Opioids

Question 1

Name Weak and Strong Opioids

Answer 1

Weak: middle of pain ladder

1. Codiene (Prodrug, weak bases, absorbed in slightly alkaline environment in unionised form, metabolised by ctochrome P450 in the liver – consider oral availability)
2. Dihydrocodiene,
3. Tramadol

Ceiling effect, increasing dosage causes side effects without improving analgesia

Strong: highest pain ladder

1. Morhine (controlled release for background pain, twice daily with 12hrs interval; normal release for breakthrough pain, prescribe as required. In acte pain setting, from normal release to controlled release)
2. Diamorphine (semisynthetic morphine derative, more soluble therefore less volume needed when given parenterally),
3. Oxycodone,
4. Methadone(longest duration, substitude for opioid addicts, sugary syrup revent injection, present with gross dental decay)
5. Fentanyl (patch used for chronic cancer pain if persistent side effects with morphine and diamorphine-last 72hrs, sticks used in battle field, absorbed from buccal mucosa)
6. Ramifentinyl (brief duration, given by infusion, metabolised by plasma esterases)

Question 2

MOA of opioids

Answer 2

Binding to opioid receptors, most common mu receptor (MOP for endogenous opioid beta endorphin), activating G protein intracellular signalling

(1) opening of K+ channels, outflux of K+, hyperpolarisation
(2) inhibit influx of Ca2+, less like to depolarise
(3) inhibt Adenylate Cyclase from converting ATP to cAMP, hence reduce excocytosis and neurotransmitter release

Question 3

Opioid Antagonists

Answer 3

Merely higher affinity for opioid receptors but no intrinsic activity

Nalaxone used for opioid overdose - IV. Not generating withdrawl seizures but to increase respiratoin to prevent hypoxia

Naltrexone used when substance abuser trying to stay clean

Question 4

Effects of Morphine on CNS, respiratory, CVS, GI, Renal and Endocrine systems

Answer 4

CNS:

1. Analgesia
2. Sedation
3. Addiction/dependence
4. Meiosis - pupil constriction due to mu receptor on EW nucleus

Respiratory:

1. respiratory suppression - esp resp rate, monitor CO₂ levels
2. Antitussive - used in cough medicine
3. Bronchoconstriction due to histamine release from mast cells

GI:

1. reduced motililty - constipation - laxatives prescribed as adjuvant- Senna, docusate
2. Nauzea due to effect on CTZ and vestibule apparatus - antiemetics prescribed as adjuvant - metoclopramide and haloperidol

Renal:

• Urinary retention

Endocrine:

1. Decreased production of ACTH, prolactin - common precursor POMC
2. Increased production of ADH - urinary retention
3. Suppression of immunity

Skin:

1. Urticaria
2. Itch esp in epidural route - used in labour pain and abdominal surgery