#tasmar

[venicewalls]

[y-rhywbeth2]

Lore: Common Phrases and Words #2

Accuracy Disclaimer & The Other Stuff [tldr: D&D lore is a giant conflicting mess. Larian's lore is also a conflicting mess. You learn to take what you want and leave the rest]

Abeir-Toril Why it's called the "Forgotten" Realms History | Time & Festivals | Lexicon [1] [2]| Languages | Living in Faerûn [1] [?] | Notable Organisations | Magic | Baldurs Gate | Waterdeep | The Underdark | Geography and Human Cultures --- WIP

Some more random assorted Common vocabulary and phrases - including some LGBT+ terminology and yet more swearing.

An interesting note about insults in the Realms is that you're encouraged to be creative about them. Performers in particular, like playwrights and minstrels, keep a cycle of new and creative phrases coming and going among the population (Earth has social media for its memes, on Toril you can blame the bards).

'tis and 'twas are not uncommonly heard peppered into speech now and then, though the everyday variants we use are just as common.

Badauler - Nonsense, Hogwash

To be "Right darlburl" / "Proper darlburl" - Pissed off

"The thrust of it" - "the gist of it"

Galad! - Wow!

Anyhail - Anyway

Mayhap - Perhaps "Perhaps" is used only in appropriate social settings as fancy etiquette, and only by the upper class and those who wish to affect such mannerisms (bards and the upper middle-class).

Casking - Vandalism (Sword Coast dialect)

a Nightblood - A thief

"The blood of the night" - Thieving, a phrase used by professionals in the trade.

a Sharpjaw - Juvenile delinquent

a Thruster - An aggressively ambitious social climber (not necessarily derogatory)

Brightbird/s - Lover/s

a Rose [Waterdhavian dialect] - Somebody you're in love with, anyone from a crush to a soulmate a Rose [outside of Waterdeep] - A Submissive [BDSM].

a Fancyman/Fancylad/Fancylass - A partner whom the speaker disapproves of. (So, like, your boyfriend knocks on the door and your mother, who hates him, answers, she'll inform you that your "fancylad" is around again.

Power - Divine magic

a Tavernmaster - Barkeeper

a Clevershanks - Know-it-all (usually used for men) a Clevertongue - Know-it-all (usually used for women)

a Highborn - Noble (polite) a Highnose - Noble (rude), also means "has a stick-up-their-ass"

a Holy-nose - Priest; mildly rude, but more rough than offensive.

a Thruss - Lesbian a Liyan - Gay man (elvish loanword) a Praed - Gay man (gnomish loanword)

a Dathna - Twink

a Harnor - Butch

a Tasmar - Bisexual (masc.) a Shaeda - Bisexual (fem.) (elven loanword)

a "No-thorn" - Asexual

a One - An agender term, similar to using they/them.

Sildur - Trans I didn't see much extrapolation on this one, so I assume it's an adjective: a sildur woman, a sildur man, a sildur one or just "I'm sildur" when providing your gender, I guess.

a Brightcoin - Nouveau Riche. Somebody rising through the social ranks.

a Highmantle - Old Money, or somebody with the etiquette and bearing of one

a Turncoin, Coin lass, Coin lad - Sex worker. Something of a generic term, but also refers more specifically to those unaffiliated with brothels and festhalls.

a Laughing-lad/lass, Highcoin lass/lad - A more affluent sex-worker

a Brightspear, Highcoin Lady/Lord - Sex workers who play the part of the noble and draw clients from that crowd.

"Sark!" - The impolite way to say "gods fucking damn it!" (in contrast to haularake - the polite way to say it)

"Bind me and tar me" - An oath of astonishment, milder but similar in form to "well, fuck me." "Bind me" - short version

"Dark!" - "Damn it!"

"Straek" - "Go drown yourself, right now and painfully." No, really, that's the translation given.

"To stlarn up" - to screw up "Stlarning it up" - Screwing up "Stlarn" - a mild "damn" "Stlarning [thing]" - "Bloody [thing]"

"Tluin" - an emphatic "fuck off"

"Those of all the Nine Hells take you!” - the full version of "Hells"

"Happy Dancing Hobgoblins" - a curse used by the old fashioned and parents trying too hard not to swear in front of infants, rather like that old lady I once met on a train who unironically used "jiminy cricket." Hobgoblins are noted to be unimpressed by this particular phrase.

[waterdeepthroat]

if there are words for gay men (dathna), lesbians (thruss) and bisexual men (tasmar), what do you call a bisexual woman in faerûn??

[zarag0]

Babel #not

[gigantobooks]

Krak Komiks #5 - Τάσος Μαραγκός (Tasmar) 2010

[thoughtfullyblogger]

Ένας Τζήμερος

“ΕΝΑΣ ΤΖΗΜΕΡΟΣ” Αδέσποτα Σκίτσα #115 του Τάσου Μαραγκού (Tasmar) – Εφημερίδα των Συντακτών. 02/07/2016. #straydoodles Αδέσποτα Σκίτσα #115. Εφημερίδα των Συντακτών. 02072016. #straydoodles (more…)

[greekblogs]

Ένας Τζήμερος

“ΕΝΑΣ ΤΖΗΜΕΡΟΣ” Αδέσποτα Σκίτσα #115 του Τάσου Μαραγκού (Tasmar) – Εφημερίδα των Συντακτών. 02/07/2016. #straydoodles Αδέσποτα Σκίτσα #115. Εφημερίδα των Συντακτών. 02072016. #straydoodles (more…)

[skandaladiaplokidiafthora]

Ένας Τζήμερος

“ΕΝΑΣ ΤΖΗΜΕΡΟΣ” Αδέσποτα Σκίτσα #115 του Τάσου Μαραγκού (Tasmar) – Εφημερίδα των Συντακτών. 02/07/2016. #straydoodles Αδέσποτα Σκίτσα #115. Εφημερίδα των Συντακτών. 02072016. #straydoodles (more…)

[netakias]

Ένας Τζήμερος

“ΕΝΑΣ ΤΖΗΜΕΡΟΣ” Αδέσποτα Σκίτσα #115 του Τάσου Μαραγκού (Tasmar) – Εφημερίδα των Συντακτών. 02/07/2016. #straydoodles Αδέσποτα Σκίτσα #115. Εφημερίδα των Συντακτών. 02072016. #straydoodles (more…)

[theathenszinebibliotheque]

AZB @ SIKINOS VOL.3 — Join us this year as we return to Sikinos island for the third time (check 2018 & 2019 past events). During the weekend of the 17th and the 18th of July 2021 (from 19:00 to 22:00), AZB will present at the yard of the old school of Kastro village all the zines that were added to the library since summer of 2019. Also, on Saturday the 17th of July we will hold an open zine workshop (at 19:00) on how to make an one-page zine.

Free entrance. — The event is sponsored by the Municipality of Sikinos and is supported by the SNFPHI (The Stavros Niarchos Foundation Public Humanities Initiative at Columbia University). — List of zines (in alphabetical order) participating at the exhibition "AZB @ Sikinos VOL.3":

• _Brut — Álvaro Fernández • 15. August 2020. A day in the life — Various • 1998-2018: 20 years making zines!/20 anos zinando! — Julie Albuquerque • Abnormal — George Tourlas • Abrasion — Kati Akraio • Airlines on paper — Tefra90 • An illustrated guide to insta-emotions — Kati Akraio • Anartchy — Jens Besser & Shlomo Faber • Another day in the office — Sophia Tolika • Armarolla, issues #1-4 — Stelios Hadjithomas • Around Labor, Art, and the Auratic Condition (This is Not a Love Song) — Various • ArtSexDrugsRevolution.gr — Θείο Τραγί • Atomphysik — Philip Joa • Autobioskat — Georgios Plastok • Berliner Mortis Zine — Livor Mortis Zine & Berliner Mauern • Bernd — Daria Rubisch • Blurry territory, notes for a topography of curiosity — Georgios Plastok & Alfred Fabricius • body / struck, issue 1 — Ifigeneia Ilia-Georgiadou & Angelos Kalogerias • Boys! Männer! — Michalis Pichler • Camila — Julie Albuquerque • Carousel #4 — Various • CcBnC issue[1]: prall — Prall • Cheesyphus — Dennis Muñoz Espadiña • Choose your fighter — Jovana Ćubović & Nataša Mihailović • Claustrophobic Tendencies — Never Brush My Teeth • Cockroach Milk — Never Brush My Teeth • Confused Jack — Inés Ballesteros • Crucial Zine, 2019/20 Winter Holiday Special — Various • Crucial Zine, issues #8-11 — Various • Crucial Zine,The CB1 years/MMVIII-MMXI — Various • Dadatek: a manifesto against techno — filtig • DCIM — Κυκλοθυμία & το σφάλμα • Deadiario — Julie Albuquerque • Desired landscapes, issue #3 — Various • Divine Furies Trilogy: The Oracle, The Rescue & The Wedding Night — Nikos Kachrimanis • Do polaroids dream of instant cameras? — Nikos K. Kantarakias • Doors of Athens — Death Vallée & Tarta Ross • Doors of Kypseli — Eleanor Lines • Dotter — Aimilia Balaska • Enterprise Projects Journal, issues #1-4 — Kostas Stasinopoulos, Evita Tsokanta, Myrto Katsimicha, Panos Giannikopoulos • Faces n' Chases, vol.01 — RTMONE & Nadia Stasinou • Finding New Problems — Andromache Kokkinou • Footnotes, issue C — Various • For the love of God — Sinde Butler • Garm zine — Ιωάννης Καρμανιώλος • Giant-size Holy Shit Comix! — Tasmar • Goodbye Horses — Mass Control Superviolence • Graffiti from an American Refugee — Pockets • Greatest hits — Michalis Pichler • GRIP — Aidan Frere-Smith • Gutzine — Various • Hallow Zine — AUB Zine Society (various) • Haras 2nd class — Sarah Maria Schmidt/Haras (Ananas) • Have some change — Mass Control Superviolence • Help — Andromache Kokkinou • Herbal healing: Making Fire Cider — J Henry Hansen • Hibernation — Fred Afraid • Holy shit comix!, issue #3 — Tasmar • Home Is Where The Heart Is — Aidan Frere-Smith • Hotfoot Terrors — Never Brush My Teeth • How to exist at the beach as a non-conforming body — Asparagus Plumosa • How to make your own one-page zine / Πως να φτιάξεις το δικό σου μονοσέλιδο ζιν — The Athens Zine Bibliotheque • I wonder if they could hear me jerking off and other closet fag tips — Unknown • Imaginary Memories, coloring book — RTMONE • Indie music: From fans to professionals — Athanasia Daskalopoulou, Alexandros Skandalis, Maria Dianellou, Fay Daskalopoulou • İşkembe çorbası - Χαϊκού για γερό στομάχι — Χάρης Αλεξίου • Kavourakia Ta — Queer Ink • Kiefer on dirtbike — Tefra90 • Let's talk about feelings — Unknown • Lethargic Punch — Never Brush My Teeth • Light your future bright, 2nd edition — Barba Dee • Livor Mortis Zine #1 Hype in the Hypogeum — SBF Ruttley • Livor Mortis Zine #13 Mo Honey Mo Problems — SBF Ruttley • Livor Mortis Zine #2 Party Hits Vol.2 — SBF Ruttley • Livor Mortis Zine #6(66) The Number of the Beast — SBF Ruttley • Lord — DED2: APESK, ΗΓΗ • Lost in the city — Inés Ballesteros • Lung-Independent music fanzine, issue #6 — Various • Manual — Leifur Ýmir Eyjólfsson • Map of Santorini, Greece — Lila Ruby King & One Quarter Greek • Mercury Retrograde — Asparagus Plumosa • Moan, issue one — Various • Modern savior — Marianna Papageorgiou • Monsanto Company Earnings Call Transcript — Michalis Pichler • Moth. — Asparagus Plumosa • My first bike touring adventure — J Henry Hansen • My pen won't break, but borders will. — Parwana Amiri • Neo Mythological — The Krah • Neptune Square Neptune or my midlife crisis — J Henry Hansen • Networking with an attitude! — Julia Evans • NEW YORK POST flag profile — Michalis Pichler • Newspaper from the American West — Antonis Theodoridis • Not Dead Yet, vol.1 — Various • Nothingness — Manuel Hernández Ruiz • Official Portrait — Lewis Bush • Parental Leave — Anne-Laure Franchette • Peach + Eggplant — AUB Zine Society (various) • Perzine Prompts, Power to your voice — Andromache Kokkinou • Peza vs. Noir (NAC 1st Year Zine) — Neo-Apollonia Crew • Poor Appetite — Folded City • Pour Une Nouvelle Nouvelle Sculpture Grecque — Stamatis Schizakis • Pro-typos, fiction newspaper, Design Walk 2012 — pi6 • Psychedelic Art — AUB Zine Society (various) • Quasar — Ctin • Queer Ink DIY zine — Queer Ink • Queer βίωμα τραύμα και μνήμη — Mochi & Smar • Quotidien — Georgios Plastok • Room around a page — Chloë van Diepen • Self important — Kati Akraio • Soft cake — Sarah Maria Schmidt/Haras (Ananas) • Solo : A broad, issues: #2 & #3 — J Henry Hansen • Solo Diver — Solo Diver • Some call them balkans, 6 acts/books — The Ground Tour Project • Some fallen umbrellas and something else — Michalis Pichler • Sonic Urbanism — &beyond • Street Crawler, issues #1-2 — Aidan Frere-Smith • Summer Time!!! … And how to survive it! — Asparagus Plumosa • Sunny Days, the A-dash issue — A-dash (various) • Swimming outside the stream (vol.I-IV) — Karan Reshad • Talk to me — Born, Think & Yiakou • The adventures of Betty X — Krista Raisa • The Architect is absent — kyklàda.press • The Athens Zine Bibliotheque People — Nadia Stasinou • The bugbook! — Stefania Patrikiou • The cemetery is a forest — Olga Vereli & Katerina Markoulaki • The dreams of Charlotte — Charlotte & Inés Ballesteros • The Feminine Sublime — Rakel McMahon, Katrín Inga Jónsdóttir Hjördísardóttir & Eva Isleifs • The Gum Issue Magazine, issues #1-3 — Various • The international pop no.1, La Sabotage — Dominik Leitner • The Krah illustra zine (1997-2020) — The Krah • The Krah sketchbook, issue #1 — The Krah • The lioness only swims when she has to — Margarita Athanasiou • The Olive tree and the old woman — Parwana Amiri • The search for what doesn't exist begins — Leifur Ýmir Eyjólfsson • The space in between — Chloë van Diepen • The Ultimate Book Coat, User's Guide—Dah Yee Noh • The urban encounters zine — Various • The Urge — Tairis Dimitris • The worst street journal, issue #4 — Dimitris Mitropoulos • Things we don’t talk about — J Henry Hansen • This is my b. world — b. • Tinted window, issue #1: Hervé Guibert — Various • To make radical poetry from home: zine & catalogue — Various • Tomorrow Land — Jana Jarosova • Torso: The Athens Zine Bibliotheque issue — Andrew Nicholas • Torso: IZM July 2019 issue — Andrew Nicholas • Torso: Wild (16 issues) — Andrew Nicholas • TRAINS (FTBTP) — Livor Mortis Zine • Tunnel Up/Tunnel Down, a zine about virtual private networks — Mara Karagianni • Unlimited Card Zine — Noam Assayag & Nick Splendorr • Until the darkness was gone… — J Henry Hansen • Untitled — Stefania Patrikiou • Untitled — Kunstlerexemplar • Untitled — Michael Oskar Wlaschitz • Untitled, vol.1 — Aidan Frere-Smith • Untouchable!! Unreachable!! — Cara Farman & Cameron Lynch • Versifier — William Lee a.k.a. Shannon Flegel • Vielleicht Schwammerl — Kati Akraio • Von Eisen Und Wind — Klára Zahrádková • We are Stefan Werc — Tiny Hand Collective • What I wore yesterday — Asparagus Plumosa • Why do bunnies need to go to therapy? — Queer Ink • Writing new titles for an unfinished novel — Esther Kempf • You stay at home all day and daydream about shoulder dislocations — Never Brush My Teeth • You were born naked and the rest is drag — Amor de Primas • Zine 02 — Various • Zine of zines: "Pause" — Emily Randall • Zine-Ception! A zine about zines — Asparagus Plumosa • 7 αγαπημένα μέρη στη Σίκινο — These Are A Few Of Our Favorite Things • 7 θρεπτικές ουσίες που πρέπει να προσέξεις σε περίπτωση αιφνίδιας χορτοφαγίας — Margarita Athanasiou • 90 ίχνη — Αλέκος Κοάν & Φώντας • Άτιτλο — Liz Papadaki • Εδραιωτικό τετράδιο φιλίας ε#1 — Maria Paneta • Εμβοές, Πεταλούδες της λήθης — Νικόλας Μαλεβίτσης • ένα προς δύο (1:2) — Nikos Staikoglou • Εξομολογήσεις — Various • Η πρώτη τελευταία και παντοτινή Μπιενάλε του Ψηλορείτη, Παναγιώτης Λουκάς & Μαλβίνα Παναγιωτίδη — Stamatis Schizakis • Η πρώτη τελευταία και παντοτινή Μπιενάλε του Ψηλορείτη, Ρένα Παπασπύρου — Stamatis Schizakis • Η πρώτη τελευταία και παντοτινή Μπιενάλε του Ψηλορείτη, Φοίβη Γιαννίση — Stamatis Schizakis • Θα βγαίνω θα πίνω — Asparagus Plumosa • Θέρως — μ² • Καλοκαίρι από απόσταση — Νίκος Καπετάνιος • Λένα Λεπιδόπτερα — Eloish Leigh • Λίπος Άλμπατρος #6 — Joanne Alexopoulou • Μια εποχή στον χαρτοπόλεμο — Αντώνιος Βάθης • Νεωτερισμοί — Χάρης Αλεξίου • Ντελίριο — Μαρία Κωνσταντοπούλου • Οι παγωμάρες μέρες του Πηλίου — Αναστασία Δαφερέρα • Πευκόραμα — Christina Karavida & Louis Bitsikokos • Ποιήματα για Πόκεμον — #TextMe_Lab • Πολιτικά χοντρέλες — Σοφία Αποστολίδου, Hodan Warsame, Φωτεινή Κάκκαρη & Βασιλική Λαζαρίδου • Πώς να φτιάξεις χαρτί στο σπιτάκι σου και να τυπώσεις διάφορα πράγματα ανάλογα με την όρεξή σου και το budget σου, εγχειρίδιο part 1 — Νέλλη & Χριστίνα • Σαντορίνη: μια σύντομη εισαγωγή — Θάνος Ν. Στασινόπουλος • Σαράντα δύο — Silent • Σεμπρία, τεύχη #1-3 — Κύριος Φλανέριος • Σου 'χω πει ποτέ — Tango with lions • Τα θερινά — Χάρης Αλεξίου • Τι τρώνε οι κότες; — Νικόλας Φαράκλας • Τρυφερά υφαίστεια ως το μεδούδι χωρίς επιστροφή — Αντώνιος Βάθης • Φούιτ, τεύχη ΙΙΙ, ΙV & V — Various • Χαίρομαι που είσαι φίλη μου — Asparagus Plumosa • Χαμένο σαν σταφίδα σε μωσαϊκό — Never Brush My Teeth • Ψηφίδες / Pixels (12 books) — miss dialectic • Ψωμί — Paky Vlassopoulou

List of zines that we forgot in Athens (will be presented in 2022 at "AZB @ Sikinos VOL.4"): • 38°32’S 143°58’E — Mirella & Arur Kokk • Berlin Love Me — Αντώνιος Βάθης • Do I have self esteem? — Alex Schauwecker • freedom machine — Mirella & Arur Kokk • Kerozine, issue #1 — The Shop Lifters Collective • Tabloid, issue #1 — Various • διαχωρισμός — Mirella & Arur Kokk • Η πρώτη μου βαβέλ — Tasmar

[13nadimusik]

Kita kenalan asyik dengan talent 13 Nadi Musik yang satu ini @ridhotasmar, sosok lelaki yang unik serta berparas khas.. single pertamanya yang berjudul diam-diam cinta mendapatkan respon positif, dikarenakan single tersebut memiliki komponen nada yang easy buay didengar dan diserap hati dan pikiran kita, coba deh kamu kepoin diam-diam cintanya Ridho Tasmar.. saat pertama kali dengar langsung sreg di hati.... #ridhotasmar #musikdistribution #musikindonesiakeren https://instagr.am/p/CPDxJp3HKcK/

[cultures-world]

@artefr @arte.tv Je sais tomber Disponible sur Arte replay jusqu’au 05/06/2021 Kevin, un jeune homme de 20 ans, sans emploi, retourne chez ses parents en Picardie où il se résout à travailler dans un élevage porcin. Se rendant à son travail, il est heurté sans gravité  par une automobiliste qui, rassurée, le quitte en lui adressant un beau sourire. Séduit par ce visage, il se met à sa recherche. Il découvre qu’elle fait de la voltige dans un cirque équestre. Pour se rapprocher d’elle il se met à cette discipline. Ils vont bientôt s’aimer et tenter de profiter de leur tout nouveau bonheur quand la vie en décide autrement… Cette belle histoire contée par Alain Tasmar et superbement interprétée par Benjamin Voisin et Margot Bancilhon, montre le chemin tortueux de l’apprentissage de la vie d’un jeune homme à la recherche de lui-même. Léa Berroche et Hervé Lejosne https://www.instagram.com/p/CObWfB1LCzS/?igshid=y6tj8ugqndpj

[kritikarehani]

Which Parkinson’s Disease treatments are approved for patients?

Parkinson’s Disease is a debilitating disease that is caused by degeneration of nerve cells in the brain known as the substantia nigra that controls movement. 

The present Parkinson’s disease treatment options that are given to the patients include medication, complementary and supportive therapies (such as diet, exercise, physical therapy, occupational therapy, and speech therapy), and surgery. The approved medication therapies are categorized into seven groups that include Levodopa, Carbidopa-levodopa infusion (Duodopa), Dopamine agonists (Mirapex, Requip, Neupro), MAO B inhibitors (Zelapar, Azilect, Xadago), Catechol O-methyltransferase (COMT) inhibitors (Tasmar, Comtan), Anticholinergics (Cogentin, Artane), and Amantadine.  

The treatment with monoamine oxidase-B (MAO-B) inhibitors, amantadine (Symmetrel), or anticholinergics may modestly improve mild symptoms; however, most patients need levodopa or a dopamine agonist. The most frequently prescribed combination drugs are carbidopa/levodopa (cocareldopa [sinemet, pharmacopa, atamet]) and benserazide/levodopa (co-beneldopa [Madopar]). More recently, continuous intestinal infusion of levodopa gel (Duodopa [AbbVie Limited]) has shown to be effective in terms of decreasing severe motor fluctuations when compared to oral levodopa. However, this treatment is currently prohibitively expensive for widespread use. Levodopa with a DOPA decarboxylase inhibitor is usually a first-line

Parkinson’s disease treatment option.   

For patients with advanced Parkinson’s Disease, most surgeries are preferred. Most of the Parkinson’s disease treatments are aimed at helping the tremor or rigidity that comes with the Disease.  

Several approved therapies drive the current Parkinson’s Disease therapeutic landscape in the US. The available Parkinson’s Disease therapeutics options aim to offer significant symptomatic relief of the motor and non-motor symptoms.

There are many pharmaceutical and biotech companies like Prevail Therapeutics, Axovant Gene Therapies, Neurocrine Biosciences/Voyager Therapeutics, Denali Therapeutics that are researching new therapies to target other aspects of pathology, namely genetic mutations, and Lewy bodies (a hallmark feature of Parkinson’s Disease).

Of  Parkinson’s Disease emerging therapies, the most anticipated product to get launched is VY-ADCC (Voyager Therapeutics). Apart from this, other products include Istradefylline (Kyowa Kirin), Opicapone (Neurocrine Biosciences), P2B001 (Pharma Two B Ltd), LY03003 (Luye Pharma), ABBV-951 (AbbVie), APL-130277 (Sunovion Pharma), Accordion Pill (Intec Pharma) and many more.

Click here for a detailed report: https://www.delveinsight.com/report-store/parkinsons-disease-market-size-analysis-treatment

[gigantobooks]

Krak Komiks #4 - Τάσος Μαραγκός (Tasmar) 2009

[biomedgrid]

Biomed Grid | Update on Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a progressive nervous system disorder that affect movement and present other symptoms, that can be different for everyone and the exact cause of this damage is still unknown. Parkinson’s disease can’t be cured, medications and surgeries might significantly improve their symptoms, these must be prescribed by the neurologist, but it is important to understand how the medication works, what do we expect from them and what other options are available today. In this review the goal is introduce and explain to PD patients and their caregivers the PD: symptoms, stages, treatments, causes and types.

Keywords:  Parkinson’s disease; Tremors; Movement disorders; Postural instability; Levodopa; Parkinsonism; Idiopathic Parkinson’s; Atypical parkinsonism

Abbrevations:  PD: Parkinson’s Disease; CNS: Central Nervous System; MRI: Magnetic Resonance Imaging; STN: Subthalamic Nucleus; GPI: Globus Pallidus Internal; DBS: Deep Brain Stimulation; IPG: Implanted Pulse Generator; UPDRS: Unified Parkinson’s Disease Rating Scale; L-DOPA: Levodopa; LRRK2: Leucine-Rich Repeat Kinase 2; PARK7: Parkinsonism Associated Deglycase; PRKN: Parkin Rbr E3 Ubiquitin Protein Ligase; TMS: Transcranial Magnetic Stimulation; THC: Tetrahydrocannabinol; CBD: Cannabidiol; TCE: Trichloroethylene; CSE: Chronic Solvent Encephalopathy; MSA: Multiple System Atrophy; PSP: Progressive Supranuclear Palsy; CBS: Corticobasal Syndrome; DLB: Dementia with Lewy Bodies; VP: Vascular Parkinsonism; PBA: Pseudobulbar Affect

Introduction

Parkinson’s Disease (PD) is a progressive neurodegenerative disease producing neuronal cell death, presenting loss of dopamineproduction in the brain area known as substancia nigra [1], altering the central nervous system CNS (brain and spinal cord), and affecting the regulation of the human movements and emotions. the exact cause of this damage is still unknown, and currently there is no cure for Parkinson’s disease. PD is a form of extrapyramidal disorder that affects movements disorder caused by damage to the extrapyramidal tract, a network of nerves that controls movements.

PD is a typical movement disorder [2] and the 2nd most common neurodegenerative condition after Alzheimer’s disease. PD is a continuous neurological disorder where the symptoms continue to worsen gradually [3]. PD is a highly variable disease, meaning that different patients have different combinations of symptoms, and those symptoms can be at varying severity levels.

Symptoms of PD

The main symptoms of PD are of three kinds: primary motors, secondary motors and non-motors [4]. Where

Motors (Directly Related to Movement)

a. Tremors (shaking) in the limbs,

b. Rigidity (muscle stiffness),

c. Bradykinesia (slowness of movements),

d. Postural instability (impaired balance or difficulty standing or walking,

Secondary Motor (Consequence of Movement Disorders)

a. Hypomimia - loss of facial expressions known also as Parkinson mask.

b. Freezing of gait or shuffling gait – the gait, or way of walking, may be affected by a temporary hesitation (freezing) or dragging of the feet (shuffling).

c. Unwanted accelerations – movements which are too quick, which may appear in movement or in speech.

d. Speech difficulty or changes in speech – including slurred speech or softness of voice e. Stooped posture – the body leans forward, and the head may be slightly turned down.

f. Dystonia – prolonged muscle contractions that can cause twisting of body parts or repetitive movements.

g. Impaired fine motor dexterity – difficulty with precise hand and finger movement, such as in writing, sewing, or fastening buttons.

h. Poverty of movement – lack of natural, subtle movements like the decreased arm swing during walking

i. Akathisia – restless movement, which may appear as being jumpy or fidgety.

j. Difficulty swallowing – challenges swallowing can also cause drooling or excess saliva.

k. Cramping – muscles may stay in a contracted position and cause pain

l. Sexual dysfunction – decreased sex drive, inability to orgasm, erectile dysfunction in men, decreased lubrication in women, or pain with intercourse in women.

Non-Motors (no Related to Movement Disorders)

a. Fatigue – excessive tiredness that isn’t relieved with sleep

b. Digestive issues – difficulty swallowing, nausea, bloating, and/or constipation

c. Sleep problems – including difficulty falling asleep, staying asleep, vivid dreams, physically acting out dreams, sleep apnea and sleep attacks (patients may be suddenly overcome with drowsiness and fall asleep).

d. Orthostatic hypotension – low blood pressure that occurs when rising to a standing position.

e. Increased sweating.

f. Increased drooling.

g. Pain – which may accompany muscle rigidity.

h. Hyposmia – reduced sense of smell.

i. Mood changes – including apathy, depression, anxiety and Pseudobulbar Affect PBA (frequent, involuntary and uncontrollable outbursts of crying or laughing)

j. Cognitive changes – including memory difficulties, slowed thinking, confusion, impaired visual-spatial skills (such as getting lost in familiar locations), and dementia.

k. Psychotic symptoms – including hallucinations, paranoia, and agitation.

l. Incontinence _Urinary problems.

m. Orthostatic hypotension (OH) - change of arterial pressure with postural changes

n. Melanoma - an invasive form of skin cancer that has been found to develop more often in people with Parkinson’s.

PD stages

There are typical patterns of progression in Parkinson’s disease that are defined in five stages, Not everyone will experience all the symptoms of Parkinson’s, and if they do, they won’t necessarily experience them in quite the same order or at the same intensity. The typical five stages are summarized in (Table 1).

Table 1: The typical five stages of Parkinson’s.

PD Treatments

There are a variety of treatments that can help manage the motor symptoms and improve the quality of life, but there is no known treatment to stop or slow the disease progression that is different in each patient. The current treatments available must be prescribed by a neurologist, these are: medications, surgical treatments and complementary/alternative therapies.

Medications

Levodopa is the most efficacious medication for PD, it is converted to dopamine. When initiated the levodopa treatment improves symptoms through the day and night. Overtime patients develop OFF time. Off time is the time during the day when PD symptoms return or worsen, typically 40% in 5 years, 90% in 10 years [1]. Off time PD symptoms may include motor, secondary motors and non-motors. Off periods is the sum of four times that levodopa is not working:

a. Early morning Off -patients typically present with poor motor function in the morning when they wake up, before the first dose of levodopa [6],

b. Wearing Off - symptoms of Parkinson’s start to return or worsen before the next dose of levodopa is due [7],

c. Delayed On – delay in the onset of benefit of a levodopa dose [8],

d. Dose Failure - when there is no benefit from dose of levodopa [9].

Current medication for PD [

10

].

Levodopa - The most potent medication for Parkinson’s disease (PD) is levodopa. Its development in the late 1960s represents one of the most important breakthroughs in the history of medicine. Levodopa in pill form is absorbed in the blood from the small intestine and travels through the blood to the brain, where it is converted into dopamine, needed by the body for movement. Plain levodopa produces nausea and vomiting.

a. Carbidopa/levodopa remains the most effective drug to treat PD. The addition of carbidopa prevents levodopa from being converted into dopamine prematurely in the bloodstream, allowing more of it to get to the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms [11].

b. Carbidopa/levodopa (Sinemet®)- Levodopa is combined with carbidopa to prevent nausea and vomiting as side effect.

c. Carbidopa/levodopa (Rytary®) is a combination of long and short-acting capsule.

d. Carbidopa/levodopa (Parcopa®) is formulation that dissolves in the mouth without water.

e. Carbidopa/levodopa (Stalevo®) is combined formulation that includes the COMT inhibitor entacapone.

f. Dopamine Agonists [12]. They stimulate the parts of the human brain influenced by dopamine. In effect, the brain is tricked into thinking it is receiving the dopamine it needs. Dopamine agonists can be taken alone or in combination with medications containing levodopa. The most commonly prescribe oral pill are: pramipexole (Mirapex), ropinirole (Requip), rotigotine transdermal system (Neupro®), Bromocriptine (Parlodel®) and one special apomorphine (Apokyn), is a powerful and fast-acting injectable medication that promptly relieves symptoms of PD within minutes, but only provides 30 to 60 minutes of benefit. Its main advantage is its rapid effect. It is used for people who experience sudden wearing-off spells when their PD medication abruptly stops working, leaving them unexpectedly immobile.

g. Amantadine. it is a mild agent that is used in early PD to help tremor. In recent years, amantadine has also been found useful in reducing dyskinesias that occur with dopamine medication. h. COMT Inhibitors are used to prolong the effect of levodopa by blocking its metabolism. COMT Inhibitors are used primarily to help with “wearing off,” in which the effect of levodopa becomes short-lived. The most common are: Carbidopa/ levodopa (Stalevo®), Entacapone (Comtan®) and Tolcapone (Tasmar®)

i. Anticholinergic Drugs. They decrease the activity of acetylcholine, a neurotransmitter that regulates movement. It can be helpful for tremor and may ease dystonia associated with wearing-off or peak-dose effect. The most common are: trihexyphenidyl (Artane®), benztropine mesylate (Cogentin®) and procyclidine (no longer available in the U.S.), among others.

j. MAO-B Inhibitors. They block an enzyme in the brain that breaks down levodopa, this makes more dopamine available and reduces some of the motor symptoms of PD. When used together with other medications, MAO-B inhibitors may reduce “off” time and extend “on” time. They have been shown to delay the need for Sinemet when prescribed in the earliest stage of PD and have been approved for use in later stages of PD to boost the effects of Sinemet. The most common used are: Selegiline also called Depreny (Eldepryl® and Zelapar®) and rasagiline (Azilect®).

Caution: PD medications may have interactions with certain foods, other medications, vitamins, herbal supplements, over the counter cold pills and other remedies. Anyone taking a PD medication should talk to their doctor and pharmacist about potential drug interactions.

A summary of new treatments and future treatments for Parkinson’s disease are shown in (

Table 2

) [5]  

Table 2:Summary of new treatments and future treatments for Parkinson’s disease

    Surgical Treatments

Surgical treatments can be an effective treatment option for different symptoms of Parkinson’s disease (PD), only the symptoms that previously improved on levodopa have the potential to improve after the surgery. Surgical treatment is reserved for PD patients who have exhausted medical treatment of PD tremor or who suffer profound motor fluctuations (wearing off and dyskinesias), surgical treatments doesn’t cure PD and it does not slow PD progression. These are:

a. Carbidopa/levodopa intestinal fusion pump (DUOPA™). This is a gel formulation of the drug that requires a surgicallyplaced tube. provides 16 continuous hours of carbidopa and levodopa for motor symptoms. The small, portable infusion pump delivers carbidopa and levodopa directly into the small intestine obtaining better ON time.

b. Deep brain stimulation DBS [13]. DBS is only recommended for people who have had PD for at least four years and have motor symptoms not adequately controlled with medication. In DBS surgery, electrodes are inserted into a targeted area of the brain, using MRI (magnetic resonance imaging) and recordings of brain cell activity during the procedure. A second procedure is performed to implant an implanted pulse generator IPG, impulse generator battery (like a pacemaker). The IPG is placed under the collarbone or in the abdomen. The IPG provides an electrical impulse to a part of the brain involved in motor function. Those who undergo DBS surgery are given a controller to turn the device on or off. The most commonly utilized brain targets include the subthalamic nucleus (STN) and the Globus pallidus internal (GPI). Target choice should be tailored to a patient’s individual needs. The STN does seem to provide more medication reduction, while GPi may be slightly safer for language and cognition. Although most people still need to take medication after undergoing DBS, many people experience considerable reduction of their PD symptoms and can greatly reduce their medications. The amount of reduction varies from person to person.

Future Surgical Treatments

PD Stem Cell Therapy. Cell transplantation in PD patients include [14-16]: adrenal medullary, retinal, carotid body, patient’s fat (adipose tissue) and human and porcine fetal cells. Cell transplantation using aborted 6 to 9 weeks-old human embryos evolved historically as the most promising approach. One of the major concerns in cell transplantation for PD is the host immune response to the grafted tissue. Cell therapy for PD have been associated with significant concerns and complications.

Although the brain is often considered “immune-privileged”, there is in fact evidence that intracerebral immunologicallymediated graft rejection can and does occur [17]. The open-label studies, and the functional engraftment of the transplanted tissue – are enough to provide hope that improvements in cell replacement strategies for PD could yield tremendous positive impact on patients’ lives. The Food and Drug Administration FDA has not yet approved stem cell therapy as a treatment for Parkinson’s disease, clinical studies have demonstrated safety and potential efficacy. The FDA, however, requires further investigation before these kinds of treatment can be approved.

Complementary/Alternative Therapies

There many common Parkinson’s alternative available therapies for PD it is recommended speak with your doctor before, embarking on an alternative therapy. The most common are [18]:

a. Acupuncture, Acupuncture is recognized as a viable treatment for various illnesses and conditions. Acupuncture may improve PD‐related fatigue, but real acupuncture offers no greater benefit than sham treatments. PD‐related fatigue should be added to the growing list of conditions that acupuncture helps primarily through nonspecific or placebo effects [19].

b. Guided imagery (guided meditation), a gentle but powerful technique that focuses the imagination in proactive, positive ways. Motor imagery is a mental process by which an individual rehearses or simulates a given action. It is widely used in sport training as mental practice of action, neurological rehabilitation, and has also been employed as a research paradigm in cognitive neuroscience and cognitive psychology to investigate the content and the structure of covert processes (i.e., unconscious) that precede the execution of action. Motor imagery is thought to be helpful in treatment of neurological motor disabilities caused by stroke, Parkinson’s disease and spinal cord injuries [20].

c. Chiropractic. The theory of chiropractic care is based on the idea that the properly adjusted body, particularly the spine, is essential for health, with influence on life force and good health attained using spinal manipulation therapy for the removal of subluxations. The dosage of chiropractic care depends on the practitioner [21]. Some reports shown that the use of alternative treatment as chiropractic procedures appeared to help in Parkinson disease signs and symptoms [22].

d. Yoga, though yoga is one of the widely used mind-body medicine for health promotion, disease prevention and as a possible treatment modality for neurological disorders. Among various types of mind-body exercises, yoga was reported to be the largest and to produce the most significant beneficial effect in reducing Unified Parkinson’s Disease Rating Scale UPDRS III scores for people with mild to moderate PD [23].

e. Hypnosis might represent an interesting complementary therapeutic approach to movement disorders, as it considers not only symptoms, but also well-being, and empowers patients to take a more active role in their treatment. Well-designed studies considering some specific methodological challenges are needed to determine the possible therapeutic utility of hypnosis in movement disorders. In addition to the potential benefits for such patients, hypnosis might also be useful for studying the neuroanatomical and functional underpinnings of normal and abnormal movements [24].

f. Biofeedback seems to be a promising tool to improve gait outcomes for both healthy individuals and patient groups. However, due to differences in study designs and outcome measurements, it remains uncertain how different forms of feedback affect gait outcomes [25].

g. Aromatherapy uses plant materials and aromatic plant oils, including essential oils, and other aroma compounds for the purpose of altering one’s mood, cognitive, psychological or physical well-being. Aromatherapy in PD improve restlessness; anxiety, mood, works great; calming; relaxation; nausea; alertness; helped sleep; calming effect [26].

h. Herbal remedies are medication prepared from plants, including most of the world’s traditional remedies for disease. There are many herbal remedies that can be useful for PD but there are missing systematic approaches to test each one in neurologic diseases like PD. For example, Resveratrol as a natural polyphenolic compound extracted from red grapes, exerts neuroprotective effects on oxidative damage and neuronal damage through its antioxidant as well as antiinflammatory properties. Resveratrol has the potential to treat PD by inhibiting neuro-inflammation, apoptosis and promoting neuronal survival and can serve as a complementary medicine drug to reduce the L-DOPA dose needed to ameliorate PD [27].

i. Magnetic therapy, many studies conclude that further studies are needed on PD magnetic therapy. Investigations using repetitive Transcranial Magnetic Stimulation TMS in assessing the motor system function are still in an early phase and need further evaluation. Altogether, the value of TMS for studies of the physiology and pathophysiology of the motor system is beyond any doubt and the limits of these techniques have not yet been reached [28].

j. Massage. Parkinson’s disease typically causes muscle stiffness and rigidity, individuals who utilize massage therapy find it helps to alleviate joint and muscle stiffness.

k. Marijuana also called cannabis, is made up of two major parts: Tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the major part that causes one to feel “high.” THC can cause hallucinations and anxiety and is therefore to be used with caution, if at all, in Parkinson disease. CBD, by comparison, may help with sleep and anxiety. A few studies have suggested that marijuana helps with some aspects of Parkinson’s and may allow a person to reduce his or her use of prescription medications. But there is no definitive data on what dose of what parts of marijuana are helpful or harmful in Parkinson’s disease. The possible association of cannabinoid receptors with ubiquitin pathway needs to be studied further in order to understand its extensive role in PD. Furthermore, epigenetic modifications resulted by cannabinoid receptor activation needs to be elucidated which can be crucial to follow up the pathology of the disease [29].

PD causes

Around 80% populations with PD are considered as idiopathic because of their unknown source of etiology whereas the remaining 20% cases are presumed to be genetic. Variations in the genetic combination of certain genes elevate the risk of PD. Studies have reported that mutation in the LRRK2 (leucine-rich repeat kinase 2),PARK7 (Parkinsonism Associated Deglycase), PRKN (Parkin RBR E3 Ubiquitin Protein Ligase), PINK1 (PTEN-induced putative kinase 1) or SNCA (alpha-synuclein) contribute to the risk of PD[30].

Factor for Parkinson’s disease

Generally, scientists speculate that the interaction between gene mutations and environmental exposures can contribute to PD progression. Studies have listed few modifiable risk factors for PD, the following factors are considered as some of the causative factors of PD [31,32] are:

Exposure to pesticide: The evidence that pesticide and herbicide use is associated with an increased risk in PD, begs the question – are there specific pesticides that are most concerning? When data is collected on this topic in large populations, often the participants in the study are unaware of which specific pesticide or herbicide exposures they have had. This makes it difficult to determine which pesticides to avoid. From that data emerged paraquat and rotenone as the two most concerning pesticides [33] and Glyphosate as herbicide [34]. Where:

a. Paraquat’s mechanism of action is the production of reactive oxygen species, intracellular molecules that cause oxidative stress and damage cells.

b. Rotenone’s mechanism of action is disruption of the mitochondria, the component of the cell that creates energy for cell survival.

c. Glyphosate is the world’s most heavily applied herbicide, and an active ingredient in Roundup®

d. Well-water drinking. Rural residents who drink water from private wells are much more likely to have Parkinson’s disease, a finding that bolsters theories that farm pesticides may be partially to blame, according to a new California study [35].

e. Heavy metals, such as iron and manganese, are involved in neurologic disease. Most often these diseases are associated with abnormal environmental exposures or abnormal accumulations of heavy metals in the body. Many epidemiological studies have shown an association between PD and exposure to metals such as: mercury, lead, manganese, copper, iron, aluminium, bismuth, thallium, and zinc [38]. The combination of high concentration of iron and the neurotransmitter, dopamine, may contribute to the selective vulnerability of the brain in the substantia nigra pars compacta (SNpc) in the basal ganglia [36].

f. Solvents, case reports of parkinsonism, including PD, have been associated with exposures to various solvents, most notably trichloroethylene (TCE) [37]. The peripheral nervous system as well as the central nervous system can both be targeted. Prolonged workplace exposure to organic solvents can induce a chronic solvent encephalopathy (CSE) that persists even after the exposure is terminated [38].

g. Calcium, the international team, led by the University of Cambridge, found that calcium can mediate the interaction between small membranous structures inside nerve endings, which are important for neuronal signaling in the brain, and alpha-synuclein, the protein associated with Parkinson’s disease. Excess levels of either calcium or alpha-synuclein may be what starts the chain reaction that leads to the death of brain cells [39]. Ca2+ dysregulation and the direct consequences for mitochondrial health in PD [40].

h. Age, Parkinson’s disease can both be early- and late-onset. Many processes affected in Parkinson’s disease are linked to factors associated with age. The risk of Parkinson’s disease increases dramatically in individuals over the age of 60 and it is estimated that more than 1% of all seniors have some form of the condition [41].

i. Gender, more men than women are diagnosed with Parkinson’s disease (PD), and several gender differences have been documented in this disorder. One possible source of malefemale differences in the clinical and cognitive characteristics of PD is the effect of estrogen on dopaminergic neurons and pathways in the brain [42]

Parkinson ‘s diseases types

Parkinsonism is a constellation of signs and symptoms that are characteristically observed in Parkinson’s disease (PD), but that are not necessarily due to PD. Parkinsonism is the primary type of hypokinetic movement disorder. Parkinsonism describe the collection of signs and symptoms found in Parkinson’s disease (PD). These include slowness (bradykinesia), stiffness (rigidity), tremor and imbalance (postural instability). There are basically two general Parkinson’s types: Idiopathic Parkinson’s and atypical parkinsonism [43] (Table 3).

Table 3: The typical five stages of Parkinson’s.

    Idiopathic Parkinson’s

Idiopathic Parkinson’s is the most common form of Parkinsonism. It is a tremor predominant disorder that involves shaking and trembling. About 85% of people with parkinsonism have idiopathic Parkinson’s. This type of Parkinson’s disease can begin at an earlier age but progresses more slowly. It has a lower risk of cognitive (brain function) decline, but the tremors may be more difficult to treat than other symptoms [44].

Atypical parkinsonism

Atypical parkinsonism is less common, it is an instability and gait disorder that present more trouble with walking and balance. About 15% of people with parkinsonism have Atypical parkinsonism disorders, these are rarer conditions and more difficult to treat. This type of Parkinson’s disease happens at an older age but tends to progress quickly. Although people may experience fewer tremors or no tremors at all, they have a higher risk of cognitive decline. Atypical parkinsonism includes the following variations:

a. Multiple System Atrophy MSA includes several neurodegenerative disorders in which one or more systems in the body deteriorates as: incoordination (ataxia), dysfunction in the autonomic nervous system that automatically controls things such as blood pressure and bladder function. These are in addition to variable degrees of parkinsonism including symptoms such as slowness, stiffness and imbalance. Average age of onset is in the mid-50’s.

b. Progressive Supranuclear Palsy PSP is the most common degenerative type of atypical parkinsonism. Symptoms tend to progress more rapidly than PD. People with PSP may fall frequently early in the course of disease. Later symptoms include limitations in eye movements, particularly looking up and down, which also contributes to falls. Those with PSP also often have problems with swallowing (dysphagia), difficulty in producing speech (dysarthria), sleep problems, memory and thinking problems (dementia). Its average age of onset is in the mid-60’s.

c. Corticobasal Syndrome CBS is the least common of the atypical causes of Parkinsonism. Usually begins with symptoms affecting one limb. In addition to parkinsonism, other symptoms can include abnormal posturing of the affected limb (dystonia), fast, jerky movements (myoclonus), difficulty with some motor tasks despite normal muscle strength (apraxia), difficulty with language (aphasia) among others. Typically begins after age 60 [45].

d. Dementia with Lewy bodies DLB is a progressive, neurodegenerative disorder in which abnormal deposits of a protein called alpha-synuclein build up in multiple areas of the brain. It is second to Alzheimer’s as the most common cause of degenerative dementedly first causes progressive problems with memory and fluctuations in thinking, as well as hallucinations. These symptoms are joined later in the course of the disease by parkinsonism with slowness, stiffness and other symptoms like PD.

e. Drug-induced Parkinsonism is the most common form of what is known as secondary parkinsonism. Side effects of some drugs, especially those affecting brain dopamine levels (anti-psychotic or anti-depressant medication), can cause parkinsonism. Although tremor and postural instability may be less severe, this condition may be difficult to distinguish from Parkinson’s. Some medications can cause the development of Parkinsonism as: Antipsychotics, some antidepressants, reserpine, some calcium channel blockers and others. Usually after stopping those medications parkinsonism gradually disappears over weeks to months, though symptoms may last for up to a year.

f. Vascular Parkinsonism VP is based in evidences that suggest that multiple small strokes in key areas of the brain may cause Parkinsonism. A severe onset of parkinsonism immediately following (or progressively occurring within a year of) a stroke may indicate VP.

Conclusions

Parkinson’ disease is a neurologic disease that affect the functionality if the brain modifying the neural connectivity due to cell death. All medication and procedures available today only help to improve the quality of life of the patients, there is a big necessity to focus in more ways to accelerate the research on PD, like creating a cloud database with information about the development, new medications available, new surgical procedures, new way to early detection, new criteria’s and many other factors.

Read More About this Article: https://biomedgrid.com/fulltext/volume2/update-on-parkinsons-disease.000614.php

For more about: Journals on Biomedical Science :Biomed Grid

[azveille]

Prescrire ajoute 12 médicaments à sa liste des produits "plus dangereux qu'utiles"

La revue Prescrire a fait entrer 12 nouveaux produits dans sa liste de "médicaments autorisés plus dangereux qu'utile", publiée dans dans son numéro de décembre.

Cette liste, établie pour la huitième année consécutive, compte désormais 105 médicaments, dont 92 commercialisés en France, à écarter des soins, selon la revue.

Les 12 entrants sont:

le traitement des maux de gorge alpha-amylase, présent notamment dans Maxilase* (Sanofi)

le traitement des troubles cognitifs chez les patients âgés ginkgo biloba, que l'on retrouve notamment dans Tanakan* (Ipsen)

le naftidrofuryl (présent notamment dans Praxilene*, Merck KGaA) dans la claudication intermittente ischémique liée à une artériopathie des membres inférieurs

le pentosane polysulfate oral (Elmiron*, Bene-Arzneimittel) dans le syndrome de la vessie douloureuse

l'antitussif pentoxyvérine (Vicks sirop pectoral 0,15%* et Clarix toux sèche pentoxyvérine 0,15%*, Procter & Gamble)

le décongestionnant rhinopharyngé xylométazoline, non commercialisé en France mais en Belgique et Suisse notammentles pansements gastriques:

attapulgite (Actapulgite* ou en association dans Gastropulgite* de Mormoiron et Ipsen)

diosmectite, présent notamment dans Smecta* (Ipsen)

hydrotalcite (Rennieliquo*, Bayer)

montmorillonite beidellitique alias monmectite (Bedelix* ou en association dans Gelox*, Ipsen)

kaolin (en association dans Gastropax*, Lehning et Neutroses*, DB Pharma)

Ces cinq derniers produits sont des argiles médicamenteuses utilisées dans divers troubles intestinaux dont les diarrhées. La contamination par du plomb justifie de les écarter des soins, a indiqué Prescrire. L'ANSM a demandé en février de ne plus utiliser ces médicaments, rappelle-t-on.

La revue signale également que les traitements du diabète de type 2 du groupe des glifozines ne figurent toujours pas dans la liste des médicaments à écarter malgré une balance bénéfices-risques défavorable. La dapagliflozine ayant été autorisée dans le diabète de type 1, l'analyse de la revue de ces produits dans cette situation est en cours, a-t-elle expliqué. Il s'agit de la canagliflozine (Invokana*, Johnson & Johnson), la dapagliflozine (Forxiga*, AstraZeneca), l'empagliflozine (Jardiance*, Boehringer Ingelheim/Lilly) et de l'ertugliflozine (Steglatro*, MSD).

Prescrire a retiré de la liste le séléxipag (Uptravi*, Actelion), un agoniste des récepteurs de la prostacycline par voie orale, autorisé dans l'hypertension artérielle pulmonaire (HTAP). Ce retrait est dû au réexamen de son évaluation par Prescrire. "Pour autant, sa balance bénéfices-risques est très incertaine", note la revue, qui a constaté un excès de mortalité dans le principal essai d'évaluation clinique.

La revue souligne enfin que le myorelaxant méphénésine (Decontractyl*, Sanofi), qui avait fait son entrée sur la liste 2019, a été retiré du marché français sur décision de l'Agence nationale de sécurité du médicament et des produits de santé (ANSM). Il reste cependant commercialisé en Belgique et figure donc toujours sur la liste.

Sur la base de l'étude de l'ensemble des médicaments bénéficiant d'une autorisation de mise sur le marché (AMM) française ou européenne entre 2010 et 2019, Prescrire a établi sa liste par domaine thérapeutique, comme suit:

Cancérologie-hématologie

le défibrotide (Defitelio*, Gentium)

le mifamurtide (Mepact*, Takeda)

le nintédanib (Vargatef*, Boehringer Ingelheim)

le panobinostat (Farydak*, Novartis)

la trabectédine (Yondelis*, PharmaMar)

le vandétanib (Caprelsa*, AstraZeneca)

la vinflunine (Javlor*, Pierre Fabre)

Cardiologie

l'aliskirène (Rasilez*, Novartis)

le bézafibrate, le ciprofibrate et le fénofibrate

la dronédarone (Multaq*, Sanofi)

l'ivabradine

le nicorandil

l'olmésartan (Olmésartan, Daiichi Sankyo/Alteis*, Menarini)

la ranolazine (Ranexa*, Gilead)

la trimétazidine

le vernakalant (Brinavess*, Cardiome)

Dermatologie - Allergologie

la méquitazine (Primalan*, Pierre Fabre)

la prométhazine injectable (Phénergan*, Famel)

le tacrolimus dermique (Protopic*, Leo)

Diabétologie-nutrition

les inhibiteurs de la DPP-4 alogliptine (Vipidia* et associations, Takeda), linagliptine (Trajenta* et associations, Boehringer Ingelheim), saxagliptine (Onglyza* et associations, AstraZeneca), sitagliptine (Januvia* et associations, Merck & Co) et vildagliptine (Galvus* et associations, Novartis)

la pioglitazone (Actos*, Takeda)

l’association bupropion + naltrexone (Mysimba*, Orexigen)

l'orlistat

Douleur-rhumatologie

les coxibs célécoxib, étoricoxib et parécoxib (Dynastat*, Pfizer)

l'acéclofénac et le diclofénac

le kétoprofène en gel

le piroxicam par voie générale

la diacéréine

la glucosamine

la méphénésine (Decontractyl*, Sanofi)

le méthocarbamol (Lumirelax*, Juvisé)

le thiocolchicoside

la capsaïcine en patch (Qutenza*, Grünenthal)

le dénosumab (Prolia*, Amgen)

la quinine

l'association colchicine + poudre d'opium + tiémonium (Colchimax*, Mayoly Spindler)

l'association prednisolone + salicylate de dipropylène glycol (Cortisal*, Dexo)

Gastro-entérologie

l'acide obéticholique (Ocaliva*, Intercept)

les argiles médicamenteuses attapulgite, diosmectite, hydrotalcite (Rennieliquo*, Bayer), montmorillonite beidellitique alias monmectite (Bedelix* et Gelox*, Ipsen) et kaolin (en association dans Gastropax* et Neutroses*, Lehning et DB Pharma)

la cimétidine

la dompéridone, le dropéridol et la métopimazine (Vogalène*/Vogalib*, Teva)

le nifuroxazide

le prucalopride (Resolor*, Shire, groupe Takeda)

le trinitrate de glycéryle (Rectogesic*, Kyowa Kirin)

Gynécologie-endocrinologie

l'association estrogènes conjugués + bazédoxifène (Duavive*, Pfizer)

la tibolone (Livial*, Merck & Co)

l'ulipristal 5 mg (Esmya*, Richter)

Infectiologie

la moxifloxacine

Neurologie

le donépézil, la galantamine et la rivastigmine

la mémantine

l'alemtuzumab (Lemtrada*, Sanofi)

le natalizumab (Tysabri*, Biogen)

le tériflunomide (Aubagio*, Sanofi)

la flunarizine (Sibelium*, J&J) et l'oxétorone (Nocertone*, Sanofi)

le ginkgo biloba

le naftidrofuryl

la tolcapone (Tasmar*, Meda, groupe Mylan)

Ophtalmologie

la ciclosporine en collyre (Ikervis*, Santen)

l'idébénone (Raxone*, Santhera)

Pneumologie-ORL

l'ambroxol et la bromhexine (Bisolvon*, Sanofi)

l'oxomémazine (Toplexil*, Sanofi et génériques)

le pentoxyvérine

la pholcodine

l'alpha-amylase

l'association tixocortol + chlorhexidine

l'éphédrine, la naphazoline, l'oxymétazoline, la phényléphrine, la pseudoéphédrine, le tuaminoheptane et la xylométazoline

le mannitol inhalé (Bronchitol*, Pharmaxis)

le nintédanib (Ofev*, Boehringer Ingelheim)

le roflumilast (Daxas*, Takeda)

Psychiatrie-dépendances

l'agomélatine (Valdoxan*, Servier)

le citalopram et l'escitalopram

la duloxétine, le milnacipran et la venlafaxine

la tianeptine

la dapoxétine (Priligy*, Menarini)

l'étifoxine (Stresam*, Biocodex)

Sevrage tabagique

le bupropion (Zyban*, GSK)

Urologie

le pentosane polysulfate (Elmiron*, Bene-Arzneimittel)