Morphine

Morphine is absolutely contraindicated in patients with significant respiratory depression or acute severe asthma in an unmonitored setting. The drug's primary toxicity mechanism — brainstem respiratory depression — directly worsens any pre-existing ventilatory compromise.

Raised intracranial pressure is a relative contraindication. Morphine-induced respiratory depression produces hypercapnia, which can elevate ICP via cerebral vasodilation. Additionally, morphine's sedative effects can mask neurological deterioration.

Hepatic cirrhosis or significant hepatic impairment increases morphine oral bioavailability due to reduced first-pass UGT2B7 glucuronidation and moderately reduces IV clearance. Dose reduction required.

Renal insufficiency is a relative contraindication requiring dose reduction and enhanced monitoring. M6G accumulates when renal clearance is impaired, producing disproportionately prolonged opioid effects and elevated overdose risk even at standard doses.

Morphine crosses the placenta and is excreted in breast milk. Chronic use during pregnancy carries risk of neonatal opioid withdrawal syndrome. Use during labor may cause neonatal respiratory depression. Not absolutely contraindicated — clinical scenarios exist where morphine use is appropriate under close monitoring.

Paralytic ileus is an absolute contraindication. Morphine reduces gastrointestinal motility via enteric MOR agonism, which can worsen existing bowel obstruction to the point of perforation or ischemia.

Known hypersensitivity to morphine or other morphinan opioids is an absolute contraindication. True opioid allergy is rare but can produce anaphylaxis. Non-IgE histamine release (flushing, pruritus) is a pharmacological effect and is not a contraindication.

Concurrent MAOI use carries risk of severe respiratory depression and poorly characterized but potentially dangerous interactions. A washout period is recommended before initiating morphine in patients on MAOIs.