D2: Aspirin and Penicillin Flashcards
Define analgesics and explain the mode of action of mild analgesics
ANALGESICS: drugs that reduce pain
- Mild analgesics: prevent the production of prostaglandins in the body by inhibiting the enzyme that is responsible for synthesising prostaglandins (cyclooxygenase/COX), hence preventing the production of the chemical messengers that cause the sensations of pain, inflammation and fever
Explain how prostaglandins cause pain, inflammation and fever
PAIN:
- Prostaglandins are synthesised in damaged tissue cells, and bind to receptors, which stimulate the sensory nerve fibres at the injury site to send signals to the brain, which are interpreted as pain
INFLAMMATION:
- Prostaglandins cause dilation of the blood vessels at the injury site, which causes swelling, redness and heat (inflammation)
FEVER:
- Prostaglandins stimulate the hypothalamus to increase body temperature
Explain what aspirin is made up of
Aspirin (acetylsalicylic acid) is the ester of salicylic acid (active ingredient isolated from willow tree bark)
- Pure salicylic acid is a good analgesic, but causes severe irritation to the stomach lining, which causes vomiting and gastric bleeding
- Acetylsalicylic acid is less irritating to the stomach
State the therapeutic effects of aspirin
ASPIRIN:
1) Analgesic
2) Non-steroidal anti-inflammatory drug (NSAID)
3) Antipyretic
4) Anticoagulant (in low doses) that can act as a prophylactic (to prevent strokes, heart attacks and certain cancers)
State the possible side effects of aspirin
1) Gastric irritation:
- Prostaglandins protect the mucous layer of the stomach
- Hence, inhibiting the synthesis of prostaglandins can deplete the protective mucous layer of the stomach
- This can cause peptic ulcers and stomach bleeding
2) Hypersensitivity
- Aspirin can trigger asthma attacks in asthma patients
3) Reye’s syndrome
- Aspirin can lead to Reye’s syndrome and cause damage to the brain and liver in children under 16
4) Acidosis
- Aspirin can lower blood pH due to presence of carboxyl group
5) Synergistic effect of ethanol with aspirin
- Synergism: when 2 or more drugs taken together causes a greater effect on the body than the sum of their individual effects
- Taking aspirin with alcohol increases chances of stomach hemorrhaging
Explain how aspirin is synthesised
Ethanoic anhydride + Salicylic acid –> Aspirin + Ethanoic acid
Ethanoic anhyride + Water –> 2 Ethanoic acid (1 to aspirin)
ADDITION-ELIMINATION REACTION:
- CH₃CO group is added to aspirin (from ethanoic anhydride)
- Ethanoic acid is eliminated
OBTAINING CRUDE PRODUCT:
1) Add water to reaction mixture to breakdown unreacted ethanoic anhydride to ethanoic acid and obtain white precipitate of aspirin (aspirin has low solubility in water)
2) Filter off white precipitate and wash with cold water (to remove any soluble impurities)
3) Leave to dry
4) Calculate percentage yield*
Explain how to purify aspirin
CRUDE SAMPLE:
- Contains impurities (unreacted salicylic acid and water if not completely dried) which can be purified through crystallisation
RECRYSTALLISATION:
- When a solvent dissolves a solid that is soluble in high temperatures but less soluble in lower temperatures
- Lower concentrations of impurities will not exceed their solubility and will remain soluble/in solution even at lower temperatures
RECRYSTALLISATION OF ASPIRIN:
1) Dissolve crude product in minimum amount of hot solvent to form a close-to-saturated solution (containing dissolved aspirin and impurities)
2) Filter off insoluble impurities before mixture cools
3) Cool mixture using ice, causing the product to become less soluble and emerge from solution as solid crystals
4) Filter off impurities, which are present in smaller concentrations that do not exceed their solubility in lower temperatures and remain in solution
Understand how to characterise aspirin
PURITY:
1) Chromatography
2) Test melting point
- Pure aspirin will melt at a higher well-defined temperature, whereas impurities will lower the M.P and cause it to melt over a range of temperatures
IDENTITY:
1) IR spectroscopy
- IR spectra of aspirin: Very broad O-H peak (characteristic of carboxylic acids) + 2 C=O peaks (1 for C=O in ester group, 1 for C=O in carboxyl group)
- vs. IR spectra of salicylic acid: only 1 C=O peak (characteristic of carboxyl group; no ester)
Explain how to increase the solubility of aspirin and other drugs
- Oral administration: drug has to be dissolved in the aqueous environment of the intestines before being absorbed across the lipid membranes of the intestinal walls –> low solubility will cause slow absorption and reduced bioavailability
INCREASING SOLUBILITY OF ACIDIC DRUGS (Eg. Aspirin: contains carboxyl group)
- Create ionic (usually sodium) salt that is more soluble in water than a covalent compound (pure aspirin):
Aspirin + NaOH –> Aspirin sodium (with COO⁻ - Na⁺) + Water
INCREASING SOLUBILITY OF BASIC DRUGS:
- React with strong acid (HCl) to form the cation
Define an antibiotic
ANTIBIOTIC:
Antibacterial drugs that are toxic to bacterial cells but not human cells, as they act on sites in bacterial cells that are different/do not exist in human cells
(Eg. Penicillins)
State the structure of penicillins
PENICILLINS:
- Bicyclic structure
- Contains a β-lactam ring
- Different side-chains (R-group) in different penicillins
Explain the mechanism of penicillins on a bacterial cell wall
BACTERIAL CELL WALL:
- Contains a polymer made up of sugar chains crossed-chained with peptides
PENICILLIN:
- Irreversibly inhibits transpeptidase and deactivates it (the enzyme involved in cross-linking the polymer in the bacterial cell wall), weakening the wall and causing the cell to burst due to high osmotic pressures created by water from the surroundings entering the cell
- OH group on the side-chain of the enzyme active site reacts with the β-lactam ring instead of its usual substrate, forming a covalent bond and complex between the enzyme and penicillin, preventing any substrate molecules from entering the active site and reacting
Explain why modifying the side-chains in penicillins is important
1) Modified side-chain in Penicillin-G
- Penicillin-G: easily hydrolyzed in stomach acid and could only be administered intravenously
- Penicillin-G after side-chain modification: could resist stomach acidity and be administered orally
2) To combat bacterial resistance
- Bacterial resistance: development of bacteria that have become resistant to their antibacterial properties due to mutations in bacterial DNA that aid in their survival (Eg. By producing penicillinase that opens up the β-lactam ring and renders it inactive)
- Modified side-chains allow them to become more resistant to penicillinase
State the causes for bacterial resistance
1) Lack of patient compliance in completing full courses of antibiotics
- Failure to kill all the bacteria in injection can lead to the development of resistance in surviving bacteria
2) Overuse/misuse in humans
- Bacteria become increasingly exposed to antibacterial agents, increasing the number of resistant bacteria
3) Use to prevent occurrence of infection in healthy animal livestock
- Development of resistant bacteria that can be passed on to humans through meat and dairy products
