
a maior contribui&ccedil;&atilde;o da coca&iacute;na para a
farmacol&oacute;gia foi a identifica&ccedil;&atilde;o
dos componentes de sua f&oacute;rmula estrutural e a descoberta de que,
retirando-se o radical benzoil, a coca&iacute;na perdia sua
a&ccedil;&atilde;o anest&eacute;sica
(Cavazzani, 1994).</p>

<p style="text-align: center;"><img class="aligncenter size-full wp-image-12790" title="benzoil" src="http://antonini.med.br/portal/wp-content/uploads/2009/06/benzoil.jpg" alt="" height="84" width="108"></p>

<p style="text-align: justify;">Outro ligante de import&acirc;ncia na
estrutura da dipirona &eacute; o grupamento sulfato, respons&aacute;vel
por sua alta
solubilidade em &aacute;gua e pela sua facilidade de
absor&ccedil;&atilde;o, &eacute;
potencilamente agressivo para a medula &oacute;ssea, podendo causar
desde
neutropenias, agranilocitoses, at&eacute; aplasia de medula
&oacute;ssea, uma
patologia hematopoi&eacute;tica muito severa que s&oacute; tem um
tratamento, o
transplante de medula &oacute;ssea que, se n&atilde;o realizado em
tempo, pode levar
o indiv&iacute;duo ao &oacute;bito.</p>

<p style="text-align: justify;">Grupamento sulfato:</p>

<p style="text-align: center;"><img class="aligncenter size-full wp-image-12792" title="sulfato" src="http://antonini.med.br/portal/wp-content/uploads/2009/06/sulfato.jpg" alt="" height="120" width="104"></p>

<p style="text-align: justify;">Foi patentetada sob n&ordm; 254, pelo
Laborat&oacute;rio Hoechst em 1911, na Alemanha com o nome de
Metamizol&reg; que
hoje acabou virando nome gen&eacute;rico, como aconteceu com a
Aspirina&reg;, que
&eacute; marca registrada de &aacute;cido acetilsalic&iacute;lico,
desenvolvido pela Bayer e
que se consagrou, tornando-se um nome gen&eacute;rico.</p>

<p style="text-align: justify;">3 &ndash; MECANISMO DE
A&Ccedil;&Atilde;O</p>

<p style="text-align: justify;">Apesar de todas as pesquisas j&aacute;
realizadas apontarem para uma a&ccedil;&atilde;o bloqueadora da
hiperalgesia exercida
pela liga&ccedil;&atilde;o a um receptor perif&eacute;rico, combinado
com a&ccedil;&atilde;o espinal da
dipirona e com poucos efeitos antiedematosos e/ou
antiiflmat&oacute;rios,
alguns bancos de dados insistem em continuar afirmando que a
a&ccedil;&atilde;o da
dipirona atua unicamente por inibi&ccedil;&atilde;o de cicloxigenase,
inibindo a
s&iacute;ntese de prostaglandinas (Abbate et al, 1990; Anon, 1973;
Reynolds,
1994; Gladtke, 1983; Arellano et Sacristan, 1990).</p>

<p style="text-align: justify;">No volume 116, de setembro de 2000 do
banco de dados Drugdex (Micromedex) aparece a cita&ccedil;&atilde;o
feita no
par&aacute;grafo anteiror, ignorando os trabalhos realizados entre 1996
e 1999
por Aleksander Zampronio, Berenice B. Lorenzetti e S&eacute;rgio H.
Ferreira,
que apontam para a a&ccedil;&atilde;o perif&eacute;rica da dipirona
sobre um receptor
sin&aacute;ptico com estimula&ccedil;&atilde;o epinhal via
ativa&ccedil;&atilde;o da arginina/cGMP em
neur&ocirc;nios sensoriais prim&aacute;rios.</p>

<p style="text-align: justify;">A a&ccedil;&atilde;o antit&eacute;rmica
da dipirona pode ser
explicada pelo antagonismo direto de cininas pirog&ecirc;nicas em
receptores
do centro termo-regulador, localizado no t&aacute;lamo.</p>

<p style="text-align: justify;">4 &ndash; FARMACOCIN&Eacute;TICA</p>

<p style="text-align: justify;">4.1 &ndash; IN&Iacute;CIO DA
A&Ccedil;&Atilde;O</p>

<p style="text-align: justify;">Na hipertermia (febre), ap&oacute;s
administra&ccedil;&atilde;o oral, o efeito hipotermiante come&ccedil;a
a aparecer entre 30
minutos e no m&aacute;ximo em uma hora (Ajgaonkar et al, 1988;
Giovannini et
al, 1986; Reiner et al, 1984). O pico m&aacute;ximo de resposta ficam
entre 4
e 6 horas (Ajgaonkar et al, 1988; Giovannini et al, 1986; Reiner et al,
1984).</p>

<p style="text-align: justify;">4.2 &ndash; N&Iacute;VEL M&Aacute;XIMO
DE CONCENTRA&Ccedil;&Atilde;O PLASM&Aacute;TICA</p>

<p style="text-align: justify;">Ap&oacute;s administra&ccedil;&atilde;o
oral, pode ser
encontrado um n&iacute;vel m&aacute;ximo de concentra&ccedil;&atilde;o
ap&oacute;s 1 a 2 horas (Vlahov et
al, 1990; Flusser et al, 1988; Volz et Kellner, 1980). O n&iacute;vel
m&aacute;ximo
de concentra&ccedil;&atilde;o plasm&aacute;tica do metab&oacute;lito
ativo 4-MAA encontrado foi de
11, 21 e 41 mcg/ml, ap&oacute;s administra&ccedil;&atilde;o oral de
750, 1500 e 3000mg de
dipirona, respectivamente (Vlahov et al, 1990). Na realidade e dipirona
&eacute; uma pro-droga que &eacute; metabolizada no trato intestinal em
4-metilaminoantipirina (4-MAA), o metab&oacute;lito ativo (Vlahov et
al, 1990;
Flusser et al, 1988; Brune, 1988; Levy, 1986; Volz et Kellner, 1980). O
4-MAA &eacute; metabolizado no f&iacute;gado em 4-aminoantipirina
(4-AA), um segundo
metab&oacute;lito ativo (Brune, 1988; Flusser et al, 1988).</p>

<p style="text-align: justify;">A dipirona n&atilde;o apresenta
intera&ccedil;&otilde;es
conhecidas com alimentos ou ent&atilde;o s&atilde;o clinicametne
insignificantes
(Levy et al, 1995; Flusser et al, 1988).</p>

<p style="text-align: justify;">4.3 &ndash; S&Iacute;TIOS DE
DISTRIBUI&Ccedil;&Atilde;O</p>

<p style="text-align: justify;">Cerca de 58% do 4-MAA e 48% do 4-AA
s&atilde;o
distribuidos ligados &agrave;s prote&iacute;nas plasm&aacute;ticas
(Zylber-Katz et al,
1985). Os metab&oacute;litos da dipirona tem sido encontrados no
l&iacute;quido
c&eacute;falo-raquidiano. Em estudo controlado, 28 pacientes com
indica&ccedil;&atilde;o
terap&ecirc;utica de dipirona, tomando 1g por via oral (dois
comprimidos de
500mg) em tempos diversos (6 em 6 horas) foram submetidos a
pun&ccedil;&atilde;o
lombar em v&aacute;rios intervalos de tempo e colhido cerca de 2ml de
l&iacute;quor
sendo detectada a presen&ccedil;a dos metab&oacute;litos em
concentra&ccedil;&atilde;o menor que no
plasma, mas guardando uma propor&ccedil;&atilde;o l&iacute;quor/plasma
de ambos os
metab&oacute;litos (Cohen et al, 1998).</p>

<p style="text-align: justify;">4.4 &ndash; VOLUME DE
DISTRIBUI&Ccedil;&Atilde;O</p>

<p style="text-align: justify;">O volume de distribui&ccedil;&atilde;o
do 4-MAA &eacute; de 40 litros (Vlahov et al, 1990).</p>

<p style="text-align: justify;">4.5 &ndash; METABOLISMO</p>

<p style="text-align: justify;">4.5.1 &ndash; PAREDE INTESTINAL</p>

<p style="text-align: justify;">A metaboliza&ccedil;&atilde;o da
dipirona na parede
intestinal &eacute; extensa (Vlahov et al, 1990; Flusser et al, 1988;
Brune,
1988; Levy, 1986; Volz et Kellner, 1980).</p>

<p style="text-align: justify;">O metabolismo &eacute; feito
monoenzimaticamene por hidr&oacute;lise no trato intestinal formando o
4-MAA,
um dos seus metab&oacute;litos ativos (Vlahov et al, 1990; Flusser et
al,
1988; Brune, 1988; Levy, 1986; Volz et Kellner, 1980).</p>

<p style="text-align: justify;">4.5.2 &ndash; F&Iacute;GADO</p>

<p style="text-align: justify;">No f&iacute;gado o metabolismo
tamb&eacute;m &eacute; grande
(Flusser et al, 1988; Brune, 1988; Volz et Kellner, 1980). O 4-MAA
&eacute;
transformado em 4-AA (Brune, 1988; Flusser et al, 1988; Volz et
Kellner, 1980) e outros metab&oacute;litos inativos e de pouca
import&acirc;ncia. Em
portadores assintom&aacute;ticos de hepatite B, com
fun&ccedil;&atilde;o hep&aacute;tica normal,
testes demonstraram preju&iacute;zo no metabolismo oxidativo da
dipirona
quando comparado com sujeitos n&atilde;o portadores (Levy et al, 1997).</p>

<p style="text-align: justify;">4.5.3 &ndash; METAB&Oacute;LITOS</p>

<p style="text-align: justify;">1. 4-Metilaminoantipirina, &eacute; um
metab&oacute;lito ativo (Flusser et al, 1988; Brune, 1988).</p>

<p style="text-align: justify;">2. 4-Aminoantipirina, tamb&eacute;m
&eacute; um metab&oacute;lito ativo (Brune, 1988; Flusser et al, 1988;
Volz et Kellner, 1980).</p>

<p style="text-align: justify;">3. 4-Formil-aminoantipirina (4-FAA),
&eacute; um metab&oacute;lito inativo (Vlahov et al, 1990; Volz et
Kellner, 1980).</p>

<p style="text-align: justify;">4. 4-acetilaminoantipirina (4-AcAA),
tamb&eacute;m &eacute; inativo (Vlahov et al, 1990; Volz et Kellner,
1980).</p>

<p style="text-align: justify;">4.5.4 &ndash; EXCRE&Ccedil;&Atilde;O</p>

<p style="text-align: justify;">4.5.4.1 &ndash; Leite Materno</p>

<p style="text-align: justify;">Os metab&oacute;litos ativos da
dipirona,
tanto o 4-MAA, quanto o 4-AA podem ser encontrados em altos
n&iacute;veis no
leite materno. Est&atilde;o em concentra&ccedil;&atilde;o igual ou
at&eacute; maior que no plasma.
No entanto, os metab&oacute;litos foram encontrados no leite at&eacute;
48 horas ap&oacute;s
administra&ccedil;&atilde;o &uacute;nica de dipirona por via oral ,
devendo o uso de
dipirona ser evitado durante o aleitamento materno (Zylber-Katz et al,
1986).</p>

<p style="text-align: justify;">4.5.4.2 &ndash; Rins</p>

<p style="text-align: justify;">A excre&ccedil;&atilde;o renal &eacute;
intensa, sendo a
maior via de elimina&ccedil;&atilde;o (Vlahov et al, 1990; Volz et
Kellner, 1980). Os
metab&oacute;litos 4-FAA e 4-AcAA s&atilde;o excretados primeiramente
na urina
(Vlahov et al, 1990; Volz et Kellner, 1980).</p>

<p style="text-align: justify;">4.5.5 &ndash; MEIA VIDA</p>

<p style="text-align: justify;">O metab&oacute;lito 4-MAA tem uma meia
vida de
2 a 3 horas (Vlahov et al, 1990; Volz et Kellner, 1980). O tempo de
elimina&ccedil;&atilde;o m&eacute;dio do metab&oacute;lito 4-MAA
&eacute; significativamente aumentado nos
portadores assintom&aacute;ticos de hepatite B, quando comparado com
indiv&iacute;duos sadios. (Levy et al, 1997), enquanto o tempo de
meia-vida de
elimina&ccedil;&atilde;o do 4-FAA est&aacute; significativamente
diminuido em portadores de
hepatite B em compara&ccedil;&atilde;o com sujeitos n&atilde;o
portadores. Os tempos de
meia-vida de elimina&ccedil;&atilde;o dos metab&oacute;litos 4-MAA e
4-AcAA n&atilde;o apresentam
diferen&ccedil;as estat&iacute;sticas significantes entre os dois
grupos. (Levy et
al, 1997).</p>

<p style="text-align: justify;">O metab&oacute;lito 4-AA tem uma
meia-vida de elimina&ccedil;&atilde;o de 4 a 5 hoas (Vlahov et al,
1990; Volz et Kellner, 1980).</p>

<p style="text-align: justify;">5 &ndash; Dilui&ccedil;&atilde;o e
Estabilidade</p>

<p style="text-align: justify;">A Dipirona &eacute; compat&iacute;vel
com solu&ccedil;&atilde;o glicosada a 5%, solu&ccedil;&atilde;o de NaCl
a 0,9%<br>

e Ringer lactato*.<br>

A administra&ccedil;&atilde;o deve ser imediata em &ldquo;bolus&rdquo;
(ou em bolo) j&aacute; que a estabilidade &eacute; limitada nas<br>

tr&ecirc;s solu&ccedil;&otilde;es, devendo ser evitada a infus&atilde;o
cont&iacute;nua*.</p>

<p style="text-align: justify;">* Informa&ccedil;&otilde;es do
fabricante Aventispharma&nbsp; (fabricante da Novalgina&reg;).<br>

6 &ndash; RESTRI&Ccedil;&Otilde;ES AO USO</p>

<p style="text-align: justify;">6.1 &ndash;
CONTRA-INDICA&Ccedil;&Otilde;ES</p>

<p style="text-align: justify;">Discrasias sangu&iacute;neas ou
depress&atilde;o da
medula &oacute;ssea, hipersensibilidade, rinite, urtic&aacute;ria, asma
e rea&ccedil;&otilde;es
al&eacute;rgicas &agrave; aspirina ou outros agentes
antiinflamat&oacute;rios.</p>

<p style="text-align: justify;">6.2 &ndash; PRECAU&Ccedil;&Otilde;ES</p>

<p style="text-align: justify;">Hist&oacute;ria de &uacute;lceras
gastrointestinais,
hemorragias g&aacute;stricas ou perfura&ccedil;&otilde;es da mucosa;
disfu&ccedil;&otilde;es renais;
hipertens&atilde;o card&iacute;aca (sobrecarga ventricular esquerda) ou
disfun&ccedil;&otilde;es
card&iacute;acas agravadas por reten&ccedil;&atilde;o de fluidos e
edema; disfu&ccedil;&atilde;o hep&aacute;tica;
infec&ccedil;&otilde;es pr&eacute;-existentes; porf&iacute;ria;
deficiencia de glicose-6-fosfato
desidrogenase e uso concomitante com clorpormazina.</p>

<p style="text-align: justify;">6.3 &ndash; REA&Ccedil;&Otilde;ES
ADVERSAS</p>

<p style="text-align: justify;">Anemia hemol&iacute;tica e aplasia de
medula
&oacute;ssea tem sido reportada durante o uso de dipirona (Anon, 1986;
Sansone
et al, 1984; Lay, 1966). Agranulocitose &eacute; a ocorr&ecirc;ncia
mais frequente
durante a administra&ccedil;&atilde;o de dipirona e pode ser fatal
(Arellano et
Sacristan, 1990; Hargis et al, 1989; Kiatboonsri et Richter, 1989;
Anon, 1986; Gladtke, 1983; Anon, 1973; Bottiger et Westerholm, 1973;
Sadusk, 1965; Huguley, 1964), tendo muitos casos acontecidos durante 20
anos de uso de dipirona na Holanda (van der Klauw et al, 1998). A
incid&ecirc;ncia da indu&ccedil;&atilde;o de agranulocitose tem
varia&ccedil;&atilde;o geogr&aacute;fica.
Aparece em altas frequ&ecirc;ncias em Barcelona e Berlim e em pequnos
&iacute;ndices
em Budapest, Tel-Aviv e Sofia (Anon, 1986; Arellano et Sacristan, 1990;
Anon, 1973; Vlahov et Bacracheva, 1989) e varia de estudo para estudo.
Diferen&ccedil;as regionais s&atilde;o muito provavelmente relatadas
pela avalia&ccedil;&atilde;o e
uso em modelos em v&aacute;rios pa&iacute;ses. A incid&ecirc;ncia de
agranulocitose varia
em 1,1 por milh&atilde;o, durante a primeira semana de
administra&ccedil;&atilde;o (Anon,
1986) e um caso para cada 3000 usu&aacute;rios (Bottiger et Westerholm,
1973).
Calculos baseados em dados levantados, sugerem que o uso da dipirona
est&aacute; associado a menos de 7000 casos por ano no mundo todo
(Kiatboonsri
et Richter, 1989).</p>

<p style="text-align: justify;">Os efeitos cardiovasculares incluem
hipotens&atilde;o de moderada at&eacute; severa (Hoigne et al, 1986;
Sanahuja et al,
1990). Evidencias de hipotens&atilde;o com doses orais tamb&eacute;m
tem sido
descritas (Giovannini et al, 1986; Paeile et Gallardo, 1974).</p>

<p style="text-align: justify;">Efeitos centrais mais significativos
s&atilde;o sonol&ecirc;ncia, astenia e cefal&eacute;ia (Lehtonen et al,
1983; Paeile et Gallardo, 1974).</p>

<p style="text-align: justify;">Efeitos gastrointestinais incluem
n&aacute;usea, v&ocirc;mitos, irrita&ccedil;&atilde;o g&aacute;strica e
xerotomia, que tem sido relatadas
com a administra&ccedil;&atilde;o parenteral de dipirona (Marthak et
al, 1991;
Lehtonen et al, 1983; Paeile et Gallardo, 1974; von Szeged et Michos,
1986).</p>

<p style="text-align: justify;">Broncoespasmo tamb&eacute;m tem sido
descrito em administra&ccedil;&otilde;es cont&iacute;nuas de dipirona
(Arellano et Sacristan, 1990).</p>

<p style="text-align: justify;">Entre as rea&ccedil;&otilde;es
cut&acirc;neas pode ser
encontrado necrose epidermal t&oacute;xica, urtic&aacute;ria,
&ldquo;rash&rdquo; cut&acirc;neo (Anon,
1973; Arellano et Sacristan, 1990; Pandhi et al, 1984; Pasricha, 1979;
Lehtonen et al, 1983; Saban et al, 1991).</p>

<p style="text-align: justify;">Choque anafil&aacute;tico tamb&eacute;m
pode
acontecer, com uma incid&ecirc;ncia de 1 caso em 5000
administra&ccedil;&otilde;es (Fosseus
et Straughan, 1983; Arellano et Sacristan, 1990; Kiatboonsri et
Richter, 1988).</p>

<p style="text-align: justify;">6.4 &ndash; TERATOG&Ecirc;NESE</p>

<p style="text-align: justify;">Em estudo controlado, com
administra&ccedil;&atilde;o
de dipirona via oral durante a gravidez, mostrou que o desenvolvimento
de tumor de Wilms foi da ordem de 10,9% (com p&lt;0,05). Esse estudo
incluiu 109 casos de tumor de Wilms e 218 controles. A idade
significante dos casos ao tempo do diagn&oacute;stico foi de 41,1
meses. As
m&atilde;es foram questionadas sobre o uso de medicamentos durante a
gravidez
para se determinar a correla&ccedil;&atilde;o do desenvolvimento do
tumor e o uso de
medicamentos e a dipirona foi a mais utilizada durante a gravidez de
mulheres cujos filhos apresentaram o tumor, possivelmente devido a
facilidade de acesso &agrave; droga. Sem dados de estudos prospectivos,
o
aumento na indicencia de tumor de Wilms em crian&ccedil;as expostas
&agrave; dipirona
n&atilde;o pode ser atribuida definitivamente ao f&aacute;rmaco, no
entanto, baseado
nesses estudos o uso de dipirona durante a gravidez deve ser evitado
(Sharpe et Franco, 1996).</p>

<p style="text-align: justify;">6.5 &ndash; INTERA&Ccedil;&Otilde;ES
MEDICAMENTOSAS</p>

<p style="text-align: justify;">6.5.1 &ndash; ACENOCOUMAROL</p>

<p style="text-align: justify;">N&atilde;o foram observados efeitos
significantes nos tempos de coagula&ccedil;&atilde;o durante uso
concomitante com a
dipirona (Zylber-Katz et al, 1985), por&eacute;m sempre &eacute;
indicado o m&aacute;ximo de
cuidado e monitoriza&ccedil;&atilde;o do paciente em uso concomitante
de dipirona com
anticoagulantes orais, especialmente se houver necessidade da
adi&ccedil;&atilde;o de
um antiinflamat&oacute;rio n&atilde;o ester&oacute;ide ao tratamento. O
efeito adverso mais
comum &eacute; o aumento do risco de hemorragias.</p>

<p style="text-align: justify;">6.5.2 &ndash; ALENDRONATO</p>

<p style="text-align: justify;">Durante tr&ecirc;s anos de estudo
cl&iacute;nico
controlado, envolvendo 2027 pacientes que recebiam
antiinflamat&oacute;rios
n&atilde;o esteroidais, a incid&ecirc;ncia de efeitos adversos
gastrointestinais foi
similar entre os pacientes recebendo alendronato e pacientes recebendo
placebo. No entanto, quando administrado alendronato com AINEs, e
dipirona, a incidencia aumentava, especialmente a
irrita&ccedil;&atilde;o g&aacute;strica,
efeito tamb&eacute;m observado com a dipirona (Prod Info
Fosamax&Ograve; , 1999).</p>

<p style="text-align: justify;">6.5.3 &ndash; INIBIDORES DA ECA</p>

<p style="text-align: justify;">&Eacute; conhecida a
intera&ccedil;&atilde;o entre os
inibidores da ECA e a dipirona, podendo surgir bradicardia,
frequentemente induzida por hipercalemia (Shionori, 1993). Esse
dist&uacute;rbio pode levar a paradas card&iacute;acas (Kurata et al,
1999).</p>

<p style="text-align: justify;">6.5.4 &ndash; BLOQUEADORES
BETA-ADREN&Eacute;RGICOS</p>

<p style="text-align: justify;">Em uso concomitante de dipirona com
beta-bloqueadores, tem sido reportado aumento na tens&atilde;o arterial
e
interfer&ecirc;ncia no controle da press&atilde;o sangu&iacute;nea
(Radack et al, 1987;
Webster et al, 1984; Abate et al, 1990; Chalmers et al, 1984; Durao et
al, 1977; Salvetti et al, 1984; Watkins et al, 1980).</p>

<p style="text-align: justify;">6.5.5 &ndash; BLOQUEADORES DE CANAIS DE
C&Aacute;LCIO</p>

<p style="text-align: justify;">O uso de dipirona com bloqueadores de
canais de c&aacute;lcio (nifedipina), aumenta o risco de hemorragia
gastrintestinal (Pahor et al, 1996).<br>

7 &ndash; EFIC&Aacute;CIA COMPARATIVA</p>

<p style="text-align: justify;">7.1 &ndash; ACETAMINOFENO (Paracetamol)</p>

<p style="text-align: justify;">7.1.1 &ndash; FEBRE</p>

<p style="text-align: justify;">Dipirona na dose de 0,5g oral
demonstrou efeitos antipir&eacute;ticos mais acentuados que o
paracetamol na
mesma dose em pacientes com febre tif&oacute;ide e estudo controlado. A
redu&ccedil;&atilde;o da temperatura retal foi muito mais significativa
com dipirona
do que com paracetamol at&eacute; uma ou duas horas ap&oacute;s a
administra&ccedil;&atilde;o.
Existe uma tend&ecirc;ncia da dipirona para um efeito prolongado, em
torno de
6 horas ou mais (Ajgaonkar et al, 1988).</p>

<p style="text-align: justify;">7.2 &ndash; &Aacute;CIDO
ACETILSALIC&Iacute;LICO (Aspirina)</p>

<p style="text-align: justify;">7.2.1 &ndash; FEBRE</p>

<p style="text-align: justify;">Em um estudo pequeno, duplo-cego, o
efeito de 500mg de dipirona &ldquo;per-&oacute;s&rdquo; foi superior
&agrave; mesma dose de &aacute;cido
acetilsalic&iacute;lico no tratamento de febre (Reiner et al, 1984).</p>

<p style="text-align: justify;">7.2.2 &ndash; DOR
P&Oacute;S-OPERAT&Oacute;RIA</p>

<p style="text-align: justify;">O efeito de 500mg de dipirona 500mg
&ldquo;per-&oacute;s&rdquo; &eacute; consideravelmente superior ao do
&aacute;cido acetilsalic&iacute;lico na
mesma dose no tratamento de dor, em estudo controlado (Arellano et
Sacristan, 1990).</p>

<p style="text-align: justify;">7.3 &ndash; N-METIL-BUTIL-ESCOPOLAMINA
(Hioscina)</p>

<p style="text-align: justify;">7.3.1 &ndash; NA C&Oacute;LICA RENAL</p>

<p style="text-align: justify;">Em estudo controlado com n=96 pacientes
com c&oacute;lica renal, a hioscina em dose 20mg intravenosa foi
inefetiva na
remiss&atilde;o dos sintomas dolorosos, enquanto a dipirona na dose de
1 grama
intravenosa apresentou efeito menor que 2,5 gramas pela mesma via. 61%
dos pacientes tratados com hioscina precisaram da
adminstra&ccedil;&atilde;o conjunta
de analg&eacute;sicos narc&oacute;ticos (petidina, nalbufina, tramadol
ou morfina)
para controlar a dor, enquanto 17% e 0%, respectivamente, dos pacientes
em uso de dipirona precisaram da adi&ccedil;&atilde;o de
analg&eacute;sico opi&oacute;ide (Lloret
et al, 1987).</p>

<p style="text-align: justify;">7.4 &ndash; CLONIXINA</p>

<p style="text-align: justify;">7.4.1 &ndash; DOR NA
P&Oacute;S-HISTERECTOMIA</p>

<p style="text-align: justify;">Em estudo randomizado, duplo-cego com
n=160 pacientes divididos em 4 grupos de 40 pacientes cada, foi
administrado 30mg em bolus 15 minutos antes da cirurgia e 15mg em bolus
de clonixina ap&oacute;s a cirurgia, ou 660mg de dipirona em bolus
antes e
330mg ap&oacute;s a histerectomia. 4,4% das pacientes tratadas com
dipirona
necessitaram de doses adicionais de dipirina para controlar a dor no
p&oacute;s-operat&oacute;rio contra 11% das pacientes tratadas com
clonixina
(Rodriguez et al, 1993).</p>

<p style="text-align: justify;">7.5 &ndash; DEXTROCETOPROFENO</p>

<p style="text-align: justify;">7.5.1 &ndash; DOR NO
P&Oacute;S-OPERAT&Oacute;RIO ODONTOL&Oacute;GICO</p>

<p style="text-align: justify;">A dipirona &eacute; t&atilde;o eficaz
quanto do cetoprofeno em analgesia no p&oacute;s-operat&oacute;rio
odontol&oacute;gico (Bagan et al, 1998).</p>

<p style="text-align: justify;">7.6 &ndash; DICLOFENACO</p>

<p style="text-align: justify;">7.6.1 &ndash; NA C&Oacute;LICA RENAL</p>

<p style="text-align: justify;">inje&ccedil;&atilde;o intravenosa de
2,5 gramas de
dipirona combinada com pitofenona (um espasmol&iacute;tico semelhante
&agrave;
atropina) e fempiverinium (um espasmol&iacute;tico hom&oacute;logo da
papaverina) tem
efeito similar ao diclofenaco na dose 75mg por via intramuscular. Ou
seja, o diclofenaco em monoterapia &eacute; mais efetivo que a dipirona
em
monoterapia (Sanahuja et al, 1990).</p>

<p style="text-align: justify;">7.6.2 &ndash; NA CIATALGIA</p>

<p style="text-align: justify;">No tratamento da ciatalgia (dor do
nervo ci&aacute;tico), 2,5 gramas de dipirona intramuscular foi mais
efetivo
que 75 miligramas de diclofenaco pela mesma via em tratamento
controlado, randomizado, duplo-cego de 260 pacientes que receberam
dipirona, diclofenado ou placebo por via intramuscular. A dipirona foi
mais efetiva que o diclofenaco com in&iacute;cio do efeito ap&oacute;s
uma hora da
aplica&ccedil;&atilde;o e prolongando-se por cerca de 48 horas
(Babej-Dolle et al,
1994).</p>

<p style="text-align: justify;">7.7 &ndash; IBUPROFENO</p>

<p style="text-align: justify;">7.7.1 &ndash; NA DOR
P&Oacute;S-CIR&Uacute;RGICA</p>

<p style="text-align: justify;">Em estudo comparado entre dipirona
magnesiana intramuscular, ibuprofeno e placebo por via oral, a espectro
analg&eacute;sico e o tempo de dura&ccedil;&atilde;o da
a&ccedil;&atilde;o entre a dipirona e o ibuprofeno
foram semelhantes e superiores ao placebo (de Miguel Rivero et al,
1997).</p>

<p style="text-align: justify;">7.8 &ndash; INDOMETACINA</p>

<p style="text-align: justify;">7.8.1 &ndash; NA C&Oacute;LICA RENAL</p>

<p style="text-align: justify;">Inje&ccedil;&atilde;o intravenosa de
2,5g de dipirona
tem mostrado efeito maior que 50mg de indometacina pela mesma via, no
tratamento da c&oacute;lica ureteral em lit&iacute;ases
(c&aacute;lculos) renais (Lehtonen
et al, 1983).</p>

<p style="text-align: justify;">7.9 &ndash; KETORALAC</p>

<p style="text-align: justify;">7.9.1 &ndash; EM ANALGESIA</p>

<p style="text-align: justify;">Em estudo randomizado, comparando
aplica&ccedil;&atilde;o de 30mg de ketorolac por via intramuscular (um
AINE derivado
da pirazolona) com 2g de dipirona pela mesma via cada 12 horas em n=60
pacientes com dor de severa &agrave; moderada ap&oacute;s cirurgia
ortop&eacute;dica,
encontrou-se uma efic&aacute;cia similar entre o ketorolac e a dipirona
no
controle da dor nas primeiras 6 horas do p&oacute;s-operat&oacute;rio.
Ap&oacute;s os tr&ecirc;s
dias seguintes, a redu&ccedil;&atilde;o da intensidade da dor foi
melhor conseguida
com o ketorolac, demonstrando uma efic&aacute;cia maior deste
analg&eacute;sico em
rela&ccedil;&atilde;o &agrave; dipirona (Fernandez-Sabate et al, 1991).</p>

<p style="text-align: justify;">7.10 &ndash; MEPERIDINA (Petidina)</p>

<p style="text-align: justify;">7.10.1 &ndash; NA DOR
P&Oacute;S-CIR&Uacute;RGICA</p>

<p style="text-align: justify;">Dipirona na dose 2,5g intramuscular ou
intravenosa tem sido t&atilde;o efetivo quanto 50 ou 100mg de petidina
intravenosa no tratamento da dor p&oacute;s-cir&uacute;rgica (Patel et
al, 1980; Lal
et al, 1973; Arellano et Sacristan, 1990).</p>

<p style="text-align: justify;">7.10.2 &ndash; NA C&Oacute;LICA RENAL</p>

<p style="text-align: justify;">Doses de 2,5g de dipirona intravenosa
tem se mostrado t&atilde;o efetivo quanto 50mg de petidina intravenosa
no
tratamento da c&oacute;lica renal em c&oacute;lica ureteral em um
estudo randomizado
(Lehtonen et al, 1983).</p>

<p style="text-align: justify;">7.11 &ndash; NIMESULIDE</p>

<p style="text-align: justify;">7.11.1 &ndash; NA FEBRE</p>

<p style="text-align: justify;">Em um pequeno estudo duplo-cego, 500mg
de dipirona por via oral foi comparada em efic&aacute;cia com o
nimesulide (um
novo AINE) na dose 100mg pela mesma via, no tratamento da febre
frequentemente produzida por diversos fatores. Ambas as drogas
apresentaram o mesmo escore de efetividade e foram superioras ao
&aacute;cido
acetilsalic&iacute;lico, que tamb&eacute;m foi utilizado no estudo, em
efeito (Reiner
et al, 1984).</p>

<p style="text-align: justify;">7.11.2 &ndash; NA DOR
P&Oacute;S-CIR&Uacute;RGICA</p>

<p style="text-align: justify;">Em estudo duplo-cego em crian&ccedil;as
com
dor p&oacute;s-operat&oacute;ria foram utilizados suposit&oacute;rios
de 100mg de nimesulide
e 300mg de dipirona a cada 6 horas e ambas as drogas apresentaram a
mesma efic&aacute;cia no tratamento da dor inflamat&oacute;rio no
p&oacute;s-operat&oacute;rio das
crian&ccedil;as (Scharli et al, 1990).</p>

<p style="text-align: justify;">7.12 &ndash; PENTAZOCINE</p>

<p style="text-align: justify;">7.12.1 &ndash; NA DOR DO
P&Oacute;S-CIR&Uacute;RGICO BUCO-MAXILO-FACIL</p>

<p style="text-align: justify;">Administra&ccedil;&otilde;es orais de
dipirona na
dose 300mg e pentazocine na dose 50mg a cada 4 horas mostraram
efic&aacute;cia
semelhante em tratamento da dor no p&oacute;s-cir&uacute;rgico de
procedimentos
bucais, maxilares e faciais, em estudo duplo-cego. Neste estudo
encontrou-se efeitos adversos maiores causados pelo pentazocine em
rela&ccedil;&atilde;o &agrave; dipirona (Paeile et Gallardo, 1974).</p>

<p style="text-align: justify;">7.13 &ndash; SUPROFENO</p>

<p style="text-align: justify;">7.13.1 &ndash; NEURALGIAS CR&Ocirc;NICAS</p>

<p style="text-align: justify;">Suprofeno oral na dose 200mg 3 &agrave;
4
vezes ao dia foi t&atilde;o efetivo quanto a dipirona na dose 500mg 3 a
4
vezes ao dia no tratamento de neuralgias cronicas de moderada a severa
em estudo controlado envolvendo 60 pacientes hospitalizados (von Szeged
et Michos, 1986).</p>

<p style="text-align: justify;">7.14 &ndash; TRAMADOL</p>

<p style="text-align: justify;">7.14.1 &ndash; NA C&Oacute;LICA BILIAR
AGUDA</p>

<p style="text-align: justify;">Um estudo multic&ecirc;ntrico e
randomizado,
um grupo de 74 pacientes com c&oacute;lica aguda severa de
ves&iacute;cula biliar,
induzida por lit&iacute;ase biliar, foram comparados dipirona, 2,5g,
hioscina
20mg e tramadol 100mg, todos por via intravenosa. O temp in&iacute;cio
da
redu&ccedil;&atilde;o da dor foi significativamente menor com a
dipirona (10,9
minutos), em compara&ccedil;&atilde;o com o tramadol (15,8 minutos) e
hioscina (25,6
minutos). No grupo tratado com dipirona, 3 pacientes necessitaram de
doses adicionais da droga ap&oacute;s 20 minutos, enquanto no grupo da
hioscina 8 pacientes necessitaram de outra dose do f&aacute;rmaco e no
grupo
tratado com tramadol apenas 1 paciente necessitou de outra dose do
analg&eacute;sico (Schmieder et al, 1993).</p>

<p style="text-align: justify;">7.14.2 &ndash; NAS ODONTALGIAS</p>

<p style="text-align: justify;">Tramadol na dose 50mg por via oral e
dipirona na dose 100mg pela mesma via foram considerados equipotentes
no tratamento da dor de dente em tratamento experimental de dor
induzida, em estudo controlado envolvendo 10 indiv&iacute;duos sadios
(Rohdewald et al, 1988).</p>

<p style="text-align: justify;">7.14.3 &ndash; NA DOR
P&Oacute;S-CIR&Uacute;RGICA</p>

<p style="text-align: justify;">A efic&aacute;cia do efeito
analg&eacute;sico do
tramado (100mg intramuscular) foi comparado com uma
associa&ccedil;&atilde;o de
dipirona 500mg com difenidramina 12,5mg, drofenina 25mg e benzetilio
2,5mg, para o tratamento da dor p&oacute;s-operat&oacute;ria em um
estudo controlado,
randomizado com 60 pacientes que sofreram cirurgia abdominal. Ambas as
drogas foram administradas a cada 8 horas por 3 dias. A intensidade da
dor foi reduzida mais efetivamente com tramadol ap&oacute;s a primeria
dose e
durante os tr&ecirc;s dias de tratamento (p&lt;0,05) e a qualidade do
sono
dos pacientes foi significativamente melhor com o tramadol do que com a
dipirona associada (p&lt;0,001). Efeitos adversos apareceram em 3
pacientes do grupo com tramadol e apenas em um paciente no grupo com
dipirona associada (Canepa et al, 1993).</p>

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