Thursday, 27 March 2014

Accidental Blockbusters: Warfarin

“Of course, that’s how life is. A turn of events may seem very small at the time it’s happening, but you never really know, do you?” Tom Xavier

Warfarin is an anticoagulant currently prescribed to prevent blood clots. However it was originally introduced to the consumer world as a rat poison due to its haemorrhaging abilities.

In the early 1920’s a bizarre number of cattle in the US kept spontaneously bleeding profusely. Food sources in the area were scarce and so the cattle were being left to eat the damp, mouldy hay that was no good to anyone else. A Canadian vet twigged that the link between all of these haemorrhaging cattle was that they had consumed this unsuitable hay, and discovered that by removing the hay from the cattle’s diet, they returned to full health.

Thirty years later, the compound in the mouldy hay was finally characterised and was launched into the US market as a rat poison, proving an instant success. However a US soldier, unsuccessfully, tried to commit suicide by overdosing on this new toxin. Having been rushed to hospital, he was treated with vitamin K, the antidote, and made a full recovery, yet this started an investigation into the potential therapeutic use of the poison. And three years later, it was approved for use as an anticoagulant, with one of its first recipients being the US president at the time; Dwight D. Eisenhower.

One conspiracy theory, highlighting the dangers of warfarin and the complexity of its dosing regimen, suggests that Stalin was murdered using warfarin. As warfarin is tasteless and odourless, making it such a good rat poison, Stalin could have easily consumed it without knowing so, and he exhibited many of the symptoms commonly found in a warfarin overdose when he died.

This post was written by Graduate Research Exec Becky Geffen.
For more weird and wonderful pharamcetuical facts follow us on: @brandingscience

Wednesday, 12 March 2014

Accidental Blockbusters: Viagra

“What is luck', he said, 'but the ability to exploit accidents?” Jeanette Winterson

Viagra is a well-known name. It is used to treat over 90 % of patients with erectile dysfunction but in fact was developed for an entirely different condition.

Viagra was originally developed in Kent as a treatment for hypertension. Phase 1 trials in patients in Swansea showed that whilst it had little effect on angina, it did induce marked penile erections. And so Pfizer decided to market it for erectile dysfunction rather than hypertension.

The drug inhibits an enzyme leading to dilation of the veins increasing blood flow in certain areas. In the penis, this causes an erection. However Viagra is also used in an area linked more towards its original research field; pulmonary arterial hypertension. In this condition patients suffer from constricted blood vessels causing shortness of breath, as oxygenated blood cannot reach the heart. Viagra is used as one of the treatments for this condition to help relax the blood vessels allowing efficient blood flow to the heart.
Viagra, interestingly, has been documented as a drug of abuse in sports, as athletes believe that opening up blood vessels will enrich their muscles with oxygen, an especially useful feature in endurance events. In fact it has already been a point of controversy when the Italian cyclist, Andrea Moleta, was found with 82 Viagra pills on the Tour of Italy, hidden in toothpaste bottles. This bizarre incidence, seeing as doping on Viagra would be very unsubtle in such tight lycra, led to confusion at the time. Although no doping allegations could be made, seeing as Viagra is yet a banned drug, he was nonetheless excluded from the tour on suspicions of attempting to bypass blood doping tests.

The World Anti-Doping Agency (WADA) is currently investigating whether to ban Viagra in sport, by testing in possibly the least likely bunch of people to need the drug; collegiate athletes. Lacrosse players at Marywood University are taking part in a study to look at whether an increased blood-flow, and hence oxygen capacity, can really benefit athletes. If this is found to be the case, it will be added to WADA’s extensive list of banned substances.

Tuesday, 4 March 2014

Why I keep on getting parking tickets and you can’t seem to take your drugs


Arriving home the other day I noticed that on the table, together with the other letters, was an open envelope containing a penalty charge notice….

“What is this?” I asked, shocked.

My husband looked at me and said “You got another fine for entering and stopping on a box junction, will you ever learn not to do it?”

The truth is that we are all able to understand the implications of our behaviour. We know that certain acts will have certain consequences. And we have this in the back of our minds.

Yet why do we keep on making the same mistakes? Why is it that we ignore the warning signal? Or in other words; why does our brain fail to learn from previous experience without allowing this cause-effect chain to positively guide our behaviour, for better outcomes?

I think these questions are very much related to what happens when patients fail to comply with their treatment regimes.

We are extremely capable of assessing immediate threats. It’s something we are hardwired to do. But our brain, to a certain extent, is less skilled at assessing more long term risks. When we assess long term possibilities we get clumsy. We somehow dismiss the possibility of not getting over our sickness or injury and often overestimate our capacity to overcome symptoms even with irregular compliance to treatments.

It seems so straight forward that if you are sick, the only way to get better is by following the treatment that the doctor has suggested. And yet there are many articles, papers and research examining why patients struggle to comply with their medication regimes.

So why doesn’t the patient comply?

There are many theories to explain this. For example, some patients have illnesses where symptoms do not get in the way of everyday life, so it is easy to ignore the illness and hence the treatment. This is the Denial theory.

The cost of the treatment could also somehow explain why the patient does not comply, specifically in cases where the treatment is very expensive for the patient and no insurance company willing to cover that cost. For me, this reason only explains why the patient does not buy the treatment rather than why he refuses to follow it.

In certain cases, complex treatment regimens are a critical reason for noncompliance. They might be too difficult for a patient to follow, especially if we take into account the age and also if the patient have multiple conditions at once. I would justify that this is a reason for overdose or wrong compliance. This could be fatal, so establishing clear instruction is a must for the doctor. However, nowadays this can be overcome and treatments simplified for the patient making them easier to follow.

Others reasons might be related to the side-effect profile of the treatment; the flavour of the medicine; or even the lack of trust in the drugs. In the short term, this can explain why some people push back the time of taking their medicine or find a quick way out to avoid taking it completely.

I have observed this often with my children. If they do not “like” the flavour of a certain drug, they will try to negotiate the amount they ingest or attempt to avoid it all together. In turn this increases the likelihood that I will give up as soon as I see there is a certain improvement in their symptoms.

Don’t get me wrong, I am sure that some cases of non-compliance have a simple explanation. And we should always identify individual differences. However, I am going one step beyond these traditional theories to discuss non-compliance in terms of the subliminal human mind.

I’ve already mentioned that we do not evaluate risk in the short term the same way we evaluate risks in the long term. To put this into context, we are often more aware of the weather issues that can ruin our flight arrangements when we go on holiday than the need to recycle more to reduce the long term impact of climate change.

Early approaches in Psychology assumed that individuals behave in a rational manner, weighing information before making a decision. So, the more information you have the more likely you will accurately assess risk and hence the higher the probability you will act accordingly. In our case, the more you know about your drug and illness the more you will comply with your treatment. However, this approach is not the entire story. Evidence has shown that the possession of additional information alone, won’t shift perceptions. So, we need to understand what factors influence how individuals assess the information they are presented with - not an easy task!

And I have not yet talked about something that is becoming increasingly important in the field of behavioural economics; our emotions. Specifically, what feelings are associated with an individual’s experiences and how do these feelings guide their behaviour?

Emotions can be positive or negative, so if we associate a negative emotion with a consequence we may avoid that outcome by not pursuing it. So, a positive feeling about something will increment the probability that we repeat an action.  However, even this theory has proven to be missing pieces of the puzzle.

Research has shown that risk perception is highly dependent on intuition and experimental thinking as well as emotions.  In summary, it seems that we evaluate our environment in a rather non-rational way.

So going back to my initial questions; why I do keep collecting parking tickets, why does a patient not comply with his medication, and why we do we not do anything to avoid the dangers of climate change?

I think we assess the future in a rather blurred way and only act in the immediate present. This is a basic survival instinct, and as a result we fail to link our actions today with a potential negative outcome of tomorrow and understanding how maladaptive our behaviour can be.

What does this mean? Well, we like to take our chances, or at least I do!

This article was written by Ana Puglisi in our UK office.