CPTP 3.20 Neuropharmacology 5 Opioids

Question 1

What are the immediate concerns associated with excessive opiate use?

Answer 1

Too much opiate can suppress the pons and medulla, causing suppression of autonomic function (i.e. breathing)

Miosis and unconsciousness can also occur

Question 2

How do opioid receptors effect neuronal activity?

What can this often lead to?

Answer 2

• Increases potassium conductance, hyperpolarising neurones
  
  • Inhibits calcium entry, preventing neurotransmitter release

Inhibition of GABA-ergic interneurones, thus disinhibition of downstream neurones can occur (resulting in the increase in dopamine, etc which creates the euphoric feeling)

Question 3

What are the desirable effects of opioids

Answer 3

• Analgesia
  
  • Euphoria
  • Sedation
  • Cough suppression

Question 4

What are the adverse effects of opioids?

Answer 4

• Constipation
  
  • Respiratory depression
  • Histamine release & Immunosuppression
  • Nausea and vomiting
  • Tolerance and dependence

Question 5

Where are opioid receptors with antinociceptive effects found?

Answer 5

• Limbic areas
  
  • Medulla
  • Periaqueductal gray
  • Dorsal horns

Question 6

Which opioid receptors are there?

Answer 6

Mu (μ) receptors
• Analgesic effects in brain
• Respiratory depression
• Physical dependence

Kappa (κ) receptors
• Analgesic effects in spinal cord
• Respiratory depression
• Physical dependence

Delta (δ) receptors
• CNS and enkephalin effects
• No dependence or respiratory depression
• Aversion

Question 7

Describe the endogenous opioids which act on each opioid receptor subtype, and what they are formed from.

Answer 7

Mu (μ) receptors
• Beta-endorphin
• Formed from proopiomelanocortin

Kappa (κ) receptors
• Dynorphin A and B
• Formed from prodynorphin

Delta (δ) receptors
• Met-enkephalin and leu-enkephalin
• Formed from proenkephalin

Question 8

Name the opioid agonists in the student formulary.

Answer 8

• Codeine
  
  • Morphine
  • Diamorphine
  • Tramadol

Question 9

What can be administered to individuals only after a long amount of time after quitting opioids after an addiction, to help reverse the effects?

Why is this wait necessary and what does the drug do?

What other use does this drug have?

Answer 9

Naloxone
• Opioid competitive antagonist

Must wait a long time otherwise a potentially fatal ‘cold turkey’ event could occur

Treating morphine overdose

Question 10

Which opioid receptor subtypes are targetted by:

1) Morphine
2) Diamorphine

Answer 10

1) mu and delta

2) mu and delta

Question 11

Describe the metabolisation of morphine

Answer 11

• Metabolised by glucuronidation into the active metabolite morphine-6-gucuronide
  
  • Extensive first pass metabolism
  • Active duration of 6 hours (half life 3h)

Question 12

What are the risk groups for morphine administration?

Answer 12

• Elderly (reduced metabolism)
  
  • COPD
  • Liver and renal disease

Question 13

What is morphine used for?

Answer 13

Moderate to severe pain

Acute heart failure

Question 14

Why is morphine used for acute heart failure?

Answer 14

• Relieves pain
  
  • Reduces anxiety
  • Dilates blood vessels

Question 15

How can morphine be administered?

Answer 15

• Oral
  
  • Parenteral (IV, IM, SC)
  • Epidural

Question 16

What is heroin’s medical name?

Answer 16

Diamorpine

Question 17

What is the chemical name of diamorphine?

Describe the pharmacodynamics of diamorphine

Answer 17

Diacetylmorphine

It is deacetylated into morphine, and then follows the same pharmacokinetics and pharmacodynamics as morphine:
• Metabolised by glucuronidation into the active metabolite morphine-6-gucuronide
• Extensive first pass metabolism
• Active duration of 6 hours (half life 3h)

Question 18

How can diamorphine be administered?

Answer 18

Parenteral (IV, SC, IM)

Question 19

What is methodone?

Answer 19

An opioid agonist with the same pharmacology as morphine but a much higher half life of 24 hours which is used in substitution therapy in heroin addicts.

Used to prevent the onset of withdrawal states

Question 20

How is methodone administered?

Answer 20

Orally

Question 21

What is codeine used for?

Answer 21

Weak oral opiate for:
• Mild pain
• Diarrhoea
• Anti-tussive (suppresses coughing)

Question 22

Which opioid is used for chronic pain?

Recall its pharmacodynamics

Answer 22

Tramadol
• μ-opioid agonist
• Serotonin and noradrenaline reuptake inhibitor

Question 23

What is the benefit of tramadol’s inhibition of serotonin and noradrenaline reultake?

Answer 23

Opioid agonists work by decreasing activity of inhibitory neurones, thus disinhibiting downstream serotonergic and noradrenergic neurones (decreased activity of which causes pain and poor feeling of wellbeing i.e. not euphoria)

This effect is synergised by tramadol’s reuptake inhibition as the downstream serotonergic and noradrenergic activity is heightened

This decreases the dose of opioid agonists needed for good efficacy

Question 24

Describe the two main addiction mechanisms

Answer 24

• Chasing the dragon - due to tolerance users increase the dose needed to attain the same high
  
  • Avoidance of withdrawal

Question 25

Disinhibition in what brain region leads to increased dopamine release where?

What does this cause?

Answer 25

Disinhibition in ventral tegmental area leads to increased dopamine release in the nucleus ambiguus

Euphoria, and eventually dependence

Question 26

Why can be effective in reducing cold turkey symptoms? Why

Answer 26

α-2 adrenoreceptor agonists

Locus coeruleus activity is heightened during cold turkey symptoms