Sufentanilo

Uses

Sufentanilo is an opioid used to induce and maintain anesthesia, to act as an analgesic in labor and delivery, and to treat severe, acute pain.

The indications for this drug are as follows:

1. As an analgesic adjunct in the maintenance of balanced general anesthesia in patients who are intubated and ventilated.

2. As a primary anesthetic agent for the induction and maintenance of anesthesia with 100% oxygen in patients undergoing major surgical procedures, in patients who are intubated and ventilated, such as cardiovascular surgery or neurosurgical procedures in the sitting position, to provide favorable myocardial and cerebral oxygen balance or when extended postoperative ventilation is anticipated.

3. For epidural administration as an analgesic combined with low dose (usually 12.5 mg per administration) bupivacaine usually during labor and vaginal delivery

4. The sublingual form is indicated for the management of acute pain in adults that is severe to warrant the use of an opioid analgesic in certified medically supervised healthcare settings, including hospitals, surgical centers, and emergency departments.

Sufentanilo is also used to associated treatment for these conditions: Pain, Acute, Acute, severe Pain, General Anesthesia, Induction and Maintenance of General Anesthesia, Lumbar epidural anesthesia therapy, Short opioid analgesia requirement

How Sufentanilo works

Sufentanilo is a synthetic, potent opioid with highly selective binding to μ-opioid receptors . These receptors are widely distributed in the human brain, spinal cord, and other tissues , .

In general, opioids decrease cAMP (affecting neural signaling pathways), decrease neurotransmitter release, and cause membrane hyperpolarization, all of which contribute to the relief of painful symptoms .

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic neural transmission via G-proteins that activate effector proteins. Binding of the opiate receptor leads to the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP, located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. The release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is then inhibited .

Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist), also preventing neurotransmitter release .

Sufentanilo and other opioids open calcium-dependent inwardly rectifying potassium channels, resulting in hyperpolarization and reduced neuronal excitability , .

Toxicity

LD₅₀: 18.7 mg/kg (IV in mice)

A Note on Respiratory Depression

Major, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even in cases where it is used as recommended. Respiratory depression may lead to respiratory arrest and death if not diagnosed and treated appropriately. This drug should be administered only by persons specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, including respiration and cardiac resuscitation of patients in the age group being treated. This training must include the establishment and maintenance of a patent airway and assisted ventilation .

Carcinogenesis Long-term studies in animals to evaluate the carcinogenic potential of sufentanil have not been conducted .

Mutagenesis Sufentanilo was not found to be genotoxic in the in vitro bacterial reverse mutation assay (Ames assay) or in the in vivo rat bone marrow micronucleous assay .

Reproductive Toxicity

Sufentanilo caused embryolethality in rats and rabbits treated for 10-30 days during pregnancy with 2.5 times the maximum human dose by intravenous administration. The embryolethal effect was thought to be secondary to the toxicity for the mother animal model. No negative effects were noted in another study in rats that were treated with 20 times the maximum human dose in the period of organogenesis. The preclinical effects were only seen following administrations of levels significantly above the maximum human dose, which is therefore of minimal relevance for clinical use .

Pregnancy

May cause fetal harm

The Use in Lactation

Infants exposed to this drug through breast milk should be monitored for excess sedation and respiratory depression .

Food Interaction

• Avoid alcohol. Ingesting alcohol may potentiate the CNS depressant effects of sufentanil.
• Avoid grapefruit products. Sufentanilo is a CYP3A4 substrate; therefore, concomitant ingestion of CYP3A4 inhibitors like grapefruit products may increase serum levels of sufentanil and potentiate CNS depression.

Sufentanilo Alcohol interaction

[Moderate] GENERALLY AVOID:

Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics.

Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills.

In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

Concomitant use of opioid analgesics with ethanol should be avoided.

Sufentanilo Drug Interaction

Moderate: meperidine, hydromorphone, morphine, acetaminophen / hydrocodone, sotalol, valproic acidUnknown: sulfamethoxazole / trimethoprim, glycerin, heparin, sodium iodide, arginine, acetaminophen, vitamin a topical, bioflavonoids, levothyroxine, multivitamin, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol

Sufentanilo Disease Interaction

Major: liver disease, prematurity, acute alcohol intoxication, gastrointestinal obstruction, hypotension, intracranial pressure, respiratory depressionModerate: adrenal insufficiency, hypothyroidism, renal dysfunction, seizure disorders, urinary retention, arrhythmias

Volume of Distribution

Sufentanilo has a distribution time of 1.4 minutes and redistribution time of 17.1 minutes . The central volume of distribution after intravenous application of sufentanil is approximately 14 L and the volume of distribution at steady state is approximately 350 L .

Elimination Route

Bioavailability of a single sublingual tablet was 52%, decreasing to 35% with repeat dosing .

After epidural administration of incremental doses totaling 5 to 40 mcg sufentanil during labor and delivery, maternal and neonatal sufentanil plasma concentrations were at or near the 0.05 to 0.1 ng/mL limit of detection, and were slightly higher in mothers than in their infants .

Half Life

The elimination half-life is 164 minutes in adults when administered intravenously (IV). The elimination half-life of sufentanil is shorter (e.g. 97 +/- 42 minutes) in infants and children, and longer in neonates (e.g. 434 +/- 160 minutes) compared to that of adolescents and adults .

After a single administration of a 15 microgram sufentanil sublingual tablet, mean terminal phase half-lives in the range of 6-10 hours have been observed. After multiple administrations, a longer average terminal half-life of up to 18 hours was measured, owing to the higher plasma concentrations of sufentanil achieved after repeated dosing and due to the possibility to quantify these concentrations over a longer time period .

Clearance

The total plasma clearance after single intravenous administration is about 917 l/min .

The clearance of sufentanil in healthy neonates is approximately one-half that in adults and children. The clearance rate of sufentanil can be further reduced by up to a third in neonates with cardiovascular disease .

Elimination Route

Approximately 80% of the administered dose is excreted within 24 hours and only 2% of the dose is eliminated as unchanged drug .

Innovators Monograph

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