Opiates

Opioid vs opiate

Opioid: Analgesic drug class (inc. synthetic + semisynthetic opioids)

Opiate: Natural opioid (morphine, diamorphine, codeine)

WHO analgesia ladder

Name some weak opioids

Codeine

Dihydrocodeine

Tramadol

Name some strong opioids

• Morphine

• Fentanyl

• Oxycodone

• Buprenorphine

Difference between weak and strong opioids

Weak opioids have a “ceiling effect” where increasing the dose after a certain point has no effect (lower efficacy)

Also have a lower potency

Mechanism of action of opioids

Opioid receptors are inhibitory G-protein receptors

Activation leads to:

• Reduced neuronal cell excitability

• Reduce transmission of nociceptive signals

Which opioids are full/ partial agonist and antagonists?

Full agonists: morphine, fentanyl

Partial agonists: buprenorphine

Antagonists: naloxone

Name the different opioid receptor types

MOP: Mu / μ (2 subtypes)

KOP: Kappa / κ (3 subtypes)

DOP: Delta / δ (2 subtypes)

NOP: Nociceptin orphanin FQ peptide receptor

What opiates (natural opioids) bind to which opioid receptor?

Where are the opioids excreted? Which one has the highest bioavailability and what usually metabolises these drugs?

Renal excretion

highest bioavailability: Tramadol

Metabolism:

• almost all: CYP2D6

• morphine: Glucuronidation

• fentanyl: CYP3A4

What are the active drugs of codeine, oxycodone and tramadol?

Codeine → morphine

Oxycodone → oxymorphone

Tramadol → O-desmethyltramadol (ODT)

** catalysed by CYP2D6

Name some CYP3A4 inhibitors

** increase serum levels of buprenorphine, oxycodone

• Ciprofloxacin

• Azole antifungals

• Grapefruit juice

Name some CP2D6 inhibitors

** reduce codeine, tramadol effects

• Fluoxetine/Paroxetine

• Amiodarone

• Bupropion

Side effects of strong opioids

• Confusion/drowsiness

• Hallucinations

• Bad dreams

• Dry mouth

• Nausea & vomiting

• Constipation (usually prescribe laxatives to prevent)

Which strong opioids do I prescribe?

1. Morphine

2. (morphine not tolerated): Oxycodone

3. Fentanyl if:
   • Need high doses for chronic pain
   • CKD (metabolised to inactive compounds)

Which weak opioids do I prescribe?

What is azathioprine used for?

It is an immunosuppressant used in:

• Chrons

• SLE

• Rheumatoid arthritis