D2 Aspirin and Penicillin

Question 1

When are two drugs synergetic?

Answer 1

When they increase each other’s effectiveness when taken together

Question 2

What produces a synergistic effect with aspirin?

Answer 2

Alcohol (ethanol)

Question 3

Explain the bioavailability of aspirin.

Answer 3

• Aspirin is a largely non-polar molecule and therefore it has low solubility in water
• This solubility can be increased by reacting it with aqueous NaOH (an alkali such as NaOH or NaHCO3), forming an ionic salt
• This increasis its bioavailability

Drugs which contain an acidic or basic group can be chemically modified to form an ionic salt

Question 4

List the disadvantages of aspirin.

Answer 4

• It can cause bleeding in the stomach lining (effects are more acute when taken with alcohol)
• Can cause Reye’s disease in children under 12 (liver and brain disorder)
• Allergic responses include skin rash, respiratory difficulty and shock
• Exceeding the safe dose is fatal, as it leads to acidosis (lowering of bood pH)

Question 5

What is aspirin used for?

Answer 5

• Analgesic. Used in pain relief
• Anti-inflammatory agent. Relied dorm swelling associated with arthritis and minor injury
• Antipyretic. Reduces fever
• Anticoagulant. It prevents blood from clotting so it prevents the recurrence of strokes and heart attaks.
• It also acts as a prophylactic due to its ability to prevent clotting. (usefull agains HIV)

Question 6

How can we determine the purity of aspirin?

Answer 6

Melting points
* The purity of products is determined using melting points
* Aspitin has a melting point of 138-140º and salicylic acid has a melting point of 159º
* Impurities lower the melting point and cause it to melt over a wider temperature range.

Infrared spectrum

Question 7

How is aspirin produced?

Answer 7

It is an ester derivate of saliculic acid, which is more palatable and less irritable to the body. Aspirin is produced through eterification by reacting salicylic acid with ethanoic anhydride.

1. Concentrated H2SO4 (sulphuric acid) is added to the reaction mixture which is warmed gently
2. The product is cooled to form crystals which are then suction filtered and washed with cold water
3. The aspirin is purified in a process known as recrystallization; this involves dissolving the impure crustals in a small volume of hot ethanol
4. Water is then added and the solution is cooled slowly and then chilled
5. The acetysalicilic acid (aspitin) will recrystallize, and the unreacted salycilic acid remains dissolved in the solution

2. Aspirin has very low solubility in cold water, so this process removes the soluble acids but not the aspirin

Question 8

Explain the solubility of aspirin.

Answer 8

• Aspirin is a lergely non-polar molecule and therefore has low solubility in water
• The solubility of aspirin can be increased by reacting with aqueous NaOH forming and ionic salt

Drugs which contain an acidic or basic group can be chemically modified to form an ionic salt (increasing their bioavailability)

Question 9

How does aspirin work?

Answer 9

Aspirin works by blocking the action of the enzymes that produce prostaglandins. It prevents the prostaglandins from being synthesized, thereby reducing or eliminating the pain.

Prostaglandis are involved in the transmission of pain impulses to the brain, as well as causing fever and swelling.

Question 10

What are mild analgesics? Give examples.

Answer 10

Analgesics are drugs that function as painkillers. Mild analgesics works by blocing the sensation of pain at the source
* Aspirin, paracetamol, ibuprofen…

Question 11

What happens when pain receptors are stimulated and how do mild analgesics work when this happens?

Answer 11

1. Pain receptors in the brain are stimulated byprostglandis. These are released from cells damaged by thermal, mechanical or chemical energy.
2. Thanks to this, the body is able to detect pain.
3. Once released, prostglandites mediate the inflammatory response by causing the dilatation of blood vessels near the site of injury. This causes swelling, increased temporary pain, and a rise in temperature.

Painkillers block the pathway between the source of pain and the receptor in the brain.

Question 12

What are penicillins?

Answer 12

They are a group of antibiotics used to treat a wide range of bacterial infections by inhibiting the growth of the bacteria

Question 13

How is penicillin administered?

General penicillin and penicillin G

Answer 13

• Penicillin can be taken orally or via injection
• Penicillin G is broken down by stomach acids so it has to be directly injected into the blood

Question 14

What are antibiotics?

Answer 14

Chemicals produced from microorganisms that act against other microorganisms

Question 15

How can antibiotic resistance be prevented?

Answer 15

Synthesising different form of penicillin by modifying the side chain (beta-lactam ring must remain)
* Methicillin
* Amoxicillin
* Penicillin G/V

Control and restriction
* Legislation
* Prescription-only drug
* Encourage doctors not to prescribe antibiotics when other treatments are effective

Education of patients in the importance of completing the full course of antibiotic treatment

Question 16

What do resistant bacteria do?

Answer 16

Penicillase or beta-lactamase open penicillin’s four membered ring rendering it inactive.

Question 17

How are mutations of bacteria spread?

Resistant bacteria

Answer 17

Increased by antibiotic use

Question 18

Describe the structure of penicillin

Answer 18

Penicillin is formed from two amino acids (cysteine and valine)

The molecule has a nucleus of a five-membered ring containing a sulphur atom and a four-membered ring containing a cyclic amide group known as beta-lactam

Beta-lactam: raqueta (3C 1N 1O conectado con double bond)

Beta-lactam is the molecule responsible for it’s antibacterial properties

Question 19

Describe the beta-lactam ring and define one of its properties

Angles and bonds

Answer 19

The bond angles in the beta-lactam rings are reduced from 120º (sp2 1C) and 109.5º (sp3 2C 1N) to 90º, putting a strain in the bonds. This weakens the bonds making them easily breakable.

This is the key to the molecule’s biological activity

Question 20

Where do antibiotics come from?

Answer 20

fungi

Question 21

What is the most efficient way to make penicillin more resitant to the penicillinase enzyme?

Answer 21

by modifying the side chain

Question 22

How do beta-lactam antibiotics work?

Answer 22

Beta-lactam antibiotics disrupt the formation of cell walls in bacteria by inhibiting the enzymes responsible for creating cross-links in the cell wall.

1. Beta-lactam comes into contact with bacteria
2. The ring open and binds irreveribly at the active site of the enzyme responsible for catalyzing cross-linking in the cell wall of bacteria
3. Deactivation of the enzyme prevents the bacterial cell wall from forming afain
4. Microorganisms fill up with water, causing them to burst and die

Do not understand step 2

Question 23

What are the expected angles of the beta-lactam ring and what are the actual ones?

Answer 23

The expected angles are 109.5º and 120º and the actual ones are 90º