Science

http://www.sciencemag.org/news/2017/12/old-drug-alcoholism-finds-new-life-cancer-treatment

An old drug for alcoholism finds new life as cancer treatment

By Jocelyn KaiserDec. 6, 2017 , 1:00 PM

By age 38, the patient’s breast cancer had spread to her bones, a typically fatal turn of events. She became an alcoholic, and her doctors stopped all cancer treatment, instead giving her a drug to discourage her drinking. She died 10 years later, after an inebriated fall from a window. But an autopsy revealed something unexpected: Her bone tumors had melted away, leaving only a few cancer cells in her marrow.

That 1971 case report, along with numerous lab studies, have suggested that the 6-decade-old drug disulfiram (commercially known as Antabuse), which makes people feel sick from drinking small amounts of alcohol, might also be a cancer fighter. Now, researchers have finally figured out how—by blocking a molecule that is part of a process that gets rid of cellular waste.

“This paper solves a puzzle that has persisted in cancer research for decades,” says cancer biologist Michele Pagano of New York University School of Medicine in New York City, who was not involved in the study.

Starting in the 1970s, scientists found that disulfiram killed cancer cells and slowed tumor growth in animals. It increased survival in women who had breast tumors removed in a small clinical trial published in 1993. But since then, disulfiram hasn’t gotten much attention for treating cancer, partly because scientists disagreed about how it worked.

In the new study, a Danish-Czech-U.S. team first firmed up the drug’s anticancer effects by combing through Denmark’s unique cancer registry—more than 240,000 cases diagnosed between 2000 and 2013, along with data on the medications each patient took. Of the more than 3000 patients taking Antabuse, the cancer death rate was 34% lower for the 1177 who stayed on the drug compared with those who stopped taking it, the researchers report today in Nature. The drug was an equal opportunity anticancer weapon; its benefits held for prostate, breast, and colon cancer, as well as cancer overall.

The researchers also confirmed that disulfiram slows the growth of breast cancer tumors in mice, particularly if combined with a copper supplement, which was already known to enhance its effects. They then showed that when the mice broke down disulfiram, its main metabolite, ditiocarb, forms a complex with copper that blocks the machinery that cells use to dispose of misfolded and unneeded proteins. “Everything is frozen,” says cancer biologist Jiri Bartek of the Danish Cancer Society Research Center in Copenhagen, a co-leader of the study. Partly because of the resulting protein buildup, the cancer cells become stressed and die.

Although some approved cancer drugs and others in development interfere with the same protein cleanup process, known as the ubiquitin-proteasome system, disulfiram targets only a specific molecular complex within this machinery. That could explain why it is so effective, Pagano says. Bartek’s team also solved another puzzle—why normal cells aren’t harmed by disulfiram, even when patients take it for years. For unclear reasons, the copper metabolite is 10 times more abundant in tumor tissue compared with other tissues, the group found.

Despite the compelling 1971 anecdote, disulfiram probably “is not a cure” for most cancer patients, cautions cancer biologist Thomas Helleday of the Karolinska Institute in Stockholm. However, the drug could help extend the lives of patients with metastatic cancer—it’s already shown evidence of doing so when combined with chemotherapy in a small lung cancer trial. Bartek and collaborators are now launching trials to test a disulfiram-copper combo as a treatment for metastatic breast and colon cancers and for glioblastoma, a type of brain cancer. 

Finding a new use for an approved drug is appealing because the compound has already passed safety testing. However, “big pharma probably won’t be interested” in developing disulfiram for cancer because there’s no patent protection on the drug, Bartek says. Still, if the pending clinical trials provide convincing evidence, Halleday points out, oncologists could go ahead and prescribe it anyway as an inexpensive treatment.

http://www.alkoholizam.com/lecenje4.htm

Zloupotreba Antabusa

Kod lečenja alkoholizma se u terapiju uvode i izvesni lekovi, od kojih je najvažniji Antabus.

Za hemijsko sredstvo Antabus vezuje se svojstvo da jednom uzeto onemogućava konzumiranje alkoholnih pića, zbog reakcije koje nastaju tom prilikom. Antabus se u upotrebi nalazipod raznim fabričkim imenima, kao na primer: Tetidis, Abstinil, Aversan, Esperal, itd. Hemijska svojstva i delovanje su im ista, pa i u slučajevima kada se bolesniku daju u obliku tablete ili injekcije.

Ukoliko se posle uzimanja Antabusa konzumira alkoholno piće, pojavljuju se jako izraženi simptomi intoksikacije. U početku se pojavljuje povišeni krvni pritisak, crvenilo u licu, lupanje srca, gušenje, glavobolja, mučnina i povraćanje, strah propraćen širenjem zenica, itd., sve do mogućnosti nastanka smrtnih komplikacija. Bolesniku sa pomenutim reakcijama može se pružiti pomoć isključivo u zdravstvenim organizacijama uz pomoć sredstava za dezoksidaciju.

Svakoj Antabus terapiji mora da prethodi saglasnost pacijenta, nakon toga se pristupa pripremno - ispitnim radnjama kao što su na primer: pregled krvi, kardiovaskularni pregledi, internistički pregledi, itd. Tek nakon saglasnosti bolesnika i svih potrebnih pregleda otpočinje se sa upotrebom Antabusa.

Na osnovu do sada uočenih karakteristika u primeni Antabusa, mogu se sumirati neka pozitivna i negativna mišljenja o njemu.

Pozitivne strane primene Antabusa:

1. Upotreba Antabusa daje podršku i snagu alkoholičaru da neko vreme ne pije, s tim što se u međuvremenu mogu realizovati druge metode lečenja alkoholizma, koje garantuju trajniji rezultat.

2. Antabus ima izvanredno pomoćno psihoterapijsko delovanje kod alkoholičara koji je motivisan za lečenje i koji je uključen u kompleksne socijalne - psihijatrijske postupke.

3. Antabus ima minimalno toksično (otrovno) delovanje (gotovo ne merljivo), te ga bolesnik može uzimati duže vreme (nekoliko godina), bez potrebe specijalnih laboratorijskih kontrola.

Negativne strane primene Antabusa:

1. Davanje Antabusa bolesniku bez njegovog pristanka je zabranjeno, zbog opasnosti nastanka teških posledica usled paralelnog uzimanja Antabusa i alkoholnog pića, zbog čega u nekim slučajevima mogu nastupiti i smrtni slučajevi.

2. Usled upotrebe Antabusa mogu da se pojave i tz. antabus psihoze. One predstavljaju lakše ili teže psihičke reakcije, a pojavljuju se u obliku akutnog ili hroničnog psihosindroma.

3. Prestankom upotrebe Antabusa, bolesnik može ponovo otpočeti sa pijenjem alkoholnih pića, bez prisustva ranije opisanih štetnih reakcija, ukoliko u međuvremenu nije započet psihoterapijski i socioterapijski tretman.

4. Moguće su smetnje lakše prirode, iako bolesnik ne pije alkoholna pića, kao np.: preterana pospanost, umor, slabljenje polne moći i dr.

5. Antabus ne leči alkoholizam.

Mnogima se čini da je Antabus dovoljan da se prestane sa pijenjem. Zbog toga pokušavaju da bez lekarskog uputstva daju drugome Antabus. Tada mogu da nastupe komplikacijekoje nisu poželjne, a koje mogu biti vrlo opasne.

Prvo, može se dogoditi da osoba i ne zna da je uzela lek. To je sistem dobronamerne podvale, kada se lek rastvara u čaju, kafi ili jelu i skriveno daje alkoholičaru.

Sve sa nadom da će to uticati da se dotičnoj osobi zgadi alkohol i da ga više ne pije. Međutim, zbog pijenja pića na Antabus, može doći do Antabus - alkoholne reakcije, što je opisano gore. Alkoholičar ne razume šta ne valja, zašto ima ove simptome. Osoba koja mu je podmetnula Antabus i ako sluti da je zbog toga došlo do ovih burnih reakcija, ne sme da prizna. Zato se ne zove odmah hitna pomoć, što često za posledicu ima smrtni ishod.

Drugo, lek se može predozirati, dati u momentu kada je osoba pod dejstvom alkohola, a tada mogu da nastupe i konfuzna psihička reagovanja u vidu toksičke psihoze ili duševnih poremećenosti, kada alkoholičar reaguje paničnim strahom, depresijom i eventualnim pokušajem samoubistva ili ugrožavanjem tuđih života.

Kao što se vidi, davanje Antabusa bez konsultovanja sa lekarom je jako rizično i opasno. Nažalost, kada se to dogodi (zbog dobronamernih razloga) i kada dođe do neželjenih efekata, odmah se okrivljuje lek, a ne nestručno i nedozvoljeno manipulisanje lekom. Nije lek krivac, nego osoba koja je na svoju ruku upotrebila lek na nedozvoljen način.

Bolje je porazgovarati sa alkoholičarem i pronaći način na koji se može na njega uticati kako bi prihvatio lečenje. A u dispanzeru će lekari odrediti pravu dozu Antabusa.