Morphine

Question 1

What is the pKa of morphine?

Answer 1

8

Question 2

How much of morphine is unionized at plasma pH?

Answer 2

23% unionized

Question 3

What % of morphine is protein bound?

Answer 3

35%

Question 4

What is the relative lipid solubility of morphine?

Answer 4

1

Question 5

What is the terminal half life of morphine?

Answer 5

3hrs

Question 6

What is the clearance of morphine?

Answer 6

10 - 20 ml/min/kg

Question 7

What is the volume of distribution of morphine?

Answer 7

2-3 litres/kg

Question 8

What are the SEs of morphine?

Answer 8

• histamine release
• bronchospasm in asthmatics
• And same as fentanyl:
  
  • bradycardia
  • hypotension
  • resp depression
  • PONV
  • urine retention
  • constipation and itch

Question 9

What are the uses of morphine?

Answer 9

• analgesia
• sedation in ITU
• palliative care
• CCF

Question 10

What are the CVS effects of morphine?

Answer 10

• no direct effects
• if histamine release occurs, may cause hypotension
• mild bradycardia secondary to reduced sympathetic tone

Question 11

What are the RS effects of morphine?

Answer 11

• dose dependent respiratory depression
• decreased sensitivity to pCO2
• antitussive
• bronchospasm with histamine release

Question 12

What are the CNS effects of morphine?

Answer 12

• analgesia
• sedation
• eurphoria
• hallucinations
• meiosis (edinger-westphal nucleus)
• seizures and muscular rigidity with high doses

Question 13

What are the GI SEs of morphine?

Answer 13

• decreased gut motility
• decreased gastric acid, pancreatic and bile secretion
• N&V - CTZ stimulation via 5-HT3 and dopamine receptors

Question 14

What are the GU effects of morphine?

Answer 14

• increased uterine tone, bladder detrusor and sphincter muscles, can cause retention

Question 15

What are the skin SEs of morphine?

Answer 15

• pruritis
• rash

Question 16

What are the endocrine effects of morphine?

Answer 16

• decreased ACTH
• decreased gonadotrophic hormones
• increased ADH causing hypernatraemia and water secretion

Question 17

What are the chemical properties of morphine?

Answer 17

• naturally occurring phenanthrene derivative
• weak base - pKa 8, ionised in stomach

Question 18

What is the absorption/distribution of morphine?

Answer 18

• 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

Question 19

What is the MOA of morphine?

Answer 19

• 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

Question 20

What is the metabolism and excretion of morphine?

Answer 20

• 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

Question 21

What is the dose of morphine?

Answer 21

• 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