NSAIDs - the debate that continues to inflame!

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A good friend of mine, who just happens to be a retired medical man, recently fell and broke his hip. Nothing too unusual for a man in his seventies, but when we visited him in hospital he was furtively hiding his pain medication in a tissue and tucking it under his pillow. “It’s an Anti-Inflammatory” he confided conspiratorially The look of  confusion on my face prompted him to continue “They might be OK for pain relief but they interfere with bone healing and I want to get back on my feet as quickly as possible”.

I have to admit to always being a little nervous about using NSAIDs - Non steroidal Anti-Inflammatory Drugs - having studied medicine during the period when Phenylbutazone, the first proper NSAID, was introduced. BTZ, as it was popularly called at the time, was later discovered to cause bone marrow depression in many of those who took them and swiftly removed from “The Market” . 

But first a piece of history:

The fascinating ability to treat fever and inflammation dates back about 2500 (400 B.C.) years ago to a time when the Greek physician Hippocrates prescribed an extract from willow bark and leaves. Later in the 17th century, the active ingredient of willow bark Salicin was identified in Europe. Acetylsalicyclic acid (Aspirin), a more palatable form of Salicin, was produced commercially by Bayer in 1899. However, the mechanism of action of anti-inflammatory and analgesic agents such as aspirin, and its later derivative Indomethacin, were not discovered until the early 1960’s when medical science was really beginning to find it’s feet. Things really changed in the seventies, when John Vane discovered the mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) opening the door to a pandoras box of new pharmaceuticals to treat pain and inflammation.

Since then the place of NSAIDs has become embedded in our lexicon of treatments for all things that involve inflammation and pain - especially those involving our joints. But the target tissues for these medications don’t just lie in our bones and joints, they are also to be found throughout the body in our stomachs, our kidneys, our hearts and our brains too. As time has gone by, the goal of Pharmaceutical Companies has been to develop medications that produce fewer side effects whilst maintaining their anti-inflammatory effects.

So what are the possible side effects of NSAIDs

• Stomach ulcers
• Raised blood pressure
• Kidney Disease
• Liver disease
• Bleeding
• Induce asthma attacks
• Rashes, drowsiness, headaches

All of these side effects reflect the areas around the body that these medications have a collateral action upon, as well as the inflamed areas they’re principally targeted at.

A concern that I’ve had for many years is that some of these NSAIDs are now available “Over the counter” and are commonly used in children too.

WHAT I AM NOT SAYING IS THAT THESE MEDICATIONS ARE DANGEROUS AND SHOULD BE BANNED

rather

THESE ARE CHEMICALS THAT CAN HAVE SERIOUS AND SOMETIMES FATAL CONSEQUENCES IF NOT USED PROPERLY.

The vast majority of childhood inflammations and infections will settle without the use of medications. Common sense and patience are far better treatments than rushing to the Pharmacy for a magical “quick fix” - because that is exactly where those “quick fixes” should remain, in the realms of fantasy and fairy tales!

The human body has evolved brilliantly over the millennia to deal with minor injuries, minor illnesses and local inflammations. For major stuff you should always seek medical advice, because in most cases, Doctors do know more than you do.

But let me finish by saying that although Doctors know a vast amount about the human body, they are still far, far, far away from knowing everything. My medical friend with his broken hip refused his NSAIDs because he believed that NSAIDs slowed bone healing. Well, a thorough search of all the scientific papers written on the subject came to the conclusion:

“There is no robust clinical and/or scientific evidence to discard the use of NSAIDs in patients suffering from a fracture, but equal lack of evidence does not constitute proof of the absence of an effect. The majority of the available evidence is based on animal findings and these results should be interpreted with caution due to the differences in physiological mechanisms between humans and animals. ….. Till then, clinicians should treat NSAIDs as a risk factor for bone healing impairment and (they) should be avoided in high-risk patients.” 

ScientificWorldJournal. 2012; 2012: 606404.

“Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis”

Ippokratis Pountos, 1 Theodora Georgouli, 1 Giorgio M. Calori, 2 and Peter V. Giannoudis 1, 3 , *

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259713/

Asthma needs to be treated seriously and treated well.

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Asthma can be a terrible scourge. An asthmatic attack is like having to breath through a thin straw 24 hours a day  because of the changes that happen to the network of tubes that make up the lungs.

Asthma is a combination of inflammation and muscular contraction affecting the tubes - or bronchioles - within the lungs. The inflammation is to the lining of the tubes, and when the lining gets thicker then the lumen - or open part of the tube where the air travels through - has to get narrower. The inflammation also affects the quality of the mucous produced by the lining: instead of having a watery consistency it becomes thicker and more sticky not only making it difficult to clear from the lungs, but also leads to plug formation which can block some of the smaller airways.

In asthma, the circular muscle that controls the diameter of the Bronchioles become thicker and more sensitive to varying stimuli such as cigarette smoke, viruses, chemicals, exercise etc. And it's this combination of narrow inflamed tubes and increased sensitivity to stimuli that can move an asthmatic with reasonably comfortable breathing to someone seriously struggling to breath in an Emergency Department. Thankfully, we now have very effective medications that can help prevent most of these serious consequences of Asthma, but the concern is that patients are not getting the best treatment through lack of "compliance" - not taking their medications properly - or as in the case of some children, they are being given inappropriate treatment.

The medications we have for preventing asthma are based on Steroids, and these are nearly always given by inhaler, though they can be supplemented by oral medication if control is poor and the symptoms bad. Another type of anti-inflammation medication which is not a Steroid, is know as a Leukotrene Receptor Antagonist - LTRA's - and these usually come in tablet form. LTRAs are not "first choice" meds, but can be added to inhaled steroids if the steroids are not giving maximum control.

To relieve the spasm of the thickened circular muscle, Doctors have been using Salbutamol for over 50 years. The problem with salbutamol is that it only lasts about 4 hours, but his has been overcome by a more recent medication known as Salmeterol that is known as a Long Acting Beta Agonist, and its the combination of long acting Beta Agonists and inhaled steroids that has been used in adult Asthma regimes for many years. But this is NOT the ideal for 90% of childhood asthmatics.

Asthmatics should be controlled where possible by Inhaled Steroids: and the least effective dose is the preferred dose. If the inhaled steroid is not sufficient then there are three step-up options for poorly controlled asthmatics on inhaled corticosteroids:

adding a long-acting beta2 agonist
adding a leukotriene receptor antagonist
increasing the dose of inhaled corticosteroids.

The addition of a leukotriene receptor antagonist is the preferred option for children with ongoing activity-related asthma. Long-acting beta2 agonists are not recommended for children
five years or younger.

If you are an asthmatic, or your child is an asthmatic, you should have a written Asthma Management Plan which needs to be reviewed and updated by your treating Doctor on a regular basis. If you don't have an Asthma Plan, get one: it could save your life.


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Asthma prevention

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Asthma is caused by a combination of inflammation and irritation, and if the two arrive at the same time then an asthmatic can find themselves in serious trouble! So prevent, and be aware.

In asthmatics, the inflammation is to the inside of the airways within the lungs. As these airways get smaller and smaller, the effects of inflammation on the inner lining have a bigger and bigger impact.  Environmental irritation causes contraction of the muscles that control the "openess" of these tubes, and if the space is small in the first place then they're only going to get really tight once they've been irritated!

So if you have a tendency to suffer from asthma and you're heading out into the "Great Outdoors", PLEASE go well prepared because sometimes you just don't know what might trigger that asthma attack and you might be a long way away from support and help. Simple things like insect bites, smoke from a camp fire, a fruit bar with nut oil, or even just a change in the weather can trigger an episode.

Prevention is the key to good asthma control. Getting any inflammation under control and making sure that you can avoid "Triggers" where possible are both fundamental to preventing a potentially serious asthmatic attacks. According to Dr. James Sublett, chairman of the American College of Allergy, Asthma and Immunology Public Relations Committee,  "Planning ahead, seeing an allergist and knowing the causes of allergy and asthma, even those with the most sensitive noses and lungs can enjoy summer fun".

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Asthma - refine your technique

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   I was reading the Australian Prescriber catching up with the latest advice for Doctors on controlling asthma, and was disturbed by some of the information I found there. Thankfully the number of deaths has fallen over the years and yet asthma still causes considerable health problems and impacts on the lives of many millions around the world.

Although medications haven't changed fundamentally over the years, the way they are used and the way patients should be reviewed has. But we are falling dramatically short of good and effective care partly due to poor education and partly due to poor compliance by the asthmatics themselves: " more than half of the people aged 15–34 years (who have asthma) .. (pick up their) medications only once in a year. Most patients use their inhalers incorrectly, and only 22% of patients have a written asthma action plan". These are not encouraging findings!

Picking up on the poor technique of most asthmatics, I've cut and pasted the suggestions from the Oz Prescriber so that those of you with asthma, or who have children/adolescents with asthma, can review what you are/they are doing and see if you can do it better.

                                                     Common problems with inhaler devices

• breathing out through the inhaler mouthpiece leads to condensation and clogging of the nozzle
• difficulty actuating inhaler (for patients with arthritis, an aid may be available and fitted around the inhaler to ensure easier use)
• failure to coordinate actuation with inhalation. At its worst, medication will be seen to escape from the top of the inhaler.
• too fast an inhalation
• failure to hold breath after inhalation
• multiple actuations without shaking between doses, or on the same breath
• failure to replace cap on inhaler (leaves patient at risk of inhaling foreign bodies from pocket or handbag)
• failure to use a spacer with an inhaled corticosteroid-containing medication (the spacer increases lung deposition and hence efficacy, and reduces the risk of local adverse effects)

                                              Pressurized metered dose inhaler with spacer

• failure to prepare spacer before first use, to reduce the static charge which will otherwise prevent medication reaching the airways (wash in warm detergent water, do not rinse, allow to air dry,
• reassemble; there is no need to prime with puffs of a salbutamol inhaler)
• too-frequent washing without detergent priming (regenerates the static charge)
• sticky valve (the spacer should be washed once a month as above, or if the valve sticks)
• multiple actuations of preventer inhaler into the spacer at one time
• delay between actuation and inhalation
• too-fast inhalation, without a breath-hold at the end

                                                                       Autohaler

• failing to lift the lever before inhaling
• stopping breathing in when the click is heard
• failure to hold breath

                                                                      Accuhaler

• breathing out into inhaler
• not loading dose (by pushing lever) before inhaling
• not holding breath after inhalation
• not closing inhaler cover after use

                                                                      Turbuhaler

• not holding Turbuhaler upright during priming (loading) of dose
• not twisting base both around and back (note: it does not matter whether the click is heard at the end of rotation around, or at the end of the rotation back, as long as the base is rotated in
• both directions)
• not breathing in strongly enough
• not holding breath after inhaling dose
• breathing out into inhaler

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Asthma Prevention: you've gotta suck it up!

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Most Doctors who write prescriptions for their patients live under the impression that the patient will follow the Doctors advice and take the medications "As directed". Sadly, in a great number of cases this is not the truth: antibiotic courses are not completed, contraceptive pills are missed, 'Statin usage drops off as the patient feels OK - the list is depressingly long. One of the key principals of modern medicine is Prevention, and that means that patients need to comply with the advice given, if we are to achieve a good level of success.

Asthma is a good case example. In asthma, a trio of events occurs,

• Inflammation of the lining of the airways leading to a narrower tube through which to breath.
• A thickening of the normal dust-trapping, watery mucous secreted by the inner lining, which leads to blocking of the narrowed airways with these thick, sticky mucous plugs.
• A thickening of the circular muscle that controls the diameter of these small breathing tubes and which exacerbates the overall narrowing of these smaller airways.

In an asthma "attack", some irritant or triggering event - smoke, virus infection, stress - causes the circular muscles in the tubes to contract and narrow the tube, reducing airflow. Now if the diameter of that airway is already narrow due to inflammation, and has thick mucous plugs blocking up the smaller tubes, then the patient is going to wheeze and to get very short of breath: sometimes fatally so!

So the key to reducing the risks of suffering a significant asthma attack is to reduce the inflammation so that the airways are at their maximal diameter, and to make sure that they are not clogged with tenacious mucous: enter the principal of using Inhaled Cortico-Steroids (ICS). If it's going to be effective and keep people out of hospital, then they've got to take the medications on a daily basis. This has been backed up by research just released by the Henry Ford Centre in the US where lead author Dr Keorki Williams reported "We found that every 25 percent increase in ICS adherence was associated with an 11 percent decrease in asthma attacks, but most importantly, we found that causal use of these medications is not enough, especially among patients whose asthma is not controlled. Patients must use their asthma controller medication as prescribed if they want to have the best chance of preventing serious asthma attacks."

As my dear old Mum used to say: "An ounce of prevention is worth more than a pound of cure".
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