option D- medicinal chemistry (D.2) Flashcards
what is aspirin?
a mild analgesic
how do mild analgesics function?
by intercepting the pain stimulus at the source, often by interfering with the production of substances that cause pain, swelling or fever/
describe why salicylic acid (2-hydrobenzoic acid) cannot be used in its pure form
it causes severe digestive problems such as stomach irritation, bleeding and diarrhoea
how was salicylic acid first isolated?
it was taken from the bark of willow tree
how can the side effects of salicylic acid be minimised?
by using the chemically modified salicylic acid, known as acetylsalicylic acid or aspirin
how is aspirin prepared from salicylic acid?
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.
what are mild analgesics also known as ?
non-narcotic analgesics
non-steroidal anti-inflammatory drugs (NSAIDs)
how are mild analgesics different to strong analgesics?
mild analgesics affect the nervous system by intercepting the pain stimulus at the source.
describe the two main effects that aspirin has on the body
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
describe the main side effect of aspirin
the anticlotting action of aspirin can lead to excessive bleeding and ulceration of the stomach.
what is the synergetic side effect of aspirin?
the fact that stomach bleeding significantly increases when aspirin is taken with alcohol or other anticoagulants. This is an example of a drug interaction
why is aspirin’s bioavailability limited?
because it is almost insoluble in water.
describe how soluble aspirin can be made
- 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
why is the bioavailability of soluble aspirin only slightly higher than that of plain aspirin?
the sodium salt is immediately converted back into aspirin by the reaction with hydrochloric acid in the stomach
what are penicillins?
antibiotics produced by fungi
what is a core structure of penicillins?
the four-membered beta-lactam ring (refer to textbook) which is responsible for the antibacterial properties of the drugs
what makes the amide group in beta lactam rings so reactive?
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
how does a penicillin antibiotic work (chemically)?
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.
what are some of the disadvantages of natural medicines?
- 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 .
what is a prophylactic medicine?
a medication or a treatment designed and used to prevent a disease from occurring.
why did antibiotic resistance arise?
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
how does penicillinase work?
this enzyme is able to deactivate benzylpenicillin and prevent it from binding to transpeptidase.
how was bacterial resistance fought?
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
Why did scientists have to create a new class of antibacterial drugs and what did this cause?
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.
what does the treatment of infectious diseases caused by MDR bacteria require?
the use of a cocktail of different antibiotics and strict patient compliance to medical procedures.
