Butorphanol
Risk Factor: CM*
Class: CENTRAL NERVOUS SYSTEM DRUGS
/ Narcotic Agonist-Antagonist Analgesics
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
No reports linking the use of butorphanol with congenital defects have been located. Because it has both narcotic agonist and antagonist properties, prolonged use during gestation may result in fetal addiction with subsequent withdrawal in the newborn (see also Pentazocine). The drug is commercially available as injection and nasal spray formulations.
No teratogenic effects were observed in reproduction studies in rats and rabbits administered butorphanol during organogenesis (1). An increased frequency of stillbirth was observed in rats given 1 mg/kg (5.9 mg/m2) SC and in rabbits dosed orally with 30 mg/kg (360 mg/m2) and 60 mg/kg (720 mg/m2).
At term, butorphanol rapidly crosses the placenta, producing cord serum levels averaging 84% of maternal concentrations (2,3). Depressant effects on the newborn from in utero exposure during labor are similar to those seen with meperidine (2,3 and 4).
The use of 1 mg of butorphanol combined with 25 mg of promethazine administered intravenously to a woman in active labor was associated with a sinusoidal fetal heart rate pattern (5). Onset of the pattern occurred 6 minutes after drug injection and persisted for approximately 58 minutes. The newborn infant showed no effects from the abnormal heart pattern. A subsequent study to determine the incidence of sinusoidal fetal heart rate pattern after butorphanol administration was published in 1986 (6). Fifty-one women in labor who received butorphanol, 1 mg IV, were compared with a control group of 55 women who did not receive narcotic analgesia. Sinusoidal fetal heart rate pattern was observed in 75% (38 of 51) of the treated women vs. 13% (7 of 55) of controls (p <0.001). The mean time of onset of the abnormal tracing was 12.74 minutes after butorphanol with a duration of 31.26 minutes. This duration was significantly longer than that observed in the nontreated controls (13.86 minutes; p <0.02). Because no short-term maternal or neonatal adverse effects were observed, the investigators concluded that, in the absence of other signs, the abnormal heart rate pattern was not indicative of fetal hypoxia (6).
A study comparing the effects of maternal analgesics on neonatal neurobehavior was conducted in 135 patients during their 1st day of life (7). Maternal analgesia consisted of 1 mg of butorphanol (N=68) or 40 mg of meperidine (N=67). No difference between the drugs was observed.
[*Risk Factor D if used for prolonged periods or in high doses at term.]
Breast Feeding Summary
Butorphanol passes into breast milk in concentrations paralleling levels in maternal serum (3). Milk:plasma ratios after intramuscular (12 mg) or oral (8 mg) doses were 0.7 and 1.9, respectively. Using 2 mg intramuscularly or 8 mg orally four times per day would result in 4 g excreted in the full daily milk output (1000 mL). Although it has not been studied, this amount is probably insignificant. The American Academy of Pediatrics considers butorphanol to be compatible with breast feeding (8).
References
- Product information. Stadol NS. Bristol-Myers Squibb, 2000.
- Maduska AL, Hajghassemali M. A double-blind comparison of butorphanol and meperidine in labour: maternal pain relief and effect on the newborn. Can Anaesth Soc J 1978;25:398404.
- Pittman KA, Smyth RD, Losada M, Zighelboim I, Maduska AL, Sunshine A. Human perinatal distribution of butorphanol. Am J Obstet Gynecol 1980;138:797800.
- Quilligan EJ, Keegan KA, Donahue MJ. Double-blind comparison of intravenously injected butorphanol and meperidine in parturients. Int J Gynaecol Obstet 1980;18:3637.
- Angel JL, Knuppel RA, Lake M. Sinusoidal fetal heart rate pattern associated with intravenous butorphanol administration: a case report. Am J Obstet Gynecol 1984;149:4657.
- Hatjis CG, Meis PJ. Sinusoidal fetal heart rate pattern associated with butorphanol administration. Obstet Gynecol 1986;67:37780.
- Hodgkinson R, Huff RW, Hayashi RH, Husain FJ. Double-blind comparison of maternal analgesia and neonatal neurobehaviour following intravenous butorphanol and meperidine. J Int Med Res 1979;7:22430.
-
Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
Questions and Answers
Trying to find a Medicare Part D insurance company that pays for butorphanol Tartrate Nasal Spray for my mom?,
check with medicare - they would have a list of them
My Dog has a prescription for butorphanol.?, I'm looking for a pharmocology description with details on compound and side effect / adverse reaction. Anyone know where I can find that on line?
"Butorphanol (INN) is a morphinan-type synthetic opioid analgesic marketed in the U.S. under the trade name Stadol. It is most closely structurally related to dextromethorphan. Butorphanol is available only as butorphanol tartrate in injectable and intranasal spray formulations."
http://en.wikipedia.org/wiki/Butorphanol
Discovery and development of Ketorolac and Butorphanol?,
Ketorolac
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Ketorolac
(±)-5-benzoyl-2,3-dihydro-
1H-pyrrolizine-1-carboxylic acid,
2-amino-2-(hydroxymethyl)-1,3-propaned...
IUPAC name
CAS number
74103-06-3 ATC code
M01AB15
PubChem
3826 DrugBank
N/A
Chemical formula C15H13NO3
Molecular weight 376.4 g/mol
Bioavailability 100% (All routes)
Metabolism Hepatic
Elimination half-life 3.5-9.2 hrs, young adults;
4.7-8.6 hrs, elderly (mean age 72)
Excretion Renal:91.4% (mean)
Biliary:6.1% (mean)
Pregnancy category C: (USA)
C: (AUS)
Legal status Prescription only
Routes of administration Oral
Intramuscular
Intravenous
Ketorolac or ketorolac tromethamine (marketed as Toradol® - generics have been approved) is a non-steroidal anti-inflammatory drug (NSAID) in the family of propionic acids, often used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. Ketorolac acts by inhibiting bodily synthesis of prostaglandins. Ketorolac in its oral and intramuscular preparations is a racemic mixture of R-(+)(which is the salt 1H-Pyrrolizine-1-carboxylic acid,5-benzoyl-2,3-dihydro- ketorolac) and S-(-) (which does not have the 1H-Pyrrolizine-1-carboxylic acid,5-benzoyl-2,3-dihydro group) ketorolac.
The brand name Toradol was coined by the Syntex company of the United States.
This article does not cover Acular® or ophthalmic ketorolac.
Contents [hide]
1 Chemistry
2 Mechanism of action
3 Indications
4 Contraindications
5 Adverse effects
6 Warnings and precautions
7 Notes
8 Dosage, availability and price
9 See also
10 References
11 External links
[edit]
Chemistry
Ketorolac, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, ibuprofen etc.) contains a chiral carbon in the β-position of the propionate moiety. As such there are two possible enantiomers of ketorolac with the potential for different biological effects and metabolism for each enantiomer.
NSAIDs are not recommended for use with other NSAIDs because of the potential for additive side effects.
The protein-binding effect of most non-aspirin NSAIDs is inhibited by the presence of aspirin in the blood.
[edit]
Mechanism of action
The primary mechanism of action responsible for Ketorolac's anti-inflammatory/antipyretic/analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the the enzyme cyclooxygenase (COX). Like most NSAIDs, Ketorolac is a non-selective cyclooxygenase inhibitor.
As with other NSAIDs, the mechanism of the drug is associated with the chiral S form. Conversion of the R enantiomer into the S enantiomer has been shown to occur in the metabolism of ibuprofen; it is unknown whether it occurs in the metabolism of ketorolac.
Image:Ketorolac bottles.jpg
Some bottles of ketorolac.[edit]
Indications
Ketorolac is indicated for short-term management of pain (up to five days).
[edit]
Contraindications
Ketorolac is contraindicated against patients with a previously demonstrated hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).
[edit]
Adverse effects
Similar to other NSAIDs. See inset "Ketorolac adverse effects."
Ketorolac adverse effects.
Body system. Effects.
General. Edema. Less frequently, hypersensitivity reactions (such as anaphylaxis, bronchospasm, laryngeal edema, tongue edema, hypotension), flushing, weight gain, or fever. Very infrequently, asthenia.
Cardiovascular. Hypertension. Less frequently, palpitation, pallor, or syncope.
Dermatologic. Rash or pruritus. Less frequently, Lyell's syndrome, Stevens-Johnson syndrome, musculo-papular rash, exfoliative dermatitis, or urticaria.
Gastrointestinal. Nausea, dyspepsia, gastrointestinal pain, constipation, diarrhea, flatulence, gastrointestinal fullness, vomiting or stomatitis. Less frequently, peptic ulceration, gastrointestinal hemorrhage, gastrointestinal perforation, melena, rectal bleeding, gastritis, eructation, anorexia, or increased appetite. Very infrequently, pancreatitis.
Hemic and lymphatic. Purpura. Less frequently, postoperative wound hemorrhage, thrombocytopenia, epistaxis, or anemia. Very infrequently, leukopenia or eosinophilia.
Neurological. Drowsiness, dizziness, headache, sweating, injection site pain. Less frequently convulsions, vertigo, tremors, abnormal dreams, hallucinations, or euphoria. Very infrequently, paresthesia, depression, insomnia, inability to concentrate, nervousness, excessive thirst, dry mouth, abnormal thinking, hyperkinesis, or stupor.
Respiratory. Less frequently, dyspnea, asthma and pulmonary edema. Very infrequently, rhinitis or cough.
Urogenital. Less frequently, acute renal failure. Very infrequently polyuria or increased urinary frequency.
[edit]
Warnings and precautions
The most serious risks associated with ketorolac are, as with other NSAIDs, gastrointestinal ulcerations, bleeding and perforation; renal events ranging from interstitial nephritis to complete renal failure; hemorhage, and hypersensitivity reactions.
As with other NSAIDs, fluid and solute retention and edema have been reported with ketorolac; ketorolac elevated liver protein levels; it also inhibits platelet aggregation and may be associated with an increased risk of bleeding.
It should be noted that when administered intraveinously through the same IV catheter as Morphine the two drugs have been known to sometimes combine to form a precipitate in the IV, which may block the line. Line flushing with a syringe of saline can push the blockage through.
[edit]
Notes
Ketorolac is not recommended for pre-operative analgesia or co-administration with anesthesia because it inhibits platelet aggregation.
Ketorolac is not recommended for obstetric analgesia because it has not been adequately tested for obstetrical administration and has demonstrable fetal toxicity in laboratory animals.
Ketorolac has been co-administered with meperidine and morphine without apparent adverse effects.
Ketorolac is not recommended for long-term chronic pain patients.
[edit]
Dosage, availability and price
Oral dosage is 10 mg; price for 30 tablets hovers around US$25.
Injected dosages are 15, 30 and 60 mg; price for 10 vials of 30 mg each is around US$45, making the intramuscular preparation considerably more expensive per dose. One 60-mg dose would require the administration by injection of two vials, at about $9 per dose.
This drug cannot be sold over-the-counter and must be administered only with a prescription.
[edit]
See also
Ibuprofen
Naproxen
Ketoprofen
Flurbiprofen
Propionic acids
NSAID
Analgesics
Ketorolac (Ophthalmic)
[edit]
References
Handley, D.A., P. Carvoni, J.E. McCray, J.R. McCullough (1998). "Preclinical Enantioselective Pharmacology of (R)- and (S)- Ketorolac.", J Clin Pharmacol 38, 25-35.
1993. Physicians' Desk Reference, Forty-seventh edition. Montvale, N.J., Medical Economics Co. I
if someone took butorphanol pain medicen for cats would it be the same as taking the kind for people?,
I don't think it's advisable to take medication intended for animals even if it has the same name and same ingredients. Are you even serious?
what happens during paradoxical reaction to butorphanol?, Can someone explain the process behind a paradoxical reaction (specifically to butorphanol) , why it happens, what should be done to reverse this, and possible presentations?
(would intercostal retractions/respiratory distress be probable? agitation?) If possible get very specific, i.e. down to the receptors and metabolism.. hehe :)
There are many ways in which butorphanol can cause problems. If it is given with a narcotic agonist, butorphanol may precipitate withdrawals due to the receptors it it binds to (will talk about this in the next paragraph). By itself, in higher doses, it can cause delerium, hallucinations and dysphoria. Again, this has to do with the receptors it binds to. But if you are talking about Paradoxical reactions, then this is purely because of its actions at the Kappa receptor.
There is evidence that has been shown that with mixed Kappa agonist-Mu antagonist drugs (like Butorphanol, Nubain, Fortral), they can sometimes worsen pain at lower doses. For example, 5mg of Nalbuphine (Nubain) can cause profound anti-analgesia in men but will produce pain relief in higher doses like 20mg. This is very common (but by no means unique) in drugs that act solely at the Kappa opioid receptor to produce pain relief. In addition, they also exhibit gender polymorphisms (they affect Men and Women differently). This applies to Pentazocine (Fortral), Nalbuphine (Nubain), Butorphanol (Stadol) and even higher doses of Nalorphine which produces analgesia via kappa-1 receptors.
This paradoxical reaction can be alleviated with a sub-analgesic (low dose not sufficient for pain relief) dose of Morphine.
Hope this helps. Drop me a line if you need more.
EDIT: Yes that is correct. And putting the patient in more pain if s/he is already in pain, may make the patient very agitated. Now the other thing is that by themselves, Butorphanol, Fortral (pentazocine), cyclazocine and nalbuphine, can cause dysphoria, delerium, excitation and hallucinations. This is because again, of the activity at the kappa receptors (eg. Salvia Divinorum's primary component acts at this receptor too). I didn't mention this earlier because these symptoms aren't classified as *paradoxical*. It's classified as a side-effect. Breathing/respiratory issues are not common amongst the kappa-agonist Mu-antagonist drugs, since respiratory depression is produced mainly via the mu-2 receptors.
Some opioids induce histamine release, and this can cause hypotension secondary to vasodilation and bronchospasm. But butorphanol is not associated with any kind of histamine release. However bronchospasm is listed as a rare side-effect with butorphanol.
EDIT2: You can summarize like this:
Generally with mixed agonist-antagonists like this, they do produce analgesia via the kappa receptors. However, in low doses they can sometimes produce a paradoxical anti-analgesia effect which can be relieve by a low, sub-analgesic dose of Morphine.
Valium, Butorphanol, and Phenobarbital- adverse reaction? (regarding my husky)?, I hope there's someone out there who can help me with this. My dog, a siberian husky, had 4 seizures throughout the night Monday - into tuesday. This was from a loud noise (it happened before in Feb and he was on pheno for a short time but then was able to come off of it). We took him to an ER vet Tuesday morning around 6:30 and he walked into the clinic, acting mostly back to normal. They gave Valium. He reacted hyper to it. THey gave more, with the same result. They then gave Butorphanol. After that, he was a wreck. He was not able to move, walk or do anything. He was breathing rapidly, eyes dilated, and whimpering excessively. This is basically the state he's been in since. We took him off ALL meds yesterday and he is now able to somewhat hold his head up and eat from a tongue depressor and drink out of a bowl (with his head resting on it). He still cannot stand up and is very distressed. He has also been running slight fevers. Please, if someone has any idea what is going on or what we can do to help I'd be so thankful. The doctors don't really know what to do. Thank you.
Both the Phenobarbital and Valium are central nervous system depressants, the Butorphanol is an opiod-like medication that can raise the threshold at which central nervous system depression occurs. While I understand they wanted to counteract the hyperactive reaction from the valium, all 3 appear to have created the sedated state that you're describing.
I am honestly in no position whatsoever to second-guess an ER vet, but I would take him to your regular vet or a specialist. Valium is given for seizures, as is the phenobarbital--did they still have him on all 3 concurrently until you took him off everything yesterday?
Approximately how many sprays is in a 2.5ml bottle of stadol?, it is 10mg/ml butorphanol tartrate nasal spray. How many sprays?
It says in most of the medication information sheets. I've seen it listed as 14-17 squirts. Some people find one squirt is too much Stadol for them, so they dilute it with saline solution so that it lasts longer (more squirts) and aren't effected so much by the side effects.
I've heard of people who use saline to prime it first, so that the medication isn't wasted, too.
am i going to pass my drug test?, I have a drug test for a job this coming Friday, the 1st. I smoked weed back in December but I hadn't smoked it for a while before that.
However in the past 2 weeks or so I've been in a lot of pain from work (I really should just go to the doctor and get my own prescription...) and have been taking my boyfriend's muscle relaxers, percocet, and his butorphanol nasal spray (Stadol).
I haven't taken anything since yesterday (just a zanaflex) and everyone is telling me I should be okay since most of this stuff (besides the weed, and I don't know about the Stadol) should be out of my system in 72 hours?
It's just a standard urine test... and I've got 6 days to get clean if I'm not already.
Help?
if it is a hair exam type drug test then your out of luck cause that wont go away for years other than that your fine
I am addicted to barbiturates. Is it okay to go cold turkey?, I get butorphanol tartrate prescribed to me for migraine. I have realized that I got addicted to it pretty quickly. I like their "high" and I reach for them to get high even if I don't have a migraine. I called my neurologist whose assistant said to phase it out slowly, and if I can't, to go to the ER. I would rather try going cold turkey though. I have my sister around for assistance. I want to be done with this as quickly as possible. Are there medical risks to going cold turkey? The last dose I took today was at 10:00 am eastern (it is now 6 pm)and it was smaller than my regular doses. I have been in pain (headache) all day but held off taking any of it. I would like to try and make it through the night without any, even if it means lying in bed in pain watching bad movies.
It's dangerous to go off any medication cold turkey, especially these. Why not try just to take them as prescribed so you don't have to suffer. If the habit is too strong to abuse and you really can't do it by weaning yourself off then you need to go to the hospital. If you don't, you take the risk of everything from seizures to even death. If you go to the hospital then as your being weaned off of that then you'll be given something that's safe for the headaches so you don't have to suffer. I'm having a hard time with your neurologist's assistant instructing you what to do unless she has a nursing license and then she's borderline with how the laws are with patient instruction. Your doctor should have been informed and you should have been told how he wants you to handle this. I'm almost positive he wouldn't want you doing this alone or even with a friend. It's just too dangerous. Please check back with the office tomorrow and talk to the doctor first. In the meantime then stay with your medication as needed as prescribed.Good luck with this and please be safe
