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This month I have the pleasure of introducing you to ferrous sulphate: it's riveting! Class Ferrous sulphate belongs to a group of medicines known as "oral iron" Mechanism of Action Ferrous sulphate is composed of ferrous iron and it's sulphate salt. Once ingested, and whilst winding its way through the gastrointestinal tract, a proportion of the ferrous sulphate will cleave into its component parts (i.e. the ferrous iron part and the sulphate part). The former (the bit that floats along as ferrous iron) will be absorbed into the body. Now, to reach the blood stream the ferrous iron has to pass into the wall of the gastrointestinal tract, be converted into ferritin (more on that in a second) and then be transported out the other side and into the circulation. So, what’s ferritin? I’m glad you asked. Well, because free iron is reactive and toxic to the body, it becomes attached to a protein to prevent it from causing mischief – the resulting combination of iron and protein is called ferritin. Ferritin is the way in which iron is stored, therefore it is found in the blood stream and also within tissue “storage sites”, such as the liver. Another protein worth mentioning is one known as transferrin. This character patrols the circulation and rapidly sweeps up any free iron. Once it has collected 2 iron ions (which is it’s maximum load) it drops them off at one of the body's storage sites for safe keeping, as ferritin. It also acts as a porter, so when iron is needed by a site such as bone marrow, transferrin takes some out of the ferritin storage and delivers it. Why does bone marrow need iron? As you may know, iron is contained within a large protein known as haemoglobin. Haemoglobin is produced in the liver and bone marrow. The role of haemoglobin is to bind onto blood gases – predominantly oxygen – and transport it around the body in order to fuel our muscles and tissues. It does this via the blood – specifically red blood cells known as erythrocytes – which contain approximately 270 million haemoglobin each! So there you have it – iron is the central component of haemoglobin, the body’s oxygen transporter. In terms of mechanism of action however, ferrous sulphate has no intrinsic therapeutic activity – meaning that once it is absorbed it has no independent chemical effect and acts the same as dietary iron. Simply put, it is a “supplement”. Indication A deficit of iron results in a condition known as iron deficiency anaemia, or IDA. As we’ve discussed, iron contained within haemoglobin is vital to our oxygen transport system. A lack of haemoglobin causes tiredness, an inability to concentrate, weakness, inability to regulate temperature and a general lack of energy. A bit like how you feel after sitting in a stuffy and poorly ventilated office or classroom for the day! Iron supplementation aims to correct this deficit; first by elevating the individual’s levels of haemoglobin, and secondly by restoring the stores of ferritin within the body. The latter takes about 3 months, once the patient has achieved a normal haemoglobin level. Random fact Did you know, there’s enough iron in a healthy human to make a whole nail? Thanks for reading. Have a marvellous weekend, wherever you are!

Happy Friday, All. This month I have the pleasure of introducing you to morphine sulphate: it's dreamy! Class Morphine sulphate belongs to the class of drugs known as opioids. Mechanism of Action As far as we are aware, there are three different opioid receptors in the body: mu (µ), delta (δ) and kappa (κ). This is interesting for a couple of reasons. Firstly it indicates the presence of endogenous opioid-like chemicals (i.e. they occur naturally, within our bodies). And secondly, it suggests that these opioid-like chemicals can produce a broad range of effects. Wow! So I can create morphine? No... not quite. The three naturally-occurring opioid-like peptides are: endorphins (this word is a portmanteau of “endogenous morphine”), enkephalins and dynorphins. You’ve probably heard of endorphins – they're the “feel good” hormones that have a high affinity for the µ receptors. That means that although they’ll bind with the other receptors, they’d prefer to hang out with µ. Don’t feel too sorry for the other guys though – enkephalins usually buddy up with δ and the dynorphins are fond of keeping the κ receptors happy. So what happens when one of these "naturally-occurring opioids" latches onto a receptor? Well, the receptors are situated on neurones (nerve cells responsible for transmitting messages around the body) and when one of the "naturally-occurring" opioids binds to it the action potential of the cell is changed. What on earth is an “action potential”?! I’m glad you asked. Think of it like the amount of force required to tip over a glass of water. If the force applied to the glass is too weak, we don't reach the crucial tipping-point and nothing happens. However, if sufficient force is applied, then the glass will tip over and the water will spill out. In relation to our neurone, once the action potential ("tipping point") has been reached, then neurotransmitters are released, and a message is transmitted. The action potential (i.e. the level of force needed to cause an effect) can be altered. To return to our analogy, we can make it easier or harder to tip the glass of water over e.g by changing the slope of the table or by putting a weight into the glass. This is where the opioid receptors on the neurone (and peptides that bind to them) come into play. Some chemicals will reduce the action potential - this makes it easier for an electrical stimulus reach the action potential and cause the release of neurotransmitters. Opioids increase the action potential - this makes it less likely for an action potential to be reached, and therefore for the neurone to release its neurotransmitters messengers. OK - so if I have lots of naturally-occurring opioids in my system, my neurones will fire less frequently. What does that really mean? How does it affect me? The impact of a naturally-occurring opioid joining forces with one of the opioid receptors will depend –broadly – on two key factors: Where it’s located. Unsurprisingly, the ones in your brain will have a different effect to the ones in your intestines! Which neurotransmitter "messengers" are released. There are lots. Once these guys are let loose, they also encourage or inhibit other proteins, which can encourage or inhibit yet more proteins... You get the point. It can get complicated! OK - so I get the impression that a really wide range of things can happen depending on which peptides and receptors are involved, and where they are located... but could you give me any examples? Sure. Let's run through the predominant locations and “responsibilities” of the µ, δ and κ receptors and talk about what happens when morphine is one the scene. µ receptors (these are the ones that are usually modulated by endorphins). In the brain, these are found in greatest number in the periaquaductal gray region, which is responsible for modulating our perception of pain. By interacting with the µ receptor, morphine interrupts this “pain message” to produce an analgesic (painkilling) effect. They are also found in the nucleus acumbens in the brain, a region that is responsible for our sensation of pleasure. The feeling of pleasure is associated with reward-seeking behaviour, which can manifest itself as euphoria and addiction – both of which are well-recognised effects of opioids. We also find this receptor in the intestinal tract, where activation reduces the motility of the gut. This is what is responsible for a troubling side-effect of morphine, particularly for those who take opioids long-term: constipation. As an aside, I find it a bit disappointing that the same receptor is responsible for all of these effects. Wouldn't it be great if we could achieve pain-relief without constipation and the problem of addiction? Unfortunately, the representation of µ receptors in these two areas suggests that all of these effects are inextricably linked. δ receptors (these are the ones that are often modulated by enkephalins). By breeding mice that don’t exhibit these receptors, scientists have found that the δ receptor is associated with our management of stress. We think that this is probably because it results in the release of the neurotransmitters noradrenaline and serotonin. At this receptor, enkephalin (and morphine) will cause a reduction in both anxiety and depression. κ receptors (these ones are usually modulated by dynorphins). These receptors are also expressed in the periaquaductal gray (the pain centre), as well as in pain neurones distributed in the spinal cord and around the body. They don't quite behave as you might expect, because although some of these sites will produce analgesia... others will increase an individual’s sensitivity to pain. We think that they may be associated with complex issues like neuropathic pain. In addition the κ receptor is located in the hypothalamus – this region of the brain controls a whole host of activities including stress, attachment behaviour and appetite. Don't forget that opioids will make release of neurotransmitters less likely. So, morphine acting on this receptor will cause dysphoric adverse effects like depression, dissociation, delirium, hallucinations and hunger. Indication Morphine sulphate is used in the treatment of severe pain. Random Fact Morphine can be naturally derived from the poppy (Papaver somniferens) and is named after Morpheus, the Greek god of sleep. Thanks for reading. Have a marvellous weekend, wherever you are!