Tilidine

BRAND NAMES: 

• Valoron: One of the most well-known brand names for tilidine. In some countries, like Germany, it is sold in a combination formula with naloxone under the name Valoron N.

• Valtran: Another common brand name for tilidine. In countries like Belgium, it is sold in a combination with naloxone.

• Tilidin (generic): This name is used in some countries, such as Germany and Switzerland.

MECHANISM OF ACTION

• Tilidine is a prodrug, meaning it is inactive by itself and must be metabolized in the body to become effective.

• After oral administration, tilidine is rapidly converted in the liver to its active metabolite called nortilidine.

• Nortilidine acts as an agonist at the mu-opioid receptors (μ-opioid receptors) in the central nervous system.

• By binding to these receptors, nortilidine inhibits the transmission of pain signals by:

• Reducing the release of neurotransmitters involved in pain pathways.

• Hyperpolarizing nerve cells, making them less excitable.

• This leads to analgesic effects—reducing the sensation and perception of pain.

PHARMACOKINETICS

Absorption:

After oral administration, tilidine is quickly and fully absorbed; however, as a prodrug, it has very low bioavailability because it undergoes extensive first-pass metabolism. Its pain-relieving effects are mainly due to its active metabolite, nortilidine.

Distribution:

Tilidine is an opioid prodrug that is widely distributed in the body after being rapidly absorbed. However, its distribution is characterized by an extensive first-pass metabolism in the liver, which converts it into its active metabolite, nortilidine. Therefore, the distribution of tilidine is not as significant as the distribution of nortilidine.

Metabolism:

Tilidine is an opioid prodrug that is extensively metabolized in the liver to its active metabolite, nortilidine, and then to a secondary metabolite, bisnortilidine. The vast majority of tilidine's analgesic effect is attributed to nortilidine, which has a much higher affinity for opioid receptors than the parent drug.

Excretion:

• Tilidine and its metabolites are primarily eliminated through the kidneys via urine.

• A smaller portion is excreted in the feces.

• The active metabolite, nortilidine, and other metabolites are cleared renally.

• The elimination half-life of tilidine is approximately 3–5 hours, but this can vary depending on individual metabolism and kidney function.

PHARMACODYNAMICS

Tilidine is an opioid analgesic that exerts its effects primarily through its active metabolite, nortilidine, which acts as an agonist at the mu-opioid receptors in the central nervous system. Activation of these receptors leads to inhibition of ascending pain pathways, altering the perception and emotional response to pain. This results in effective analgesia, especially for moderate to severe pain.

ADMINISTRATION

Tilidine can be administered orally (by mouth), rectally (as a suppository), or by injection (subcutaneous, intramuscular, or intravenous). It is an opioid analgesic used for treating moderate to severe pain, and its administration is carefully managed by healthcare providers.

DOSAGE AND STRENGTH 

Dosage and strength information for tilidine, a prescription medication, should always be obtained from a qualified healthcare provider. The appropriate dosage depends on the specific formulation prescribed and is often given in combination with naloxone to help prevent misuse.

DRUG INTERACTIONS 

Tilidine, like other opioids, has several potential drug interactions that should be carefully considered to avoid serious side effects. One major concern is the use of central nervous system (CNS) depressants, such as benzodiazepines, alcohol, other opioids, and certain sleeping pills or antipsychotics. When combined with Tilidine, these can lead to increased sedation, respiratory depression, coma, or even death. Caution is also necessary when using monoamine oxidase inhibitors (MAOIs), as their combination with Tilidine may result in dangerous reactions like serotonin syndrome or hypertensive crisis. It's recommended to avoid MAOIs for at least 14 days before starting Tilidine.

FOOD INTERACTIONS 

Tilidine can generally be taken with or without food; however, taking it with food may help reduce gastrointestinal side effects such as nausea or stomach discomfort. There are no major food interactions known with Tilidine, but it is advisable to avoid alcohol completely during treatment. Alcohol can dangerously enhance the sedative and respiratory depressant effects of Tilidine, increasing the risk of severe side effects like dizziness, drowsiness, low blood pressure, or even respiratory failure.

CONTRAINDICATIONS

Contraindications for Tilidine Hydrochloride include a known allergy or hypersensitivity to the drug or any of its ingredients, the presence of severe respiratory disorders, and cases of acute intoxication involving alcohol or other central nervous system (CNS) depressants.

SIDE EFFECTS

• Dizziness

• Nausea and vomiting

• Drowsiness and fatigue

• Constipation

• Headache

• Nervousness

• Increased sweating

• Diarrhea (less common)

OVER DOSE 

A tilidine overdose is a life-threatening medical emergency caused by taking too much of the potent opioid painkiller. It can cause respiratory depression, unconsciousness, and cardiac arrest. 

TOXICITY

Tilidine, like other opioids, can be toxic in high doses or when misused. Overdose may lead to serious and potentially life-threatening effects, primarily due to its central nervous system (CNS) and respiratory depressant properties. Symptoms of Tilidine toxicity include extreme drowsiness, slurred speech, muscle weakness, cold or clammy skin, low blood pressure, bradycardia (slow heart rate), and severe respiratory depression, which can progress to coma or death if not treated promptly.