Is there still a place for pharmacobotany in modern anesthesiology?

Abstracts

JUSTIFICATIVA E OBJETIVOS: Recentemente, o uso de chás medicinais - infusões, decoctos, tisanas, tinturas - ou medicamentos de origem vegetal vem sendo retomado de maneira sistemática e crescente na profilaxia e tratamento das doenças, ao lado da terapêutica convencional, na maioria dos países ocidentais. A presente revisão objetiva analisar as principais plantas que serviram como base de progresso para a moderna terapêutica anestesiológica através de sua utilização como modelos moleculares para síntese orgânica na moderna química fina de ponta, bem como fornecer mais embasamento sobre benefícios, potenciais efeitos adversos, interações e risco de efeitos colaterais que possam afetar o ato anestésico no paciente cirúrgico usuário habitual de fitoterapia. CONTEÚDO: Considerações anestesiológicas selecionadas são discutidas focalizando uma pequena revisão sobre ervas medicinais mais populares que foram essenciais no desenvolvimento de uma farmacologia anestesiológica e, ainda, as potenciais interações de plantas medicinais usadas por pacientes para tratar suas doenças ou controlar seus sintomas com drogas sintéticas usadas na anestesia. CONCLUSÕES: Enquanto a Medicina especializada fascina-se cada vez mais com a tecnologia avançada de novos fármacos e de fantásticos monitores, cresce em vários países o número de pacientes que desejam uma abordagem mais holística com rejeição dos modernos métodos de tratamento, optando por chás, meditações, dietas vegetarianas, anti-oxidantes, entre outros. Cabe ao anestesiologista avaliar quanto o conhecimento de farmacognosia e de farmacobotânica pode ajudá-lo na prática anestésica e, principalmente, na segurança de seu paciente.

ANESTESIOLOGIA; DROGAS; DROGAS

SPECIAL ARTICLE

Is there still a place for pharmacobotany in modern anesthesiology? ^*

¿La farmacobotánica, aún tiene lugar en la moderna anestesiología?

Nilton Bezerra do Vale, TSA, M.D.

Professor Adjunto de Farmacologia e Anestesiologia da Universidade Federal do Rio Grande do Norte, RN

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: Recently, the use of medicinal teas - infusions, decoction, tisanes, dyeings - or drugs of vegetal origin are being systematically and increasingly revived to prevent and treat diseases together with conventional medicine in most Western countries. This review aimed at analyzing major herbs that were the basis for the progress of modern anesthetic therapy through their use as molecular models for organic synthesis in fine leading edge modern chemistry, as well as shedding more light on the advantages, potential adverse effects, interactions and risks for side-effects which may affect anesthesia in surgical patients users of phytotherapy.

CONTENTS: Selected anesthesiologic considerations are discussed focusing a brief review of popular herbs essentials on the development of anesthetic pharmacology and the potential drug-herb interactions between synthetic drugs used in anesthesia and the medicinal herbs used by patients in their illness and symptoms management.

CONCLUSIONS: While specialized Medicine is increasingly fascinated by the advanced technology of new drugs and fantastic monitors, there is an increasing trend in several countries for a more holistic approach and rejection of new treatment methods, with an option for teas, meditation, vegetarian diets and anti-oxidants, among others. It is the anesthesiologist’s role to evaluate how much pharmacognosy and pharmacobotany knowledge may help him in the anesthetic practice and, especially, in patients safety.

Key words: ANESTHESIOLOGY; DRUGS: farmacobotany, interation

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Recientemente, el uso de tés medicinales - infusiones, decocciones, tisanas, tinturas - o medicamentos de origen vegetal viene siendo retomado de manera sistemática y creciente en la profilaxis y tratamiento de las enfermedades al lado de la terapéutica convencional en la mayoría de los países occidentales. La presente revisión objetiva analizar las principales plantas que servirán como base de progreso para la moderna terapéutica anestesiólogica a través de su utilización como modelos moleculares para síntesis orgánica en la moderna química fina de punta, bien como suministrar más fundamento sobre beneficios, potenciales efectos adversos, interacciones y riesgo de efectos colaterales que puedan afectar el acto anestésico en el paciente cirúrgico usuario habitual de la fitoterapia.

CONTENIDO: Son discutidas las consideraciones anestesiológicas seleccionadas, focalizando una pequeña revisión sobre hierbas medicinales más populares que fueron esenciales en el desenvolvimiento de una farmacología anestesiológica y aún, las potenciales interacciones de plantas medicinales usadas por pacientes para tratar sus enfermedades o controlar sus síntomas con drogas sintéticas usadas en la anestesia.

CONCLUSIONES: En cuanto la Medicina especializada se fascina cada vez más con la tecnología avanzada de nuevos fármacos y de fantásticos monitores, crece en varios países el número de pacientes que desean una abordaje mas holística con rechazo de los modernos métodos de tratamiento, optando por tés, meditaciones, dietas vegetarianas, anti-oxidantes, entre otros. Cabe al anestesiologista evaluar cuanto el conocimiento de farmacognosia y de farmacobotánica puede ayudarlo en la práctica anestésica y, principalmente, en la seguridad de su paciente.

ORIGIN

If according to Darwin, life evolution has started in the sea, it is also true that land and water plants photosynthesis has provided the necessary biomass for vegetal and animal self-reproduction energy through the interaction of sun photons and chlorophyll. Chemical phytosynthetic reactions on leaves of land plants and seaweeds have allowed for unicellular beings evolution into more complex pluricellular ones with high calorie waste, in addition to protecting them against cosmic and solar radiation through the gaseous atmosphere which still surrounds the earth ^1-3.

In the last 10 thousand years of Homo sapiens agricultural civilization history, vegetal products, sources of glucidic, lipidic and proteic foods were the food chain energetic and structural basis assuring their migrations to hunt, plant, harvest and war. Ingredients for religious rituals, for parties celebrating life, sex and death, in additional to medicinal or magical use by witch doctors and medicine men have also originated from the plants. All medical history researchers are unanimous in stating that the first therapist must have been a farmer or a witch, traditionally or ritually using teas, liniments, inhalations and fumigations to relieve internal diseases or treat wounds acquired in daily hunting or sporadic wars.

The first recorded medical herbarium (2838-2698 b.C) was incremented by the Chinese emperor Shen Nung, who has catalogued approximately 365 medicinal herbs and poisons used under Pan Ku’s (creation god) Taoist inspiration: chaos ordination would depend on the ordination of two opposed poles: yang - light, sky, heat, left; and yin - darkness, earth, cold, right. Around 1500 b.C., Hindu medicine basis was already disclosed in two sacred texts: Veda (Learning) and Ayurveda (Long Time Learning). The Hindu physician Susruta had available 760 medicinal herbs, such as Cannabis indica, sleep inducing herb, and Rauwolphia serpentina, daily injected sedative by the India pacifist and liberator Mahatma Gandhi until his death in 1948. In the Western world (1553-1550 a.C.), a papyrus was found by Georg Ebers in 1873 in the Egyptian region of Luxor, describing the therapeutic use of more than 700 plants used by the priests at the same time when Imhotep would build the Great Pyramids. Hypocrates (364 a.C.), who has replaced the fatalism of gods by clinical observation in treating patients, would already recommend the use of opium (Papaver somniferum capsule juice) which had been brought from the East by the conqueror Alexander the Great. The Greek king Mitridates (120-63 a.C.) has tested poisons and potential antidotes in his slaves. Dioscorides (100 a.C.) - father of the Greek pharmacy - already used minerals, animal products and more than 700 plants described in his treaty Materia Medica.

Avicena’s work in the Christian era (980 - 1037) - Canons - which has introduced alcohol, camphor, nux vomica (Strychnos nux vomica), balm-mint (Melissa officinalis) and croton oil (Codiacum variegatum) in Arabian medicine, is to be highlighted. The Swiss Paracelcius (1493 - 1541), interested in magic, alchemy, cabala and medicine, has stated that plants have on their shapes their medicinal indication and has widespread the use of opium in Europe; he was the first to describe in hen the soporiferous effect of “vitriol oil” (ether) obtained by the Spanish Lullius (1275) by adding sulfuric acid to old wine. Withering (1741 - 1799) has introduced in the United Kingdom the use of digitalis to treat hydrops. Digitalis is still used in congestive heart failure (increased intracellular Ca⁺⁺ by ATPase Na⁺ K⁺ blockade). From the Peruvian bitter quinquina, already used as antipyretic in Europe since 1640, Pelletier and Caventou (1820) have isolated the two major alkaloids: l-cinchonidine and l-quinine, first anti-malaria drug effective against Plasmadium falciparum and to treat “palpitations”; subsequently it would give origin to group an heart anti-arrhythmic drug d-quinidine (Wenkebach, 1923). In 1874, Dr. Sinfronio Olimpio Cesar Coutinho has studied the Brazilian plant Pilocarpus jaborandi, the alkaloid of which (pilocarpine) is still used to treat glaucoma. In 1877, Gilette would use oral morphine for labor analgesia. Before ether inhalation in 1846 (Morton), alcohol inebriating action in its different fermented presentations (wine, beer, etc.), but especially in its distilled presentation with higher ethanol content (rum, whisky, vodka, sake, etc.), has been used as a single agent to “anesthetize” patients submitted to painful surgical interventions. In 1928, Fleming has isolated the Penicillium notatum fungus, the antibiotic which would divide medicine history in two periods: before and after penicillin ^1-7.

In the 19^th Century, the replacement of alchemy’s empirics by experimental chemistry has allowed for lab synthesis of new organic substances and was a determining factor for the technological and industrial revolution for the accelerated production of new drugs. The discovery of urea by Wöhler in 1828 and the carbon quadrivalence postulate proposed by Kekulé in 1857, were the basis for malonyl-urea synthesis (barbituric acid) by Adolph von Bayer in 1864. The modification of such molecule would be the basis for the discovery of new more liposoluble barbiturates which, for 60 years, are part of anesthesia pharmacological and marketing history as hypnotics, anesthetic inducers, amnesiacs and anticonvulsivants.

In the first Brazilian Pharmacopoeia edition (1929), most drugs were still of vegetal origin, while in the last edition, medicinal herbs were less than 5% ⁴, in spite of Brazil having the world’s largest biological diversity because in Amazon alone there are 600 thousand vegetal species of which only 5% were studied. Alkaloids are major products for pharmacognosy, toxicology and medicine. From vegetal origin, alkaloids are basic and levororatory, that is, with levogyrous optic isomerism similar to organic membrane-composing aminoacids. They have always contributed for the progress of anesthetic pharmacology for their different effects, or even acting as a model structure for molecular rearrangements for the chemical composition of new semi-synthetic or synthetic agents of known anesthetic importance: l-morphine, l-ephedrine, l-scopolamine, l-cocaine, pilocarpine, strychnine, among others ^1-7.

Recently, the use of medicinal teas - infusions, decoction, tisanes, dyeings - or drugs of vegetal origin are being systematically and increasingly revived to prevent and treat diseases together with conventional medicine in most Western countries ^8,9. On the other hand, potential surgical patients are also using “natural” vegetal drugs, be it as a food complement, energy or vitamin supplement, be it only based on media information or even in search for alternative therapies when official pharmacology fails in healing their diseases. Physicians and patients are not always able to find adequate literature to duly evaluate advantages and risks of this alternative therapy, especially when their major use is encouraged by non-conventional medical practices, such as Chinese medicine, holistic medicine, Hindu medical therapy, macrobiotics, among others. Other less noble therapies related to charlatanism and quackery also prescribing mineral, animal and vegetal drugs should also not be disregarded. Preoperative phytotherapic drugs, which are xenobiotic, may affect the anesthetic act by interacting with anesthetic agents both in the pharmacokinetic and the pharmacodynamic phase ^2-9.

This review aimed at analyzing major herbs that were the basis for the progress of modern anesthetic therapy through their use as molecular models for organic synthesis in fine leading edge modern chemistry, as well as shedding more light on the advantages, potential adverse effects, interactions and risks for side-effects which may affect anesthesia in surgical patients users of phytotherapy.

MAJOR HERBS FOR ANESTHESIOLOGICAL DRUGS ARMAMENTARIUM

Medicinal herbs and/or vegetable origin principles may participate in the basic triad of anesthesia: analgesia, amnesia and miorelaxation, added to autonomic stability maintenance ^2,7.

Analgesia

Analgesia may be induced by epidural injection of Na⁺ channel blockers or by drugs interacting with protein G in CNS endogenous peptidic receptors - µ, k, d - which help cell hyperpolarization (K⁺ inflow).

Papaver somniferum - Byproducts: l-morphine (Sertürner, 1803) and tebaine. The phenantrenic alkaloid extracted from poppy capsules - morphine - is the most important analgesic today and was named after Morpheus, the God of Dreams. Its commercial distribution is controlled as from the last century, initially by the League of Nations and today by the UN because it may lead to abuse and physical dependence. Most poppy plantations supplying the pharmaceutical market and also fostering illegal drug traffic are located in Asia. Morphine and especially its semi-synthetic and synthetic analogs, assure analgesia and spinal anesthesia stability, quality and potency ^2,7,10.

Erythroxylon coca - Byproduct: l-cocaine (Nieman, 1860). The bush (E. coca) was a gift received in dream by the Andean God Manco Capac, grandfather of Atahualpa (King Sun decapitated by the Spanish Pizarro in 1533) for the Inca peasants to chew its leaves and recover their energies under the rarefied air of Andean plateaus (more than 3000 meters above sea level). Acid salt (pH 4.0 - 5.0), local anesthetic by extraction in HCI medium, was extracted from Mariani wine (Europe) and coca-cola (USA) in 1903 and was banned by the League of Nations (1913) due to the risk of abuse. Freud has written a monograph on cocaine (Über Coca), praising its euphoric action and pope Lion XIII (1863 - 1865) has distinguished Mariani as benefactor of humankind. Currently, the only medical use of the alkaloid is to avoid nose bleeding during tracheal intubation (USA) through its intrinsic vasoconstrictor (endogenous catecholamine reuptake blockade) and local anesthetics effect ^2,7,10,11.

Arundo donax - Byproducts: lidocaine (Löfgren & Lundquist, 1943) and tryptamine (von Euler, 1929). Achiralic lidocaine was synthesized as from the methylation of a grass byproduct which, “for being so bitter, was rejected even by camels” in Asian plateaus, namely isograss. Clinically evaluated in the post-war period by Gordh (1947), lidocaine has become the prototype of new non histaminergic oral anesthetics - amino-amide group - with liver metabolism and more prolonged effects ^11-13.

Miorelaxation

Neuromuscular blockers (NMB) interrupt the transmission of nervous impulses in the nicotinic receptor (endplate) providing different levels of muscle paralysis and very important for intra-abdominal surgeries. Major plants acting as the structural model for chemical synthesis are ^2,7,14,15:

Strychnos toxifera - Byproduct: alcuronium (nortoxiferin).

Benzylisoquilinic group

Chondodendron tomentosum - Byproducts: d-tubocurarine (King, 1935), intocostrine (Griffith & Johson, 1942), bebeerine (Scholtz, 1913) and chondrocurare (Vital Brasil, 1947).

Leontice lentopetalum - Petaline byproducts (Stenlake, 1981): atracurium (Hughes, 1981), composed of a blend of 10 stereoisomers (3 cis and 7 trans), mivacurium (Savarese, 1988) composed of 3 stereoisomers (trans-trans, cist-trans, cis-cis), doxacurium (Basta, 1988) and cisatracurium (Stenlake, 1993) with just one cis isomer. In clinical doses, histamine release is directly related to the number of isomers in the final quinolinic NMB mixture, what makes atracurium the less histaminergic in the benzylisoquilinic group.

Amino-Steroid Group

Malouetia baquaertiana - major byproducts: long-lasting pancuronium (Baird, 1967), vecuronium (Agoston, 1980), which is the most cardio-stable, rocuronium (Muir, 1989), of fastest induction (± 1 minute) and rapacuronium (released by FDA in 1997), which was temporarily withdrawn from the market by Organom Co. (04/04/2001) due to the high incidence of bronchospasms (> 3%) with five fatal accidents.

Curiosities: The same British explorer - Sir Walter Raleigh - who took the first curare samples used in hunting by Amazon Indians (1596) to the UK, has also taken Nicotiana tabacum leaves from Virginia (USA) to the British Elizabethan Court in 1570, spreading smoking to the whole British empire and making smoking the most pervasive vice of current adult population. In 1618, the British adventurer was executed by the Spanish crown. Flora from most important river basins in the planet were sources of vegetal extracts the molecular model of which were decisive in the synthesis of major adepolarizing NMBs: from the Amazon river, Chondodendron and Strychnos (d-tubocurarine and nortoxiferine), from the Niles river Leontice (isoquinolines) and from Congo river Malouetia (amino-steroids).

Anesthetic Adjuvants

Some semi-synthetic or synthetic byproducts of medicinal herbs still have an important role in treating hypodynamic states, moreover during spinal sympathetic chemical block, to control vagal action, decurarization, arrhythmia and heart failure.

Ephedra sinica (ma huang) - Originated from Chinese deserts its stem has major alkaloids: l-ephedrine (30-90%), isolated by Nagai in 1887 and pseudoephedrine. Ephedrine is an a and b adrenergic amine with mixed hypertensive and cardiostimulating action, but may cause tachyphylaxis when continuously used; it has central stimulating, midriatric and bronchodilating activity in addition to being a nasal decongestive. Interaction may cause hypertension and arrhythmias during inhalational anesthesia with halothane. It is very useful in correcting spinal block hypotension, especially in obstetric anesthesia, due to a lower decrease in uterus-placental irrigation ^2,16,17.

Curiosity: Already used by Shen Nung around the year 2700 b.C and present in the 2^nd Chinese Pharmacopoeia edited in 1552 by Li Shi-Chen - the Great Herbarium - ma huang was presented as antipyretic, circulation stimulant, anti-spasmodic and anti-coughing. It was only in 1927 that Labat used ephedrine to control spinal anesthesia hypotension, four years after having been introduced in Eastern medicine by Chen and Schmidt.

Atropa belladonna - Atropine provides muscarinic M₁ and M₂ vagal blockade, assuring the control of bradycardia caused by cholinergic (opioids, pilocarpines, prostigmine) and cardiopressant drugs (halothane, Ca⁺⁺ antagonists, b blockers, bupivacaine), the control of sialorrhea and neuroleptic impregnation reversion ^2,7,15.

Curiosity: Midriatric and cycloplegic properties were used by European ladies-in-waiting to make their eyes prettier and more attractive (from Italian: bella = pretty; donna = lady); the difficulty in promptly adapting to close-far view made the users very popular among young men present to the party because it was very difficult to see who was who in ballrooms poorly illuminated by candles and chandeliers.

Physostigma venenosum (Calabar bean or Eseré nut) - physostigmine (Jobst & Hesse, 1875) is a tertiary anti-cholinesterase amine used to treat central cholinergic syndrome, in decurarization and as emergence agent in sedation with benzodiazepinics ^2,7,17.

Curiosity: The Calabar bean (Western Africa) was used in the lye test during tribal trials of people under suspicion of crime or theft; the innocent person would promptly eat the portion, which would cause vomiting for its stomach irritating action; the criminal or thief, terrified with the public judgment and knowing the wisdom of the witch, would drink the potion slowly, in small sips, which would allow for the alkaloid reabsorbtion and exacerbation of severe central and peripheral cholinergic effects.

Digitalis lanata - digoxin: myocardial ATPase Na⁺/K⁺ inhibiting glycoside, used as cardiotonic (positive inotropism with less ATP consumption) and in treating tachyarrhythmias (anti-adrenergic effect) ^2,7.

Curiosity: The initial success of Withering in treating an edematous woman - hydrops - has justified its initial indication as diuretic for its primary effect in the kidneys and not as a consequence of hemodynamic improvement as a function of higher heart inotropism. It was only with the modern vasodilating therapies that digitalis has lost its unique place as an effective drug in treating congestive heart failure ².

POTENTIAL INTERACTIONS OF PHYTOTHERAPIC DRUGS AND ANESTHESIA

The chronic use of teas and diet supplementations may interfere with anesthesia as their effects potentiate or inhibit hypnosis, analgesia and myorelaxation, or even interfere with cardiovascular stability. Preanesthetic or anesthetic evaluation should be used to question patients or relatives about the type of plant, herb or vegetal product being used, for how long and how much. When in doubt about the potential toxic interaction on central nervous system (CNS), cardiovascular system (CVS), coagulation cascade or liver, kidney and GI functions, common sense asks for discontinuing them one to two weeks before surgery ^19-23.

Patients diet may interfere in their mood, sleep induction and well-being. So, a normal diet based on lentils, soybeans, wheat and potato favors benzodiazepinics anxiolitic activity on CNS, moreover if patients are vegetarian and do not eat red meat and sausages rich in tyrosine (catecholamine precursor). Since serotonin is a slow brain waves sleep mediator, routine intake of dairy products, white chicken meat, nuts and bananas (rich in tryptophans), sugars (help intestinal absorption) and even K⁺ rich vegetables (lettuce, spinach, coconut juice, etc.) help sleep induction and hypnotic effects ^2,7,24-31.

Hypnotic Effect Potentiation

This interaction is more important for postoperative potential hypoxia as a consequence of respiratory depression by residual sedation, moreover in elderly and obese patients submitted to general anesthesia. Different sedation levels may be observed as a consequence of the hypnotic-sedative combination used during anesthesia.

Valeriana officinalis (valeriana) - Total extract of this European plant root has essential oils acting on the GABA_A receptor, responsible for hypnosis (sleep inductor) and ansiolysis. It may potentiate hypnotics or opioid analgesics effects ^24-27.

Piper methysticum (kava-kava) - The rhizomes of this Pacific Islands plant have 5% to 8% of kava-lactones which, for acting in the limbic system have myoarelaxing, anticonvulsant, analgesic and ansiolitic activities. Lactones potentiate alcohol, barbiturates, benzodiazepinics and anti-depressants ^28,29.

Hypericum perforatum (St. John’s wort) - The extract of this European plant has antidepressant properties by inhibiting neuronal monoamine reuptake and by IMAO activity. In addition to potentiate classic antidepressants, there are reports in prolonged effects of simultaneously used hypnotics ^4,30.

Cannabis sativa (marijuana): D9 and D8 - tetrahy- drocannabinol with hypnotic, sedative, analgesic, anticonvulsivant, amnesic, antiemetic and intraocular pressure decrease effects, in addition to the hallucinogen effect. Cannabinoids cause somnolence associated to tachycardia, xerostomia and panic at emergence ^29,30.

Hypnotic teas: Pimpinella anisum (fennel), Melissa officinalis (balm-mint), Cybopoghon citrates (lemon- scented verbena, lemongrass), Passiflora edulis (passion fruit) and Matricaria chamomilla (chamomile) teas have a mild sedative action (essential oils? flavanoids? Cisterpenes?) and may prolong hypnotic effects ^22,23,32.

Ethylic alcohol - extracted from plants by fermentation (low content < 12%) and by distillation (< 60%) in stills (Arabian method), it was considered the life elixir (acqua vitae) in Medieval Europe. Condemned by the Bible, Torah and especially the Koran, ethanol was also described as a crime inducer in the Elizabethan age (16^th Century) and was totally banned in the USA - dry law - from 1929 to 1933, without success. When associated to smoking, alcoholism is a dependence extremely difficult to treat. In fact, in spite of an initial euphoria, its major effect is to depress CNS in a dose-dependent manner, potentiating all hypnotics, sedatives, analgesics and general anesthetics ²⁴.

Decreased Hypnotic Effects

Coffea arabica - Original from Ethiopia, it was spread throughout the Ottoman Empire with medical or religious objectives, such as the “Muslim wine”, because the Koran prohibits alcoholic wine. Well adapted in Brazil, its seeds produce caffeine - phosphodiesterase-blocking methylxanthine with emergence effects. A mild dependence on its stimulating effect is worldwide accepted without restrictions. Excess coffee is clinically recognized as causing insomnia and gastritis. This xanthine is used as Coadjuvant for post-dural puncture headache analgesia, as a respiratory stimulant in neonatology and as a coadjuvant in decreasing adult sleep apnea. Other plants are also xanthine producers, although with less caffeine: Paulinea cupana (guarana), Theobroma cacao (cocoa), Ilex paraguaensis (Paraguay tea), Cola acuminata (coca-cola), Thea sinensis (black tea) ³³.

Ephedra sinica (ma huang) - Chinese plant with mixed adrenergic effect which may be used as a stimulant or nasal decongestive and may cause panic attack, hypertensive crisis and heart arrhythmias. It is counterindicated in parturients using the uterine retractor methylergonovine, in pheochromocytoma patients and in IMAO users ^16,17,22,23.

Erytroxylon coca - Andean plant the alkaloid of which - cocaine - when nasally aspirated as a power or inhaled as smoke by “crack” burning at 90 ºC is stimulating, convulsive, anorexic and aphrodisiac. Its aspiration increases ketamine or halothane cardiac toxicity (tachyarrhythmias), with or without seizures with a high risk for acute lung edema and cardiac arrest. Cocaine is an important abuse drug with severe social implications ^22,23,34,35.

Panax ginseng (ginseng) - The root acts as “psychological adaptogenic” decreasing fatigue and stress; it may cause hypertension and tachycardia when associated to ephedrine, and insomnia after higher doses, especially in users of minor xanthine-containing stimulants (coffee, guarana, coca-cola, etc.) ^29,31.

Increased Neuromuscular Block

Botulinic and saxitonin toxins increase the risk for hypoxia due to poor recovery of curare paralyzing effects (NMB) or to increased residual inhalational or intravenous anesthetics effects.

Clostridium botulinum (anaerobic bacteria) - this bacteria’s botulinic toxin blocks presynaptic acetylcholine release potentiating NMB respiratory paralysis effects ^2,14.

Gonyaulax catanella, tamerensis (red tide weeds) - the ingestion of a fish poisoned by saxitoxin blocks nervous membrane sodium channel entry gate (adepolarizing effect), potentiating NMBs myorelaxant effects ^2,14.

Increased Cardiovascular Toxicity

Hemodynamic unbalance is more evident in general inhalational anesthesia with halothane or in intravenous anesthesia with ketamine by the appearance of severe cardiovascular abnormalities, especially severe arrhythmias ^32-34.

Ephedra sinica (ma huang) - Mixed effect adrenergic which may be used as stimulant, nasal decongestive and to correct spinal anesthesia hypotension. It may cause panic attack and hypertension. Severe arrhythmias have been reported in patients under alkaloids when receiving digitalis, and during anesthesia with halothane or ketamine. It is counterindicated in parturients using the uterine retractor methylergonovine, in pheochromocytoma patients and in IMAO users ^16,17,33.

Erytroxylon coca - Andean plant the alkaloid of which (aspirated powder or “crack” inhaled smoke) increases ketamine and halothane cardiac toxicity by intense sympathetic stimulation, and hypertension and tachyarrhythmias may be followed by seizures and hypoxia with very high life-threatening risk: acute lung edema and cardiac arrest ^23,33,34.

Nicotiana tabacum - Plant seeds were taken from Brazil to France by Andre Thevet in 1556 who have called it “nicotiana” after Jean Nicot who described its medicinal and powerful properties (1559). From its leaves, Posselt & Reiman (1828) have extracted nicotine, a medium stimulant responsible for the most widely spread chemical dependence socially accepted. When chronically used, the alkaloid determines an increase in carboxyhemoglobinemia in addition to causing pathological chronic obstrutive pulmonary disease and coronary disease, which make anesthetic induction difficult, as well as causing cancer (carcinogenic smoke components) and low fetal weight by uterus-placental vasoconstriction ^2,23.

Panax ginseng (ginseng) - Asian ginseng roots are rich in ginsenosides (5-7%) which improve intellectual performance (anti-stress) and work as “psychological adaptogenic”. Panaxanes may decrease blood glucose and improve the immune system. They may also cause hypertension and tachycardia in hypertensive and non-compensated cardiac patients or in interaction with ephedrine and cocaine users or even users of minor stimulants (xanthines) ^19,29,35.

Cannabis sativa - The smoke of cigarettes (“marijuana”, “hemp”) made of flowers, leaves or resin (haxixe) is rich in psychoactive cannabidiols causing hallucination, conjunctival hyperemia and tachycardia (sympathetic stimulation) ^22,23.

Claviceps purpurea - Fungus contaminating rye by the presence of ergotamine and which may induce Saint Antony’s disease (ergotism) by lower limbs ischemia and hallucinations (LSD-25 precursor). The intravenous use of themethylate byproduct - methylergonovine - as post partum uterine retractor may cause tachycardia, arterial hypertension, vomiting and may toxically interact with halothane, ketamine and ephedrine (tachyarrhythmias) ^22,23,33.

Datura stramonium, arborea, fastuosa - Popularly called “purple empire” “wild anguria”, “Jimson weed”, they are rich in l-hioscine and hioscinamine with atropininc activity and may cause tachycardia, dry mouth and skin, agitation and hallucination ^2,7,18.

Hypericum perforatum (St. John’s wort) - Antidepressant with IMAO and brain monoamine reuptake blocking activity, it may increase blood pressure and cause agitation, mental confusion and somnolence in surgical patients ^4,19.

Glycyrrhiza glabra (liquorice) - Its rhizome extract may cause hypertension, edema, hypokalemia (arrhythmogenic?) and platelet changes by inhibiting cortisol and aldosterone metabolism ^19,29,30.

Increased Bleeding Risk

Most important for anticoagulant users, dyscrasia patients and in spinal anesthesia, especially when catheters are used for local anesthetic injection.

Gingko biloba (gingko) - The leaves of this Chinese tree, which may live for 1000 years, are rich in lactone terpenes (6% bioflavonoids) with vasodilating properties, and flavone glycosides (23%) used in several elderly pathologies (amnesia, retinopathy, claudication, etc.). It may increase bleeding risk, especially in patients under fibrinolytic therapy by PAF inhibition ^36,37.

Allium sativum (garlic) - Garlic (liliaceae) has fibrinolytic, anti-platelet, antioxidant, hypotensive (presence of prostaglandins) and cholesterol-decreasing properties ^36,39.

Zingiber officinale (ginger) - Asian plant (zingiberaceae) inhibiting platelet aggregation, in addition to being antiemetic and mildly analgesic ^40,41.

Panax ginseng (ginseng) - May decrease platelet aggregation and should be avoided in patients under heparin, oral anticoagulants or salicilates ^35,42,43.

Salix alba (willow) - European plant (espiraceae) from which salicylin has been extracted by Leroux in 1829, but salicylic acid synthesis was only attained in 1899 (Hoffman, from Bayer); in addition to being antipyretic and anti-inflammatory, it irreversibly inhibits platelet cycloxygenase (antithrom-boxane A₂) increasing bleeding risk for one week ⁴⁴.

CONCLUSIONS

The routine use of fitotherapy, diet complementation with products of vegetal origin or a vegetarian diet should be part of the preanesthetic or anesthetic evaluation questionnaire, mostly in the female population, so that preventive measures are taken against possible drug interactions and peri and postoperative safety measures are implemented. In the absence of updated pharmacognosic knowledge, a good preventive advise for routine users of medicinal plants with interaction potential would be to discontinue medication 1 or 2 weeks before surgery ^{4,19,24,43-47}.

One must bear in mind that the dominant laymen culture has a “green” ecological risk bias fostered by media: “natural” medicines extracted from plants must be safer than synthetic drugs. Fist of all, the active principle varies from plant to plant as a function of biodiversity, genetic code, climate conditions, seasonal changes, rainfall indicators, light, underground water, soil conditions, etc. A good example has happened in Brazil in the 19^th Century: aiming at better controlling malaria, Emperor Pedro I has brought from Peru, to plant in Campos do Jordão, quinquina seedlings to extract the anti-malaria drug from the bark; however, only a negligible amount of quinine was obtained! Secondly, there are known toxic and mortal poison producing plants, even under ICU intensive care, such as Abrus precatorius, castor bean ricin (Ricinus communis), ground manioc poisonous juice (Manihot utilissima) - linamarine and cyanide - Gonyaulax seaweed saxitonine, physic nut toxin (Jathropa curcas) and calcium oxalate of the aningapara cactus (Diffenbachia picta), among others.

Finally, there is the need for further and better controlled studies and tests with vegetal origin products aiming at obtaining more reliable parameters as to perioperative risk and/or safety of medicinal plants. It is well known that vegetal origin products are among the most potent histamine releasing drugs in anesthesia, such as penicillin, vancomycin, d-tubocurarine, cocaine, procaine, salicylin and morphine, among others ^2,9,15,44-48.

Vegetal byproducts used in homeopathy do not pose a major drug interaction risk during anesthesia due to their low doses. Minimum “effective” drug decreases to a millesimal level during dynamization, that is, well below the therapeutic window.

While specialized medicine is increasingly fascinated by the advanced technology of new drugs and fantastic monitors, there is an increasing trend in several countries for a more holistic approach and rejection of new treatment methods, with an option for teas, meditation, vegetarian diets and anti-oxidants, among others. It is the anesthesiologist’s role to evaluate how much pharmacognosy and pharmacobotany knowledge may help him in the anesthetic practice and, especially, in patients safety.

REFERENCES

Submitted for publication September 22, 2001

Accepted for publication November 29, 2001

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Correspondence to

Dr. Nilton Bezerra do Vale

Address: Av. Getúlio Vargas, 558/702 Petrópolis

ZIP: 59012-360 City: Natal, Brazil

*

Received from Departamento de Biofísica e Farmacologia, Centro de Biociências da Universidade Federal do Rio Grande do Norte, RN

Publication Dates

• Publication in this collection
  18 Oct 2005
• Date of issue
  June 2002

History

• Received
  22 Sept 2001
• Accepted
  29 Nov 2001