Opium
Opium
Generic Name
Opium
Mechanism
- Primary action: Activation of *mu‑opioid receptors* (MOR) in the central and peripheral nervous systems, resulting in inhibition of GABAergic interneurons, decreased release of catecholamines and prostaglandins, and hyperpolarization of postsynaptic neurons.
- Secondary constituents
- *Thebaine*: A potent mu‑receptor antagonist; contributes to antitussive and spasmolytic effects without strong analgesia.
- *Papaverine*: Non‑selective phosphodiesterase inhibitor → smooth‑muscle relaxation; helpful in relieving spasms.
- *Noscapine*: Antitussive via vagal nerve inhibition and modulation of central chemoreceptors.
The net result is ↓pain perception, ↓cough reflex, ↓smooth‑muscle tone, and ↑safety margin when combined with other analgesics.
Pharmacokinetics
| Parameter | Typical values (oral) |
| Absorption | 30–60 % oral bioavailability; peak plasma ⬆ 4–6 hr after ingestion |
| Distribution | Lipid‑soluble; plasma protein binding ~90 % (primarily to albumin) |
| Metabolism | Hepatic CYP2D6, CYP3A4 → morphine, codeine, thebaine → morphine‑6‑glucuronide (active) |
| Excretion | Renal (≈30 %) and fecal (≈60 %) as unchanged alkaloids and metabolites |
| Half‑life | Morphine 2–4 hr; codeine 3–5 hr; thebaine <1 hr (rapid clearance) |
| Special populations | ↓CYP2D6 activity ⇒ reduced codeine conversion; hepatic impairment prolongs morphine exposure |
Indications
- Severe acute and chronic pain (e.g., cancer, post‑operative) – when synthetic opioids are inaccessible or contraindicated.
- Cough suppression – cough syrups formulated with extracted alkaloids (≥30 % thebaine).
- Spasmodic gastrointestinal and genitourinary disorders – due to papaverine’s antispasmodic effect.
- Adjunctive therapy in anesthesia – low‑dose infusions for intra‑operative analgesia.
Contraindications
- Absolute
- Known hypersensitivity to opiates
- Severe respiratory depression or uncontrolled apnea
- Severe bronchial asthma with active exacerbation
- Pregnancy (3rd trimester) and lactation unless no alternatives
- Pediatric <12 yrs (unless for severe pain and no alternatives)
- Relative
- Opioid dependence or abuse history
- Severe hepatic or renal dysfunction (dose adjustment required)
- Severe hypotension or shock
- Concurrent CNS depressants (benzodiazepines, alcohol, barbiturates)
- CYP2D6 poor metabolizer status → unpredictable codeine conversion
- Warnings
- Respiratory depression – most serious adverse effect; requires continuous monitoring.
- Addiction & Withdrawal – risk increases with prolonged use.
- Drug interactions: CYP450 inhibitors (ketoconazole, cimetidine) ↑ morphine levels; CYP2D6 inducers (rifampin, phenytoin) ↓ codeine efficacy.
- Constraint in cardiac disease: may precipitate hypotension via V‑reflex.
Dosing
> Note: Modern practice prefers isolated alkaloids (morphine, codeine). The following gives a rough equivalent for opium decoction.
| Clinical scenario | Oral | Intravenous (IV) | Notes |
| Chronic moderate pain | 3–6 g × 3–4 × day (≈60–80 mg morphine eq/day) | 10–20 mg morphine IV every 4–6 hr | Aim for moderate analgesia. |
| Severe acute pain/Iv infusion | – | Morphine‑based infusion: 0.1 mg/kg/h (equivalent to 5–10 g opium) | Titrate to pain score; monitor RR and O₂ sat. |
| Cough | 0.5–1 g × lozenge, 4 × day | – | Prefer thebaine‑rich extracts. |
| Spasmolytic use | 3–6 g for GI/UTS spasm | – | Papaverine‑rich fraction better. |
*Adjust for age, weight, renal/hepatic function, and opioid tolerance.*
Adverse Effects
- Common
- *Sedation / Euphoria*
- *Nausea / Vomiting* (≈25 %)
- *Constipation* (≈30 %)
- *Respiratory depression (mild)*
- *Hypotension* (≈5 %)
- Serious
- *Respiratory failure / apnea*
- *Severe hypotension / shock*
- *Allergic reactions* (rare)
- *Addiction / physical dependence*
- *Seizures* (rare in high doses)
Monitoring
- Vitals: RR, SpO₂, BP, pulse, level of consciousness (Ramsay or MOAAS) every 15–30 min in first 2 hr.
- Pain scores (VAS/NRS) hourly for first 6 hr, then every 4 hr.
- Bowel function: stool frequency; address constipation early (laxatives, stool softeners).
- Respiratory pattern: watch for hypoventilation or apnea.
- Lab tests: CBC, CMP, liver enzymes every 48–72 hr for inpatient stays >48 hr.
- Urine drug screen if abuse risk identified.
Clinical Pearls
- Differentiate opium from isolated morphine: Opium is a crude mixture; its alkaloid profile yields a *balanced* analgesic + antitussive effect.
- Thebaine’s role: Though a MOR antagonist, it dampens cough reflex via central vagus modulation; hence *thebaine‑rich syrup* remains a gold‑standard cough suppressant in many countries.
- Papaverine for spasmolysis: Share potent vasodilatory & smooth‑muscle relaxant activity; consider an adjunct when using opium for abdominal cramping.
- CYP2D6 impact on codeine: Use genotyping or clinical response to predict codeine conversion; consider morphine directly when unreliable.
- Opium dosing by weight is rarely applied: Use morphine equivalents for precision; weight‑based dosing is recommended when using IV morphine derived from opium for accurate titration.
- Avoid “cough throat‑sprays” containing opium in patients with COPD or sleep apnea; the risk of respiratory depression outweighs benefits.
- Tapering schedule: Begin with a 10–20 % dose reduction every 3–4 days to mitigate withdrawal; 24‑hr bath of sedatives (e.g., clonidine) may ease transition.
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• Key take‑away: *Opium* remains a clinically valuable but complex natural opioid. Modern analgesic protocols should lean toward purified alkaloids for dose precision, yet its unique mixture of morphine, codeine, thebaine, and papaverine confers distinctive analgesic, antitussive, and spasmolytic effects valuable in specific therapeutic niches.