Generic Name

Hydrocodone

Mechanism

• Hydrocodone is a *semi‑synthetic opioid* that exerts its analgesic effect primarily by binding to µ‑opioid receptors in the central nervous system (CNS).
• Activation of these receptors leads to inhibition of adenylate cyclase, reduced cAMP, and decreased release of excitatory neurotransmitters (glutamate, substance P).
• The result is diminished neuronal excitability and attenuated transmission of nociceptive signals.
• Because it is a *pro‑drug* in relation to hydromorphone formation, hepatic conversion via CYP2D6 augments its potency.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentrations occur 1–2 h after ingestion.
• Distribution: Widely distributed; high lipid solubility facilitates CNS penetration; plasma protein binding ~60%.
• Metabolism: Primarily hepatic via CYP2D6 (µ‑opioid active metabolite) and CYP3A4 (glucuronidation).
• Elimination: Renal excretion of metabolites; half‑life ≈ 3‑4 h (shorter in rapid metabolizers).
• Drug interactions: Potentiated by CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) and inhibitors of CYP3A4 (e.g., ketoconazole); CYP2D6 inducers (e.g., codeine, phenobarbital) may decrease analgesic effect.

Indications

• Moderate to severe pain requiring opioid analgesia, including:
• Post‑operative pain
• Acute injury pain
• Chronic pain when other analgesics are inadequate
• Often combined with acetaminophen or ibuprofen for synergistic effect (e.g., oxycodone‑acetaminophen).
• Not approved for pre‑medication or for use in mild pain.

Contraindications

• Contraindications:
• Severe respiratory depression or hypoventilation
• Acute or severe bronchial asthma
• Known hypersensitivity to opioids
• Severe hepatic impairment (CYP2D6 activity loss)
• Warnings:
• Respiratory depression—monitor respirations, especially in overdose or when combined with CNS depressants.
• Addiction, abuse, and dependence—high misuse potential; prescribe per CDC opioid guidelines.
• CYP2D6 deficiency—may lead to variable analgesic response; consider alternative analgesics.
• Drug interactions (e.g., benzodiazepines, alcohol) heighten risk of CNS depression.

Dosing

• Adults:
• Oral immediate‑release: 5–10 mg PO every 4–6 h as needed (max 60 mg/24 h).
• Oral controlled‑release: 15–30 mg PO every 12 h (max 120 mg/24 h).
• Elderly / renal/hepatic impairment: Start at the lower end; titrate cautiously.
• Children (approved in specific formulations): weight‑based dosing (0.4–0.8 mg/kg PO q8‑12 h).
• With acetaminophen: Do not exceed 4 g/24 h of acetaminophen component.
• Administration Tips: Take with food to reduce GI upset; avoid alcohol and other CNS depressants.

Adverse Effects

• Common:
• Sedation, dizziness, and impaired cognition
• Nausea/vomiting
• Constipation (first‑degree GI motility slowdown)
• Dry mouth (xerostomia)
• Serious:
• Respiratory depression leading to hypoventilation or apnea
• Severe hypotension (rare)
• Seizures (especially in overdose or with GABAergic drugs)
• Pseudo‑cholinesterase deficiency–related prolonged paralysis in overdose
• Psychotic reactions or mood changes in predisposed individuals

Monitoring

• Respiratory: Rate, tidal volume; watch for signs of hypoventilation.
• Mental status: Alertness, sedation scale (Ramsay).
• Pain level: Numeric Rating Scale (NRS) or Visual Analog Scale (VAS).
• GI effects: Monitor for constipation, use bowel regimen prophylaxis.
• Serum acetaminophen: In combined preparations, especially at higher doses.
• Liver function: Baseline and periodic ALT/AST if long‑term therapy.
• Drug interactions: Screen for CYP2D6 inhibitors/inducers and co‑prescribed CNS depressants.

Clinical Pearls

• Quick Titration: Start at the *lower 5 mg* dose, particularly in novices; titrate every 4–6 h based on pain relief and side‑effect profile.
• Switching to Controlled‑Release: Only when steady‑state analgesia is achieved; do not split immediate‑release tablets.
• Use of Naloxone: In accidental over‑dose, 0.4 mg IV every 2–3 min; be prepared for repeated dosing due to the short half‑life.
• Avoid Overlap: Do not give two opioid formulations simultaneously unless clinically justified; monitor cumulative opioid dose.
• CYP2D6 Genotyping: Consider in patients not achieving adequate analgesia despite standard dosing, especially when concomitant CYP2D6 inhibitors are used.

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• *This drug card consolidates core pharmacologic information for Hydrocodone, aimed at medical students and clinicians seeking evidence‑based, precise guidance.*