D2

Question 1

Pain

Answer 1

Pain signals indicate that our body has sustained or is under threat of damage, causing us to give attention to site of pain and cease an action or behaviour that results in pain

Question 2

Analgesics

Answer 2

A compound that reduces or prevents pain - usually do not cause numbness or alter consciousness and they do not cure disease
Can be classified as mild or strong depending on where the pain signal is blocked

Question 3

Pain response

Answer 3

Pain threshold controlled by specific nerve receptors (nociceptors)
These are sensitive to the release of prostaglandins (responsible for the transmission of pain impulses from the source of pain to the brain)
Prostaglandins released from the damaged cells and they mediate the inflammatory repsonse

Question 4

Mild analgesics

Answer 4

Control pain levels by intercepting the pain impulse before it reaches the brain via interaction with the enzyme cyclooxygenase
Classified as non-narcotics as they do not interact with the brain
Include aspirin, ibuprofen, paracetamol

Question 5

Strong analgesics

Answer 5

Work by blocking receptors in the brain and central nervous system so they cannot receive pain impulses

Question 6

Aspirin history

Answer 6

400BCE - chewing willow bark = remedy for treatment of pain and fever
1800s - proven this remedy was effective due to active ingredient salicin which was converted to salicylic acid inside body
1897 - Felix Hoffmann developed modification by replacing the hydroxyl group with an ester, forming acetylsalicylic acid (aspirin)

Question 7

Aspirin synthesis

Answer 7

Ethanoic anhydride produced by reacting 2 ethanoic acid molecules together
One of the CH3COO groups reacts, acting as carboxylic acid and reacts with alkanol of the salicylic acid to produce acetylsalicylic acid
Unreacted ethanoic anhydride converted to ethanoic acid by addition of water
Products need to be isolated and purified before packaged into tablets

Question 8

Aspirin synthesis - diagram

Answer 8

Question 9

Infrared spectra of salicylic acid and aspirin

Answer 9

a) is salicylic acid
b) is aspirin
Main differences:
Second peak from 1700-1750 due to presence of ester in aspirin
Peak from 3200-3600 in salicylic acid due to OH group

Question 10

Hydrolysis of aspirin in small intestine

Answer 10

Acetylsalicylic acid relatively tasteless and easier on stomach
Once it passes into small intestine’s alkaline conditions, reacts with water and converts into salicylic acid

Question 11

Alterations of aspirin for increased bioavailability and reduced side effects

Answer 11

Coatings and different buffering compounds often included in tablets that delay activity until it reaches small intestine
Solubility of aspirin is limited in aqueous solutions which limits the amount that can be effectively transported in blood plasma
Alteration of carboxylic acid functionality to an ionic salt can increase aqueous solubility

Question 12

Paracetamol (acetaminophen)

Answer 12

Hepatotoxic (toxic to liver)
Primary breakdown of paracetamol in liver
Contains an amide functional
Not considered an NSAID - different mode of action
More likely to be prescribed to pregnant women and children for mild pain - delivered as liquid + tablets and has fewer side effects

Question 13

Ibruprofen

Answer 13

NSAID that operates by inhibiting the formation of prostaglandins by inhibition of the cyclooxygenase enzyme and the arachidonic acid pathway
Low water solubility so often administered as a lysine salt

Question 14

Advantages and disadvantages of aspirin

Answer 14

Ad: shows antipyretic action as well as anti-inflammatory effects, useful in preventing the recurrence of heart attacks because it thins the blood
Dis: Can cause ulceration and stomach bleeding, allergic reaction, Reye’s syndrome (potentially fatal liver and brain disorder in children)

Question 15

Advantages and disadvantages of paracetamol

Answer 15

Ad: shows antipyretic action, very safe in correct dose for adults, children, pregnant women
Dis: Not much anti-inflammatory action, can cause blood disorders and kidney damage (rare), overdose may cause serious liver damage, brain damage, death

Question 16

Prophylactic effects of aspirin

Answer 16

prophylactic - treatment that is taken to prevent disease rather than treat it
When taken with alcohol, there is a synergistic effect which causes aspirin side effects to be increased
Blood thinning and anti-coagulant properties are prescribed for patients at risk of blood clot following surgery or as a prophylactic effect against heart disease or stroke

Question 17

Antibacterials

Answer 17

Drugs that kill or inhibit growth of bacteria - Synthetic compounds that destroy bacteria/microorganisms
Earlier synthetic compounds like prontosil

Question 18

Antibiotics

Answer 18

Compounds that act to kill bacteria/microorganisms that are derived from other microorganisms
e.g. penicillins - group of compounds that are produced by microorganisms (mould) and kill harmful microorganisms

Question 19

Infectious diseases caused by bacteria

Answer 19

Tuberculosis, syphilis, cholera, salmonella, bronchitis, anthrax, meningitis, gonorrhoea, chlamydia

Question 20

Penicillin

Answer 20

Alexander Flemming - discovered penicillin while investigating bacterium in 1929
Howard Florey and Ernst Chain were able to isolate the active compound (penicillin G) from mould and demonstrate its effectiveness as an antibacterial agent - were able to grow large amounts in corn-steep liquor
Wasn’t until 1950s that structure of penicillin was discovered and chemists were able to start synthesising it

Question 21

Penicillin structure

Answer 21

Structure of penicillin G resolved by Dorothy Hodgkin using X-ray crystallography
Main structure considered a dipeptide that has a beta-lactam ring

Question 22

Penicillin activity

Answer 22

Part of a class of compounds known as beta-lactams
Kill bacteria by interfering with cell wall production during replication
Susceptible to enzymes produced by some bacteria known as B-Lactamase
When cell wall fails to form properly it causes water to enter the bacterium via osmosis until eventually the bacterial cell undergoes lysis

Question 23

Penicillin mode of action

Answer 23

Kills bacteria by inhibiting cell wall production
Water enters and bacteria explodes
Changing side chain on penicillin gives it different properties

Question 24

Importance of the B-lactam ring in penicillin

Answer 24

Bond angles forced smaller into 90 degrees (standard is 109 and 120)
Strain makes nitrogen in ring highly reactive
Amine group reacts irreversibly with the transpeptidase enzymes present in the bacterial wall
These enzymes are critical to cell wall stabilisation and formation in bacteria
Without active enzyme, cell wall bursts and bacteria survives

Question 25

Semi-synthetic penicillins

Answer 25

e.g. ampicillin - penicillin molecules that have been midified by replacing the side-chain with other atoms or groups of atoms
Reduce occurrence of penicillin resistant bacteria as they are able to withstand action of enzyme penicillinase, resistance to breakdown or deactivation by stomach acid - take orally, when administered in combination with clavulanic acid penicillins exhibit greater resistance to enzyme degradation

Question 26

Antibiotic resistance

Answer 26

1. Few bacteria are drug resistant
2. Antibiotics kill bacteria causing illness as well as good bacteria protecting body from infection
3. Drug-resistant bacteria now allowed to grow and take over
4. Some bacteria give their drug-resistance to other bacteria
   Antibiotic resistance declared by WHO as one of the most pressing global threats to human health

Question 27

Issues relating to resistance

Answer 27

Patient compliance: patients don’t complete full course of antibiotcs, results in prolonging disease as not all bacteria killed, allowing bacteria to survive causes more mutations
Overprescription: allergic reactions by patients, wiping out harmless bacteria in alimentary canal, destroyed bacteria may be replaced by more harmful bacteria
Antibacterials in animal feedstock: antibiotics end up in food chain - can be administered to animals who don’t have disease