Paracetamol - the bedrock of health

The country has been abuzz since news broke that local production of paracetamol may have stopped due to the soaring cost of raw materials.

Even though Federal Health Minister Abdul Qadir Patel came out to refute the reports, there remain public concerns surrounding the availability and, more importantly, the price of a drug deemed by many to be one of the basic medicines.

Let us find out what it is and why there is such a problem:

What is paracetamol

Paracetamol is a pain killer. It is an an analgesic anti-pyretic drug.

It is commonly used to treat fevers and provide relief for mild to moderate pain. It is also used to remedy colds and flu.

Given its non-lethal nature and narcotic impacts, it is cleared for over-the-counter sales.

Where did it come from?

Like most modern medicinal drugs, paracetamol was ‘cooked up’ in a lab.

In 1877, Harmon Northrop Morse synthesized paracetamol at Johns Hopkins University.

He used a process called ‘reduction’ whereby any base ingredient is heated, and excess materials are allowed to evaporate, leaving a ‘reduced’ residue.

Morse reduced p-nitrophenol with tin in glacial acetic acid in his lab.

It took ten years, after determining the essential ingredients of the drug, for clinical pharmacologist Joseph von Mering to try paracetamol on humans in 1887.

At the time, phenacetin was considered safer than paracetamol, and paracetamol had to take a backseat for the next sixty-odd years.

Later, in the 1940s, it became known that compared to phenacetin and acetanilide, acetaminophen - the active ingredient in paracetamol - was a prodrug with none of the side effects of the others.

What is it made of?

Paracetamol is primarily made of acetaminophen. It is created using a process called acetylation of the para-aminophenol (obtained by reduction of para-nitrophenol) with acetic acid or acetic anhydride.

Once its alcohol version is created – acetaminophenol, its nitration yields ortho- (2-) and para- (4-) nitrophenols.

These two can be separated using distillation.

The 4-nitrophenol is then reduced to 4-aminophenol. It is then acetylated to give the final ingredient.

It is a wholly chemical product.

How does it work?

Scientists believe that once paracetamol enters the body, it is metabolized to 4-aminophenol.

In this form, it can link with the fatty acid arachidonic acid forming N-arachidonoylphenolamine (AM404) – a naturally occurring cannabinoid (a group of molecules which activate specific receptors in the brain and spinal cord – its famous member is tetrahydrocannabinol (THC), the primary psychoactive compound found in cannabis).

AM404 is thought to bind to the cannabinoid CB1 receptors and block them, preventing other molecules from binding and triggering pain signals.

Hence, it effectively ‘switches off’ the pain signals.

It also binds to receptors which stop the COX-2 enzyme from forming inflammatory compounds.

Hence giving paracetamol not only the pain relieving properties but also the ability to reduce inflammation, as well as lower fever.

How long does it take to work

Paracetamol is usually ingested orally and is commonly available in tablet form.

Typically, it can take up to an hour for a tablet to dissolve, enter the bloodstream and take effect.

Who can take panadol

Most people can take paracetamol. A special syrup version is made for infants but can be administered only in the prescribed dosage.

Pregnant and lactating women can also take paracetamol, albeit in prescribed doses.

However, if you have had an allergic reaction to paracetamol or any other medicines in the past, it is best to check with your doctor first.

Those with liver or kidney problems have an above-average consumption of alcohol, take medicine for epilepsy or tuberculosis or warfarin, and also need to be careful when taking paracetamol.

Where is it made?

Even though it is a chemical, it is made only in specific countries.

These include Argentina, Brazil, China, Colombia, France, Germany, India, Japan, Mexico, Poland, South Korea, Romania, Taiwan, Turkey, the UK and the USA.

Pakistan is not one of the countries where its raw materials are synthesized.

This means that it has to import the raw material or finished form before packing it for local supply.

Major sources

China and India are the biggest sources of raw materials for paracetamol and most other drugs.

Pakistan used to import goods worth $2 billion from India.

That all changed in 2019 when India revoked the special status of the disputed territory of Illegally Indian Occupied Jammu and Kashmir (IIOJK).

But in the aftermath of the coronavirus pandemic, Islamabad softened its stance and allowed the import of drugs and pharmaceutics into the country.

At the moment, imports from India have a volume of around $290 million.

As a result of this paradigm shift, the country turned to China as the major source of pharmaceutic raw materials.

Pricing impacts

Since April, the rupee has been on a downward spiral, losing about Rs47 in value, from Rs182.82 in April to Rs229.82 today.

This has caused rampant inflation in all sectors, contributing primarily to a compound increase in production costs from increased power costs, transportation costs and other material costs.

Paracetamol’s major manufacturer and distributor in the country, too, cited rising costs and the reluctance of the government to allow for an increase in prices by the Drug Regulatory Authority of Pakistan (DRAP) as the reason for shutting down production.