option D- medicinal chemistry (D.2)

Question 1

what is aspirin?

Answer 1

a mild analgesic

Question 2

how do mild analgesics function?

Answer 2

by intercepting the pain stimulus at the source, often by interfering with the production of substances that cause pain, swelling or fever/

Question 3

describe why salicylic acid (2-hydrobenzoic acid) cannot be used in its pure form

Answer 3

it causes severe digestive problems such as stomach irritation, bleeding and diarrhoea

Question 4

how was salicylic acid first isolated?

Answer 4

it was taken from the bark of willow tree

Question 4

how can the side effects of salicylic acid be minimised?

Answer 4

by using the chemically modified salicylic acid, known as acetylsalicylic acid or aspirin

Question 5

how is aspirin prepared from salicylic acid?

Answer 5

via a condensation reaction

salicylic acid + ethanoic anhydride -> aspirin + ethanoic acid

SA is mixed with excess ethanoic anhydride and several drops of catalyst (conc phosphoric acid). the mixture is heated for a short time, diluted with water and allowed to cool down slowly, producing crystals of aspirin. The obtained product is usually impure so needs to be recrystallised from hot ethanol.

The identity of the product can be confirmed by IR spectroscopy and determining its melting point.

Question 6

what are mild analgesics also known as ?

Answer 6

non-narcotic analgesics

non-steroidal anti-inflammatory drugs (NSAIDs)

Question 6

how are mild analgesics different to strong analgesics?

Answer 6

mild analgesics affect the nervous system by intercepting the pain stimulus at the source.

Question 7

describe the two main effects that aspirin has on the body

Answer 7

aspirin irreversibly binds to the enzyme cyclooxygenase and suppresses the production of prostaglandins, which are responsible for fever, swelling and the transmission of pain impulses from the site of injury to the brain

prostaglandins are also involved in the production of thromboxjnes, which stimulate the aggregation of platelets (thrombocytes) and blood clotting. So aspirin acts as n anticoagulant, reducing the risk of strokes and heart attacks

Question 8

describe the main side effect of aspirin

Answer 8

the anticlotting action of aspirin can lead to excessive bleeding and ulceration of the stomach.

Question 9

what is the synergetic side effect of aspirin?

Answer 9

the fact that stomach bleeding significantly increases when aspirin is taken with alcohol or other anticoagulants. This is an example of a drug interaction

Question 9

why is aspirin’s bioavailability limited?

Answer 9

because it is almost insoluble in water.

Question 10

describe how soluble aspirin can be made

Answer 10

• the carboxyl group can be neutralised with sodium hydroxide, producing the water-soluble sodium salt of the acid
• in aqueous solution this dissociates into sodium cations and acetylsalicylate ions, which form multiple ion-dipole interactions and hydrogen bonds with water

Question 11

why is the bioavailability of soluble aspirin only slightly higher than that of plain aspirin?

Answer 11

the sodium salt is immediately converted back into aspirin by the reaction with hydrochloric acid in the stomach

Question 12

what are penicillins?

Answer 12

antibiotics produced by fungi

Question 13

what is a core structure of penicillins?

Answer 13

the four-membered beta-lactam ring (refer to textbook) which is responsible for the antibacterial properties of the drugs

Question 14

what makes the amide group in beta lactam rings so reactive?

Answer 14

the bond angles of the carbon and nitrogen atoms in this ring are ~90’- such bond angles create significant ring strain, making the group very reactive

Question 15

how does a penicillin antibiotic work (chemically)?

Answer 15

once in bacteria the beta-lactam ring opens and irreversibly binds to the enzyme transpeptidase, which is responsible for cross-linking of bacterial cell walls. This weakens the cell walls in multiplying bacteria and makes them more permeable to water. the osmotic pressure causes water to enter the bacteria til they burst open and die.

Question 16

what are some of the disadvantages of natural medicines?

Answer 16

• low efficiency
• variable composition
• instability
• side effects caused by the presence of many bioinactive substances in the same material

this means scientists have to work to identify, isolate and modify the relevant chemical properties of natural compounds .

Question 16

what is a prophylactic medicine?

Answer 16

a medication or a treatment designed and used to prevent a disease from occurring.

Question 16

why did antibiotic resistance arise?

Answer 16

penicillin was routinely described across the world for treating minor illnesses or even as a prophylactic medicine. As a result, certain Bacteria mutated and developed varying degrees of antibiotic resistance due to increased production of the enzyme penicillinase. Over time bacteria w high levels of penicillinase became dominant

Question 17

how does penicillinase work?

Answer 17

this enzyme is able to deactivate benzylpenicillin and prevent it from binding to transpeptidase.

Question 18

how was bacterial resistance fought?

Answer 18

new penicillins with modified side chains were developed.

• These penicillins could not be deactivated by penicillinase and were effective against a wider range of bacteria.
• Some modified penicillins were stable in the acidic environment of the stomach and thus could be administered orally

Question 19

Why did scientists have to create a new class of antibacterial drugs and what did this cause?

Answer 19

new strands of constantly mutating bacteria became resistant to most strands of penicillins.

This led to the development of multi drug resistance (MDR) in bacteria.

Question 20

what does the treatment of infectious diseases caused by MDR bacteria require?

Answer 20

the use of a cocktail of different antibiotics and strict patient compliance to medical procedures.