A short history of anti-rheumatic therapy - V. Analgesics

Abstract

L a cessazione del dolore è una delle prime cose che il malato richiede al medico ed uno dei primi doveri di quest'ultimo ("divinum opus est sedare dolorem"). Nel linguaggio popolare, almeno in Toscana, ma probabilmente da molte altre parti, le malattie reumatiche sono identifi cate come "i dolori" per antonomasia. Per questo motivo i farmaci destinati ad attenuare il dolore, cioè gli analgesici -il termine "analgesia" (ossia "senza dolore": da "αλγος", dolore, preceduto dall'alfa privativo) è stato utilizzato per la prima volta da Democrito, fi losofo greco del V sec a.C. (1) -hanno un posto di rilievo nella terapia delle malattie reumatiche, anche se il vero compito del reumatologo non sarebbe quello di eliminare il dolore in quanto tale, ma semmai di rimuoverne le cause. Naturalmente il dolore non si combatte solo con i farmaci, ma i farmaci sono sempre stati una componente essenziale nella terapia del dolore (2). I primi farmaci del dolore sono stati, come era ovvio, d'origine vegetale. I popoli primitivi -e l'etnologia può portarne numerosi esempi -hanno identifi cato molte piante che sono in grado di lenire il dolore e le hanno usate e le usano sia per applicazione esterna che per ingestione. Gli Etruschi ed i Romani, ad esempio, impiegavano localmente degli impacchi di malva, un'usanza che persiste ancora nelle campagne. Le radici della mandragora venivano utilizzate soprattutto per combattere la sterilità -un effetto ricordato anche nella Bibbia e reso celebre da una commedia di Niccolò Machiavelli -ma tra le virtù magiche di questa pianta vi era anche il suo potere analgesico (3). Il più "classico" tra gli analgesici d'origine vegetale è però l'oppio, estratto dalle capsule ancora immature di una varietà di papavero, il Papaver somniferum (Fig. 1). Recenti ricerche di archeo-botanica hanno dimostrato che questa specie di papavero era coltivata in Europa nel tardo neolitico, cioè in epoca preistorica (4), anche se questo non signifi ca -o quanto meno rende del tutto ipotetico -che se ne conoscessero o se ne utilizzassero le proprietà. Queste pro- SUMMARYThe pharmacological treatment of pain has very ancient origins, when plant-derived products were used, including mandrake extracts and opium, a dried latex obtained from Papaver somniferum. In the XVI and XVII centuries opium came into the preparation of two compounds widely used for pain relief: laudanum and Dover's powder. The analgesic properties of extracts of willow bark were then recognized and later, in the second half of the XIX century, experimental studies on chemically synthesized analgesics were planned, thus promoting the marketing of some derivatives of para-amino-phenol and pyrazole, the predecessors of paracetamol and metamizol. In the XX century, nonsteroidal anti-inflammatory drugs were synthesized, such as phenylbutazone, which was initially considered primarily a pain medication. The introduction on the market of centrally acting analgesics, such as tramadol, sometimes used in the treatment of rheumatic pain. is quite recent.

Plant latex: A natural source of pharmaceuticals and pesticides

“…[133] Lupeol is a multitarget agent with immense anti-inflammatory potential and target key molecular pathways which involve nuclear factor kappa B (NFκB), cFLIP, Fas, Kras, phosphatidylinositol-3kinase (PI3K)/Akt and Wnt/β-catenin in a variety of cells. [134] It also functions as a therapeutic and chemopreventive agent for treatment of inflammation and cancer. [135] Besides this, few synthetic products such as phenylbutazone are useful as analgesics.…”

“…[135] Besides this, few synthetic products such as phenylbutazone are useful as analgesics. Tramadol is used for the treatment of rheumatic pain [134] while lactucin work as a stronger analgesic and anti-inflammatory agent. [136] It is a pain relieving medicine of abdominal colic, painful menstruation, or muscle spasms.…”

“…[136] Similarly, natural rubber latex (NRL) (Hevea brasiliensis (Hev-b) induce autism. [145] Lupeol acetate also significantly inhibits carrageenan dextran-induced paw oedemas, as well as affect the neutrophil migration to the peritoneal cavity, [134] while Synadenium grantii latex is poisonous and causes erythroderma in patients. [129] Similary, latex from Euphorbia lactea contain tirucallol, a tetracyclic triterpene, which suppress ear edema in mouse and also effect influx of polymorphonuclear cells in response to topical application of 12-O-tetradecanoylphorbol-acetate (TPA) in the mouse ear.…”

Chemical bioactivity of plant latex as an herbal panacea

“…Likewise, latex from Himatanthus drasticus belonging to family apocynaceae which consists of lupeon that is pentacyclic triperpene which exhibit anti-inflammatory activities induce production of few biologically active components like lupeol acetate and pentacyclic triterpene lupeol exhibits pro-inflammatory cytokines (Osadebe & Okoye, 2003). For the treatment of inflammation and cancer it acts as chemoprotective as well as therapeutic agent (Pasero & Marson, 2011). Additionally, some synthetic compounds like phenylbutazone are beneficial like analgesics.…”

Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular, Neurodegenerative, Diabetes and Cancer Disease Therapy

“…It looks like the chemical advances of the 19th–20th centuries promoted the development of non-steroidal anti-inflammatory drugs (NSAIDs), most of which were initially organic acids, and later on non-acidic compounds were discovered [ 4 ]. It was agreed that aspirin was recognized as the progenitor of the pharmacotherapeutic class of NSAIDs medicines and the first in the class of medicine was phenylbutazone in 1946 and indomethacin in the 1960s [ 5 ] continuing with other NSAIDs, including ibuprofen, diclofenac, naproxen, piroxicam [ 6 ]. The progress of new NSAIDs development and introduction to the market was derived by the discovery of the mechanism of action NSAIDs drugs based on the inhibition synthesis of prostaglandins via an arachidonic acid pathway.…”