(+)-Morphine

(+)-Morphine, also known simply as morphine, is a naturally occurring opiate alkaloid derived from the opium poppy, Papaver somniferum. It is a potent analgesic (pain reliever) and remains one of the most effective medications for severe pain. (+)-Morphine acts primarily on the mu-opioid receptor (μ-opioid receptor) in the central nervous system, producing its characteristic effects of pain relief, sedation, euphoria, and respiratory depression.

History:

Morphine was first isolated in 1804 by Friedrich Sertürner, a German pharmacist, who initially named it "morphium" after Morpheus, the Greek god of dreams. Its widespread use began in the mid-19th century following the development of the hypodermic syringe, which allowed for more efficient and rapid administration. While its analgesic properties were highly valued, its addictive potential soon became apparent, leading to significant social and medical problems.

Pharmacology:

Morphine's primary mechanism of action involves binding to and activating mu-opioid receptors, which are G-protein coupled receptors. Activation of these receptors in the brain and spinal cord inhibits the transmission of pain signals. It also affects other receptors, including the kappa-opioid and delta-opioid receptors, although to a lesser extent.

Morphine is typically administered orally, intravenously, intramuscularly, or subcutaneously. It undergoes significant first-pass metabolism in the liver, reducing its oral bioavailability. Morphine is metabolized primarily by glucuronidation in the liver to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). M6G is also an active metabolite and contributes to the analgesic effects of morphine, while M3G does not provide analgesia and may contribute to some adverse effects.

Uses:

(+)-Morphine is primarily used for the treatment of severe acute and chronic pain. Common uses include:

• Post-operative pain
• Cancer pain
• Pain associated with myocardial infarction
• Pain from traumatic injuries
• Palliative care and end-of-life care

Adverse Effects:

The most common side effects of morphine include:

• Constipation
• Nausea and vomiting
• Sedation
• Dizziness
• Itching (pruritus)
• Respiratory depression
• Hypotension (low blood pressure)
• Urinary retention

Tolerance and Dependence:

Prolonged use of morphine can lead to tolerance, where higher doses are needed to achieve the same analgesic effect. Physical and psychological dependence can also develop, leading to withdrawal symptoms upon discontinuation of the drug. These withdrawal symptoms can include anxiety, muscle aches, sweating, diarrhea, and abdominal cramping. Due to its high potential for abuse and addiction, morphine is a controlled substance in most countries.

Contraindications:

Morphine is contraindicated in patients with:

• Known hypersensitivity to morphine or other opioid analgesics
• Significant respiratory depression
• Acute or severe bronchial asthma
• Paralytic ileus
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs.
• Severe liver or kidney impairment should be considered for dosage adjustments.

Formulations:

Morphine is available in various formulations, including:

• Immediate-release tablets and solutions
• Extended-release tablets and capsules
• Injectable solutions
• Rectal suppositories