D3: Opiates

Question 1

Define an opiate

Answer 1

OPIATE: natural narcotic (sleep-inducing) strong analgesic drugs derived from opium (juice of the opium poppy)
- Opium: contains 25 different alkaloids (nitrogen-containing compounds), including morphine (primarily responsible for the biological effects of opium) and codeine (milder analgesic existing in smaller proportions)

Question 2

Explain the mode of action of strong analgesics (vs. mild analgesics)

Answer 2

STRONG ANALGESICS: temporarily bind directly to the opioid receptor sites in the brain, preventing the transmission of pain impulses and increasing increasing the pain threshold without depressing the nervous system, even though pain is still occurring in the affected area and is still being transmitted via the peripheral nervous system

Question 3

Explain the therapeutic effects, short-term side effects and long-term side effects of opiate use

Answer 3

THERAPEUTIC EFFECT:
- Analgesia
- Sedation
- Short-term control of diarrhoea
- Suppression of the cough reflex

SHORT-TERM SIDE EFFECTS:
- Nausea/vomiting
- Constipation
- Respiratory depression
- Drowsiness
- Euphoria (addictive property)

LONG-TERM SIDE EFFECTS:
- Chronic constipation
- Decrease in sex drive
- Psychological dependence: user craves drug after being deprived of it for a short time and must get further supplies to satisfy their need
- Physical dependence: user’s body cannot function without the drug, and deprivation results in withdrawal symptoms (anxiety, cold sweats, vomiting, leg jerking)
[Treated by gradually decreasing the dose of the drug and administering methadone, which also binds to the opioid receptor sites but has a prolonged action that reduces cravings and prevents withdrawal symptoms]
- Tolerance: user requires higher doses to achieve the same effect (both therapeutic and addictive)

Question 4

Compare and contrast the structures of morphine, codeine and diamorphine

Answer 4

COMPARE:
- Morphine, codeine and diamorphine all contain a tertiary amine group and a phenyl functional group

CONTRAST:
- Codeine contains 1 methoxyl group (ether) instead of a second hydroxyl group (OH) , whereas morphine has 2 hydroxyl/phenol (OH attached directly to a benzene ring) groups
[The blood-brain barrier allows small lipid-soluble molecules across while hindering large polar molecules. While codeine passes through the blood-brain barrier more easily due to the replacement of the polar OH group with the less polar ether group, it is less potent than morphine, as the steric interference of the methyl group means that codeine has to be acted on by enzymes in the body to be converted into morphine)

• Diamorphine contains 2 ester groups, whereas morphine contains 2 hydroxyl groups
  [Diamorphine is more potent than morphine, as the replacement of the polar OH groups with the less polar ester groups allows it to pass through the blood-brain barrier more easily. It is also metabolised into morphine by enzymes in the body more easily than codeine.]

Question 5

State how diamorphine (morphine derivative) is synthesised

Answer 5

Morphine + 2 Ethanoic anhydride –> Diamorphine + 2 Ethanoic acid

[Addition-elimination/Esterification/Condensation]

Question 6

State how codeine is synthesised

Answer 6

Morphine + Iodomethane + Potassium Hydroxide (strong base) –> Codeine + Potassium Iodide + Water

Nucleophilic substitution:
- Slightly acidic phenol group reacts with the base to produce O⁻
- O⁻ attacks the δ⁺ C atom of CH₃I