Question

The CDC recommends a COVID-19 infected patient to take paracetamol? What are the symptoms relieved by paracetamol? Explain the mechanism of action in our body

Answer 1

Paracetamol/acetaminophen is one of the most popular and most commonly used analgesic and antipyretic drugs around the world and is recommended as first-line therapy for pain and fever. It is available without a prescription, both in mono- and multi-component preparations with other allergy medications, cold medications, sleep medications, pain relievers, and other products. Acetaminophen has both antipyretic and analgesic effects.

It is available in a variety of forms including syrup form, regular tablets, effervescent tablets, injection, suppository, chewable form and other forms.

It is mainly used for

· Analgesic action

· Antipyretic action

· It is the drug of choice in patients that cannot be treated with non-steroidal anti-inflammatory drugs (NSAID), such as people with bronchial asthma, peptic ulcer disease, hemophilia, salicylate-sensitized people, children under 12 years of age, pregnant or breastfeeding women.

· Paracetamol is a well-tolerated drug and produces few side effects on the gastrointestinal tract, while they are quite common with NSAID’s. Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation (like salicylates).

· Allergic reactions are rare occurrences following acetaminophen use

· In general, acetaminophen is used for the treatment of mild to moderate pain and reduction of fever.

· For taking care of the fever associated with many illnesses, including COVID-19, physicians suggest taking acetaminophen—known internationally as paracetamol.

· It is currently recommended to COVID 19 patients as approximately 80 percent of all COVID-19 cases exhibit only mild to moderate symptoms that don’t require hospitalization. Initial symptoms of COVID-19 are dry cough, fever, malaise. Doctors recommend that these patients self-isolate, stay hydrated, eat well, and manage their symptoms as best they can. It will not cure COVID 19 but will provide symptomatic relief.

This preference is because ibuprofen and related drugs called NSAID’s can have harmful side effects, including kidney injury, stomach ulcers, and gastrointestinal bleeding. It does not mean ibuprofen and NSAIDs worsen outcomes with the coronavirus, it is because paracetamol has a better safer profile.

However Acetaminophen also comes with hazards, and people should:

1. Do not use more of this medication than is recommended. An overdose of paracetamol can cause serious harm. The maximum amount of paracetamol for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day. Exceeding this daily maximum can cause acute liver injury. Acetaminophen overdose is the most common cause of acute liver failure in the United States

2. Do not take if you are allergic paracetamol, although it is rare

3. Do not take it if having existing liver damage.

4. Note all the medicines taken, since over-the-counter medicines over-the-counter cough, cold, allergy, or pain medication and some sleep aids often contain acetaminophen. If one is using certain products together he may accidentally use too much paracetamol. Read the label of any other medicine before using it to see if it contains paracetamol, acetaminophen.

5. Avoid drinking alcohol when taking acetaminophen. Alcohol may increase your risk of liver damage while taking paracetamol.

Mechanism of action
Although paracetamol was discovered over 100 years ago and was approved for clinical use by FDA in 1951and has been widely used in medical practice for more than half the century, its mechanism of action has not been elucidated until now.

It is thought that it exerts its analgesic effect due to due to its ability to inhibit the cyclooxygenase (COX) pathways. It is thought to exert central actions which ultimately lead to the alleviation of pain symptoms. One theory is that acetaminophen increases the pain threshold probably by selectively inhibiting an isoform of the COX enzyme known as the COX-3. Cox-3 enzyme is unique from different from known variants COX-1 and COX-2. In studies COX-3 was found in the dog’s brain and is hypothesized to be present in the human brain too but is not universally accepted. Acetaminophen (paracetamol) blocks COX indirectly. Cyclooxygenase enzymes are involved in prostaglandin synthesis. Prostaglandins are responsible for eliciting pain sensations.

Paracetamol does NOT inhibit other isomers of cyclooxygenase namely COX-1 and COX-2 and it which NSAIDs do and it also does NOT belong to NSAIDs.

Paracetamol mainly inhibits prostaglandin synthesis in the brain but cannot inhibit prostaglandin synthesis in the peripheral tissues, which results in analgesic, antipyretic action without any anti-inflammatory activity.

Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no anti-inflammatory effects.

Another theory is it probably inhibits the reuptake of one or more endocannabinoids, such as Anandamide. Endocannabinoids are endogenous molecules (produced by the body) that act on cannabinoids receptor to modulate pain. Paracetamol is metabolized to a compound with a very similar structure to Anandamide. This compound is thought to inhibit the reuptake of Anandamide into brain cells, thus increasing Anandamide concentration in the synapsis and accounting for the analgesic power of paracetamol.

The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat.

So the exact mechanism of action of this drug is not fully understood at this time, but future research may contribute to deeper knowledge.