Mesa-redonda: A nutrição e a fitoterapia
As particularidades da prescrição de fitoterápicos
Prof. Leandro Medeiros Farmacêutico e doutorando em Inovação Terapêutica | UFPE
Grupo de Pesquisas em Práticas Integrativas e Complementares | FG/Laureate International Universities Coordenação da pós-graduação em Fitoterapia: prescrição e aplicabilidade clínica | iPGS
Grupo de Trabalho em Fitoterapia | CRN6
Salvador, 2014
3"
PLANTAS"MEDICINAIS"(Lei"5991/1973)"
DROGAS"VEGETAIS"
DERIVADO(VEGETAL((EXTRATOS)(
FITOTERÁPICO(
MANIPULADO" INDUSTRIALIZADO(
MEDICAMENTO(FITOTERÁPICO(
(REGISTRO"COMUM"OU"SIMPLIFICADO)"(RDC"26/2014)"
PRODUTO(TRADICIONAL(FITOTERÁPICO((REGISTRO"
SIMPLIFICADO"OU"NOTIFICADO)"(RDC"26/2014"e"IN"02/2014)"
(FARMÁCIAS(DE(MANIPULACÃO((RDC"67/2007"/"
87/2008)"
FARMÁCIAS(VIVAS((RDC"18/2013)"
Uso"medicinal"
Chás"alimenLcios"(RDC(27/2010;(RDC(219/2006;(RDC(267/2005;(RDC(277/2005(
Uso"não"medicinal"
Chás"medicinais"(RDC"26/2014)"
Uso"medicinal"
CHÁS MEDICINAIS
– Substitui o termo “droga vegetal notificado”
– Drogas vegetais com fins medicinais a serem preparadas por infusão, decocção ou maceração pelo consumidor
– Entram na categoria de produto tradicional fitoterápico
– Não podem conter excipientes em suas formulações (apenas drogas vegetais)
CARACTERÍSTICA DOS FITOTERÁPICOS
low-density lipoprotein (LDL) in vitro in a concentration-dependent manner.(10) Silybin appears to be the constituent ofsilymarin responsible for the LDL antioxidant effect. In contrast,silichristin and silydianin appeared to act as pro-oxidants, butwithout significantly reducing the total LDL antioxidant capacityof silymarin.Free radicals are recognised as having an important role in
several pathological processes, including inflammation, necrosis,fibrosis, atherosclerosis, carcinogenesis and ageing and in thehepatotoxic mechanisms of various substances. The antioxidantactivity of silymarin is thought to contibute to its hepatoprotectiveproperties.(11, G55)
Hepatoprotective properties In vitro studies using isolatedhepatocytes have documented the protective activity of silymarinand several of its components against cell damage induced byvarious cytotoxic substances.(1)
In vivo studies in rats and mice have demonstrated thehepatoprotective activity of silymarin and silybin in acute livertoxicity induced by various toxic agents with different mechan-isms of action, including carbon tetrachloride, galactosamine,thioacetamide, ethanol, paracetamol (acetaminophen), thallium,phalloidin and a-amanitin (the main toxic constituents of themushroom A. phalloides).(1) Experimental studies in chronic livertoxicity induced by repeated administration of carbon tetrachlor-ide, heavy metals, thioacetamide and several drugs, includingazathioprine and indometacin, have also demonstrated thatadministration of silymarin and silybin protects againstdamage.(1) Other studies have reported protective effects ofsilymarin against liver injury induced by ischaemia(12) and gammairradiation.(13)
Studies in rabbits fed a high-fat diet for 12 weeks have shownthat histopathological alterations were least advanced in animalswhich also received a silymarin–phospholipid complex.(14) In rats,silymarin inhibited the development of diet-induced hypercholes-terolaemia.(15) The hypocholesterolaemic effects of silymarin maybe due to the effects of silymarin on lipoprotein metabolism.(16)
The effects of silymarin on biliary bile salt secretion have beenseen in studies in rats.(17) Intraperitoneal silymarin (25, 50, 100and 150mg/kg/day) for five days induced a dose-dependentincrease in bile flow and bile salt secretion. Stimulation of bilesalt secretion was mainly accounted for by an increase in thebiliary secretion of the hepatoprotective bile salts b-muricholateand ursodeoxycholate.
Nephroprotective properties Silibinin injected into rats prior toadministration of cisplatin afforded protection of glomerular andproximal tubular function.(18, 19) Silibinin does not affect thecytotoxic activity of cisplatin.(19) Intraperitoneal silibinin (5mg/kg) administered to rats 30 minutes before ciclosporin decreasedciclosporin-induced lipid peroxidation but produced no protectiveeffect on the glomerular filtration rate.(20)
Anticancer activity Silybin at concentrations of 0.1–20 mmol/Linhibited the growth of drug-resistant ovarian cancer cells anddoxorubicin-resistant breast cancer cells in vitro.(21) Furthermore,silybin in the range of 0.1–1.0 mmol/L potentiated the effect ofcisplatin and doxorubicin in experimental tumour cell lines. Whenapplied to the skin of SENCAR mice, silymarin gave protectionagainst the effects of the tumour promoters 12-O-tetradecanoyl-phorbol (TPA) and okaidic acid (OA).(22) Topical application ofsilymarin prior to that of TPA and OA completely inhibitedinduction of tumour necrosis factor a (TNFa) mRNA expressionin the epidermis. Substantial protection from photocarcinogenesisin mice treated with phorbol ester or 7,12-dimethylbenz(a)anthracene has been demonstrated.(23) The antitumour effect isprimarily at stage 1 tumour promotion and silymarin acts byinhibiting cyclooxygenase 2 (COX-2) and interleukin 1a (IL-1a).(24) Such effects may involve inhibition of promoter-inducedoedema, hyperplasia, the proliferation index and oxidant state.(25)
Treatment of serum-starved human prostate carcinoma DU145cells with silymarin resulted in significant inhibition of transform-ing growth factor a (TGFa)-mediated activation of the epidermalgrowth factor receptor erbB1.(26) There was also a decrease intyrosine phosphorylation of an immediate downstream target, theadapter protein SHC, together with a decrease in binding toerbB1. In the silymarin-treated cell lines there was a significantinduction of the cyclin-dependent kinase inhibitors (CDKIs) Cip1/p21 and Kip/p27 concomitant with a significant decrease in CDK4expression, but no changes in the levels of CDK2 and CDK6 andtheir associated cyclins E and D1, respectively. Additionalexperiments showed that there was a significant inhibition ofconstitutive tyrosine phosphorylation of both erbB1 and SHC, but
Figure 2 Milk thistle (Silybum marianum).
Figure 3 Milk thistle – dried drug substance (leaf).
Milk Thistle 431
M
Dosage
Dosages for oral administration (adults) for traditional usesrecommended in standard herbal reference texts are given below.
Fruit Crude drug 12–15 g daily in divided doses (equivalent tosilymarin 200–400mg daily).(G3)
Herb Approximately 1.5 g of finely chopped material as a tea, twoor three cups daily.The doses of silymarin used in clinical trials have ranged from
280–800mg/day (equivalent to milk thistle extract 400–1140mg/day standardised to contain 70% silibinin).(3) For hepaticdisorders, doses of up to 140mg (equivalent to 60mg silibinin)two or three times daily have been suggested.(G43)
In Germany, the recommended regimen for treatment ofAmanita phalloides poisoning with a standardised silymarinpreparation (Legalon) is a total dose of silibinin (as the disodiumdihemisuccinate) (20mg/kg body weight) over 24 hours, dividedinto four intravenous infusions each given over a 2-hourperiod.(G43, G55)
Pharmacological Actions
Several pharmacological activities have been documented for milkthistle fruit, including hepatoprotective, antioxidant, anti-inflam-matory, antifibrotic and antitumour properties, as well asinhibition of lipid peroxidation, stimulation of protein biosynth-
esis and acceleration of liver regeneration. Silymarin (an isomermixture comprising mainly silibinin, silichristin and silidianin) isthe pharmacologically active component of milk thistle fruit;silibinin is the main component of silymarin. There is an extensiveliterature on the pharmacological effects of silymarin andsilibinin, particularly with regard to their hepatoprotectiveactivity which provides supporting evidence for the clinical uses.The pharmacology and clinical efficacy of milk thistle have beenreviewed.(1–3,G50, G55) The following represents a summary ofselected publications on this subject.There is a lack of research investigating the pharmacological
effects of preparations of milk thistle leaf.(G2,G32,G35)
In vitro and animal studies
Antioxidant activity Silymarin and silibinin (silybin) areantioxidants that react with free radicals (e.g. reactive oxygenspecies) transforming them into more stable and less reactivecompounds.(1, 4–6) Silymarin and silybin have been reported toinihibit lipid peroxidation induced by iron-linked systems in ratliver microsomes(7, 8) and protect against phenylhydrazine-inducedlipid peroxidation in rat erythrocytes.(1) Furthermore, in rats,intraperitoneal silymarin has been shown to increase totalglutathione in the liver, intestine and stomach and to improvethe reduced glutathione to oxidised glutathione ratio.(9) Silymarinhas been shown to inhibit copper-induced oxidation of human
Figure 1 Selected constituents of milk thistle.
430 Milk Thistle
M
Dosage
Dosages for oral administration (adults) for traditional usesrecommended in standard herbal reference texts are given below.
Fruit Crude drug 12–15 g daily in divided doses (equivalent tosilymarin 200–400mg daily).(G3)
Herb Approximately 1.5 g of finely chopped material as a tea, twoor three cups daily.The doses of silymarin used in clinical trials have ranged from
280–800mg/day (equivalent to milk thistle extract 400–1140mg/day standardised to contain 70% silibinin).(3) For hepaticdisorders, doses of up to 140mg (equivalent to 60mg silibinin)two or three times daily have been suggested.(G43)
In Germany, the recommended regimen for treatment ofAmanita phalloides poisoning with a standardised silymarinpreparation (Legalon) is a total dose of silibinin (as the disodiumdihemisuccinate) (20mg/kg body weight) over 24 hours, dividedinto four intravenous infusions each given over a 2-hourperiod.(G43, G55)
Pharmacological Actions
Several pharmacological activities have been documented for milkthistle fruit, including hepatoprotective, antioxidant, anti-inflam-matory, antifibrotic and antitumour properties, as well asinhibition of lipid peroxidation, stimulation of protein biosynth-
esis and acceleration of liver regeneration. Silymarin (an isomermixture comprising mainly silibinin, silichristin and silidianin) isthe pharmacologically active component of milk thistle fruit;silibinin is the main component of silymarin. There is an extensiveliterature on the pharmacological effects of silymarin andsilibinin, particularly with regard to their hepatoprotectiveactivity which provides supporting evidence for the clinical uses.The pharmacology and clinical efficacy of milk thistle have beenreviewed.(1–3,G50, G55) The following represents a summary ofselected publications on this subject.There is a lack of research investigating the pharmacological
effects of preparations of milk thistle leaf.(G2,G32,G35)
In vitro and animal studies
Antioxidant activity Silymarin and silibinin (silybin) areantioxidants that react with free radicals (e.g. reactive oxygenspecies) transforming them into more stable and less reactivecompounds.(1, 4–6) Silymarin and silybin have been reported toinihibit lipid peroxidation induced by iron-linked systems in ratliver microsomes(7, 8) and protect against phenylhydrazine-inducedlipid peroxidation in rat erythrocytes.(1) Furthermore, in rats,intraperitoneal silymarin has been shown to increase totalglutathione in the liver, intestine and stomach and to improvethe reduced glutathione to oxidised glutathione ratio.(9) Silymarinhas been shown to inhibit copper-induced oxidation of human
Figure 1 Selected constituents of milk thistle.
430 Milk Thistle
M
Dosage
Dosages for oral administration (adults) for traditional usesrecommended in standard herbal reference texts are given below.
Fruit Crude drug 12–15 g daily in divided doses (equivalent tosilymarin 200–400mg daily).(G3)
Herb Approximately 1.5 g of finely chopped material as a tea, twoor three cups daily.The doses of silymarin used in clinical trials have ranged from
280–800mg/day (equivalent to milk thistle extract 400–1140mg/day standardised to contain 70% silibinin).(3) For hepaticdisorders, doses of up to 140mg (equivalent to 60mg silibinin)two or three times daily have been suggested.(G43)
In Germany, the recommended regimen for treatment ofAmanita phalloides poisoning with a standardised silymarinpreparation (Legalon) is a total dose of silibinin (as the disodiumdihemisuccinate) (20mg/kg body weight) over 24 hours, dividedinto four intravenous infusions each given over a 2-hourperiod.(G43, G55)
Pharmacological Actions
Several pharmacological activities have been documented for milkthistle fruit, including hepatoprotective, antioxidant, anti-inflam-matory, antifibrotic and antitumour properties, as well asinhibition of lipid peroxidation, stimulation of protein biosynth-
esis and acceleration of liver regeneration. Silymarin (an isomermixture comprising mainly silibinin, silichristin and silidianin) isthe pharmacologically active component of milk thistle fruit;silibinin is the main component of silymarin. There is an extensiveliterature on the pharmacological effects of silymarin andsilibinin, particularly with regard to their hepatoprotectiveactivity which provides supporting evidence for the clinical uses.The pharmacology and clinical efficacy of milk thistle have beenreviewed.(1–3,G50, G55) The following represents a summary ofselected publications on this subject.There is a lack of research investigating the pharmacological
effects of preparations of milk thistle leaf.(G2,G32,G35)
In vitro and animal studies
Antioxidant activity Silymarin and silibinin (silybin) areantioxidants that react with free radicals (e.g. reactive oxygenspecies) transforming them into more stable and less reactivecompounds.(1, 4–6) Silymarin and silybin have been reported toinihibit lipid peroxidation induced by iron-linked systems in ratliver microsomes(7, 8) and protect against phenylhydrazine-inducedlipid peroxidation in rat erythrocytes.(1) Furthermore, in rats,intraperitoneal silymarin has been shown to increase totalglutathione in the liver, intestine and stomach and to improvethe reduced glutathione to oxidised glutathione ratio.(9) Silymarinhas been shown to inhibit copper-induced oxidation of human
Figure 1 Selected constituents of milk thistle.
430 Milk Thistle
M
Dosage
Dosages for oral administration (adults) for traditional usesrecommended in standard herbal reference texts are given below.
Fruit Crude drug 12–15 g daily in divided doses (equivalent tosilymarin 200–400mg daily).(G3)
Herb Approximately 1.5 g of finely chopped material as a tea, twoor three cups daily.The doses of silymarin used in clinical trials have ranged from
280–800mg/day (equivalent to milk thistle extract 400–1140mg/day standardised to contain 70% silibinin).(3) For hepaticdisorders, doses of up to 140mg (equivalent to 60mg silibinin)two or three times daily have been suggested.(G43)
In Germany, the recommended regimen for treatment ofAmanita phalloides poisoning with a standardised silymarinpreparation (Legalon) is a total dose of silibinin (as the disodiumdihemisuccinate) (20mg/kg body weight) over 24 hours, dividedinto four intravenous infusions each given over a 2-hourperiod.(G43, G55)
Pharmacological Actions
Several pharmacological activities have been documented for milkthistle fruit, including hepatoprotective, antioxidant, anti-inflam-matory, antifibrotic and antitumour properties, as well asinhibition of lipid peroxidation, stimulation of protein biosynth-
esis and acceleration of liver regeneration. Silymarin (an isomermixture comprising mainly silibinin, silichristin and silidianin) isthe pharmacologically active component of milk thistle fruit;silibinin is the main component of silymarin. There is an extensiveliterature on the pharmacological effects of silymarin andsilibinin, particularly with regard to their hepatoprotectiveactivity which provides supporting evidence for the clinical uses.The pharmacology and clinical efficacy of milk thistle have beenreviewed.(1–3,G50, G55) The following represents a summary ofselected publications on this subject.There is a lack of research investigating the pharmacological
effects of preparations of milk thistle leaf.(G2,G32,G35)
In vitro and animal studies
Antioxidant activity Silymarin and silibinin (silybin) areantioxidants that react with free radicals (e.g. reactive oxygenspecies) transforming them into more stable and less reactivecompounds.(1, 4–6) Silymarin and silybin have been reported toinihibit lipid peroxidation induced by iron-linked systems in ratliver microsomes(7, 8) and protect against phenylhydrazine-inducedlipid peroxidation in rat erythrocytes.(1) Furthermore, in rats,intraperitoneal silymarin has been shown to increase totalglutathione in the liver, intestine and stomach and to improvethe reduced glutathione to oxidised glutathione ratio.(9) Silymarinhas been shown to inhibit copper-induced oxidation of human
Figure 1 Selected constituents of milk thistle.
430 Milk Thistle
MDosage
Dosages for oral administration (adults) for traditional usesrecommended in standard herbal reference texts are given below.
Fruit Crude drug 12–15 g daily in divided doses (equivalent tosilymarin 200–400mg daily).(G3)
Herb Approximately 1.5 g of finely chopped material as a tea, twoor three cups daily.The doses of silymarin used in clinical trials have ranged from
280–800mg/day (equivalent to milk thistle extract 400–1140mg/day standardised to contain 70% silibinin).(3) For hepaticdisorders, doses of up to 140mg (equivalent to 60mg silibinin)two or three times daily have been suggested.(G43)
In Germany, the recommended regimen for treatment ofAmanita phalloides poisoning with a standardised silymarinpreparation (Legalon) is a total dose of silibinin (as the disodiumdihemisuccinate) (20mg/kg body weight) over 24 hours, dividedinto four intravenous infusions each given over a 2-hourperiod.(G43, G55)
Pharmacological Actions
Several pharmacological activities have been documented for milkthistle fruit, including hepatoprotective, antioxidant, anti-inflam-matory, antifibrotic and antitumour properties, as well asinhibition of lipid peroxidation, stimulation of protein biosynth-
esis and acceleration of liver regeneration. Silymarin (an isomermixture comprising mainly silibinin, silichristin and silidianin) isthe pharmacologically active component of milk thistle fruit;silibinin is the main component of silymarin. There is an extensiveliterature on the pharmacological effects of silymarin andsilibinin, particularly with regard to their hepatoprotectiveactivity which provides supporting evidence for the clinical uses.The pharmacology and clinical efficacy of milk thistle have beenreviewed.(1–3,G50, G55) The following represents a summary ofselected publications on this subject.There is a lack of research investigating the pharmacological
effects of preparations of milk thistle leaf.(G2,G32,G35)
In vitro and animal studies
Antioxidant activity Silymarin and silibinin (silybin) areantioxidants that react with free radicals (e.g. reactive oxygenspecies) transforming them into more stable and less reactivecompounds.(1, 4–6) Silymarin and silybin have been reported toinihibit lipid peroxidation induced by iron-linked systems in ratliver microsomes(7, 8) and protect against phenylhydrazine-inducedlipid peroxidation in rat erythrocytes.(1) Furthermore, in rats,intraperitoneal silymarin has been shown to increase totalglutathione in the liver, intestine and stomach and to improvethe reduced glutathione to oxidised glutathione ratio.(9) Silymarinhas been shown to inhibit copper-induced oxidation of human
Figure 1 Selected constituents of milk thistle.
430 Milk Thistle
M
Silybum marianum
PRESCRIÇÃO DE FITOTERÁPICOS POR NUTRICIONISTAS
CFN | RE 525/2013
Isentos de prescrição médica
Exclusivamente por via oral
Não associado a substâncias bioativas, mesmo que de origem vegetal, ou ainda a nutrientes
Relacionados com o campo de atuação do nutricionista
Baseados em evidências científicas ou na tradicionalidade de uso
Informações gerais
• Dados do nutricionista (nome, endereço, contatos, número de registro no CRN)
• Dados do paciente (nome)
O que deve constar em uma prescrição de fitoterápicos?
CFN, 2013
O que deve constar em uma prescrição de fitoterápicos?Prescrição de chás medicinais
Nome botânico da(s) espécie(s) vegetal(is) (sendo opcional, adicionar o nome popular)
Droga vegetal
Parte da planta utilizada
Forma de preparo
Quantidade da droga vegetal / dose
Tempo de contato da droga vegetal com a água
Técnica de preparo: infusão, decocção ou maceração
Modo de uso
Quantidade a ser tomada
Horário, frequência e duração do tratamentoAnvisa, 2014
CFN, 2013
O que deve constar em uma prescrição de fitoterápicos?Prescrição de chás medicinais
Utilizar referências oficiais para o preparo de chás
Formulário de Fitoterápicos da Farmacopeia Brasileira (2011)
RDC 10/2010 (ANVISA)
Referências bibliográficas listadas na RDC 26/2014 (ANVISA)
Anvisa, 2014CFN, 2013
Dra. Joyce Gomes de MoraesCRN6: 3484
Para: Aline Kelly da Silva
Rx:Allium sativum (alho) …. droga vegetal do bulbo
Modo de preparo:
• Cobrir o conteúdo de 1 colher de café rasa em 30 mL de água• Deixar em temperatura ambiente por 1 hora• Agitar ocasionalmente e coar
Tomar 1 cálice (30 mL), 2x/dia, antes das refeições, por 3 meses.
Dra. Joyce Gomes de MoraesCRN6: 3484
Para: Aline Kelly da Silva
Rx:Cinnamomum verum (canela) …. droga vegetal da casca
Modo de preparo:
• Colocar o conteúdo de 4 colheres de café rasa em 150 mL de água fria• Ferver por cerca de 3 a 5 minutos• Deixar em contato por 15 minutos• Coar, em seguida
Tomar 1 xícara (150 mL), 3x/dia, antes das refeições, por 3 meses.
Dra. Joyce Gomes de MoraesCRN6: 3484
Para: Aline Kelly da Silva
Rx:Cynara scolymus (alcachofra) …. droga vegetal da folha
Modo de preparo:
• Colocar 150 mL (1 xícara) de água fervente sobre 1 colher de sobremesa da droga vegetal, em um recipiente apropriado
• Abafar por cerca de 15 minutos• Coar, em seguida
Tomar 1 xícara (150 mL), 3x/dia, antes das refeições, sempre que os sintomas surgirem.
O que deve constar em uma prescrição de fitoterápicos?Prescrição de medicamentos fitoterápicos, produtos tradicionais fitoterápicos e fitoterápicos manipulados
Nome botânico da(s) espécie(s) vegetal(is) (sendo opcional, adicionar o nome popular)
Derivado da droga vegetal (extrato seco, tintura, extrato líquido) ou droga vegetal (pó)
Padronização do marcador (para derivados da droga vegetal)
Posologia
Via de administração e forma farmacêutica
Dosagem (dose, frequência e duração do tratamento)
Modo de uso
Quantidade a ser tomada
Horário, frequência e duração do tratamentoAnvisa, 2014
CFN, 2013
Dra. Joyce Gomes de MoraesCRN6: 3484
Para: Aline Kelly da Silva
Rx:
Tomar uma dose, logo após as refeições, 2x ao dia, por 60 dias.
Obs.: Não repetir receita.
Allium sativum (extrato seco, 5% de alicina) 50 mg
Camellia sinensis (extrato seco, 50% de polifenois totais)
250 mg
Aviar em cápsulas 120 doses
Dra. Joyce Gomes de MoraesCRN6: 3484
Para: Aline Kelly da Silva
Rx:
Diluir o conteúdo de um sachê em 1 copo d’água e tomar 30 minutos antes das refeições,2x ao dia, por 30 dias.
Obs.: Não repetir receita.
Plantago ovata (pó) 3,0 g
Amorphophallus kinjac (pó) 1,0 g
Aviar em sachê 60 doses
Pontos críticos
A RE 525/2013 não contempla a prescrição de fitoterápicos industrializados pelo nome comercial
Prescrição de fármacos alopáticos (sintéticos ou semissintéticos), fitofármacos (medicamentos) e substâncias bioativos isolados/nutracêuticos (alimentos) por nutricionistas
Associações de extratos vegetais: sinergismo farmacológico
Padronização do marcador
Formas farmacêuticas e adesão ao tratamento
Relacionamento nutricionista-farmacêutico
E-mail: [email protected]
Facebook: @leandro.a.medeiros
Twitter: @PharmD_Leandro
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Obrigado!