Mechanism of Action

• Stimulation of central and peripheral opioid receptors.

Effects and Side Effects

• Central Depressive Effects:
  • Analgesia, respiratory depression, sedation, anxiolysis.
  • Orthostatic dysfunction, dysphoria.
  • Suppression of cough and vomiting reflex (delayed effect).
  • Lowering of seizure threshold.
• Central Activating Effects:
  • Euphoria, nausea/vomiting (early effect).
  • Miosis, skeletal muscle rigidity.
• Peripheral Effects:
  • Delayed gastric emptying.
  • Spasmogenic effects on smooth muscle:
    • Spastic constipation, urinary retention, biliary stasis.
  • Increased bronchial secretion, bronchoconstriction.
  • Hypotension due to histamine release.

Key Points

• Respiratory Depression:
  • Pain serves as a strong respiratory drive, counteracting opioid-induced respiratory depression.
  • Respiratory depression typically occurs only with significant overdose or concurrent use of other respiratory depressants.
• Constipation:
  • Affects nearly all patients on regular opioid therapy (no tolerance develops).
  • Treatment: Prophylactic and continuous laxative use, such as:
    • Lactulose (e.g., Bifiteral), initial dose: 20–40 ml.
    • Bisacodyl (e.g., Laxoberal), initial dose: 10–15 drops.
    • Adjust dosage as needed.
• Nausea and Vomiting:
  • Common during the initiation of opioid therapy (tolerance develops).
  • Treatment: Metoclopramide (e.g., Paspertin), 3 × 10 mg daily.
• Withdrawal Symptoms:
  • Occur after abrupt cessation of long-term opioid therapy.
  • Symptoms: Anxiety, restlessness, insomnia, yawning, sweating, runny nose, mydriasis, tremors, cramps, pain, increased blood pressure and heart rate, nausea.
  • Rarely significant in pain management contexts.
• Tolerance Development:
  • Decreased opioid effectiveness can occur after days or weeks of continuous therapy.
  • Central effects are primarily affected.
  • Likely with short-acting opioids or parenteral administration due to reduced endogenous opioid production.
  • Prevention: Use extended-release formulations and fixed schedules to avoid breakthrough pain.

Administration Guidance

• Dosage:
  • Tailor dosage to the patient’s condition:
    • Increased requirement in severe pain with stable circulation.
    • Reduced requirement in shock or somnolence.
  • Avoid “as-needed” prescriptions for chronic pain; use a fixed schedule to prevent breakthrough pain.
• Dependency Risk:
  • Addiction is highly unlikely with appropriate opioid use following the WHO analgesic ladder.

Indications

• Severe pain.

Contraindications

• Absolute or Relative:
  • Children under 1 year, pregnancy, and lactation.
  • Respiratory insufficiency or impaired respiratory drive.
  • Urinary tract stenosis, prostatic hyperplasia with residual urine formation.
  • Obstructive or inflammatory bowel diseases (e.g., ileus).
  • Shock, risk of addiction.

Antidote

• Naloxone (Narcanti):
  • For opioid overdose.
• Initial Dose: 0.4–2 mg IV, repeat every 3–5 minutes if necessary.
• Note: Ineffective for buprenorphine.

Notes on Dosage

• Dosage varies based on the patient’s condition:
• Increased doses may be required in cases of severe pain with stable hemodynamics.
• Reduced doses may be necessary in shock or somnolent states.
• The listed dosages serve as general guidelines and may require adjustments.

Low-Potency Opioids

• Characteristics:
  • Lower analgesic potency compared to morphine.
  • Not classified as narcotics (non-BtM).

Common Low-Potency Opioids

Tramadol

• Forms: Capsules (50 mg), long-release tablets (100/150/200 mg), suppositories (100 mg), injections (50/100 mg).
• Dosage:
  • Single dose: 50–200 mg.
  • Repeat every 4 hours (long-release every 12 hours).
  • Maximum daily dose: 600 mg/day.
• Notable Side Effects:
  • Frequent nausea and vomiting.
  • Minimal constipation and respiratory depression.

Tilidine/Naloxone

• Forms: Drops (50/4 mg), capsules (50/4 mg), long-release tablets (50/4 to 150/12 mg).
• Dosage:
  • Single dose: 50/4–150/12 mg.
  • Repeat every 4–6 hours (long-release every 12 hours).
  • Maximum daily dose: 600/48 mg/day.
• Special Feature:
  • Naloxone component prevents absorption after oral administration.
  • Rare nausea, vomiting, or constipation.

Dihydrocodeine

• Forms: Retard tablets (60/90/120 mg).
• Dosage:
  • Single dose: 60–120 mg.
  • Repeat every 12 hours.
  • Maximum daily dose: 240 mg/day.

High-Potency Opioids for Chronic Pain Therapy

Common High-Potency Opioids

Morphine

• Forms:
  • Morphine sulfate: Retard tablets (10/30/60/100/200 mg), granules (20/30/60/100/200 mg), suppositories (10/20/30 mg).
  • Morphine hydrochloride: Ampoules (10/20 mg).
• Dosage:
  • Oral: 10–200 mg; repeat every 8 hours (long-release every 12–24 hours). No maximum dose; side effects limit the dose.
  • Parenteral: 5–20 mg (or more) subcutaneous, intramuscular, or slow intravenous infusion. Repeat every 4 hours.

Levomethadone

• Forms: Ampoules (2.5 mg) or oral drops (5 mg/20 drops).
• Dosage:
  • 2.5 mg intravenously or up to 15 mg orally, subcutaneously, or intramuscularly.
  • Repeat every 6–12 hours.
  • No maximum dose; side effects limit the dose.

Buprenorphine

• Forms: Sublingual tablets (0.2/0.4 mg), ampoules (0.3 mg).
• Dosage:
  • 1–2 tablets sublingually or 1 ampoule intramuscularly/slow intravenous infusion.
  • Repeat every 8 hours.
  • Maximum daily dose: 15 mg.
• Important Note: Naloxone cannot reverse buprenorphine-induced respiratory depression. Use Doxapram if needed.

Hydromorphone

• Forms: Retard capsules (4/8/16/24 mg), ampoules (2 mg).
• Dosage:
  • Oral: 4–24 mg; repeat every 12 hours.
  • Parenteral: 1–1.5 mg IV, 1–2 mg IM or SC.

Fentanyl

• Forms:
  • Transdermal patches (25/50/75/100 µg/h, duration 48–72 hours).
  • Oral transmucosal (200–1600 µg per unit).
• Dosage:
• Transdermal: Start with 25 µg/h, titrate as needed.
• Oral-transmucosal: Administer via applicator for breakthrough pain; onset within 5 minutes.

Notes on Usage

• Antidote for Overdose: Naloxone (Narcanti 0.4 mg/ml):
  • Initial dose: 0.4–2 mg IV.
  • Repeat every 3–5 minutes if necessary.
  • Ineffective for buprenorphine overdose.
• Respiratory Depression Treatment for Buprenorphine: Doxapram (Dopram):
  • 4 ampoules (20 mg/amp) in 250 ml saline infused over 1 hour IV.

High-Potency Opioids for Acute Pain Therapy

Common High-Potency Opioids

Buprenorphin, Levomethadone, Morphine

• Refer to chronic pain therapy section for details.

Pentazocine

• Forms: Ampoules (30 mg), capsules (50 mg), suppositories (50 mg).
• Dosage:
  • Single dose: 1 ampoule intramuscularly or slowly intravenously.
  • Repeat every 3–4 hours.
  • Maximum daily dose: 360 mg.
• Special Feature: Increases blood pressure, no spasmogenic effect.

Pethidine

• Forms: Ampoules (50/100 mg), drops (50 mg/20), suppositories (100 mg).
• Dosage:
  • Single dose: 1 ampoule subcutaneously, intramuscularly, or slowly intravenously.
  • Repeat every 2–3 hours.
  • Maximum daily dose: 500 mg.
• Special Feature: No spasmogenic effect.

Piritramide

• Form: Ampoules (15 mg).
• Dosage:
  • Single dose: 1 ampoule intramuscularly or slowly intravenously.
  • Repeat every 4–6 hours.
  • Maximum daily dose: 300 mg.
• Special Feature: No histamine release.

Equianalgesic Doses of Opioids

Notes

1. Ceiling Effect:

• Applies to some medications (e.g., Tramadol, Tilidine/Naloxone, Buprenorphine).
• Further dose increases do not enhance analgesic effects.

1. Higher Doses:

• For most other opioids, much higher daily doses are possible depending on patient needs (e.g., up to 2400 mg/day of Morphine).