Is Paracetamol and Aspirin Safe?

A former lady patient of mine phoned me last evening that she has been taking 6-8 tablets of paracetamol  2-3 times a day for the last two weeks for her “stomach pain” without much effect. She sought  my advice if there are other ways to treat her nagging abdominal pain.

I will not deal with her chronic abdominal or “stomachache” as I have no clue what caused it. She needs to be investigated in a hospital with upper GI endoscopy or ultra-sonography and other diagnostic procedures.
 

Colicky abdominal pain, could be anything from gastric ulceration, ulcerative colitis, bile reflux, pancreatitis… colic spasm…down to kidney stones and appendicitis.  I am not going to deal with all these without her getting a proper diagnosis in a hospital in the first place.

What I am more concerned was,  she told me she has been taking high doses of paracetamol over the last two weeks and asked me if this is okay?  

This would be more  safer and sensible for me to pen here 

I was aghast by what she told me, wondering if she has not been poisoned by all those paracetamol 

I thought I should write a small article here to share with readers  in my whatsapp  group or in this blog about medication at high sustained doses including such common and seemingly “safe” over-the-counter (OTC) medication like paracetamol  which is freely available,  sometime even from Indian-Muslim tea stalls at night or cigarette shops and coffee shops  

Safety and Clinical Effects:

 

First of all  paracetamol is quite a safe medicine usually prescribed for mild pain, for flu and cold. The usual safe dose is just 1 -2 tablets twice or three times a day for just 2 -3 days. Like all medicines it becomes unsafe if overdose. 

In some prescription paracetamol may be combined with codeine or with dihyrocodeine. Sometimes for better analgesic effect it may be given with Tramadol hydrochloride since Tramadol is a centrally acting synthetic opioid analgesic. All are safe at the recommended dose given in the literature by the drug companies.

Although paracetamol is an OTC medicine people make it a habit of buying large amounts to commit suicide or to treat chronic pains like this former patient of mine. 

In some countries  people try to commit suicide using paracetamol, although in Malaysia they jump into the sea from Penang Bridge,  or from a flat or a shopping mall instead of seeking psychological and spiritual counseling 

Overdose:

But what is the toxicological effects from an over dose with paracetamol ? 

Sometimes an overdose with paracetamol may not be deliberate, but rather accidental when taking another medication that already contains paracetamol in combination with another drug such as with dextropropoxyphene (Co-proxamol).  

But to be honest,  paracetamol is quite safe with very little side effect. In fact there were very few unpleasant  effect reported  with single  paracetamol dose, not combined with other drugs as far as I know.   

The only unpleasant effect of an overdose is mainly nausea in the next 24 hours, unless there is a severe overdose with over 10 tablets in a single dose. 

An overdose if prolonged and sustained causes liver damage and deterioration may be certain specially when ingested together with alcohol.  Alcohol is toxic to the liver even though it can be metabolized by alcohol dehydrogenase. 

In some patients an overdose may advance to fulminant hepatic failure (FHF) or acute liver failure. In some cases reported there may also advance to renal failure due to acute tubular necrosis.

Mechanism of Toxicity: 

Under normal therapeutic dose (1 -2 tablets) od, bd, or tds (once, twice or three times a day), paracetamol is metabolized (broken down in the body) in the liver, being conjugated to give the gluromide or its sulphate. 

In the event of an overdose, this mechanism of conjugation is over loaded. It will then take a different pathway to produce a toxic metabolite called N-acetyl-benzoquinoneimine which can still be inactivated by an endogenous (inside the body) antioxidant called glutathione (GSH) in the liver.

In the technical language of pharmacology to be more precise, if you do not mind me using more precise technical language, the N-acetyl-p-benzoquinone imine (NAPQI) is the breakdown product of paracetamol. 

It  is the secondary reactive cytochrome P450-reactive metabolite formed. It then becomes toxic when GSH is depleted by an overdose of paracetamol. 

Glutathione is an essential antidote to overdose. 

In very simple lay language, this simply means the liver antioxidant glutathione detoxifies the paracetamol and makes it safe to take. 

Sorry I cannot explain simpler than this. Pharmacodynamics (mode of action of drugs) is very complicated medical science to explain to lay readers.

  

But if there is an over dose, this liver antioxidant will be used up quickly, and once the store of glutathione is used up, damage to the liver cells (hepatocytes) is certain.

The fatal dose depends from individual-to-individual such as the state of nutrition, body weight or other high risk groups such as alcoholics

Management (treatment):

Normally in acute toxicity with paracetamol, a competent and highly-knowledgeable emergency doctor (some, not all doctors have that gift) in an urgent situation will administer N-acetylcysteine. This is a very effective antidote by merely replenishing the glutathione stores.  It is as simple as that. 

However, this has to be given intravenously within the first 8 hours after an overdose. Amount to be administered depends on overdose, duration of the ingestion, weight of person and of course the paracetamol blood levels monitored by an analytical scientist or a toxicologist in a laboratory. 

Aspirin:

This former patient then asked me what about aspirin? Aspirin (acetyl salicylic acid) too have side effects. Aspirin is the oldest and safest analgesic (pain killer) known.

In fact aspirin was originally derived from a herbal medicine called salicin from willow trees, the leaves are the diet of beavers.

Salicin is chemically related to aspirin. Scientists then acetylated salicin to make it into aspirin which is acetyl salicylic acid. That does not mean aspirin is very safe just because it was originally a herbal medicine.  It may be less safe after pharmaceutical scientists altered its molecular structure into synthetic  aspirin.

Kinetics: 

When consumed, the acetyl function group bridge is broken down. The two parts of the molecule are then formed, namely, glucose and salicyl alcohol. They are then metabolized separately. The body then oxidizes the alcohol function; while the aromatic part is finally metabolized to salicylic acid giving the natural herbal the same effect as aspirin. 

In fact over 45 % of the modern synthetic drugs prescribed in the hospitals today originally came from the plants as their origin until pharmaceutical chemists make a synthetic  analogue of them by mimicking their molecular structures.

Herbal in Origin:

The original natural botanical medicines have much less side effects, although slower in action,  but much more stable and long lasting in their therapeutic  properties. They are clinically much more effective in the long run, and because of this realization, herbal and botanical medicines have been used effectively for thousands of years, by all civilization and cultures until the synthetic factory versions came into being for mass production.  Salicin tastes bitter like quinine.

Clinical-Toxicological Effects:

The clinical-toxicological effects of aspirin varies on the amount taken and the weight of the subject. The pharmacological effects are hyperventilation, epigastric pains (stomach pains), tinnitus (ringing in the ears), deafness, and in acute cases coma and convulsion. Aspirin acts as a stimulant in the brain, and thus causes hyperventilation.

Some people also try to commit suicide with other analgesic (pain killers) such as using non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen, diclofenac. Mefenamic acid poisoning often causes convulsion.  

I shall write about “rape drugs” later as some ladies have also asked me not long ago after some readers sent us a whatsapp message about them some two weeks ago.  

Forensic toxicology is very interesting at least to me as a former medical toxicologist with MIT

Stay away from all drugs including all those dozens of necessary medications given by doctors unless absolutely necessary. Pill popping should NEVER be the culture to stay healthy.

Holistic Health &  Natural Medicine:

 

Nutrition, physical and mental activities, social and spiritual well-being, sharing life experience and knowledge with others, healthy habits and lifestyles and seeking wisdom from God towards these is the best medicine (other than laughter – just laugh at what I write here if you wish, and you have done well for the New Year 2019)

Cheers to you all, my gentle readers

jb lim 

January 3, 2019