[Verse 1]
Swallow that morphine, hit the gut, get absorbed slow
Bioavailability low, bout thirty percent though
First-pass metabolism tearing through the portal vein
Liver chops it up before it ever hits the brain
Immediate release spikes fast, modified release stays flat
Formulation matters, write that pharmacology fact
Transdermal fentanyl depot building in the skin
Transmucosal hits the bloodstream, bypasses first-pass then
Food can slow absorption, fatty meals delay the peak
Context shapes the kinetics every single time you speak
[Chorus]
Two-D-six and three-A-four, UGT-two-B-seven
Active metabolites determining what the patient's getting
Vd and protein binding, lipophilicity key
Fentanyl dissolves in fat, morphine stays more free
Half-life, steady state, accumulation runs the game
Linear or nonlinear — the dose-exposure ain't the same
[Verse 2]
Distribution, talk volume — spread across the tissues wide
Fentanyl got crazy lipophilicity, crosses every divide
High Vd means it's hiding deep in fat and muscle stores
Morphine stays more hydrophilic, smaller Vd scores
Protein binding — albumin grabs acidic drugs up tight
Alpha-one glycoprotein holds the basics overnight
Blood-brain barrier's the gatekeeper, P-glycoprotein pump
Kicks opioids right back out, efflux over the hump
That's why CNS penetration varies drug to drug
Lipophilicity the skeleton key turning in that lock
[Chorus]
Two-D-six and three-A-four, UGT-two-B-seven
Active metabolites determining what the patient's getting
Vd and protein binding, lipophilicity key
Fentanyl dissolves in fat, morphine stays more free
Half-life, steady state, accumulation runs the game
Linear or nonlinear — the dose-exposure ain't the same
[Verse 3]
Now metabolism — CYP enzymes on the clock
Two-D-six converts codeine and tramadol to the shock
O-desmethyltramadol is the active compound there
Poor metabolizers get no relief, ultra-rapid beware
Three-A-four handles fentanyl, methadone in the queue
CYP-two-C-nine working NSAIDs all the way through
UGT-two-B-seven glucuronidates morphine at the six
Morphine-six-glucuronide potent — that's the analgesic fix
Morphine-three-glucuronide? Neuroexcitatory, watch for that
Normeperidine from meperidine causes seizures, fact
[Bridge]
Infusion running hours long, context-sensitive half-time climbs
Fentanyl accumulates, remifentanil declines
Renal clearance matters when the metabolites stack
M-six-G builds up in failure, hits the patient hard back
Loading dose fills the volume fast so plasma levels rise
Maintenance keeps it steady — five half-lives til you stabilize
Nonlinear kinetics, saturation at the enzyme seat
Methadone's the wild card — unpredictable defeat