FENTANYL CITRATE / DROPERIDOL
Chemistry - Fentanyl citrate, a very potent opiate agonist, occurs as a white, crystalline powder. Itis sparingly soluble in water and soluble in alcohol. It is odorless and tasteless (not recommendedfor taste test because of extreme potency) with a pKa of 8.3 and a melting point between 147°-152°C.
Droperidol, a butyrophenone neuroleptic agent, occurs as a white to light tan, amorphous ormacrocrystalline powder. One gram is soluble in 10 L of water and 600 ml of alcohol. It is odorlessand tasteless (not recommended for taste test because of extreme potency) with a pKa of 7.6 and amelting point between 144°-148°C.
The combination commercially available products (Innovar® and Innovar®-Vet) have pH's ofapproximately 3-3.5.
Dugs by Trissel; see bibliography) for more specific information.
Analgesics. When used together droperidol/fentanyl will induce considerable neuroleptanalgesia.
The actions of droperidol are said to potentiate the analgesic effects of fentanyl.
In dogs, Innovar® can cause decreased heart rates secondary to increased vagal tone and a decrease in arterial blood pressures. In cats, increased heart rates can be noted as well as a decrease in blood pressure.
Uses, Indications - Droperidol/fentanyl is approved in veterinary medicine only for use in the dog.
It is indicated alone as a combination analgesic/tranquilizer for minor surgical, dental andorthopedic procedures and manipulations of short duration or (in combination with other generalanesthetics) for major surgical procedures. It is condsidered by some clinicians to be the drug ofchoice as a chemical restraining agent in aggresive dogs. Fentanyl/droperidol has also been used asa tranquilizer/analgesic in cats.
Contraindications/Precautions - This combination is not approved for use in food producinganimals. Use cautiously with other CNS depressants, dosages of other anesthetics may need to bereduced when given after Innovar®. Pentobarbital dosages (for anesthesia) must be reduced for 4hours after Innovar®. Perivascular injections may be irritating to surrounding tissue; avoid extravasation. Australian terriers may be resistant to the neuroleptanalgesic effects of Innovar® at usual doses, but exhibit side effects of tremors, excessive salivation, bradycardia, and diarrhea.
A syndrome described as "woody chest" can occur after rapid IV administration. The thoracicmusculature becomes very rigid and interferes with normal breathing, but can be treated withnaloxone, or mechanical ventilation and muscle relaxant agents.
CNS stimulation, ataxia, and abnormal behavior (squealing, "goose-stepping", stumbling intoobjects) can be seen in pigs following IM administration.
IM or SQ injection may cause irritation and pain at the injection site.
Overdosage - Overdosage may produce profound respiratory and/or CNS depression in mostspecies. Newborns may be more susceptible to these effects than adult animals. Other toxic effectsmay include cardiovascular collapse, tremors, neck rigidity, and seizures. Naloxone is the agent ofchoice in treating respiratory depression. In massive overdoses, naloxone doses may need to berepeated, animals should be closely observed as naloxone's effects may diminish before sub-toxiclevels of fentanyl are attained. Mechanical respiratory support should also be considered in cases ofsevere respiratory depression. 4-aminopyridine has been demonstrated to act as an antagonist todroperidol in the dog at a dose 0.5 mg/kg IV, but it is not available in an approved commerciallyavailable dosage form.
Pentobarbital (6.6 mg/kg) has been suggested as a treatment for CNS effects (seizures) and extension and rigidity of the neck. Extreme caution must be used as barbiturates and narcotics can have additive respiratory depression effects.
For butyrephenones (droperidol): CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) may cause additive CNS depression if used with butyrephenones.
Laboratory Interactions - Plasma amylase and lipase values may be increased for up to 24hours following administration of opiate analgesics as they may increase biliary tract pressure.
Droperidol, a butyrophenone neuroleptic agent, occurs as a white to light tan, amorphous ormacrocrystalline powder. One gram is soluble in 10 L of water and 600 ml of alcohol. It is odorlessand tasteless (not recommended for taste test because of extreme potency) with a pKa of 7.6 and amelting point between 144°-148°C.
The combination commercially available products (Innovar® and Innovar®-Vet) have pH's ofapproximately 3-3.5.
Storage, Stability, Compatibility
Intact ampules and vials should be stored at room temperature and out of light. Innovar® has been reported to be compatible when mixed with the following agents: D5W, lactated Ringer's, D5 in lactated Ringer's, normal saline, benzquinamide, glycopyrrolate, heparin sodium, hydrocortisone sodium succinate, potassium chloride, and sodium bicarbonate. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used, and it is suggested to consult specialized references (e.g., Handbook on InjectableDugs by Trissel; see bibliography) for more specific information.
Pharmacology - FENTANYL CITRATE/DROPERIDOL
The butyrephenones (e.g., droperidol) as a class cause tranquilization and sedation (sedation may be less so than with the phenothiazines), anti-emetic activity, reduced motor activity, and inhibition of CNS catecholamines (dopamine, norepinephrine). The pharmacology of the opiate agonists are discussed in more detail in the monograph, Narcotic (opiate) AgonistAnalgesics. When used together droperidol/fentanyl will induce considerable neuroleptanalgesia.
The actions of droperidol are said to potentiate the analgesic effects of fentanyl.
In dogs, Innovar® can cause decreased heart rates secondary to increased vagal tone and a decrease in arterial blood pressures. In cats, increased heart rates can be noted as well as a decrease in blood pressure.
Uses, Indications - Droperidol/fentanyl is approved in veterinary medicine only for use in the dog.
It is indicated alone as a combination analgesic/tranquilizer for minor surgical, dental andorthopedic procedures and manipulations of short duration or (in combination with other generalanesthetics) for major surgical procedures. It is condsidered by some clinicians to be the drug ofchoice as a chemical restraining agent in aggresive dogs. Fentanyl/droperidol has also been used asa tranquilizer/analgesic in cats.
Pharmacokinetics - FENTANYL CITRATE/DROPERIDOL
No veterinary references regarding the pharmacokinetics of these agents werelocated. The onset of action after IV administration in dogs occurs within minutes and slightlylonger after IM administration. In cats, after SQ injection, the onset of effect occurs within 20-30minutes. Both drugs are metabolized in the liver and are eliminated in the urine (both as metabolitesand unchanged drug). Duration of effect (at usual doses) after IM administration in dogs isgenerally 30-40 minutes, most animals will be sedated for several hours after anesthetic actions haveceased. Approximately 1.5 hours are necessary for dogs to recover after IV administration.Contraindications/Precautions - This combination is not approved for use in food producinganimals. Use cautiously with other CNS depressants, dosages of other anesthetics may need to bereduced when given after Innovar®. Pentobarbital dosages (for anesthesia) must be reduced for 4hours after Innovar®. Perivascular injections may be irritating to surrounding tissue; avoid extravasation. Australian terriers may be resistant to the neuroleptanalgesic effects of Innovar® at usual doses, but exhibit side effects of tremors, excessive salivation, bradycardia, and diarrhea.
Adverse Effects, Warnings
In dogs, adverse effects with Innovar® are usually dose related andmost commonly observed at the higher end of the dosing range. They include defecation, flatulence, respiratory depression, panting, nystagmus, head tremors, pain after IM injection, and personalitychanges (rare). Bradycardia and salivation can be seen if the animal is not pretreated with atropineor other anticholinergic agents. Animals may show a startle reaction following stimuli (e.g., loudnoises) and rarely seizures may develop.A syndrome described as "woody chest" can occur after rapid IV administration. The thoracicmusculature becomes very rigid and interferes with normal breathing, but can be treated withnaloxone, or mechanical ventilation and muscle relaxant agents.
CNS stimulation, ataxia, and abnormal behavior (squealing, "goose-stepping", stumbling intoobjects) can be seen in pigs following IM administration.
IM or SQ injection may cause irritation and pain at the injection site.
Overdosage - Overdosage may produce profound respiratory and/or CNS depression in mostspecies. Newborns may be more susceptible to these effects than adult animals. Other toxic effectsmay include cardiovascular collapse, tremors, neck rigidity, and seizures. Naloxone is the agent ofchoice in treating respiratory depression. In massive overdoses, naloxone doses may need to berepeated, animals should be closely observed as naloxone's effects may diminish before sub-toxiclevels of fentanyl are attained. Mechanical respiratory support should also be considered in cases ofsevere respiratory depression. 4-aminopyridine has been demonstrated to act as an antagonist todroperidol in the dog at a dose 0.5 mg/kg IV, but it is not available in an approved commerciallyavailable dosage form.
Pentobarbital (6.6 mg/kg) has been suggested as a treatment for CNS effects (seizures) and extension and rigidity of the neck. Extreme caution must be used as barbiturates and narcotics can have additive respiratory depression effects.
Drug Interactions
For opiates (fentanyl): Other CNS depressants (e.g., anesthetic agents, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc.) may cause increased CNS orrespiratory depression when used with opiates. Opiate analgesics are contraindicated in patientsreceiving monamine oxidase (MOA) inhibitors (rarely used in veterinary medicine) for at least14 days after receiving MOA inhibitors (in humans).For butyrephenones (droperidol): CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) may cause additive CNS depression if used with butyrephenones.
Laboratory Interactions - Plasma amylase and lipase values may be increased for up to 24hours following administration of opiate analgesics as they may increase biliary tract pressure.