Paracetamol – All you Need to Know

Before moving on to the next popular Painkiller, let’s take a brief look into the history of painkillers.

History of Painkillers

Opium has been known since the earliest times. It is a dark brown resinous material obtained from poppy capsules (Papaver somniferum). It contains two different types of chemicals called alkaloids.

In 1806, active principle was first isolated from Opium and named ‘Morphine’ after the Greek God of Dreams ‘Morpheus’ for its tendency to cause sleep. A few years later, a paper was published describing how morphine brought pain relief and much-needed sleep to an ailing young girl. This stimulated widespread medical interest. From its earliest application, it was used as a form of pain relief, and that is still how it is meant to be used today. Morphine served as a precursor to a large number of synthetic and semisynthetic compounds called opioids, with actions similar to morphine (agonist) or opposite (antagonist) to it.   

A high degree of tolerance can be developed to morphine and related opioids if taken repeatedly. Tolerance is dependent on the dose and frequency of consumption. Larger doses, repeated frequently, induce tolerance more rapidly. Concern about abuse has been a major limiting factor in the use of morphine and other opioids.

As we have seen before there are another set of drugs used for pain, which are chemically and structurally different from the Opioids, the NSAIDs. Phenacetin is one such drug introduced in 1887, extensively used for its analgesic and antipyretic action but was banned after being abused.  However, its active metabolite (de-ethylated) called acetaminophen introduced in the last century and in use since the 1950s – is what we know today as “PARACETAMOL “.

Paracetamol

Paracetamol is most commonly used medicine by people of all age groups, right from newborns to the elderly, pregnant as well as lactating women, in other disease states where aspirin is prohibited.

Unlike aspirin, it does not affect the acid-base balance in our body. Gastric (stomach) irritation is insignificant; mucosal erosion and bleeding are very rare and can occur only in cases of overdosing. It does not affect platelet function or clotting factors and has no effect on the cardio-vascular system.

How does Paracetamol affect our Body?

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• Analgesic and Antipyretic –The central analgesic action of paracetamol is like that of aspirin, i.e., it raises the pain threshold but has a weak anti-inflammatory component. The analgesic effect of paracetamol and aspirin is additive. Paracetamol is a very good and promptly acting antipyretic.

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• Anti-inflammatory –It is a poor inhibitor of PGs (prostaglandins) in the peripheral tissues but is more active on COX in the brain, hence showing negligible anti-inflammatory action. The discrepancy in antipyretic, analgesic, and anti-inflammatory action is due to its inability to inhibit COX in the presence of peroxides, which are generated at the site of inflammation but not present in the brain.

How does our Body React to Paracetamol?

Our body shows very good absorption of paracetamol after an oral dose and distributes it uniformly. It is metabolized or broken down in the liver (by conjugation with glucuronic acid and sulfate) and excreted in urine rapidly.

The half-life of paracetamol, or plasma t1/2, is 2–3 hours (which means it takes 2–3 hours for the concentration of paracetamol to decrease by half of its initial concentration), and the effects of a single oral dose last for 3-5 hours.

Adverse Effects

At antipyretic doses i.e., when given for fever, Paracetamol is safe and well tolerated.

What is Acute Paracetamol Poisoning?

It occurs in individuals who cannot metabolize paracetamol in the liver. Early manifestations include nausea, vomiting, abdominal pain, and liver tenderness. After 12–18 hours, cells in the liver begin to get damaged, followed by damage to renal tubules (kidneys), which leads to a drop in sugar levels, which may progress to coma if not attended to immediately. Subsequently, jaundice occurs. Further course depends on the dose of paracetamol; if the initial poisoning dose isn’t high, then recovery can happen with supportive treatment; in cases of very high doses, it can prove to be fatal.

What causes Paracetamol Toxicity?

After the therapeutic effect of 3-5 hours, paracetamol is broken down (metabolized) in the liver, which produces a very reactive metabolite, NABQI (N-acetyl-p-benzoquinone imine), which is detoxified in the liver itself (by conjugation with glutathione).

When very large quantities of paracetamol are consumed, the capacity of liver cells that carry out the detoxification of NABQI gets saturated, hepatic glutathione is depleted, and the amount of NABQI increases in our body. As a result, NABQI binds proteins in liver cells and renal tubules, resulting in their damage.

Specific Antidote

N-Acetyl cysteine is a specific antidote for Paracetamol poisoning.

Uses

Paracetamol is one of the most commonly used OTC analgesics and antipyretic medicines. It is one of the best drugs to be used for its antipyretic effect, i.e., for fever (no risk of Reye’s syndrome). Children can take paracetamol for fevers occurring for any reason. It does not have significant drug interactions; thus, it may be preferred over aspirin for most minor conditions.

Choice of Non- Steroidal Anti-inflammatory Drugs

Efficacy differences among the different NSAIDs are minor, but they have their own spectrum of adverse effects. No single drug is superior to all others for a given patient.

The cause and nature of pain, along with considerations for risk factors in the given patient like age, co-morbidities, and allergies, govern the selection of NSAIDs. Also, the past response of the patient to the particular medicine and individual preference has to be considered.

If one NSAID is unsatisfactory for a person, it does not mean all others are the same. Some patients feel "better" after consuming a particular drug, while others may not be able to relate to them. No drug works in the same way for two different individuals. It is in this context that the availability of such a wide range of NSAIDs may be welcome.

Having known this, self-medication and referring medicine to relatives and friends MUST BE STRICTLY AVOIDED as medicine which works for one individual may not work for others. 

*Before consuming any medication, the doctor’s advice is MANDATORY.