Morphine Flashcards
What is the pKa of morphine?
8
How much of morphine is unionized at plasma pH?
23% unionized
What % of morphine is protein bound?
35%
What is the relative lipid solubility of morphine?
1
What is the terminal half life of morphine?
3hrs
What is the clearance of morphine?
10 - 20 ml/min/kg
What is the volume of distribution of morphine?
2-3 litres/kg
What are the SEs of morphine?
- histamine release
- bronchospasm in asthmatics
- And same as fentanyl:
- bradycardia
- hypotension
- resp depression
- PONV
- urine retention
- constipation and itch
What are the uses of morphine?
- analgesia
- sedation in ITU
- palliative care
- CCF
What are the CVS effects of morphine?
- no direct effects
- if histamine release occurs, may cause hypotension
- mild bradycardia secondary to reduced sympathetic tone
What are the RS effects of morphine?
- dose dependent respiratory depression
- decreased sensitivity to pCO2
- antitussive
- bronchospasm with histamine release
What are the CNS effects of morphine?
- analgesia
- sedation
- eurphoria
- hallucinations
- meiosis (edinger-westphal nucleus)
- seizures and muscular rigidity with high doses
What are the GI SEs of morphine?
- decreased gut motility
- decreased gastric acid, pancreatic and bile secretion
- N&V - CTZ stimulation via 5-HT3 and dopamine receptors
What are the GU effects of morphine?
- increased uterine tone, bladder detrusor and sphincter muscles, can cause retention
What are the skin SEs of morphine?
- pruritis
- rash
What are the endocrine effects of morphine?
- decreased ACTH
- decreased gonadotrophic hormones
- increased ADH causing hypernatraemia and water secretion
What are the chemical properties of morphine?
- naturally occurring phenanthrene derivative
- weak base - pKa 8, ionised in stomach
What is the absorption/distribution of morphine?
- well absorbed orally (from small bowel as ionised in stomach)
- extensive first pass metabolism
- oral bioavailability at 15-20%
- 20-40% PPB
- low lipid solubility
- peak effect 10-30 mins, duration 3-4hrs
What is the MOA of morphine?
- agonist at MOP and KOP G-Protein coupled opioid receptors
- binding of the ligand causes the following events:
- closure of voltage gated calcium channels
- decreased cAMP production
- stimulation of K efflux from cell
- hyperpolarisation of cell membrane and decreased excitability of cell decreased neurotransmitter release and pain transmission
What is the metabolism and excretion of morphine?
- hepatic metabolism to
- morphine 3 glucuronide (inactive
- morphine 6 glucuronide (active + 13x more potent than morphine)
- excreted in urine
- neonates have increased sensitivity due to immature hepatic metabolism
- dose with care in liver impairment
What is the dose of morphine?
- oral - 5 - 40mg/4hrly
- rectal - 15 - 30mg/4hrly
- IV - 0.05 - 0.1 mg/kg 4hrly
- IM/SC - 0.1 - 0.2mg/kg 4hrly
- intrathecal - 0.1 - 1mg
- epidural - 1 - 5mg
