D.3 Analgesics

D.3.1 Describe and explain the different ways that analgesics prevent pain.
Mild analgesics e.g. aspirin, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen
- prevents stimulation of nerve endings at the site of pain
- inhibits prostaglandin release from the site of injury (gives inflammation, fever and pain relief)
- analgesics do not interfere with brain function, therefore are called non-narcotics
** Paracetamol - inhibits prostaglandin release in brain than site of injury

Strong analgesics e.g. morphine related opioids
- binds to opioid receptors in the brain. It blocks pain signals transmitting between brain cells, so it alters perception of pain.
- can cause drowsiness or possible changes in mood/behaviour
called narcotics
- most effective painkillers
** has side effects and potential problems with dependence (usage must be medically supervised)

D.3.2 Describe the use of derivatives of salicylic acid as mild analgesics, and compare the advantages and disadvantages of using aspirin and paracetamol (acetaminophen)
Salicylic acid - tastes bad, patient vomits
Aspirin - ester derivative of salicylic acid
- less irritation to stomach, more palatable - still effective as an analgesic
- treatment of headache, toothache and sore throat
- can help reduce fever (an antipyretic) and inflammation
- used to provide relief from rheumatic pain and arthritis
- blocks synthesis of prostaglandins
- reduces blood clotting possibilities (useful in treatment of patients at risk from heart attack or strokes)
**but therefore it's also unsuitable (potentially dangerous) for people whose blood does not clot easily or after a surgery where blood clotting is necessary
- reduce risk of colon cancer (but additional data is needed)
- irritation/ulceration (possible bleeding) of stomach/duodenum
if taken with alcohol, it increases the risk of the above
- asthmatic people are also allergic to aspirin
**not for children under 12 - has been linked to Reye's syndrome, a rare and fatal liver/brain disorder
- available in various coatings/ buffering components - can delay activity until it is in the small intestine to alleviate some side-effects

Paracetamol (acetaminophen)

- reduces prostaglandin production in the brain, but not the rest of the body (so not effective in reducing inflammation)

- one of the safest analgesics if taken correctly

- does not usually irritate the stomach

- allergic reactions are rare

- overdose/ chronic use can cause severe, possibly fatal kidney/liver/brain damage

- with ethanol, toxic effect may increase

Conclusion:

D.3.3 Compare the structures of morphine, codeine and diamorphine (heroin, a semi-synthetic opiate)
Strong analgesics (narcotics)
- related to opium: codeine, morphine, heroin (increasing effects)
- acts on CNS to block pain perception
- can cause:
constipation
suppression of cough reflex
constriction of eye pupil
narcotic effects

Codeine

- 0.5% in raw opium

- used in prepation with non-narcotic drugs e.g. aspirin and paracetamol in second stage of pain management step ladder (WHO analgesics ladder above)

- used in cough medications and short-term treatment of diarrhea 

Morphine

- 10% in raw opium 

- used in management of severe pain, such as in advanced cancer

- can be habit forming and can lead to dependence, therefore use must be medically and professionally regulated

Heroin

- in opium, but usually obtained by esterification of morphine, so called 'semi-synthetic' drug

- medically used only in Britain and Belgium legally for relief of severe pain

- most rapidly acting and most abused narcotic

- produces euphoric effects, but additional use has a high chance of causing addiction and increased tolerance

- dependence can lead to withdrawal symptoms/ other associated problems

D.3.4 Discuss the advantages and disadvantages of using morphine and its derivatives as strong analgesics.
Narcotic effects
Ad:
- feeling of well-being and contentment
- dulls pain and lessens fear/tension
- euphoric feeling

Disad:
- regular use: constipation, reduced libido, loss of appetite and poor nutrition
- dependence occurs relatively quickly, therefore suffers withdrawal symptoms e.g. cold sweat, anxiety when withheld
- increasing tolerance, need higher doses for desired effect
- injections, may obtain HIV/hepatitis 

Alternative: Methadone
- taken orally and has longer duration
- can reduce drug craving and prevent symptoms of withdrawal

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They have a common basic structure, therefore similar properties, but has some different functional groups.

For heroin:
- Morphine's -OH esterifies into ethanoate in reaction with ethanoic acid (CH3COOH)
- loss of -OH makes the drug less polar, therefore more lipid soluble and can cross blood-brain barrier quicker (hence it's a faster acting drug)
- once in the brain the heroin hydrolyzes back into morphine by reversed esterification reaction

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