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Observations on a sedated cat, and links to Chlorpromazine, an antipsychotic in humans

// April 10th, 2013 // Comments Off on Observations on a sedated cat, and links to Chlorpromazine, an antipsychotic in humans // Drugs

What a year! I’ve been around the world (Canada, USA, Argentina, Chile, Denmark, Germany, France, Ireland, England, Hong Kong) to be finally reunited with my kitty cat Phobos back in Adelaide, Australia. I know most pirates have a parrot, but I prefer my pets fluffy.

I had just over a month in my home town (during which time I haven’t blogged so much, as I was seeing everybody back home and the house I was staying in didn’t have internet access), and then had to move again. This time to Melbourne, a larger city full of trendy coffee shops, where my partner is studying at University.

It’s a seven hour drive from Adelaide to Melbourne, and the cat would be coming too. Oh dear. Phobos is not one for cars. Like me, she prefers fresh air and sunshine to exhaust and headlights. She’s not good at hiding her displeasure. On the short trips we’ve taken before, she spends the entire time mewling most heartbreakingly, building up into a reverberating crescendo of “RAAAAAaaaaaaAAAAAaaaawaaarrrrr” and then panting for air. It’s quite upsetting.

That, for seven hours? Forget it! So we went to the vet and got some cat sedatives.

The vet gave us some ACP 10mg tablets, the active ingredient is Acepromazine. It is used for pets, including cats, dogs and sometimes horses. In the UK it’s not allowed to be used in horses intended for human consumption, which is hilarious in light of all the ruckus lately about humans eating horses without intending to. Perhaps a little anti-anxiety medication in the “steaks” would not have gone awry?

I shouldn’t jest, I was in the UK when the story broke and I’m pretty sure I accidentally ate horse. I must remember not to eat meat in the UK… you’d think we’d remember that from the mad cow outbreak in the 80’s. Speaking of mad cow, the fourth case in the US was identified in April 2012 in California, perhaps a month before I was there last year. Sure, it was in a dairy cow and bovine spongiform encephalopathy is not passed on by milk, but still…

Anyway, back to the cat! I gave her one tablet and within 15 minutes it had kicked in. Her eyes became unfocused and her third eyelids crept up. I’m glad the vet warned me of that one, it looked creepy – a layer of pinkish white arising from the corner of her nose and covering about a third of her eyes. The third eyelid has a protective function and it’s visible if the eye is injured, as a side effect of sedation, and during deep sleep.

Next she lost some motor control of her back legs and tail, like she had to move her whole hips to get her legs to move forward. Later she would start stepping backwards when she tried to curl into a ball, until she hit a wall and then stopped. She looked like a cowboy kitty.

The real test was when we got her in the car. She had a halfhearted meow or two, tried to look out the window, and then sat on my lap and rested quite peacefully. Acepromazine is an anti-anxiety drug, and she really didn’t seem anxious at all. Every hour or so she’d go for a little walk across our lap and quickly get worn out and go back to sitting with us or sleeping.

So it seemed good to me. She seemed less stressed.

Acepromazine

Acepromazine

As we were driving, and it’s a long drive, the topic changed to how much easier it was for the cat to be calm, not really for us but mostly for Phobos herself. What about with kids, then? We both knew that some kids are pretty loud and upset on plane flights (not all, but some), and we’ve heard of people who sedate their children with some cough medicine (or even stronger stuff.) It seems pretty unethical to me, on first glance and being childless myself. So why is it different to sedate a cat?

Perhaps it’s partly an age thing… I’m not sure I would sedate a kitten, for example. I have no problem with adult humans sedating themselves on flights, in fact I have a friend who does it due to extreme anxiety and sinus pain. But that’s also a question of consent, and even a grown cat can’t consent to taking drugs.

The next logical step in this conversation was “Do cat sedatives work on humans too?” And now I’m settled in Melbourne with high speed cable internet, I can tell you the answer for Acepromazine is yes, as it was used as an antipsychotic in humans during the 1950’s. However, it is no longer used in humans, and one of the reason’s that it is prescribed by vets is because it is much less likely to be misused recreationally than a morphine-based drug.

Chlorpromazine

Chlorpromazine

Although it’s no longer used as an antipsychotic, the closely related Chlorpromazine is. Chlorpromazine (or Thorazine in the US) has been used since the 1950’s, about the same time that Acepromazine was briefly used. The drug became very popular and was aggressively marketed, but it’s far from perfect. It’s one of the drugs given to patients in Ken Kesey’s book One Flew Over the Cuckoo’s Nest. That book is very critical of society’s reliance on drugs, and the overuse of medication to control mood and make patients compliant.

I agree, I think there is an overprescription of behavioural and mood drugs. All drugs have side-effects, and they should be taken seriously – especially if someone is taking a drug long-term. Also, in my opinion, western society today has a particularly strict view on “normal” and people who don’t fit in with the norm are medicalised.

Chlorpromazine is still used long-term as a treatment for schizophrenia, and I’d rather not give an opinion on that because it’s such a complex issue. However, a long-term usage as prescribed by doctors is surely different to the descriptions in One Flew which was decades ago, very extreme, and let’s not forget, fictional. Both are different again to a short-term one-dose of the closely related Acepromazine to a cat.

It’s hard (often impossible) to know what’s happening in an animal’s head. Hell, it’s hard enough to know what’s happening in your own head sometimes! It’s entirely possible that she hated the experience, that she felt vulnerable and dissociated and confused – but there’s no evidence that this was the case. However, I do know (as far as it is possible to know) that she hates being in a car when she’s not sedated because she cries and cries. So for such a long journey I think the benefits outweighed the risks.

Altogether, I was pleased with Acepromazine. Phobos has completely recovered and is back to her usual inquisitive, scampering self.

Fever dreams – the true tale of Richard Spruce

// March 26th, 2012 // 4 Comments » // Drugs

Richard Spruce had seen some strange villages since arriving in South America in 1849, but this one took the cake. It was a ghost town. Every door was shut tight against the hot, humid jungle, while inside people slumbered away the sunlight.

Being the adventurous sort, he couldn’t comprehend such laziness, not, that is, until he mopped his clammy brow. His hand returned smeared with squashed mosquitoes and his own bright red blood.

He reflected, not for the first time, that life in the jungle wasn’t all it was cracked up to be, all things considered. Charles Darwin had joyfully described the Brazilian rainforest as “a great wild, untidy, luxuriant hothouse.” The tales of Alfred Wallace, a fellow young botanist, absolutely dripped with adventure.

Money truly did grow on trees here – there was a fortune to be made by transporting unusual plant species to England, where new novelties for Victorian gardens fetched a pretty penny.

Plus, the trailblazers in taxonomy whispered, it was delightfully warm, warm being a most thrilling word to Brits.

Had they mentioned the innumerable insects? If so, he still hadn’t expected the particular, primal discomforts of living in a cloud of whining and dining mosquitoes. Likewise, he hadn’t realised that breathing the air’s rich humidity would be as drinking tepid whisky through a straw. Nor how hot the nights were, wrapped tight as a flower bud in his stockings and blanket with a handkerchief over the face to ward away bloodsucking bats.

Nonetheless, Richard Spruce was not one to fret. He was of unfazeable stock, and though inch of his bare skin was soon in welts (not to mention his unmentionables), he followed the river and its plethora of plants to plunder. The cloud of mosquitoes followed too.

It’s not surprising what happened next.

The fever came on suddenly; a shivering, sweating, aching fever that rendered him helpless, striking him down mid-step on the border of Venezuela and Colombia.

His guides carried him shaking to a village. He knew the symptoms, hell he’d seen it before, but he denied his own diagnosis. Though he had the cure in his pocket, quinine from the bark from the Cinchona tree, he was loath to take its bitter rescue. He didn’t want it to be malaria.

Like a pot of swamp water on the boil, was his brain, his temperature climbing like lianas, curling like fern fronds, perching like epiphytic orchids. Images sprung forth from his fertile mind. The first two days he flashed on those damn mosquitoes, a haze of infected blood cells bursting. It didn’t make sense! The mosquitoes had left him three days ago. Certainly it wasn’t malaria, certainly, for it had been weeks since he was around the bad air of stale water, giving the Italian term mal’aria. Still he kept seeing mosquitoes.

As the fever broke into freezing chills, Richard’s guides began to mutter. When those chills turned once more to fever, they sensed his impending demise and sold his scientific equipment for rum. The patient was in no condition to care.

Spruce was stuck on mosquitoes, thriving in stagnant water and stale air, their droning drilled through his brain. He shrunk to the size of a grain of pollen and was sucked up like whisky through a mosquito’s straw. Inside the mosquito gut (it sure was hot and sticky) blood cells burst to release hideous parasites. These sex cells, for he identified them thus as surely as an anther and stigma, combined inside the mosquito. In the gut wall they formed cysts full of eggs. Or were they seeds? Or ferns?

Whatever they were, they grew for over a week, and exploded (much like his mind) yielding youngsters that frolicked freely.

Richard wasn’t frolicking. By the twinges in his aching joints, he knew the pangs of an elderly mosquito carrying young parasites, which had moved to his salivary gland to yield virulent juices. Next time he ate, dipping his mosquito’s double straw through the skin, spitting and sucking simultaneously, he would administer his chemical cocktail – anaesthetics to dull the pain, anti-blood clotting agents and, of course, the parasites.

Through the whisky straw Richard swirled, straight to the liver. His own liver, human and wracked with heat. From the liver, parasites paraded to the blood cells. Inside they ate oxygen-carrying haemoglobin and ran round after round of asexual reproduction, like spores or strawberry runners, each strawberry red and juicy, dripping. Each round took three days to replicate, feast and rupture the blood cells, like clockwork, and his body followed the same ticking cycle, burning fever following freezing chills following fever. Tick. Tick. Tick.

Richard shivered.

From outside he heard the nurse employed for his care, drunkenly yell “die, you English dog, that we may have a merry valorio with your dollars.” Well may she want a valorio, or watch night, but Richard was no a corpse.

After fifteen days of dreaming fever, he relented. Malaria it was. He took the bark of Cinchona trees, which kept him alive (just) by reducing his extreme body heat and causing the haemoglobin-chomping parasites to choke on their own waste. Such sweet relief from such bitter bark.

Thirty-eight days after his collapse, Richard was alive, but exhausted. His full recovery took many months more though, naturally, he kept collecting plants once he found new equipment.

Trudging onwards, Richard felt naught but respect and gratitude for the fine tree, Cinchona (though he preferred moss as a general rule).

Ten years later, having bushwhacked his way through saucer-sized tarantulas and marching fire ants, Richard found himself in the Andes. Gone were the South American rainforests, here roamed high altitude winds and freezing snows. After so long in the heat, the extreme chilliness didn’t suit him at all. But, onwards and upwards, as they say, and he was here to hunt Cinchona trees.

The trees were in high demand by the British and Dutch, both needing supplies for their malaria-wracked colonies. They had no steady supply, as the species had never been cultivated. There were sincere concerns that people would harvest it into extinction.

Richard spent a cold, windswept year collecting seeds and growing young plants. Almost 700 seedlings, well wrapped in moss, were tended all the way to England by a gardener assigned to their care. From the survivors, more than two hundred thousand precious plants were sent on to grow in Indian plantations.

Richard’s success with the species that saved his life did nothing less than change the world, making the heart of Africa habitable and saving millions of lives – but in the end he paid for it with his own health. Another disease cost him the use of his limbs, and he spent the rest of his days on a small pension in Britain.

Today, malaria kills around two million people each year and infects 200 million more. It has quite possibly killed more people throughout history than all our wars and plagues combined. Quinine, along with other chemicals, is still used for cures and prevention, and is gathered from the decedents of Richard Spruce’s trees.

Drinking notes: Enjoy this true tale with warm whisky or gin and tonic. Small quantities of Quinine are added to some brands of tonic water for flavour. Fluorescent, the chemical glows under black light. Many thanks to highly informative Flower Hunters by Mary and John Gribbin for the biography of Richard Spruce.

Have a nap and let your computer cure cancer

// October 18th, 2010 // 2 Comments » // Drugs, How Things Work, Recent Research, Science Communication

computer doing science

Image by John Watson

While waiting for inspiration to strike a solid introduction into my head, my computer screen went blank. Good ol’ MacBook conserving energy! But letting your computer go idle doesn’t mean you have to waste its processing power. Why not cure cancer with grid computing?

It’s a kind of parallel computing, which breaks up complex problems into smaller calculations and then solves them at the same time. Instead of one processor working on one calculation a time, a group of processors work on different calculations together. Dual-core computers is one way to do it. Grid computing is another.

Grid computing is like a massive virtual computer whose processors are computers linked by a central software.

World Community Grid is one group which utilises the personal computers of over half a million volunteers around the globe. Their software switches on when the computer is idle and runs virtual experiments, calculating and number crunching its way through chemical simulations. They provide this public grid to humanitarian research projects.

Childhood cancer
One of the projects they are running is helping to solve childhood cancer by finding potential new drugs for neuroblastoma, one of the most common solid tumors in children. In some people the tumors do not respond well to chemotherapy. This research is hoping to turn this around by targeting three proteins which are important to the cancer’s survival. Knock out those proteins and the cancer will in turn be knocked out by chemo.

Good plan, but how to knock out the proteins? That’s where the grid comes in.

There are three million potential drug candidates who MIGHT bind to one of the proteins and knock them out. Of course, that’s a lot of laboratory time right there. A computer would be better, but to run these nine million virtual experiments would take 8000 years. By working with the public grid they expect the project to be finished in just two years. Possibly less.

That’s a big saving on time and grant money. It’s rational based drug design (which I blogged about here) taken to a crowd sourcing extreme. They are trying a similar thing to discover dengue fever drugs.

Carbon Nanotubes

Image by Mstroeck

Clean Water
Drug design isn’t the only industry using the World Community Grid. Last month universities in Australia and China announced they are running simulations through the grid to find out how to filter water using nanotubes.

Nanotubes are small tubes that only water molecules can fit through. Not bacteria, not even viruses. It’s a great way to get rid of water dwelling nasties and desalinate sea water. But with such small pores you would expect the pressure and energy needed to force water through the filter to be incredible. And incredibly expensive. But in 2005 experiments showed that actually the water flowed pretty fast through the filters.

Why? Possibly the water molecules touching the nanotubes act more like ice and reduce friction. But who knows? To find out exactly what’s happening they’re running realistic simulations using the grid. The outcome could lead to huge improvements in water availability, potentially saving millions of lives a year in the developing world.

Like the idea of grid computing? Sign up to the World Community Grid here, and let your down time make a difference.

Antibiotic beer, as drunk by the ancient Nubians

// September 8th, 2010 // 4 Comments » // Drugs, Recent Research

Image by Peter Trimming

Today’s schooner of science is literally science in a schooner. Plus it comes with a new career path – bioarcheologist, expert in ancient diets.

George Armelagos is the bioarcheologist in question, and he’d been studying the ancient Nubians who lived just south of ancient Egypt in present-day Sudan.

George was looking at some bones and found evidence that they had been exposed to tetracycline, an antibiotic. Tetracycline is absorbed into bone, and fluoresces green. It’s sometimes used to measure bone growth – take tetracycline at day 0, again at day 12, and at day 21 take a biopsy. The distance between the two green lines will show how far the bone grew in 12 days.

Anyhoo, tetracycline in bones from 350-550 AD is weird, seeing as we first invented antibiotics with the discovery of penicillin in 1928. Now we find out the ancient Nubians beat us to it, and as with all great ideas they came up with it over a beer.

The grain they used to ferment the beer contained streptomyces bacteria, which produces tetracycline as a kind of germ warfare. Like penicillin comes from a fungus, tetracycline is made by a bacteria. It’s a bad-ass antibacterial that can treat disease like chlamydia, gonorrhea, and pneumonia which are caused by bacteria. It can even kill Yersinia pestis cause of the black plague.

Were the ancient Nubians drinking it by accidental contamination, intentional medication, or did streptomyces bacteria just grew on the corpses?

To find out they needed (da dada dum!) a CHEMIST! This particular hero was Mark Nelson, who dissolved the bones in some hardcore hydrogen fluoride – “the most dangerous acid on the planet,” according to Mark. Woah. After showing the bones who was boss, Mark mass spec’d the shizz out of them and discovered a metric buttload of tetracycline, confirming that it was ingested and in high quantities.

The scientist duo concluded that this was a brew with a purpose – an antibiotic alcoholic. Even the bones from a four year old child contained a lot of tetracycline, perhaps he was given the antibacterial to cure a disease.

My question is, why are WE not taking our antibiotics in beer? That would be SO much better!

ResearchBlogging.orgNelson ML, Dinardo A, Hochberg J, & Armelagos GJ (2010). Brief communication: Mass spectroscopic characterization of tetracycline in the skeletal remains of an ancient population from Sudanese Nubia 350-550 CE. American journal of physical anthropology, 143 (1), 151-4 PMID: 20564518

Did the CIA spike a bakery in France with hallucinogens?

// August 27th, 2010 // 6 Comments » // Drugs, Poisons, Sex and Reproduction, The Realm of Bizzare, Unethics

On August 15, 1951 a small town in southern France called Pont-Saint-Esprit briefly entered the twilight zone. Hundreds of people reported acute psychotic episodes and physical symptoms such as nausea. They experienced traumatic hallucinations, and 50 of those affected were put in asylums. Five died. The event was later traced back to pain maudit – cursed bread.

In 2009 American journalist Hank Albarelli cited evidence that it was actually caused by CIA experiments into LSD. His book A Terrible Mistakesuggests the mass hallucinations experienced that day was a government funded field experiment into the newly found drug.

There would be potential for LSD to be used as chemical warfare – sprayed onto an army it would turn soldiers into… well… I don’t know but with guns involved I think it would be bad. I’m not sure if his conclusion is correct, but his article makes a compelling argument.

I have to say, conspiracy theories really do it for me. I think they’re great. Nothing like a little paranoia to keep you on your toes. There are, however, other opinions on what caused the Pont-Saint-Esprit madness.

One explanation is ergotism. Ergot is a group of fungi (most prominently Claviceps purpurea) which grow on rye, wheat and related grain-producing when-I-grow-up-I-want-to-be-bread plants. The fungus produces a neat little cocktail of alkaloid drugs which cause spasms, diarrhea, nausea and hallucinations – similar to those experienced at Pont-Saint-Esprit that fateful day.

In fact, the psychosis could have been caused by ergot or LSD, both have similar symptoms. LSD was first derived from the ergot alkaloid ergotamine. Controlled doses of ergot poisons have been used to treat migraine headaches and control bleeding after childbirth. Accidental, and dangerous, ingestion of ergot was known as Saint Anthony’s Fire (not to be confused with Saint Elmo’s Fire) for the monks of Saint Anthony who were really good at treating it. Ergotism was also blamed for Agent Scully’s hallucinations in the episode Never Again, where she gets a badass tattoo with some red ink that could have been coloured with ergot.

Greek myth time! In Ancient Greece annual initiation ceremonies were held for the cult of Persephone and Demeter. Demeter was the goddess of grain, farming and plenty, a bit of an Earth mother goddess with rich wheat coloured hair and a flowing dress. She guaranteed a good harvest. She had a daughter called Persephone, who loved the flowers. One day when Persephone was looking at some flowers in a field, Hades the god of the underworld noticed her, opened up the ground and abducted her. When Demeter noticed her daughter was gone, she was stricken with grief and refused to bring the harvest.

Persephone was trapped in the underworld for months on end. Desperate for her hand in marriage, Hades would offer her food, but Persephone know not to eat the food of the dead or she would never be able to leave. However one day Hades offered her a pomegranate, her favourite dish, and she ate six seeds.

Up in the mortal world, the land was dying. People were starving, having never experienced such famine. No matter how they prayed to the goddess she would not bring the harvest. Seeing the despair of the people, Zeus the king of the gods went down to his brother Hades and asked if he could bring Persephone back to her mother. Awkward conversation ensued.

Hades finally agreed, but oh noes! Persephone had eaten the food of the dead! The six pomegranate seeds meant that she had to spend six months of the year in the underworld as Hades wife. The other six months she would live with Demeter her mother. That’s why we have the seasons – autumn and winter when Demeter mourns, spring and summer when Demeter is reunited with her daughter.

Anyhoo, to be initiated into the Demeter and Persephone cult was called the Eleusinian Mysteries, some mysteries including this myth with added details. I think some of the mysteries included the use of pomegranate as a contraceptive (the link between fertility and death, perhaps.) You also had to fast during the initiation, and afterwards you would drink a barley drink called Kykeon and great revelations would be revealed.

Kykeon, made of barley, quite possibly tainted with ergot. Revelation or hallucination, you tell me.






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