Tramadol-Induced Hyponatremia- An Overview

Introduction

Hyponatremia caused by Tramadol is a biochemical side-effect of the drug. Tramadol is a painkiller medicine that is used to relieve moderate to severe pain, including pain after surgery. It is available both in immediate-release and extended-release versions. For continuous chronic pain, extended-release capsules or tablets are being used. It belongs to the opioid group of painkillers.

There are several side effects of the medicine, such as dizziness, nausea, vomiting, constipation, muscle aches and pain, itching, skin rashes, loss of strength, weakness, feeling of warmth, increased heart rate, increase in blood pressure, pain in the arms and legs, pain in the stomach, hyponatremia, etc.

Hyponatremia is a condition in which there is a decrease in the level of sodium in the body. An electrolyte imbalance might be associated with a long hospital stay or mortality. The sodium ion is a very important electrolyte. Sodium is required by the body to carry out various functions properly. It is an electrolyte located in the blood and the extracellular fluid. It keeps the body fluids in perfect balance and helps in the proper functioning of the muscles and nerves. The average blood sodium level is around 135 to 145 milliequivalents per liter (mEq/L). Sodium levels below 135 mEq/L suggest hyponatremia.

What Are the Symptoms Of Hyponatremia?

Symptoms of hyponatremia include,

• Nausea.

• Vomiting.

• Headache.

• Confusion.

• Loss of energy.

• Restlessness.

• Muscle weakness.

• Drowsiness.

• Fatigue.

• Irritability.

• Muscle spasms.

• Cramps.

Whereas sodium concentration lower than 120 mEqL/L can cause severe symptoms like seizures, coma, respiratory arrest, or mortality.

Hyponatremia is classified into three types: hypovolemic type, euvolemic type and hypervolemic type. The hypovolemic type occurs due to prolonged use of thiazide diuretics, a group of drugs that induce urine outflow. The euvolemic type is due to inappropriate secretion of antidiuretic hormone (SIADH). The hypervolemic type occurs when excessive water retention leads to the dilution of the sodium ions, thus causing hyponatremia.

Sodium helps to regulate the water content inside and around the cells. Hyponatremia is caused by certain medications, some medical conditions, or by drinking too much water leading to dilution of the sodium content in the body. This rise in the level of water causes the cells to swell. This swelling causes a lot of health problems ranging from mild to life-threatening.

How Tramadol Causes Hyponatremia?

Tramadol belongs to the family of opioid analgesics or painkillers. Opioid analgesics are a group of painkillers like opiates such as morphine but are not prepared from opium. The exact mechanism of action of Tramadol is not known. The development of hyponatremia due to Tramadol is an incidental effect. Several case studies were performed on patients receiving Tramadol after surgery.

Normally during pain, a neuron or nerve transmits the sensation to the brain. The brain reads the signal and then transmits the pain sensation back through the nerves. Tramadol and other painkillers block the painful sensation from reaching the brain. Thus one does not feel pain after consuming Tramadol. The brain has certain receptors for pain. There are three types of opioid receptors located in the brain. One of those is the mu receptor. Tramadol specifically acts on the mu-opioid receptor and binds to it, blocking the nerve from communicating the pain signal to the brain. Tramadol causes hyponatremia via a few mechanisms.

They are,

• The first mechanism suggests that Tramadol inhibits serotonin and norepinephrine reuptake; these neurotransmitters activate the pain-stopping pathways in the spinal cord. Serotonin is a chemical messenger that carries messages from the brain's nerves to the different parts of the body. Norepinephrine or noradrenaline is a chemical that acts both as a neurotransmitter and a hormone. Tramadol increases the release of serotonin to achieve its painkiller effect, thus increasing the level of serotonin in the brain. Increased serotonin levels and selective serotonin reuptake inhibitors stimulate the release of antidiuretic (ADH) hormone, thus causing hyponatremia.

• The second mechanism could be the inappropriate secretion of antidiuretic hormone (SIADH). It is a common side effect of opioid painkillers and could cause hyponatremia. SIADH is a condition in which the body makes excessive amounts of the antidiuretic hormone or ADH. ADH helps the kidneys regulate the amount of water lost from the body through urine. So, when there is excessive production of ADH, the body retains too much water, causing an increase in the fluid volume with a lesser concentration of sodium, thus resulting in hyponatremia.

• Certain side effects of Tramadol, such as nausea and vomiting Tramadol may also lead to the release of the antidiuretic hormone or ADH, causing hyponatremia.

• Tramadol might also stimulate the thirst center in the brain leading to increased uptake of water, thus lowering the sodium concentration and causing hyponatremia.

• Tramadol overdose may also cause a decrease in sodium ion concentration.

Conclusion:-

Hyponatremia induced by Tramadol is a random and rare side effect. Tramadol is a widely used painkiller because of its negligible side effect on respiration rate. Both opioid and serotonin pathways together can cause hyponatremia. Medications that increase the concentration of serotonin might cause the release of ADH in individuals who are not dehydrated. Due to this,Tramadol is capable of causing hyponatremia related to SIADH in some patients. Doctors should be vigilant while prescribing the drug.

Patients showing a decrease in sodium concentration should be monitored, and the dose of Tramadol should be reduced or discontinued. Sodium levels should be monitored while prescribing Tramadol or any other opioid painkiller, especially in the elderly population and others who are already taking medications such as diuretics (drugs that increase the production of urine) or SSRI (selective serotonin reuptake inhibitors), an antidepressant drug, because the intake of these drugs also makes them prone to hyponatremia. This rare side effect of Tramadol-causing hyponatremia should be considered while prescribing the drug.