What Is Morphine & What Is Its Role?

Have you ever been in the situation of using morphine? This substance is used in medicine in a wide variety of cases.

History of Morphine

Morphine was isolated in 1804 by Friedrich Wilhelm Adam Sertürner, a German pharmacist who named it “morphium.” In 1853, after the hypodermic needle development, morphine`s use started to be widespread especially as sedative or analgesic, but also to treat opiate addiction or depression.

The “morphine” term comes from the Morpheus, who was the God of Dreams in Greek mythology, a name received because of the effects produced.

What Is Morphine?

Morphine represents an alkaloid that is derived from opium, which is extracted from a poppy species (Papaver somniferum), its concentration in the extract of opium being of 8% to 14%. Once it reaches the organism, it stimulates opioid receptors, leading to a large variety of effects.

After extraction, this substance presents itself with white prisms less soluble in ether and water, soluble in hard water, ethanol, chloroform, amyl alcohol, benzene and even less soluble in ammonia. Gross morphine from the black market might have different concentrations, depending on the methods through which they are obtained and purification processes.

Morphine is quickly absorbed after the parenteral administration (iv and/or sc), or inhalation (powders). After oral administration, a first passage of the liver will occur, with a bioavailability of 20% to 30%. Maximum plasma concentration is reached in 10 to 20 minutes from the iv or sc administration. The substance is linked to 35% of plasma proteins and has a half-life of 2 to 3 hours. The absorption in the intestine is very slow and is mostly distributed in the kidneys, spleen and liver, however, without being accumulated in the tissues. Small amounts of this particular substance pass through the blood-brain barrier and reach the level of the central nervous system.

At the liver level, after a sulfuronoconfunction and glucuronide, 6-glucuronide-morphine is obtained, being the main active metabolite and which has a potency 2 times higher than that of morphine, and in the brain even 100 time higher. 6-glucuronide-morphine is responsible for analgesic action when the chronic administration of morphine is concerned.

When people with chronic renal failure are involved, this metabolite has the tendency to accumulate, this also being the explanation for the duration and potency of the action of morphine when these patients are concerned.

It`s eliminated in proportion of 90% through the kidneys under the form of 3-, 6-glucuronide-morphine, and in a smaller amount under non-transformed form. Ten percent is eliminated through faeces (small amounts of morphine can be detected in faeces and urine for a few days from the last dose). Fifty percent of morphine is eliminated from the organism in 4 to 5 hours.

Morphine along with its natural and synthetic derivatives are frequent named opiates or opioids. These last ones are among the most powerful analgesic medications, but the main disadvantage is that is causes severe drug addiction. These drugs are considered narcotic substances that have hallucinogenic effects.

What Is the Role of Morphine?

This specific substance is a powerful pain reliever. It has been used for similar purposes for years. Because morphine is very addictive, it`s use has been associated with high psychological and physical dependence.

Among the main uses of this substance, we include:

• Pain relief due to myocardial infarction or heart attack.
• Relief of the serious joint and bone pain that is associated with sickle cell crisis.
• General anesthesia for the patient`s sedation.
• Local anesthesia, like epidural or spinal anesthesia.
• Pain relief due to serious injuries, like the ones caused by road traffic accidents.
• Relief of pain caused by kidney stones or renal colic.
• Relief of serious joint pain due to disabling diseases, like osteoarthritis or rheumatoid arthritis.
• Relief of pain in patients with terminal cancer.
• A cough suppressant in situation where cough is quite serious.
• Relief of serious diarrhea.

Toxic Action

The mechanisms of producing the serious toxic effects that morphinomimetics might generate are generally associated with actions on distinct opioid receptors.

In therapeutic doses, morphine may produce:

• Indifference;
• Diminishing spontaneous mobility;
• Somnolence;
• Heat sensation;
• Diminishing mental performance;
• Pruritus in the face.

In 10% to 20% of these particular cases, the effects are pleasantly felt.

1. Morphine at the CNS level determines:

• Analgesia – it`s manifested by canceling the effect of suffering of the painful sensation (the increase of the level of pain is moderate).
• The depression of breathing increases along with the dose (in toxic doses, it may appear the “Cheyne-Stokes” breathing), bradypnea (slow breathing being accentuated until breathing stops.
• Morphine has an antitussive effect (by depressing the bulbar cough center) – an effect that is little used in the modern technology due to the danger of addiction. The relative potency of morphine is decreasing: cough depression > respirator center depression > analgesic action.
• It stimulates the triggering chemoreceptor areas of the bulb causing nausea and vomiting (when low doses are concerned); at high doses, it depresses the center of the vomit.
• In high doses, it causes hypothermia by depressing the thermoregulatory center.
• In high doses, miosis is produced (an essential symptom for morphinomania).

2. The action of morphine on the respiratory system:

• Determines bronchospasm (it has a more accentuated effect in asthmatics).

3. The action of morphine on the digestive system:

• Decreases gastric secretion & motility.
• Increases the tone of the stomach muscles.
• Increases the tone and reduces the peristalsis of the colon and small intestine.
• Causes a decreased pancreatic secretion.
• Has a constipation effect that is pretty strong.
• Also has a gallbladder spasm.

4. The action of morphine on the genitor-urinary system:

• Has a urinary spastic action, which increases the tone of the bladder sphincter and causes urinary retention.
• Causes uterine contractions.

5. The action of morphine on the endocrine secretion:

• Stimulates ADH secretion, which results in decreased dieresis.
• Affects the activity of adenohypophysis (especially when prolonged administration is involved).
• Decreases the secretion of testosterone. – Read more!

6. The action of morphine at the vascular level:

• Leads to arteriolar and venous vasodilation, which results in hypotension.
• Depresses the circulatory reflexes.
• Causes cerebral vessel dilation (because of CO2 which accumulates by respiratory center depression).
• Increases the pressure of cere fluid;
• The vasodilation of the skin with sweating, skin congestion and pruritus.

Indications of the Administration of Morphine

• Acute pains – myocardial infarction, postoperative, acute pulmonary edema, fractures.
• Renal colic in combination with antispastics for antagonizing hypertonia.
• Neoplasm.
• Small surgery, pre-anesthesia.

Contraindications for Morphine Administration

• Cases with limiting respiratory function.
• Serious hepatic insufficiency.
• Hyperthyroidism.
• Pregnancy & breastfeeding. – Learn more!
• Labor.
• Head injuries.
• Prostate hypertrophy.
• Acute pancreatitis.
• Acute abdomen.
• Children under 2 years old.

Precautions

In the pain treatment context, increasing doses even when it comes to those that are already increased don`t commonly reveal a process of dependency.

The patient`s condition need to be reevaluated often in order to detect any behavior regarding early addiction. This most frequently shows a real necessity for analgesia, which shouldn`t be confused with a real addiction behavior.

Morphine represents a drug that can lead to addiction, letting aside its use in pain treatment, for use of purposes that are non-therapeutic: psychological and physical dependence can be noticed as well, so tolerance can be developed with repeated administration. However, the drug`s history addiction doesn`t contraindicate this particular drug if it`s really required.

Depending on the dose, pain progression and treatment duration, the discontinuation of the treatment with morphine should be achieved gradually to avoid a possible installation of withdrawal syndrome. The signs include:

• Irritability.
• Chills..
• Mildness.
• Hypersudation.
• Rhinorrhoea.
• Anorexia.
• Diarrhea.
• Arthralgia.
• Anxiety.
• Insomnia.
• Feeling hot.
• Yawning.
• Mildness.
• Lacrimation.
• Nausea.
• Abdominal cramps.
• Myalgia.

During morphine treatment, it`s advisable to monitor the respiratory function, pain intensity and attention. Drowsiness represents a symptom of respiratory decompensation.

Athletes need to be careful as morphine might result in positive anti-doping examinations.

Special Attention

Children

In general, children don`t tolerate morphine too well. It can trigger idiosyncratic reactions at low doses in some children, with paralysis of the respiratory centers.

Pregnancy & Breastfeeding

Preclinical studies performed on pregnant women have outlined that the use of morphine may be associated with malformative effects.

In humans, the available data didn`t reveal any foetotoxic or malformative effect of this substance. If used in high doses even when talking about a treatment on short term, respiratory depression might occur in the baby. However, Naloxone can be used for treating a respiratory depression in the baby.

Chronic use of this substance by the pregnant woman during the last trimester of pregnancy might lead to withdrawal syndrome in the newborn, with signs of convulsions, irritability, vomiting and even death. Thus, the use of this substance during pregnancy is advisable only if no other therapeutic alternative is used and only after making an evaluation of potential fetal risk / maternal therapeutic benefit.

Because this substance is eliminated in breast milk, breastfeeding isn`t recommended during treatment.