Sufentanil

DEA NFLIS-Drug Category -> Fentanyl and Fentanyl-related

DEA Schedule II Controlled Substance -> Opiates

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

log Kow = 3.95

2.8

3.95

Soluble

Water Solubility= 46 mg/ml /Sufentanil citrate/

Solubility in alcohol= 21 mg/ml /Sufentanil citrate/

In water, 76 mg/L at 25 °C

In water, 3,930 mg/L at pH 5.31; 3.3 mg/L at pH 7.98, both at 35 °C

1.20e-02 g/L

Breast Feeding; Lactation; Milk, Human; Analgesics, Opioid; Narcotics; Anesthetics, Intravenous; Opiates

Pharmaceuticals

96.6 °C

97 °C

7.85

pKa = 8.01

log Kow = 3.45

White powder. Soluble in water; freely soluble in methanol; sparingly soluble in acetone, ethanol, chloroform /Sufentanil citrate/

White, crystalline powder /Sufentanil citrate/

Danger

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

P260, P261, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P319, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including sufentanil citrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Sufentanil citrate/

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Opiates. Unless specifically excepted or unless in another schedule any of the following opiates, including its isomers, esters, ethers, salts and salts of isomers, esters and ethers whenever the existence of such isomers, esters, ethers, and salts is possible within the specific chemical designation, dextrorphan and levopropoxyphene excepted:. Sufentanil (DEA Code Number: 9740) is included on this list.

Vardanyan RS, Hruby; Fentanyl-related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications; Future Med Chem 6 (4): 385-412 (2014)

Satterlee GB, Skora IA; Criteria for Use of Fentanyl Citrate, Sufentanil Citrate, and Alfentanil Hydrochloride. Clin Pharm (10): 635-7 (1991).

Bovill JG; Which Potent Opioid? Important Criteria for Selection. Drugs 33 (5): 520-30 (1987).

Clotz MA, Nahata MC; Clinical Uses of Fentanyl, Sufentanil, and Alfentanil; Clin Pharm 10: 581-93 (1991). The pharmacokinetics, pharmacodynamics, and perioperative uses of fentanyl, sufentanil, and alfentanil.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Sufentanil citrate/

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. /Sufentanil citrate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Sufentanil citrate/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product. /Sufentanil citrate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. /Sufentanil citrate/

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. /Sufentanil citrate/

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /Sufentanil citrate/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Sufentanil citrate/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Sufentanil citrate/

Skin protection: Handle with gloves. /Sufentanil citrate/

Body Protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Sufentanil citrate/

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Sufentanil citrate/

Because sufentanil citrate may potentiate the effects of other CNS depressants including other opiate agonists, general anesthetics, tranquilizers, sedatives, and hypnotics (e.g., barbiturates), sufentanil should be administered with caution and dosage of at least one of the drugs should be reduced when they are used concomitantly.

Because of the inhibitory effects of pancuronium on the vagus nerve, tachycardia may occur following administration of high doses of pancuronium bromide during anesthesia with sufentanil and oxygen. Hypertension and an increase in cardiac index may also occur when sufentanil and pancuronium are administered concomitantly. To maintain a stable, lower heart rate and blood pressure during anesthesia with sufentanil and oxygen, a neuromuscular blocking agent with a lesser inhibitory effect on the vagus nerve or moderate doses of pancuronium should be used.

Cardiovascular depression, manifested by bradycardia and decreases in mean arterial pressure and cardiac output, may occur following administration of nitrous oxide concomitantly with high doses of sufentanil. Bradycardia occurs infrequently during anesthesia with sufentanil and oxygen and may be corrected by administration of atropine.

The effect of droperidol pre-treatment on the analgesic potency of morphine, fentanyl and sufentanil was assessed in mice. Acetic acid writhing test and tail immersion test were used to measure the analgesic response. The neuroleptic augments the effects of sufentanil and fentanyl. Thus, the dose-response curves for fentanyl and sufentanil were shifted to the left and the ED50 of the analgesics lowered in droperidol pre-treated animals. However, morphine analgesia was not influenced by droperidol. Combination of sufentanil or fentanyl with droperidol may be better than morphine to produce neuroleptanalgesia and anesthesia.

For more Interactions (Complete) data for Sufentanil (10 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 16,000(SRC), determined from a structure estimation method(2), indicates that sufentanil is expected to be immobile in soil(SRC). The pKa of sufentanil is 8.01(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the cation from moist soil is not expected because cations do not volatilize(SRC). Volatilization of neutral sufentanil from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 7.8X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Sufentanil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 16,000(SRC), determined from a structure estimation method(2), indicates that sufentanil is expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.01(3) indicates sufentanil will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation from water surfaces is not expected(SRC). Volatilization from water surfaces of neutral sufentanil is not expected(4) based upon an estimated Henry's Law constant of 7.8X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Sufentanil is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(5), an estimated BCF of 190(SRC), from its log Kow of 3.95(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high. Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sufentanil, which has an estimated vapor pressure of 6.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase sufentanil may be removed from the air by wet and dry deposition(SRC). Sufentanil contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Sufentanil is a solid. It is a Schedule II Controlled Substance. Sufentanil injection is used for intravenous administration as an analgesic adjunct in the maintenance of balanced general anesthesia in patients who are intubated and ventilated. In animals, sufentanil, like other opiate derivatives, is used for sedation, general anesthesia, and analgesia. HUMAN STUDIES: Acute overdose with sufentanil can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Sufentanil is a substance with a high potential for abuse similar to other opioids. ANIMAL STUDIES: Pregnant rabbits were treated with intravenous sufentanil doses of 0.005, 0.02, or 0.08 mg/kg/day. Decreased live fetuses per litter and decreased litter size in the high dose group were noted. No malformations or embryotoxic effects were noted despite maternal toxicity. Pregnant rats were treated intravenously with sufentanil 0.005, 0.02, or 0.08 mg/kg/day from Gestation Day 16 through Lactation Day 21. Sufentanil reduced birth weights in the mid- and high-dose groups, decreased live fetuses in the high-dose group, and decreased pup survival in all groups in the presence of maternal toxicity. No evidence of malformations was reported in rats. Sufentanil 7.5 ug/kg intrathecally was neurotoxic in sheep. Sufentanil did not exhibit mutagenic activity in the Ames microbial mutagen test with metabolic activation. In female rats receiving single IV doses up to 80 ug/kg, sufentanil did not produce structural chromosome mutations in the micronucleus test.

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates 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. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Sufentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids open calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of sufentanil can be estimated to be 16,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that sufentanil is expected to be immobile in soil. The pKa of sufentanil is 8.01(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ Certain opioids release histamine from cutaneous mast cells to produce local wheal and flare responses and adverse hemodynamic effects. In vivo responses to opioids suggest that cutaneous responses result from the interaction of opioids with opioid receptors on human mast cells. There are no data evaluating or comparing the opioids currently used in anesthesia. Volunteers were injected intradermally with different opioids as well as with naloxone and antihistamines to evaluate their effects on cutaneous mast cell reactivity and cutaneous vascular responses. Fentanyl and morphine produced concentration dependent wheal and flare responses in the range of 5X10-6 M to 1.5X10-3 M. Volunteers were then tested intradermally with different opioids and histamine at a 5X10-4 M concentration to determine their relative cutaneous effects. Morphine, meperidine, fentanyl, and sufentanil produced both wheal and flare responses that were significantly greater than those due to saline (p< 0.05). Naloxone, alfentanil, and nalbuphine did not produce significant wheal or flare responses. Butorphenol was followed by a significant wheal but no flare. Naloxone attentuated cutaneous wheal and flare responses to fentanyl and the flare response to morphine. Intradermal antihistamines (diphenhydramine and cimetidine) produced significant wheal and flare responses. Electron micrographs of biopsies from fentanyl induced wheals demonstrated normal mast cell architecture with no evidence of mast cell degranulation. Opioid effects on wheal and flare responses and mast cell degranulation appear independent of opioid analgesic potency. Opioids produce cutaneous vascular responses dependent on both histamine release from mast cells and direct effects on the vasculature.

/HUMAN EXPOSURE STUDIES/ Anesthetic induction may induce myocardial ischemia. A prospective randomized trial was instituted to compare the effect on ventricular function and myocardial metabolism of induction with fentanyl or its analogs sufentanil or alfentanil in 96 patients undergoing elective coronary artery bypass grafting. Hemodynamic, metabolic (coronary sinus oxygen and lactate extraction) and gated ventriculographic measurements were made awake preinduction, after induction and after intubation. Induction was performed with fentanyl 75 ug/kg, sufentanil 15 ug/kg or alfentanil 125 ug/kg and metocurine. Fentanyl induction was associated with the greatest stability of mean arterial pressure, cardiac performance, and systolic function without associated myocardial lactate production. Sufentanil produced the greatest depression of systolic function (p< 0.05) but without hemodynamic instability or myocardial lactate production in all but one patient. Induction with alfentanil produced the greatest reduction in mean arterial pressure (p< 0.05) associated with the greatest decrease in diastolic compliance (p< 0.05) and 50% incidence of myocardial lactate production (p< 0.05) with no significant change in coronary blood flow or myocardial oxygen consumption.

/SIGNS AND SYMPTOMS/ Acute overdose with Sufentanil Citrate Injection can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

/CASE REPORTS/ Epidural sufentanil infusions are routinely used for post-operative analgesia after high abdominal and thoracic surgery in our hospital. The erroneous administration of a bolus of 250 ug of sufentanil epidurally was followed by a 24 hour episode of deep analgesia and respiratory depression. The recovery from respiratory depression over a 27 hour period is described.

For more Human Toxicity Excerpts (Complete) data for Sufentanil (9 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

sufentanil

DILI Negative

Intravenous

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF of 190 was calculated in fish for sufentanil(SRC), using a log Kow of 3.95(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including sufentanil citrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Sufentanil citrate/

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Opiates. Unless specifically excepted or unless in another schedule any of the following opiates, including its isomers, esters, ethers, salts and salts of isomers, esters and ethers whenever the existence of such isomers, esters, ethers, and salts is possible within the specific chemical designation, dextrorphan and levopropoxyphene excepted:. Sufentanil (DEA Code Number: 9740) is included on this list.

N01AH03

N - Nervous system

QN - Nervous system

**Effect on the Central Nervous System (CNS)** In clinical settings, sufentanil exerts its principal pharmacologic effects on the central nervous system. Its primary therapeutic actions are analgesia and sedation. Sufentanil may increase pain tolerance and decrease the perception of pain. This drug depresses the respiratory centers, depresses the cough reflex, and constricts the pupils,. When used in balanced general anesthesia, sufentanil has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, sufentanil is approximately 5 to 7 times as potent as fentanyl. High doses of intravenous sufentanil have been shown to cause muscle rigidity, likely as a result of an effect on the substantia nigra and the striate nucleus in the brain. Sleep-inducing (hypnotic) activity can be demonstrated by EEG alterations. **Effects on the Respiratory System** Sufentanil may cause respiratory depression. **Effects on the Cardiovascular System** Sufentanil causes peripheral vasodilation which may result in orthostatic hypotension or syncope. Bradycardia may also occur. Clinical signs or symptoms of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotension. **Effects on the Gastrointestinal Tract** Sufentanil causes a reduction in motility associated with an increase in smooth muscle tone in both the antrum of the stomach and duodenum. Digestion of food in the small intestine may be delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased and lead to spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of the sphincter of Oddi, as well as temporary elevations in serum amylase.

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

We determined the binding domains of sufentanil and lofentanil in the mu opioid receptor by comparing their binding affinities to seven mu/delta and six mu/kappa chimeric receptors with those to mu, delta and kappa opioid receptors. TMHs 6 and 7 and the e3 loop of the mu opioid receptor were important for selective binding of sufentanil and lofentanil to the mu over the kappa receptor. TMHs 1-3 and the e1 loop of the mu opioid receptor conferred binding selectivity for sufentanil over the delta receptor. Thus, the region that conferred binding selectivity for sufentanil differs, depending on chimeras used. In addition, the interaction TMHs 1-3 and TMHs 6-7 was crucial for the high affinity binding of these two ligands. These two regions are likely to contain sites of interaction with the ligands or to confer conformations specific to the mu receptor.

Opioids are the most effective and widely used drugs in the treatment of severe acute and chronic pain. They act through opioid receptors that belong to the family of G protein-coupled receptors. Three classes of opioid receptors (mu, delta, kappa), expressed in the central and peripheral nervous system, have been identified. The analgesic effect of opioids is mediated through multiple pathways of opioid receptor signaling (e.g., G(i/o) coupling, cAMP inhibition, Ca(++) channel inhibition). The standard exogenous opioid analgesics used in the operating room are fentanyl, sufentanil, morphine, alfentanil, and remifentanil.

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.

In adults with normal renal and hepatic function, the plasma half-life in the initial (distribution) phase averages 0.72-1.2 minutes, the plasma half-life in the second (redistribution) phase averages 13.7-17 minutes, and the plasma half-life in the terminal (elimination) phase averages 140-158 minutes. The elimination half-life is longer (434 minutes) in neonates but shorter in infants and children (97 minutes), compared with adults and adolescents.

The liver and small intestine are the major sites of biotransformation. Sufentanil is rapidly metabolized to a number of inactive metabolites, with oxidative N- and O-dealkylation being the major routes of elimination.

Although the metabolic fate of sufentanil in humans has not been fully characterized, the drug appears to be metabolized mainly in the liver and small intestine via N-dealkylation at the piperidine nitrogen and O-demethylation. The O-demethylated metabolite appears to have about 10% of the analgesic activity of the unchanged drug. The hepatic extraction ratio of the drug (EH) has been reported to be about 0.72 following IV administration of a single 5-mcg/kg dose.

Half Life: 265 minutes

AFE2YW0IIZ

SUFENTANIL

Mechanisms of Action [MoA] - Full Opioid Agonists

Established Pharmacologic Class [EPC] - Opioid Agonist

Sufentanil is an Opioid Agonist. The mechanism of action of sufentanil is as a Full Opioid Agonist.

SUFENTANIL

Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.

Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage.

Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.

Ultrashort-acting anesthetics that are used for induction. Loss of consciousness is rapid and induction is pleasant, but there is no muscle relaxation and reflexes frequently are not reduced adequately. Repeated administration results in accumulation and prolongs the recovery time. Since these agents have little if any analgesic activity, they are seldom used alone except in brief minor procedures. (From AMA Drug Evaluations Annual, 1994, p174)

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.

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

Sufentanil 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.

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.

This randomized double-blind investigation was designed to study the placental transfer and neonatal effects of epidural sufentanil and fentanyl infused with bupivacaine for labor analgesia. Healthy parturient women (n = 36) received epidural bupivacaine alone (group B) or with fentanyl (group B-F) or sufentanil (group B-S). Group B received a 12-ml bolus of 0.25% bupivacaine followed by a 10 mL/hr infusion of 0.125% bupivacaine. Groups B-F and B-S received a 12-mL bolus of 0.125% bupivacaine with 75 ug fentanyl or 15 ug sufentanil, respectively, followed by 10 mL/hr of 0.125% bupivacaine with fentanyl 1.5 ug/mL or sufentanil 0.25 ug/mL. Maternal venous (MV) and umbilical arterial (UA) and umbilical venous (UV) bupivacaine and opioid plasma concentrations were determined. Neonatal assessment included Apgar scores, umbilical cord blood gas analyses, and neurobehavioral testing at delivery and at 2 and 24 hr of life using the Neurologic and Adaptive Capacity Score (NACS). The mean total dose of fentanyl was 136.6 +/- 13.1 micrograms (SEM), and of sufentanil, 23.8 +/- 1.8 micrograms. Although administered in a ratio of 5.7:1, fentanyl and sufentanil MV plasma concentrations were in the ratio of 27:1. UV/MV ratios were 0.37 for fentanyl and 0.81 for sufentanil. Fentanyl was detected in most UA samples, whereas sufentanil was present in only one sample. Neonatal condition was good and generally similar in all groups, with the exception of a lower NACS at 24 h in group B-F. Although the degree of placental transfer of sufentanil appeared greater than that of fentanyl, lower MV sufentanil concentrations resulted in less fetal exposure to sufentanil. The lower NACS at 24 hr in group B-F may reflect the continued presence of fentanyl in the neonate.

The effects of cirrhosis on the elimination kinetics and plasma protein binding of sufentanil were evaluated in 12 anesthetized patients with uncomplicated cirrhosis and these findings were compared with data from age-matched control anesthetized patients with normal hepatic and renal function. Sufentanil 3 ug/kg was given iv as a bolus injection and venous plasma concentrations were measured at intervals up to 10 hr. The average (+ or - standard deviation) elimination half life was 3.5 + or - 0.9 hr in controls and did not differ in cirrhotics: 4.1 + or - 0.6 hr. The plasma clearance did not differ between the two groups: 11.3 + or - 2.5 ml/min kg in controls and 10.8 + or - 4.6 ml/min kg in cirrhotic patients. The sufentanil free fraction was also similar in controls (8.3 + or - 1.5%) and in cirrhotic patients (9.6 + or - 1.8%). These data suggest that sufentanil in a single dose should have a similar duration of action in patients with uncomplicated cirrhosis and in normal patients.

Sufentanil (DEA Code Number: 9737) is a Schedule II controlled substance.

Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

Analgesics, Opioid; Adjuvants, Anesthesia; Narcotics; Anesthetics, Intravenous

MEDICATION (VET)

MEDICATION

The main use of this medication is in operating suites and critical care where pain relief is required for a short period of time. It also offers properties of sedation and this makes it a good analgesic component of anaesthetic regimen during an operation. [Wikipedia]. Also used as an analgesic adjunct in anesthesia and as a primary anesthetic drug in procedures requiring assisted ventilation and in the relief of pain.

Preparation: P.A.J. Janssen, G.H.P. Van Daele, Germany patent 2610228; eidem, United States of America patent 3998834 (both to Janssen).

Sufentanil is obtained by condensation of N-(4-methoxymethylpiperidin-4-yl)-N-phenylpropionamide with 2-thiophen-2-yl-ethyl methanesulfonate.