Opioid Analgesics

Question 1

What are the different types of pain?

Answer 1

Nociceptive pain = tissue damage

Neuropathic pain = brain/ nerve damage

Question 2

Name 3 types of analgesics

Answer 2

• Opioids
• NSAIDs
• Tricyclic antidepressants
• Anti-convulsants
• Calcium channel blockers
• Cannabinoids

Question 3

What are opioids?

Answer 3

Endogenous/synthetic compounds that produce morphine-like effects

Question 4

What are opioid receptors?

Answer 4

• Act at opioid receptors - GPCR linked to Gi –> decrease Adenylate cyclase levels
• There are 3 subtypes - mu, delta and Kappa
• MOP is most prominently linked to analgesia

Question 5

Why are opioids such good analgesics?

Answer 5

• Opioid receptors are found in the periphery, dorsal horn and periaqueductal grey matter
• Stimulation of peripheral ones stops the signal from going to the dorsal horn etc
• Stimulation of the PGM ones causes an increase in the descending inhibitory pain pathways - prevent nociceptive pain moving through the dorsal horn
• NSAIDs just act at the periphery, Opioids act at all levels to cause analgesia

Question 6

What is the cellular mechanism for opioids?

Answer 6

• They reduce synaptic transmission
• pre-synaptically they decrease the stimulation of VGCCs, decreasing NT release
• Also activate K channels, causing a potassium efflux, hyperpolarising the membrane, making it harder to fire APs, decreasing the VGCCs and so NT release
• Post-synaptically they act on K channels, causing hyperpolarisation and so decreased firing

Question 7

How do opioids switch on analgesic neuronal areas?

Answer 7

They can switch on areas such as periaqueductal grey matter and nucleus raphe magnus via disinhibition

• areas of the brain are controlled by interneurones
• if the inhibitory interneuron is turned on in the PAG, the descending pain pathway is inhibited
• when opioids switch off the interneuron and disinhibit the descending pain pathway –> analgesia

Question 8

What are some other effects of opioids?

Answer 8

• Euphoria
• Respiratory depression
• suppress cough reflex
• vomiting - stimulate area prostrema
• pupillary CONSTRICTION- stimulate oculomotor nerve and increase parasymp
• Increases GI tone
• Histamine release from mast cells
• Tolerance/dependence

Question 9

How do opioids cause Euphoria?

Answer 9

• Relief of stress - very important analgesic effect
• Caused by disinhibition of GABAnergic interneurons in reward areas
• DA release is controlled by GABA - a local inhibitory interneuron in the cleft that release GABA reduces DA release
• Opioids reduce GABA release and so increase the DA released into the cleft
  Causes Euphoria

Question 10

How do opioids cause respiratory depression?

Answer 10

• opioid receptors are found in respiratory areas of the brain that drive respiration (pre-botzinger complex, chemoreceptors in brainstem and medulla)
• suppression of respiratory pattern means that chemoreceptors are less sensitive to PCO2
• Increase in arterial CO2 would usually increase ventilation rate - the opioid prevents this
• Better tolerated than barbiturates as they dont affect the CVS
• However, resp failure is commen cause to death in opioid abuse

Question 11

Common opioids

Answer 11

• Morphine
• Codeine - less potent, usually combined with NSAIDs
• Methadone - long half-life, used for heroin addicts
• Diamorphine (heroin)

Question 12

Opioid antagonist

Answer 12

Naloxone - blocks opioid receptors, reverses morphine-induced symptoms
- used to reverse overdose

Question 13

Partial opioid agonist

Answer 13

Buprenorphine - long duration of action, treatment for heroin addiction - about half the opioid effect of morphine

Question 14

Opioid overdose symptoms

Answer 14

• pin-point pupils
• respiratory depression
• CNS depression/coma