Morphine
From Pharmacopedia
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Opioid analgesic (natural phenanthrene from opium poppy), Schedule II controlled substance, Analgesic
Morphine (sulfate)
MS Contin (ER), Kadian (ER), Avinza (ER), Roxanol (IR oral solution), Duramorph (epidural / IT), Astramorph (IV), Infumorph (intrathecal pump), MorphaBond (IR abuse-deterrent)
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Summary
Classes
Common uses
Moderate to severe acute pain (FDA)0, Severe chronic pain unresponsive to non-opioid alternatives (FDA, with CDC opioid prescribing guidance constraints)0, Cancer pain (FDA; the global gold standard, WHO essential medicine)0, Preoperative analgesia (FDA)0, Epidural and intrathecal pain management (FDA)0
Pharmacy
Starting dose
IR oral: 15-30 mg every 4 hours as needed. ER opioid-naive: 15-30 mg every 12 hours. IV/IM/SC: 2-10 mg every 3-4 hours. Epidural / intrathecal: see surgical or palliative-care protocols
Preparations
IR tablets 15, 30 mg; oral solution 10 mg/5 mL, 20 mg/mL, 100 mg/5 mL (concentrated); suppositories; ER tablets and capsules in multiple strengths; injectable 0.5-50 mg/mL
US FDA Max
No fixed ceiling; titrate to clinical effect and tolerability with CDC opioid prescribing guidance constraints on morphine-milligram-equivalent (MME) totals
Pharmacology
Routes
Oral, intravenous, intramuscular, subcutaneous, epidural, intrathecal, rectal
Onset
5-10 minutes (IV); 30 minutes (oral IR); slower for ER and rectal
Duration
3-5 hours (IR); 8-24 hours (ER); 12-24 hours (epidural / intrathecal)
Half-life
Morphine 2-4 hours; morphine-6-glucuronide active metabolite 2-4 hours (longer with renal impairment)[1]
Bioavailability
~25-40% (oral; extensive first-pass)[1]
Pregnancy
Chronic third-trimester exposure produces neonatal opioid withdrawal syndrome and respiratory depression at delivery.[citation needed]
Legal status
Schedule II controlled substance in US; WHO essential medicine[1]
Purported mechanism
Prototype μ-opioid receptor agonist, the natural reference compound from which all other opioid analgesics are characterized by relative potency. Metabolized predominantly by UGT2B7 glucuronidation to morphine-3-glucuronide (M3G, inactive at μ but possibly neuroexcitatory at high concentrations) and morphine-6-glucuronide (M6G, active μ agonist, more potent than parent morphine and renally eliminated, so accumulates in renal impairment to produce prolonged respiratory depression).0 Histamine release with IV bolus produces flushing and hypotension. Crucially, morphine is not CYP2D6-dependent (no metabolic activation step is needed, unlike codeine and hydrocodone), so analgesic efficacy is genotype-independent. The Schedule II status and the CDC opioid prescribing guidance shape current clinical use[1].
“Pendell's corner
Opium is the archetypal medicine, and morphine is its essence. Morphine is the most powerful naturally occurring analgesic in the world, and the synthetics use opium as their precursor.
— Dale Pendell, Pharmako/Poeia, p. 123
References
- ↑ 1.0 1.1 1.2 1.3 FDA Prescribing Information, MS Contin (morphine sulfate extended-release), Purdue/Mallinckrodt, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019516s058lbl.pdf