Fentanyl - instructions for use, dose, side effects, contraindications

The basic mechanisms of the analgesic effect of fentanyl are realized at the level of the spinal cord, subcortical structures and the cerebral cortex:

I. oppression of pain impulses in the afferent CNS pathways (impaired transmission of impulses from the end of the primary afferents to the intercalary neurons of the spinal cord):

1) As a result of blocking N-type calcium channels in presynaptic endings of axons of primary afferents, the release of substance P and glutamate is reduced,while the transmission of pain impulses to the intercalary neurons of the horn of the spinal cord is impaired.

2) Due to the stimulation of postsynaptic opioid receptors, the process of depolarization of the postsynaptic membrane is disrupted and the activation of the inserted neurons is inhibited by the mediator. All this leads to a violation of transmission of pain impulses at the level of the spinal cord (spinal action).

II. Strengthening the inhibitory effect of the descending antinociceptive system on the pain impulses in the afferent CNS pathways: when stimulating opioid receptors in the gray near-conductor substance and some other parts of the brain stem due to inhibition of inhibitory GABAergic neurons, activation of the descending antinociceptive system that inhibits the activity of the insertion neuron the posterior horns of the spinal cord, and, consequently, the transmission of pain impulses along the afferent pathways of the spinal cord (suprasp Other actions). Descending inhibitory influences at the level of the spinal cord are carried out with the participation of serotonin and norepinephrine.

III. Changing the emotional assessment of pain: as a result of the action of fentanyl on the higher departments of the central nervous system, the emotional assessment of pain changes, and its perception decreases (even if the feeling of pain persists, it worries the patient less).

Has a hypnotic effect (mainly in connection with the removal of the pain syndrome). Causes euphoria. With repeated administration, the development of tolerance and drug dependence is possible. Oppresses the respiratory center, excites the centers of the vagus nerve and vomiting. Increases the tone of the smooth muscles of the bile ducts, sphincters, including the urethra, bladder, sphincter of Oddi, reduces intestinal peristalsis, improves the absorption of water from the digestive tract. Reduces renal blood flow. In the blood, the content of amylase and lipase increases.

Pharmacokinetics:

To achieve an average level of anesthesia, the concentration of fentanyl should reach 15-20 ng / ml. With intravenous administration, the effect occurs in 1-3 minutes, reaches a maximum after 5-7 minutes and lasts 20-60 minutes, with intramuscular injection after 7-15 minutes. With blood proteins, up to 79% is associated. The clearance is 0.4-0.5 l / min, the half-life is 10-30 min, the volume of distribution is 60-80 l.Rapidly redistributed from the blood and brain into muscles and adipose tissue. Biotransformed in the liver (N-dealkylation and hydroxylation), kidneys, intestines and adrenal glands. It is excreted in urine (75% in the form of metabolites and 10% in unchanged form) and feces (9% in the form of metabolites). Penetrates into breast milk.

From the transdermal system (after patch application), the release of fentanyl occurs at a constant rate for 72 hours, with the therapeutic serum concentration gradually increasing in the first 12-24 hours, remaining relatively constant over the remainder of the period (half-life after the fourth application - about 17 hours). Removing the patch leads to a gradual decrease in the level.

Indications:

Neuroleptanalgesia (in combination with droperidol). Premedication (as part of certain schemes). As an anesthetic: for short-term extracorporeal operations; as an additional tool for operations under local anesthesia; with severe pain with myocardial infarction, lung infarction, renal and hepatic colic; with postoperative pain.

For dermal application: chronic pain with cancerdiseases; unrestrained pain; severe chronic pain in children older than 2 years who took opioid analgesics.

ICD-10

IX.I20-I25.I21 Acute myocardial infarction

XI.K80-K87.K80 Gallstone disease [cholelithiasis]

XIV.N20-N23.N23 Renal colic, unspecified

XVIII.R50-R69.R52.0 Acute pain

XVIII.R50-R69.R52.2 Another constant pain

XXI.Z40-Z54.Z51.4 Preparatory procedures for subsequent treatment, not elsewhere classified

Contraindications:

Bronchial asthma, drug addiction, conditions accompanied by oppression of the respiratory center, obstetrical operations, craniocerebral hypertension, hypersensitivity to fentanyl.

Acute or postoperative pain (inability to adequately adjust the dose in a short period of treatment, which can lead to severe or life-threatening hypoventilation), irritated, irradiated or damaged skin (at the site of application), diarrhea against pseudomembranous colitis caused by cephalosporins, lincosamides, penicillins, toxic dyspepsia; acute respiratory depression, pregnancy, breast-feeding, age to 18 years.

Carefully:

Bradyarrhythmia, arterial hypotension,renal and / or liver failure, acute surgical diseases of the abdominal cavity before diagnosis; respiratory failure (pneumonia, atelectasis and lung infarction, propensity to bronchospasm), head trauma, brain tumor, hypothyroidism, hepatic and / or renal colic, cholelithiasis, general severe condition, weakened patients, benign prostatic hypertrophy, urethral stricture, alcoholism , suicidal tendencies, hyperthermia, simultaneous reception of insulin, glucocorticoids, hypotensive drugs, MAO inhibitors.

Pregnancy and lactation:

Recommendations for FDA - Category C. Qualitative and well-controlled studies on humans and animals have not been conducted.

There is no information on the penetration into breast milk. Do not apply!

Dosing and Administration:

Intravenous, intramuscular, topical (transdermal system in the form of a patch). For premedication and in the postoperative period intramuscularly - to 0,05-0,1 mg, to children - 0,002 mg / kg; for introductory anesthesia - intravenously 0.1-0.2 mg; Neuroleptanalgesia - intravenously 0.2-0.6 mg (the administration is repeated every 20 minutes); in open heart surgery, 0.05-0.1 mg / kg.Locally - for 72 hours, put on a flat surface of the skin (non-irritated, with a minimal scalp, if necessary washed with clean water, without the use of detergents and thoroughly dried) and tightly pressed (the application places alternate). The dose is selected individually. Patients who had not previously taken opioids - the initial dose of 25 mcg / h; with tolerance to opiates in the transition to fentanyl treatment, the initial dose is calculated from the corresponding tables, based on the previous daily requirement for analgesics; When using a dose of more than 300 μg / h, additional or alternative routes of administration are possible.

When intravenously administered at a dose of 100-500 mcg, acute respiratory depression, up to apnea, is possible.

Side effects:

From the side digestive system: nausea, vomiting (12%, often at the beginning of therapy), constipation; dry mouth, anorexia, biliary tract spasm, cholestasis (in the main bile duct), gastralgia, stomach cramps; hepatotoxicity (dark urine, pale stool, icteric sclera and skin). In severe inflammatory bowel diseases: intestinal atony, paralytic intestinal obstruction, toxic megacolon (constipation, flatulence, nausea, spasms in the stomach, vomiting).

From the side of cardio-vascular system: reduction of blood pressure, tachycardia; bradycardia; frequency unknown - increased blood pressure.

From the side respiratory system: depression of the respiratory center; bronchospasm, atelectasis.

From the side nervous system: dizziness, fainting, drowsiness, unusual fatigue, general weakness; headache, tremor, involuntary muscular twitching, discoordination of muscle movements, paresthesia, nervousness, depression, confusion (hallucinations, depersonalization), increased intracranial pressure with the probability of subsequent cerebral circulatory disorders, insomnia; rarely - restless sleep, CNS depression; against a background of large doses - stiff muscles (especially respiratory); children - paradoxical agitation, anxiety; convulsions, nightmares, sedative or stimulating effects (especially in elderly patients), delirium, decreased ability to concentrate.

From the side genitourinary system: decreased diuresis, spasm of ureters (difficulty and pain with urination, frequent urge to urinate), decreased libido, decreased potency; spasm of the sphincter of the bladder, a violation of the outflow of urine or aggravation of this condition with prostatic hyperplasia and stenosis of the urethra.

Overdose:

Symptoms of acute and chronic overdose: cold sticky sweat, confusion, dizziness, drowsiness, decreased blood pressure, nervousness, fatigue, miosis, bradycardia, severe weakness, slow labored breathing, hypothermia, anxiety, dry mouth, delirious psychosis, intracranial hypertension before the violation of cerebral circulation), hallucinations, muscle rigidity, convulsions, in severe cases - loss of consciousness, respiratory arrest, coma.

Treatment: gastric lavage, recovery of respiration and maintenance of cardiac activity and blood pressure; intravenous injection of a specific antagonist opioid analgesics - naloxone in a single dose of 0.2-0.4 mg with repeated administration 2-3 minutes before the total dose of 10 mg; the initial dose of naloxone for children is 0.01 mg / kg.

Interaction:

Anesthetics, local for epidural or spinal anesthesia - potentiation of respiratory depression.

Antihypertensives, diuretics, other drugs that cause hypotension - potentiation of the hypotensive effect.

Benzodiazepines reduce the need for fentanyl.

Adrenoblockers - potentiation of cardiodepressive effect.

Buprenorphine - a decrease in the therapeutic effect of other μ-receptor agonists, including a reduction in respiratory depression, the emergence of withdrawal syndrome in dependent individuals.

Dinitrogen oxide - the potentiation of the depressing effect on the central nervous system, the suppression of hemodynamics (especially in individuals with chronic heart failure).

MAO inhibitors - apply with an interval of 14 days (unpredictable, up to fatal reactions are possible).

Miorelaxants - potentiation of respiratory depression.

Nalbuphine, pentazocine - depending on the dose may be fentanyl synergists or antagonists.

Naltrexone, naloxone, nalorfin - antidotes of narcotic analgesics, eliminate all their pharmacological effects, including cause withdrawal syndrome in patients with drug dependence to them.

Narcotic analgesics - mutual potentiation of effects.

Means that inhibit the central nervous system are the potentiation of the depressant effect on the central nervous system.

Phenotiazine neuroleptics - some increase, and some reduce the effects of fentanyl.

Special instructions:

Abolition of the drug is gradual. When using large doses in depleted and asthenic patients, it is possible to develop a secondary respiratory depression,associated with the release of fentanyl 1-2 hours after administration to the lumen of the stomach and subsequent resorption.

It is unacceptable to perform neuroleptanalgesia in the absence of conditions for mechanical ventilation.

With simultaneous use with insulin preparations, correction of the dosing regimen of fentanyl is required.

During treatment, do not engage in potentially hazardous activities requiring increased attention and psychomotor reactions.

Instructions

Fentanyl (Phentanylum)