1. Aspirin and penicillin

2. Aspirin
The sensation of pain – our ability to perceive pain is one of our best defense mechanisms.
Pain allows us to act in a way that reduces further damage to our bodies. For example, removing the hand from a hot plate or not being able to continue running after pulling a muscle.

3. Aspirin Pain can be acute or chronic.
Pain is unpleasant, irritating, debilitating, and can become unbearable.
Painkillers can be taken to reduce pain. Painkillers belong to group of drugs called analgesics.
Painkillers treat the symptoms (pain), not the underlying cause.

4. Aspirin
Pain is detected as a sensation by the brain when nerve messages are sent from various pain receptors located around the body.
These receptors are stimulated by chemicals known as prostaglandins .
Prostaglandins are substances made at the sites of tissue damage or infection and are involved in the healing process.
Prostaglandins control processes such as inflammation, blood flow, the formation of blood clots, and the induction of labour.

5. Aspirin
Once released, prostaglandins produce the inflammatory response.
The inflammatory response is the body's natural response that occurs immediately following tissue damage. It's main functions are to defend the body against harmful substances, dispose of dead or dying tissue and to promote the renewal of normal tissue.
The inflammatory response leads to swelling, pain and increased temperature (fever).

6. Aspirin
Aspirin and non-steroidal anti-inflammatory drugs (Nsaid) such as ibuprofen are mild analgesics.
They act by inhibiting the production of prostaglandins from the site of injury, which lowers the inflammation, the fever and the pain.
Because the analgesics do not interfere with the functioning of the brain, they are non-narcotics.

7. Aspirin
Mechanism of action of the drug aspirin. Aspirin works by preventing the production of prostaglandin: aspirin molecules (blue hexagons) enter the cell and chemically modify the cyclooxygenase enzyme (purple) to prevent prostaglandin synthesis

8. Aspirin
Since about 400 b.c. it was known that chewing willow bark reduced pain and fever.
In the early 1800's, it was shown that the active ingredient in the bark is salicin, which is converted to salicylic acid in the body.
Although salicylic acid was effective for treating pain, it tasted awful and caused vomiting.
Salicylic acid (2-hydroxybenzoic acid)

9. Aspirin
In 1890, the Bayer company in Germany made an ester derivative of salicylic acid which was more palatable and less irritable to the body; it was called aspirin.
Today, aspirin continues to be the most widely used drug in the world.
Aspirin is effective in reducing fever (antipyretic) and in providing pain relief.

10. Aspirin
To produce aspirin, salicylic acid (2-hydroxybenzoic acid) is converted into aspirin through an esterification process, in which the –OH group of the salicylic acid is converted into the ester group.
The process is carried out with ethanoic anhydride and concentrated sulfuric acid or phosphoric acid as a catalyst. Additionally, the mixture is warmed gently.
The aspirin product must then be isolated and purified from the mixture.

11. Aspirin
After the reaction is complete, the product is cooled to cause crystals to form.
Then, the product is suction filtered and washed with chilled water. Since the aspirin has a very low solubility in water at low temperature, this process allows the soluble acids to be removed without removing the aspirin product.
The product is then purified. The purification involves a technique known as recrystallization.
Recrystallization involves dissolving the impure crystals in hot ethanol, which dissolves the impure crystals. this forms a saturated solution of aspirin.
This solution is then cooled slowly. This decreases the solubility of the aspirin, so the aspirin crystallizes out of the solution and can be separated by filtration.

12. Aspirin The purity can be confirmed by melting point determination.
Pure substances have well-defined melting points, which are altered by the presence of impurities. Pure aspirin has a melting point of 138o c - 140o c, and salicylic acid has a melting point of 159o c. A mixture would have a lower melting point.
The yield of the reaction can be calculated from the mass of the salicylic acid used and the mass of the product obtained.

13. As we learned in topic 11, Infrared spectroscopy can be used to identify the presence of certain functional groups in a molecule.
Similarities:
Differences:

14. Aspirin
As mentioned before, aspirin works by blocking the synthesis of prostaglandins. This explains the analgesic effects of aspirin, as well as its effectiveness in reducing fever and inflammation.
Aspirin can also have side effects. The side effects can be positive and negative.
Aspirin is an anticoagulant- this means that it reduces the ability of the blood to clot. This makes it useful in the treatment of patients at risk for heart attacks and strokes. This side effect is also potentially dangerous if it is taken by a person whose blood doesn’t clot easily.
Negative side effects of aspirin include irritation and even ulceration of the stomach and the duodenum, which can lead to bleeding. Additionally, aspirin is not recommended for children under 12 because it has been linked to Reye’s syndrome, a potentially fatal liver and brain disorder.
The effects of aspirin are more acute when it is taken with ethanol in alcoholic drinks. The synergistic effects of ethanol and aspirin can caused increased bleeding of the stomach lining and increased risk of ulcers.

15. Aspirin
Aspirin can be modified for better absorption and better distribution (increased bioavailability)
Aspirin is taken orally and transported in the plasma of the blood in aqueous solution, however, it has a low solubility in water since it a largely non-polar molecule.
In order to increase its bioavailability, its solubility in water needs to increase. This can be accomplished through chemical modification. This involves reacting the aspirin with an alkali such as NaOH or NaHCo3, so that it forms an ionic salt.

16. Penicillin
Penicillin is an antibiotic, which is a medicine that inhibits the growth of or destroys microorganisms.
Penicillin revolutionized modern medicine.
Penicillin was Discovered by Alexander Fleming in 1928 while working on bacterial cultures. Fleming published his findings, but did not isolate or identify the active ingredient.

17. Penicillin
In the early 1940's, Howard Florey and Ernst chain isolated penicillin as the antibacterial agent produced by the penicillium mold.
In 1941, penicillin was used in human trials. Penicillin saved the lives of many soldiers in world war II.
In 1945, Dorothy Hodgkin determined the structure of penicillin G, the major constituent of the penicillium mold.

18. Penicillin
The penicillin molecule contains a five membered ring, containing a sulfur atom, attached to a four membered ring containing a cyclic amide group, known as a beta–lactam.
The beta-lactam ring contains one nitrogen atom and three carbon atoms. This is the part of the molecule responsible for its antibacterial properties.

19. Penicillin
The beta-lactam antibiotics work by disrupting the formation of the cell walls of bacteria by inhibiting a key bacterial enzyme called transpeptidase.
AS the drug approaches the enzyme, the high reactivity of the amide group in the ring causes it to bind to and deactivate the transpeptidase enzyme.
When the transpeptidase enzyme is deactivated, the bacteria is unable to construct a cell wall and it dies.

21. penicillin
Inactivation of the enzyme blocks the process of cell wall construction in the bacterium by preventing the formation of polypeptide cross-links.
Without the cross-links, the cell wall is unable to support the bacterium, so it bursts and dies.

23. Penicillin
A disadvantage of penicillin G is that it is broken down by stomach acid, so it has to be injected into the blood.
Different forms of penicillin have been developed by modifying the side chain (the R group) and this enables the drug to retain its activity when ingested in pill form.
The use of penicillin is also limited by the significant number of people who suffer from allergic responses to it.

24. Bacterial resistance to Penicillin
Bacterial resistance to penicillin and other antibiotics has become a major problem in modern medicine.
As early as the 1940s penicillin proved to be ineffective against some populations of bacteria.
These resistant bacteria produce an enzyme known as penicillinase or beta- lactamase, which can open penicillin's four-membered ring and render it inactive.
As non-resistant strains of bacteria have been wiped out by antibiotics, the population of the resistant bacteria have been able increase because they have less competition.

25. Responses to the challenge of antibiotics resistance
1. Produce different forms of penicillin that can withstand the action of penicillinase. Two penicillin derivatives that still contain the beta-lactam ring are oxacillin and methicillin. They have modified side chains (r group) that prevents the penicillinase enzyme from binding.
2. Better control and restrictions for the use of antibiotics.
3. Encourage Doctors to avoid over prescription of antibiotics when other treatments are effective.
4. Educate patients in the importance of completing the full course of antibiotics.