Morphine as painkiller

Morphine is obtained from the same plant that produces opium, the poppy plant. Morphine, named after Morpheus, the god of dreams, is the main psychoactive chemical in opium.

Together, morphine and opium belong to a larger family of drugs named the opiates, which are known for producing a wide range of effects, from sedation to constipation. It is most abundant opiate found in the dried sap of the poppy, about 8 top 14 percent of the dry weight of opium.

The Sumerians used the word hul, meaning ‘joy’ and gil, meaning ‘plant;’ when referring to the poppy plant.

Opium was used sparingly in Europe during the Middle East, but its popularity increased during the Renaissance. Until Freidrich Wilhelm Serturner isolated the active ingredients (morphine) from raw opium (he published paper on the topic in 1817), the observed physiological and pharmaceutical properties of opium resulted only from the combination of effects from the raw opium’s multiple alkaloids.

In the early 1850s, Alexander Wood, a Scottish physician, reasoned that the best way to relieve painful extremity injuries would be to inject morphine directly into the nerves that supplied the painful area.

Both the Crimean War (1851-56) and the American Civil War (1861-65) contributed towards the development of opiate abuse. The troops had free access to morphine and opium which they carried so that they could give some relief to their wounded colleagues during the fighting.

In desperation, wartime, physicians regularly used morphine to cope with war-inflicted wounds and limb amputations, gruesome products of the massive quantities of lead bullets an cannon balls fired by each sides with deadly intention in the directions of their adversaries.
Morphine as painkiller

The understanding how aspirin works

Aspirin is the most widely used painkiller in the world. It has been used to treat toothaches, headaches, arthritis and other painful maladies for 100 years.

John Vane is credited for influencing physicians to prescribe aspirin for heart problems. He showed that aspirin blocs the action of special substances in the body called prostaglandins.

On June 23, 1971, the journal Nature published three articles of the group of John Vane at the Royal College of Surgeons of England, which sent shock waves across the world.

These articles demonstrated for the first time a mechanism of action of aspirin that explained the multiple biological activities of the compound by one single pharmacological effect: inhibition of prostaglandin biosynthesis.

Prostaglandins play important regulatory roles in life processes such as digestion, blood circulation and production.

In his pioneering paper, the later Sir John Vane showed by elegant bioassay experiments that aspirin - and salicylate – preventing the synthesis of prostaglandin in cell free systems after tissue injury.

Thus, aspirin is referred to as an antiplatelet agent that is a mild blood thinner.

In the same year an informative paper was published by William L. Smith and William E. M. Lands. Using acetone powder preparations of sheep vesicular glands they demonstrated time-dependent aspirin and indomethacin inhibition, with indomethacin 100 times as effective.
The understanding how aspirin works

Felix Hoffmann and aspirin

Felix Hoffmann (1868-1946) was the son of a manufacturer in the town of Ludwigsburg in Swabia Germany. He studied chemistry and pharmacy at the University of Munich, graduating in 1893.

Legend has it that Hoffmann was searching for something to relieve his father's arthritis. His father was using salicylic acid a precursor to aspirin, for his condition in the late 19th century.

Hoffmann prepared a range of compounds by making slight modification to the structure of 2-hydroxybenzoic acid.

Dr. Felix Hoffmann

Hoffmann tried out each of the new preparations on his father the effects. Within a two-week period in August 897 Hoffmann synthesized two drugs: aspirin and heroin.

On October 10, 1897, he prepared aspirin in a purer form using an improved process. Hoffman gave some of his aspirin to his father and it worked well in relieving arthritis pain.

Aspirin reduces pain and fever by reducing the production of prostaglandins, inflammatory compounds released when cells are damaged.

The problem was that aspirin is not very soluble in water. It was first available as a powder in sachets.

Bayer then decided to pellet the powder and aspirin became the first medicine to be sold as tablets.
Felix Hoffmann and aspirin 

Egyptian Doctors in 1300 BC

Egyptian Doctors in 1300 BC
Egyptian doctors were well aware of their limitations, however and were told not to inflict unnecessary suffering on their patients, so there were many cases where they had to say – at least to themselves –‘An aliment not to be treated’.

They were recommended to take note of the treatments and medicine they used and of their effects, so that they had a record for similar cases in the future.

There were medicine to be taken internally, others to be applied to the outside of the body, and others still to be inhaled. Egyptians ingredients that can be identified today appear to be sound herbal remedies.

However some medicines had ingredients such as mice, beetles and dung which aimed o drive out the demons causing the illness.

The Egyptians had a remarkable knowledge of the way the body worked, and knew about its internal arrangement through mummifying the dead.

To them the heart was the most important organ; they knew that it pumped blood round the body and that the pulse ‘spoke the messages of the heart’. They also knew that injuries to one side of the brain affected the opposite side of the body.

Doctors sometime used surgery as well as medicine to treat patients and opened injured skulls to relieve pressure in the brain.

Before an operation the surgeon gave his patient a drink, presumably a painkiller, ‘to render it agreeable’. In the New Kingdom the painkiller might have been opium, imported from Cyprus.

Because of the importance the Egyptians attached to ritual purity the surgeon and his assistants washed themselves and purified the instruments in fire before the operation. Both of these would cut down the risk of infection.

The Egyptians were a deeply religious people and prayers would always be used as well as medicines, even for the simplest ailments.

In difficult cases, magic might be employed. It was also possible to visit the temple of a deity associated with medicine, such as Imhotep, which had priests trained as doctors.

At some temples the sick could spend a night close to the god’s sanctuary. During such a stay, called ‘incubation’, the patient might be cured by the deity, or dream of the god and receive instructions for treatment.

Even if no help was forthcoming, the sufferer was spirituality comforted.
Egyptian Doctors in 1300 BC

A Course of Treatment by Egyptian Doctors in 1300 BC

A Course of Treatment by Egyptian Doctors in 1300 BC
Egyptian doctors were well aware of their limitations, however, and were told not to inflict unnecessary suffering on their patients, so there were many case where they had to say at least – ‘An ailment not to be treated’. They were recommended to take note of the treatments and medicines they used and of their effects, so that they had a record for similar cases in the future.

There were medicines to be taken internally, other to be applied to the outside of the body, and others still to be inhaled. Egyptian ingredients that can be identified today appear to be sound herbal remedies. However, some medicines had ingredients such as mice, beetles and dung, which aimed to drive out the demons causing the illness.

The Egyptians had a remarkable knowledge of the way the body worked, and knew about its internal arrangements through mummifying the dead. For them, the heart was the most important organ; they new that it pumped blood round the body, and that the pulse ‘spoke the messages of the heart’. They also knew that injuries to one side of the brain affected the opposite side of the body.

Doctors sometimes used surgery as well as medicine to treat patients, and opened injured skulls to relieve pressure in the brain. Before an operation the surgeon gave his patient a drink, presumably a painkiller, ‘to render it agreeable’. In the New Kingdom the painkiller might have been opium, imported from Cyprus. Because of the importance the Egyptians attached to ritual purity the surgeon and his assistants washed themselves and purified the instruments in fire before the operation. Both of these would cut down the risk of infection.

The Egyptians were a deeply religious people and prayers would always be used as well as medicines, even for the simplest ailments. In difficult cases, magic might be employed. It was also possible to visit temple of a deity associated with medicine, such as Imhotep, which had priests trained as a doctors. At some temples the sick could spend a night close to the god’s sanctuary. During such stay, called ‘incubation’, the patient might be cured by the deity, or dream of the god and receive instructions for treatment. Even if no help was forth coming, the sufferer was spiritually comforted.
A Course of Treatment by Egyptian Doctors in 1300 BC

History of Paracetamol

Paracetamol is a very widely used as medicine. It is painkiller and reduces the temperature of patients with fever.

These actions are known respectively as analgesic and antipyretic.

In 1893, the white, odorless crystalline compound with a bitter taste that became known as paracetamol was discovered.

This happened at University of Strasburg when Professor Adolf Kussmaul, Department of Internal Medicine , asked two young assistants, Arnold Cahn and Paul Hepp, to treat patients with naphthalene as it had been used elsewhere as an internal antiseptic.

The medicine had little effect on worms, but, paracetamol was found in the urine of patients who had taken phenacetin, who had a great reduction in fever temperature.

In 1887, the Bayer company introduced the 4-ethoxy derivative, phenacetin, as a less toxic analogue of acetanilide.

It was highly successful product and established the Bayer Company as a leading pharmaceutical manufacturer.

Phenacetin was widely used for about 90 years until mounting concerns over carcinogecity and kidney damaging properties.

In 1889 it was demonstrated that paracetamol was a urinary metabolite of acetanilide. These discoveries, however, failed to attract much attention and were largely ignored at the time.

The use of paracetamol was first reported in 1893 by von Mehring who concluded that because of its hematological side effects of methaemoglobinaemia, it could not be recommended despite prompt antipyretic and analgesic actions.

It 1948-1949, Brodie and Axelrod discovered that paracetamol was the main metabolite of both acetanilide and phenacetin, that paracetamol experienced a resurgence of interest. As a derivative of p-aminophenol, paracetamol corresponds to the active principal metabolite phenacetin.

Their investigations showed that both acetanilide and phenacetin were metabolized into paracetamol and to which they owed their antipyretic and analgesic properties.

It was eventually ascertained that phenacetin had its own pharmacological action and was not dependent on paracetamol for its effects.

Because a high proportion of phenacetin is converted into paracetamol in the liver, however, phenacetin required a large dosage to achieve any direct analgesic effect.

In 1950 the first paracetamol product – a combination of paracetamol, aspirin and caffeine – was on the United States market under the name Triagesic.

Due to the report that Triagesic had been stricken with blood diseases, agranulocytoses, a sudden severe drop of white blood cell, it was immediately removed form the market.

Within a few years when became apparent that paracetamol had not connection with blood damage, by 1955 paracetamol was back in the American market.

In 1956, 500 mg tablets of paracetamol went on sale in the United Kingdom and its popularity as an over-the-counter analgesic rapidly increased.

This popularity was partly explained by the fact that paracetamol was proven to be easier on the stomach than some other analgesics.
History of Paracetamol