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SIDE EFFECTS OF DRUGS

 

You will see elsewhere on this site that the treatment of many neurological conditions both benign, such as migraine, or more serious, such as Parkinson’s disease require the use of drug therapy.

Any medicine, in fact more or less anything in life, carries with it a side effect.

We do not think often about the “side effects” of walking out the front door, getting in our car or going on a plane journey.  We do these tasks because it is part of modern day living.

If you walk up a flight of stairs, if you clean your house using a detergent or even climb up a stepladder there is the risk that some untoward event will happen as a consequence of that action.

In fact, the figures for household accidents and car accidents occurring within three miles of your home are quite extraordinary and make for the most depressing of reading.

It is surprising that any of us actually get out of bed.

It is not surprising that putting something alien into the body, such as a medication, will carry with it a risk.

With regard to side effects, I hear myself saying frequently that “any drug can cause any side effect in any person at any time”.

The decision whether or not you have a particular treatment is very much your own.

 

TWO EXAMPLES (EACH END OF THE SPECTRUM)

If, unfortunately, you develop appendicitis the surgeon will say to you that there is a need for an operation but there is a risk of the anaesthetic, as well as the surgical treatment.  The anaesthetic drugs can have very occasional catastrophic side effects.  The risk, however, is very low indeed.
What happens, you might ask, if you do not have your inflamed appendix removed?  The surgeon will rapidly reply that you will probably die and horribly from peritonitis and all of its complications.  Most normal people hearing this information ask politely why the surgery is not taking place sooner than immediately.

The other end of the spectrum is a cosmetic procedure say, for example, to correct bat ears.  This is an unhappy situation for those who have the condition but it is only a cosmetic deformity.

The plastic surgeon indicates that the ears can be corrected by surgical skill.  He will also indicate that there is an anaesthetic risk.  As the bat ear condition carries with it no risk to life or limb, the risk of the anaesthetic is many times the risk of the cosmetic deformity and a decision whether to go ahead with surgery must be that of the individual.

Clearly, these two examples are at the extremes of how we consider treatment versus the side effects.

 

THE BALANCE

When an individual presents with a complaint of any kind, that is a symptom, it is the primary role of the assessing neurologist to make a precise diagnosis.  Without a diagnosis it is not possible to talk about prognosis, that is what is going to happen to the individual.

Once the diagnosis is made, then treatment can be discussed.  For some people a diagnosis is all that they require, together with reassurance.  For others the level of symptom is so great that they would like treatment in order to help.  If you look at my website article on chronic migraine and pain, you will see the four primary modalities of symptom management.  The same rules apply across all conditions.

Interestingly all therapies, be they with medications or other treatments, do actually carry side effects, some less than others.  For instance, how often does an osteopath or chiropractitioner tell their clients that a manipulation of the neck may lead to death.  That occurs through the very uncommon complication of a vertebral artery dissection.  Should we frighten everybody by giving them such information or not?  I think that if the side effect is serious, then people should be warned.

With regard to drug treatment, it is effectively a balance between the level of symptom, as opposed to the risk of side effect. If the symptoms are intrusive, diminishing quality of life or having a functional impact, then you may prefer to have a pharmacological treatment.

 

WHY DO WE GET SIDE EFFECTS?

All of us comprise something like 6 billion genes that make up our whole constitution.  With so many variations it is not surprising that we react to different life stresses and events in different ways.  We are not all Olympic gold medal winners and likewise we are not all criminals.

It is very likely that each of us has a different profile for handling each and every substance that exists in the world. 

Some of us metabolise medications very quickly and others slowly.  How is it there are so many different types of painkiller, for instance?  You hear so often from people that paracetamol does not work but panadol does or similarly with ibuprofen as opposed to other anti-inflammatories.  Is this all pie in the sky or is it a reality?

Very few medications act specifically on what we wish them to do. 

On the whole thyroxine, which is a replacement for naturally occurring thyroid hormone, does what it says on the packet.  It treats the deficiency of thyroxine.  This is easy to monitor and the right dose can be found for each individual.  The side effect profile of the naturally occurring thyroxine is very few and far between.

Other drugs, such as antibiotics, do what they are supposed to do by killing bacteria but our bodies may react to them in an alien way.

All of us, I suspect, have heard of allergy to penicillin.  This is a side effect of the drug caused by an inflammatory or an immune response to penicillin which is actually produced by an organism and shown by Sir Alexander Fleming to kill bacteria.

Anyone who has had a penicillin allergy knows how unpleasant it can be, even if it is a skin rash or the much more serious anaphylactic response.
With a drug like penicillin if you get a reaction to it you do not take it again.

Other medications produce side effects because they impact on the body as a foreign chemical.  Common side effects include drowsiness, gastric upset or dizziness.  Some may cause skin rashes, others constipation and some nightmares or palpitations.  If the side effects are intrusive, then the drug is stopped.  Fortunately, for most people the side effects are transient and short-lived without long term complications.  Stopping the pills sees a cessation of the side effect in 24 hours.

For some people, if the side effect can be tolerated for a few days or even several weeks, the body gets used to the drug and the side effect goes away leaving the benefit.  This is very commonly seen in medications that are used to treat headache and all pain disorders and some blood pressure and depression drugs.  The difficulty for the physician is in convincing the individual that they should put up with a few days of feeling dizzy or drowsy in order to see if there is going to be the full benefit accruing.

The decision whether or not you continue or leave the drug alone is very much with the individual taking the medication.

The physician, however, ought to encourage if the side effects are mild or not known to be serious as a very useful treatment might be discarded too quickly.

 

HOW TO AVOID SIDE EFFECTS?

There are a number of ways that side effects can be limited.  There is an anti-epilepsy drug called lamotrigine if given too quickly, that is the dose increased too rapidly, then a skin rash which can be dangerous may emerge.  If the drug is introduced very slowly, then this makes the side effect much less likely.

Other drugs, such as carbamazepine, also an anti-epilepsy drug but used in some painful conditions, will give side effects if too big a dose is introduced initially but if a low dose is started and then the dose increased even beyond the dose where side effects occurred when it was given in too high a dose initially, then the individual can tolerate the drug without a problem.

 

SERIOUS SIDE EFFECTS

Some medications are known to have the potential to cause serious side effects.

I suspect we all know that cancer drugs, that is cytotoxic agents, are poisons.  They work by poisoning all the cells in the body but because cancer cells are less robust than normal cells they die more readily and hence the cancer drugs work.  Individuals frequently, however, suffer problems with their bone marrow, gut, liver or skin and they become much more liable to infection.  Most people tolerate these side effects because the nature of the underlying disorder is so serious.  This is a true example of balancing risks versus benefits.

Other drugs, such as those modern developments in treating multiple sclerosis, seem to be very effective but there are rare side effects that can be very dangerous and have actually been known to be lethal.

There is a very good example of this with a drug called natalizumab (tysabri).  This medication, when introduced in the United States, was in simple terms twice as effective as the other medicines that were already on release to treat the condition.  This very reasonably caused great excitement in the world of multiple sclerosis sufferers and many people were treated with the drug. 

After many tens of thousands of patients were treated it was recognised that there was a risk of a rare disorder called progressive multifocal leukoencephalopathy (PML) as a consequence of this treatment.  This condition could be lethal and, in fact, two patients initially died as a consequence of using the treatment.

As multiple sclerosis, albeit an unpleasant and disabling condition, would not normally have been lethal under those circumstances, this was regarded by the pharmaceutical company as being an unacceptable risk.  Being the United States, they immediately withdrew the drug from the market. 
This was regarded by the various drug authorities as being highly responsible behaviour because, in effect, the drug house was losing hundreds of millions of dollars of income.

What happened next may well be a surprise and I think a lesson to all of us in medicine, the regulatory authorities and patient groups.
As I understand it, the Multiple Sclerosis Society of the United States objected to the withdrawal of the drug.  Their patient groups indicated that they were so pleased with the drug and the benefits that it was giving that it was for them to decide whether or not they continued the drug or stopped it, knowing that there is this risk, albeit it rare, of a serious side effect.

This was very much an example of patient empowerment and the drug company, with the regulatory authority approval, re-introduced the medication.
As it turns out in this situation, there is now a test that indicates whether or not an individual is prone to get the sinister side effect and that is the type of development that does occur with good surveillance of side effects and appropriate thinking.

 

DOES THE CLINICIAN CARE?

Of all the decisions that clinicians make about people it is the decision about whether or not to use drug therapy that actually causes the greatest concern, perhaps equal to missing a diagnosis.  Some clinicians are more content to use drug therapy than others.  Certain specialists are comfortable, for instance, in using drugs and substances for cosmetic reasons, such as collagen filler and silicon.  The final decision, however, should always be with the patient and there should be an expectation that reasonable amounts of information should be provided.  Having said that, commonly used drugs have such a long list of side effects that it almost is not possible to relay all of them in a single consultation.

The advantage of the internet now is that any drug can be fully researched by any person and, if there are any concerns, then these should be brought to the attention of the managing clinician.  To balance that comment, however, the person who has the complaint or symptom needs to recognise that there must be an expectation of the managing doctor that they want to be helped with their symptoms.

 

MEDICATIONS THAT HARM

With so much discussion in the media about side effects and the time it takes up in the consulting room it is surprising that so many people smoke, drink to excess and use non-prescription drugs.  People who smoke, which we now know shortens life an average of 10 years, will often worry about drug side effects that may cause a little dizziness for 24 hours.  This is an enigma.

I do not underestimate the addictive properties of nicotine and alcohol and to this list painkillers and sedatives need to be added.  We all know that opiate addiction, the use of amphetamine and cocaine and even marijuana usage can undermine an individual and create a whole range of problems.  People do not take these drugs because they do harm.  They take them because initially the drugs make them feel better.  The problem, however, is that the feeling wanes with increasing doses being needed.  Then the crucial stage occurs when an individual gets no benefit but feels terrible unless the drug is taken. 

Analgesic overuse headache has as similar mechanism.  When painkillers are taken daily, or even every other day, the individual will continue having regular headaches and this means that if painkilling drugs are then not taken then the headache will occur, together with other unwanted effects that the painkillers then seem to diminish.  The headache sufferer perceives that it is the analgesic agent that is actually working when in fact it is a significant cause or contributing factor to the headache. 

Withdrawing from many of these addictive substances can be very difficult and this includes painkilling drugs.  Usually there has to be help from a caring and compassionate physician who will also use other prophylactic or preventative medicines in order to reduce the pain level.

 

THE CONSEQUENCES OF DECISION MAKING

Doctors are not the almighty.  I do accept that in my training years some may not have agreed with that principle.  There is the old joke about God and the Professor that asks the question “What is the difference between God and Professor”?  God is everywhere, Professor is everywhere but the Professor is not here today!

Someone ultimately has to make a decision about treatment.  When malignant disease is being treated or there is highly sinister disease or injury, then those decisions are automatic almost reflex and little thought needs to be given.

When there is a choice of treatments available or if the condition is benign or relatively benign, then the doctor must assume until told otherwise that the person in front of them wants to be helped.  It is reasonable to ask the doctor what they would do under the circumstance of the person presenting if they were that person or if the patient was their mother in law.  The mother in law principle of treatment is one I have followed over years.  What I mean by this is that if mother in law is kept happy, then your spouse is happy and by extension you are happy.  Get the mother in law right and life is smooth, a well oiled passageway through time.

Clinicians often do make decisions.  Sometimes these may be premature or rushed or seen that way.  The difficulty for most doctors is that time is limited, particularly for General Practitioners, and the talking and discussion does have to stop at some point.

If your symptoms are interfering with your life or causing functional handicap, then you will almost certainly want to try a medication and see if it works or gives side effects.  If the latter, they will usually be short-lived for a day and go away.  Something else would be tried and so on!