The World of Pregnancy

Toxic Action of Morphine

Morphine is the main active agent from opium, its concentration in the extract of opium being of 8% to 14%. After extraction, morphine 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.

Toxic Action of Morphine

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. Morphine 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 morphine pass through the blood-brain barrier and reach the level of the central nervous system.

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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.

Forms of Presentation & Marketing

It`s presented as a granular powder of pink, white, brown or beige color. It can be found under various pharmaceutical forms (tablets, suppositories, injectable solutions).

Ways of Consumption

Morphine is administered:

  • Injectable;
  • Oral (tablets);
  • By inhalation (powder);
  • Neoplasm.

Toxic Action

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

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The actions of the opioid receptors are:

  1. μ – supraspinal analgesia (μ1), respiratory depressin (μ2), euphoria and physical dependence.
  2. κ – spinal analgesia, miosis, sedation.
  3. Psychotomimetic ffects, vasomotor stimulation and dysphoria.
  4. δ – analgesia & changes in affective behavior.

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).

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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.
  1. 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!

5. 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.

Particularly, in addicts is manifested by leukocytosis, pulmonary edema and skin abscesses, myoglobinuria, thrombophlebitis, hyperpyrexia, endocarditis. – Read more details!

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.
  • Labor.
  • Head injuries.
  • Prostate hypertrophy.
  • Acute pancreatitis.
  • Acute abdomen.
  • Children under 2 years old.
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