Lecture 9 - Opioids 1

Question 1

What are opioids?

Answer 1

• Narcotic analgesics, i.e. drugs that produce analgesia (reduction of pain) without anaesthesia (loss of all sensation), but promote a sense of relaxation and sleep and at overdoses lead to coma and death
• 1) opiates, i.e. opium – an extract of the opium poppy plant – and substances directly derived from opium
• 2) related semisynthetic and synthetic compounds
• 3) endogenous peptides acting on the same receptors, the opioid receptors

Question 2

What are some of the physiological and psychological effects of opioids?

Answer 2

• Analgesia, respiratory depression, cough suppression, euphoria, relaxation and sleep, tranquilization, decreased blood pressure, constipation, pupil construction, hypothermia, drying of secretions, reduced sex drive, flushed and warm skin (more in notes)
• Strong effects on CNS and rest of body
• Important medical applications e.g. painkillers, cough suppression
• Abuse potential because of the euphoria
• Withdrawal signs = oppose acute effects of drug (due to neuropharmacological adaptations)

Question 3

Describe the molecular structure of opiates and related compounds and their relationship to physiological effects

Answer 3

• CH3O (codeine) = less analgesic, but also less side effects and less addictive (still very potent cough suppression)
• CH3COO (heroin) = added acetyl-groups: more lipophil, crosses blood-brain barrier more quickly, strong high (euphoria), in brain, heroin is converted to morphine
• Naloxone = opioid receptor antagonist

Question 4

How are opioids used and misused?

Answer 4

• Long history of medical use (against pain, coughing, diarrhoea) and recreational use (for euphoria and relaxation)
• Victorian times = opioid use completely unregulated, BAYER developed heroin (as preferential to morphine – marketed for faster action)
• Nowadays, medical use is strictly regulated and recreational use illegal (some require prescription)

Question 5

What is the opioid epidemic/crisis?

Answer 5

• High levels of opioid use
• Opioids are the main cause of overdose deaths
• In the UK in 2018, a total of 2,208 drug poisoning deaths had an opiate mentioned on the death certificate (51% of all drug poisoning deaths)
• Opioid crisis in US driven by overprescription
• Unregulated pharmaceutical market and private capitalist medical system

Question 6

What are the symptoms of an opioid overdose?

Answer 6

• Respiratory depression
• Miosis (pupil construction)
• Stupor (unresponsiveness)
• Hepatic injury from acetaminophen or hypoxemia
• Myoglobinuric renal failure
• Rhabdomyolysis
• Absent or hypoactive bowel sounds
• Compartment syndrome
• Hypothermia
• Possible presence of one or more fentanyl patches
• Opioid overdose can be treated by injection with the opioid antagonist naloxone (if picked up early enough)

Question 7

How harmful are opioids?

Answer 7

• Heroin second after alcohol
• Only opioids considered were heroin, methadone and buprenorphine
• Methadone and buprenorphine less dangerous (so used in withdrawal therapy)

Question 8

Describe opioid receptors

Answer 8

• There are also peripheral opioid receptors, including on peripheral nerve endings (Stein et al., 2003) and in the gastrointestinal tract (causing constipation) (Holzer, 2009)
• U opioid receptor most used for medical effects
• Endogenous compounds our body produces to have physiological effects with opioids
  (More detailed diagram in notes)

Question 9

What are the mechanisms of action of opioid receptors?

Answer 9

• Opioid receptors are G-protein-coupled receptors (after activation by ligand (opioid), interact with G-protein which has knock on effects which mediate neuronal responses e.g. interaction with ion channels or enzyme which triggers second messenger cascade)

Question 10

How do opioid receptors mediate neural inhibition?

Answer 10

• Activation of opioid receptors tends to inhibit neural activity or neurotransmitter release of the neurons carrying the opioid receptor

Question 11

What are some of the mechanisms of inhibition?

Answer 11

• Postsynaptic inhibition = opening of potassium channels, influx of potassium = inhibition of neuron
• Axoaxonic inhibition = close calcium channel, reduce neurotransmitter release
• Presynaptic autoreceptors = inhibition of neurotransmitter release from presynaptic terminal