Anti-diarrhoea drug drives cancer cells to cell death

> In cell culture, loperamide, a drug commonly used against diarrhoea, proves effective against glioblastoma cells.

How significant is this? I'm sure there are a lot of things that will kill a cancer cell in a petri dish.

A lot of chemotherapy is untargeted. The entire body is poisoned, and the cancer cells are more susceptible, for various reasons (weakness during cell division, which they do far more frequently than healthy cells, among other reasons). Hair loss, skin/nail problems, digestive tract problems, etc. These are all fast-growing cells. It's almost impossible to target cancer cells and not affect normal cells, because cancer cells aren't all that special.

That's an excellent question, and an area of active research. It differs a lot by drug, though, because of their affect on different signaling systems, different neurons, and due to indirect damage to the brain from effects elsewhere in the body:

1. E.g., cocaine as a strong vasoconstrictor can directly cause cerebral ischemia, causing hypoxic damage to the brain. Acute hypoxic damage is relatively uncommon, but atrophy due to chronic hypoxia is more common. Because the bulk of atrophy in chronic coke users is in some of the most hypoxia-sensitive areas of the brain, it might be the primary mechanism of damage.

2. Opioids can do the same via respiratory depression, even though blood flow to the brain is not impaired. Chronic opioid abusers tend to dose themselves into respiratory depression - and post-mortems show their brains to have ischemic neural damage.

3. Seizures are intrinsically neurotoxic. Damage from other sources (such as above) predisposes to seizure, which can have effects on the remainder of the brain.

4. We generally suspect there is more cell death than downregulation of neuronal receptors. When we look at the basal ganglia of chronic drug users (the dopaminergic neurons involved in the 'reward' circuit), we find atrophy, suggesting actual neuronal loss.

4b. What type of regulatory (e.g., down regulation) change occurs depends on the drug. Some drugs imitate an existing signal (e.g., opioids), so downregulation would be the homeostatic response. Coke and ecstasy stimulate dopamine release and serotonin release respectively, so we can expect a downregulation in receptors, but we may also see an upregulation in the transmitting cell in response to increased "release this signal" demands. Even that depends on the drug in question - amphetamine prompts dopamine release, so the releasing cell runs low and may increase storage levels. Coke prevents reuptake of dopamine, so active concentrations are up but the releasing cell doesn't see a change in its internal dopamine storage levels. Alcohol, on the other hand, is a glutamate blocker, which increases sensitivity to glutamate signals.

5. Opioids have been shown to be directly neurotoxic. It's unclear on whether this is a significant contributor above and beyond the respiratory depression in real life settings. In the lab, though, heroin, heroin metabolites (6-mono-acetyl morphine and morphine), fentanyl, have all been shown to be directly neurotoxic, though not all equivalently so.

6. MDMA is also shown to be directly neurotoxic, and (at least in a rat model) MDMA metabolites are more neurotoxic than MDMA itself.

7. Adulterants, through their toxic effects, also directly fuck up tissues. We see increased activation of cell-suicide pathways when heroin is induced, but we also see that the degree of activation is inversely proportional to the purity of the heroin.

I can probably go on for a while. I'm sorry if the above is a bit rambly, I didn't really stop and outline it as an essay. I hope that sheds some light, though.

I have lots of interests outside of medicine, including programming (and bookbinding, archery, powerlifting, and etc.)

I got to HN itself ... I don't know how. I delete my account about once a year to try and limit my breadcrumb trail, so I can't really look backwards and say how long I've been here, or what may have gotten me here. IIRC, it was probably due to chasing articles on startups/entrepreneurship, as I seem to think that was over-represented in my early HN reading. But it's probably been about a decade, so take that with a grain of salt.

I haven't heard of morphine being generally cardioprotective, but I'm no cardiologist. It's routinely given during heart attacks because it reduces cardiac demand, so it reduces the heart tissue that dies due to lack of oxygen during the heart attack. But that's all I really know on that one.