Opioid Analgesics Flashcards by Mollie O

Is pain objective or subjective?

Subjective

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What are the two components of pain?

Physiological
Psychological

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What is another name for the physiological perception of pain?

Nociception

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Give two scenarios where the psychological aspect of pain becomes apparent

Phantom limb pain
Intractable pain

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Which divisions of the nervous system do opioids affect?

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What type of effect do opioids have on the CNS?

Psychoactive

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What theory does the action of opioids in the PNS conform with?

The ‘gate theory’ of pain

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To where in the CNS are pain signals initially transmitted to?

The substantia gelatinosa

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Where is the substantia gelatinosa found?

The dorsal horn of the spinal cord

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What can happen to pain signals within the substantia gelatinosa?

They can be modulated

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What neurotransmitter is responsible for relaying pain signals within the substantia gelatinosa?

Substance P

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How do opioids exert their effects at the spinal level?

Inhibit the release of Substance P from the nerve terminals in the substantia gelatinosa

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What natural part of the pain pathway do opioids mimic to an extent?

Descending inhibitory nerves from the thalamus

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What do the inhibitory descending nerves from the thalamus do?

Use inhibitory interneurones to block the release of Substance P within the substantia gelatinosa

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How does rubbing an injury make it ‘better’?

Stimulation of mechanoreceptors that can have an inhibitory effect on pain transmission via the substantia gelatinosa

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What are the 3 main types of endogenous opioid peptides?

Enkephalins
Endorphins
Dynorphins

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What is the pre-cursor molecule for enkephalins?

Proenkephalin

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What is the pre-cursor molecule for endorphins?

POMC

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What else is POMC a pre-cursor for?

α-MSH
ACTH

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What is the pre-cursor molecule for dynoprhins?

Prodynorphin

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What are the two main types of enkephalins?

Met-enkephalin
Leu-enkephalin

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What is the main type of endorphin?

β-endorphin

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What are the three types of opioid receptors?

μ-opioid receptors
δ-opioid receptors
κ-opioid receptors

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Where are μ-opioid receptors generally found?

Supraspinal i.e. in the brain

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What effect does binding to μ-opioid receptors have?

Analgesia

Where are κ-opioid receptors mostly found?

Spinal cord

Where are δ-opioid receptors found?

They are widely distributed

What type of receptor are all opioid receptors?

GPCRs

Receptors at which location within the synapse are most important in pain control?

Presynaptic receptors

What effect does binding to μ-receptors have?

Opening of K⁺ channels and increased efflux of K⁺

What is the result of increased efflux of potassium?

Decreased excitability

What is the result of binding to κ-receptors?

Decreased influx of Ca²⁺ via channels

What is the result of binding to δ-receptors?

Decreased adenylate cyclase activity leading to decreased cAMP synthesis

Are the effects of the receptor sub-types limited to only one subtype?

No - each subtype can exert all of the effects i.e. cause increased efflux ok potassium, decrease calcium influx and decrease cAMP

What do all the effects of the opioid receptors have on the intracellular calcium?

Reduced entry of Ca²⁺

What is the result of decreased entrance of calcium ions?

Less release of neurotransmitter (Substance P) vesicles into the synaptic cleft

What receptor causes most of the opioid side-effects?

μ-receptors

What side-effects does μ-receptor binding have?

* Nausea * Vomiting * Constipation * Drowsiness * Miosis

What are the two big problems of long-term opioid use?

* Dependance * Tolerance

What does dependence mean in terms of opioid use?

If opiods are removed the patient sufferes from withdrawal symptoms

What does tolerance mean with respect to opiate use?

A higher dose is needed to achieve the same effect

What is the danger of opiates tolerance?

Users need a higher dose to the point where it risks respiratory depression and death

The risk of respiratory depression has what consequence on opiate prescribing?

Monitoring is required

What effect can opiates have on the CVS?

Can cause hypotension

What side-effect can be caused by κ-receptor binding?

Dysphoria

What are the type of opioid receptor binding drugs?

* Agonists * Partial agonists * Agonist/antagonist * Antagonist

Give an opioid receptor agonist

Morphine (the gold standard)

Give an opioid receptor partial agonist

Buprenorphine

Give an opioid receptor agonist/antagonist

Nalbuphine

How do opioid receptor agonist/antagonists work?

They exert an agonistic effect at one receptor sub-type and cause an antagonistic action at another

Give an opioid receptor antagonist

Naloxone

What can naloxone be used for?

Reversal of opioid induced respiratory depression

What is the half-life of morphine?

~4 hours

What is the oral bioavailability of morphine?

25%

What is the half-life of diamorphine (heroin)?

5 minutes

What is the half-life of methadone?

~24 hours

What is the oral bioavailability of methadone?

90%

What is another opioid with a good oral bioavailability?

Codeine

Does morphine enter Phase 1 metabolism?

No - it already has hydroxyl groups so enters straight into Phase 2 metabolism

To what metabolites is morphine metabolised to?

* Morphine-6-glucuronide * Morphine-3-glucuronide

Why does morphine have a ‘slightly extended half-life’?

Morphine-6-glucuronide is still an active molecule

How are morphine metabolites excreted?

In the urine

What is the result of urinary excretion of morphine metabolites?

Urine can be screened for opioid use

Despite its short half-life of 5 minutes, why is heroin the opiate of choice for substance misusers?

Becuase its structure allows for rapid entry across the blood-brain barrier where it is the metabolised to morphine after which it has the usual ~4 hour half life

What are the clinical uses of opioids?

* Analgesia * Anaesthesia

What sort of pain are opioids used to treat?

Moderate to severe pain (particularly pain with a visceral origin)

What are the indications for morphine?

* Analgesia (particularly terminal illness) * Diarrhoea

What are the indications for diamorphine?

Analgesia (in terminal illness only due to its tendency to cause dependence)

What are the indications for methadone?

Maintenance in opiod dependence

What are the indications of tramadol?

Analgesia

What are the extra-opioid effects of tramadol?

5-HT and NA re-uptake inhibition (minor anti-depressant side-effects)

What type of drug is morphine?

A pro-drug

What is codeine metabolised to?

Morphine

What converts codeine to morphine?

CYP2D6

What is the clinical significance of CYP2D6?

It has significant genetic polymorphism meaning some people cannot metabolise codeine to morphine and so receive no benefits

What is codeine used for?

Mild analgesia

What is the route of administration of morphine?

Oral

What is the indication of fentanyl?

Anaesthesia

Why does fentanyl work as an anaesthetic agent?

It has up to 100x the potency of morphine

What is the indication for pethidine?

Analgesia in labour

What is the route of administration of pethidine?

What is the dangerous side-effect of pethidine?

It is metabolised to not pethidine which can cause convulsions

What are the indications for naloxone?

* Opioid toxicity * Respiratory depression * Treatment of dependence

What are the medico-legal implications of opioid prescribing?

May are controlled drugs e.g. morphine, diamorphine and pethidine