Description

Buy Hydrocodone 30mg Online Hydrocodone is a synthetic opioid derivative of codeine.¹⁴ It is commonly used in combination with acetaminophen to control moderate to severe pain. Historically, hydrocodone has been used as a cough suppressant although this has largely been replaced by dextromethorphan in current cough and cold formulations. Hydrocodone’s more potent metabolite, hydromorphone has also found wide use as an analgesic and is frequently used in cases of severe pain. The FDA first approved Hydrocodone for use as part of the cough suppressant syrup Hycodan in March of 1943

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Hydrocodone inhibits pain signaling in both the spinal cord and brain ¹². Its actions in the brain also produce euphoria, respiratory depression, and sedation.

Mechanism of action

Hydrocodone binds to the mu opioid receptor (MOR) with the highest affinity followed by the delta opioid receptors (DOR).¹³ Hydrocodone’s agonist effect at the MOR is considered to contribute the most to its analgesic effects. Both MOR and DOR are Gi/o coupled and and produces its signal through activation of inward rectifier potassium (GIRK) channels, inhibition of voltage gated calcium channel opening, and decreased adenylyl cyclase activity.¹⁴ In the dorsal horn of the spinal cord, activation of pre-synaptic MOR on primary afferents the inhibition of calcium channel opening and increased activity of GIRK channels hyperpolarizes the neuron and prevents release of neurotransmitters. Post-synaptic MOR can also prevent activation of neurons by glutamate through the aforementioned mechanisms.

Hydrocodone can also produce several actions in the brain similarly to other opioids. Activation of MOR in the periaquaductal gray (PAG) inhibits the GABAergic tone on medulo-spinal neurons.^14,12 This allows these neurons, which project to the dorsal horn of the spinal cord, to suppress pain signalling in secondary afferents by activating inhibitory interneurons. MOR can also inhibit GABAergic neurons in the ventral tegmental area, removing the inhibitory tone on dopaminergic neurons in the nucleus accumbens and contributing to the activation of the brain’s reward and addiction pathway. The inhibitory action or MOR likely contributes to respiratory depression, sedation, and suppression of the cough reflex.

Activation of DOR may contribute to analgesia through the above mechanisms but has not been well studied.¹²

Absorption

The absolute bioavailability of hydrocodone has not been characterized due to lack of an IV formulation. The liquid formulations of hydrocodone have a Tmax of 0.83-1.33 h.^3,5 The extended release tablet formulations have a Tmax of 14-16 h.^Label The Cmax remains dose proportional over the range of 2.5-10 mg in liquid formulations and 20-120 mg in extended release formulations.^3,5,Label Administration with food increases Cmax by about 27% while Tmax and AUC remain the same.⁶ Administration with 40% ethanol has been observed to increase Cmax 2-fold with an approximate 20% increase in AUC with no change in Tmax. 20% alcohol produces no significant effect.

Volume of distribution

The apparent volume of distribution ranges widely in published literature. The official FDA labeling reports a value of 402 L.^Label Pharmacokinetic studies report values from 210-714 L with higher values associated with higher doses or single dose studies and lower values associated with lower doses and multiple dose studies.^2,3,4,5 Hydrocodone has been observed in human breast milk at levels equivalent to 1.6% of the maternal dosage.¹¹ Only 12 of the 30 women studied had detectable concentrations of hydromorphone at mean levels of 0.3 mcg/kg/day.

Protein binding

Hydrocodone is 36% bound to plasma proteins.^Label

Metabolism

Hydrocodone undergoes oxidative O-demethylation to form hydromorphone, a more potent active metabolite.⁸ Though hydromorphone is active it is not present in sufficient quantities to contribute significantly to hydrocodone’s therapeutic effects.¹ Both hydrocodone and hydromorphone form 6-α- and 6-β-hydroxy metabolites through 6-ketoreduction. The hydroxy metabolites and hydromorphone can form glucuronide conjugates. Hydrocodone also undergoes oxidative N-demthylation to norhydrocodone. O-demethylation is primarily catalyzed by CYP2D6 while N-demethylation is primarily CYP3A4.⁹

Hover over products below to view reaction partners

• Hydrocodone
  • Hydromorphone

    • Hydromorphone glucuronide conjugate

    • 6-α-hydromorphol + 6-β-hydromorphol

      • 6-β-hydromorphol glucuronide conjugate 1 + 6-β-hydromorphol glucuronide conjugate 2

      • 6-α-hydromorphol glucuronide conjugate 1 + 6-α-hydromorphol glucuronide conjugate 2

  • norhydrocodone

  • 6-α-hydrocodol + 6-β-hydrocodol

    • 6-β-hydrocodol glucuronide conjugate

    • 6-β-hydromorphol

      • 6-β-hydromorphol glucuronide conjugate 1 + 6-β-hydromorphol glucuronide conjugate 2

    • 6-α-hydromorphol

      • 6-α-hydromorphol glucuronide conjugate 1 + 6-α-hydromorphol glucuronide conjugate 2