Pain control in my elderly staffie

RE: Pain control in my elderly staffie

Bob Russell — Mon, 16 May 2016 11:13:12 GMT

I don't use tramadol as a sole painkiller but do feel many patients benefit from it. I do advise owners that it can be variable in effectiveness and in some patients, will not work at all.

This weekend our staffie has been on Previcox and Gabapentin. She is sleepy but this may be, in part because she has been sunbathing! Does appear happier!

I advise bd dosing with Tramadol.

RE: Pain control in my elderly staffie

Aine Seavers — Mon, 16 May 2016 10:09:16 GMT

This is a list kindly sent to me by another colleague who was on a pain panel reviewing analgesia-he doesnt like tramadol. I will send another list later of references a pharmacologist non clinical sent to consider whether tramadol an option-a list which a clinican turned specialist pharmacologist then reviewed and came to the conclusion that other than epidural use-there was not enough validation to be using it in a clinical setting- so if you still want that let me know as will take a few days to get access to that list.

1. Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation.

Delgado C, Bentley E, Hetzel S, Smith LJ.

J Am Vet Med Assoc. 2014 Dec 15;245(12):1375-81. doi: 10.2460/javma.245.12.1375.

This paper demonstrated increased efficacy of carprofen, a licensed preparation, over tramadol for a procedure commonly performed in general practice and associated with significant perioperative pain.

2. Dependence potential of tramadol: behavioral pharmacology in rodents.

Cha HJ, Song MJ, Lee KW, Kim EJ, Kim YH, Lee Y, Seong WK, Hong SI, Jang CG, Yoo HS, Jeong HS.

Biomol Ther (Seoul). 2014 Nov;22(6):558-62. doi: 10.4062/biomolther.2014.064. Epub 2014 Nov 30.

This paper demonstrated that tramadol has addictive potential. I have noticed this in patients myself. You may also quote me as a 'personal communication' on this if you wish.

3. Tramadol has become a controlled substance in the UK and in the USA.

a) Ketamine and tramadol reclassified.

[No authors listed]

Vet Rec. 2014 Jun 14;174(24):596. doi: 10.1136/vr.g3862.

b) Tramadol becomes controlled substance.

[No authors listed]

J Am Vet Med Assoc. 2014 Aug 15;245(4):367.

4. Vet Anaesth Analg. 2014 May;41(3):297-304. doi: 10.1111/vaa.12140. Epub 2014 Feb 27.

Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

Kögel B1, Terlinden R, Schneider J.

"Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting."

"Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs."

5. Comparison of the analgesic efficacy of perioperative firocoxib and tramadol administration in dogs undergoing tibial plateau leveling osteotomy.

Davila D, Keeshen TP, Evans RB, Conzemius MG.

J Am Vet Med Assoc. 2013 Jul 15;243(2):225-31. doi: 10.2460/javma.243.2.225.

"Dogs that received firocoxib orally, alone or in combination with tramadol, had lower pain scores, lower rescue opiate administration, and greater limb function than dogs that received only tramadol. When used alone, oral administration of tramadol may not provide sufficient analgesic efficacy to treat dogs with pain after orthopedic surgical procedures."

6. Outpatient Oral Analgesics in Dogs and Cats Beyond Nonsteroidal Antiinflammatory Drugs : An Evidence-based Approach Butch KuKanich, DVM, PhD

This was in Veterinary Clinics of North America: Small Animal Practice

Vet Clin North Am Small Anim Pract. 2013 Sep;43(5):1109-25. doi: 10.1016/j.cvsm.2013.04.007. Epub 2013 May 29.

Tramadol

Tramadol is FDA approved for the management of moderate to moderately severe pain in humans. Tramadol is metabolized into at least 30 different metabolites, but only tramadol, O-desmethyltramadol (ODM), and N,O-didesmethyltramadol (DDM) have been associated with pharmacologic effects.17 Tramadol administration produces analgesia, which is partially blocked by naloxone (mu opioid antagonist), yohimbine (alpha-2 antagonist), ketanserin (serotonin 5-hydroxytryptamine [HT]-2 antagonist), and ondansetron (5HT-3 antagonist), suggesting that all 3 receptor systems contribute to the analgesic effects. Other studies have also suggested that tramadol produces antagonist effects at muscarinic M1 receptors that can be overcome by acetylcholine administration. Further studies have shown that the mu opioid effects are primarily caused by ODM with some secondary effects of DDM, whereas the serotonin and norepinephrine effects are caused by tramadol and ODM, and the antimuscarinic effects are caused by ODM.

Pharmacokinetic studies in dogs have shown that dogs do not produce ODM as a substantial metabolite after tramadol administration; however, they do produce DDM.18 Therefore dogs are not expected to have substantial opioid effects after tramadol administration. Plasma concentrations of tramadol after administration of 10 mg/kg by mouth to dogs were slightly less than the plasma concentrations achieved in humans administered 100 mg single doses, but the concentration of ODM was 10 times less in dogs compared with humans. The elimination half-life of tramadol in dogs is more rapid (1.1 hours) compared with humans (5.6 hours). The production of DDM, which has an elimination half-life of 3.6 hours in dogs, may produce some opioid effects in dogs. Repeated doses of tramadol either decreased drug absorption or enhanced presystemic metabolism of tramadol in dogs, in which a 60% to 70% decrease in tramadol plasma concentrations resulted after just 8 days of treatment (20 mg/kg by mouth).1 The effects of multiple-day administration on the metabolites ODM and DDM were not reported.

In contrast with dogs, cats produce high concentrations of ODM after tramadol administration and as a result have prominent opioid effects.19 The concentrations of ODM after 5.2 mg/kg tramadol by mouth were 10 times higher than ODM concentrations in humans after 100 mg by mouth. The terminal half-life of ODM after oral tramadol in cats was 4.5 hours, suggesting that administration every 12 hours may be appropriate in cats. The plasma concentrations of tramadol and ODM were dose proportional from 0.5 to 4 mg/kg by mouth.20 The pharmacokinetics of repeated doses of tramadol have not been reported in cats.

A pressure pain threshold model was used to assess the effects of oral tramadol (10 mg/kg by mouth) in dogs.18 Significant increases in thresholds were observed only at 5 and 6 hours after administration. It is unclear how mechanical antinociceptive effects translate to clinical analgesic effects.

The effects of tramadol on thermal thresholds in cats have been reported.20 and 21 The thermal thresholds exceeded the 95% confidence interval at 0.75, 3, and 6 hours after 1 mg/kg tramadol, but not at 1, 2, 4, 8, and 24 hours.21 A dose titration study evaluated the effects of tramadol dosed 0.5 to 4 mg/kg by mouth in cats using a thermal threshold model. Thermal thresholds increased proportionally with increased doses.20 The duration of increased thresholds were also related to the dose, with 2 mg/kg producing significant effects from less than 6 hours to up to 13 hours after administration, 3 mg/kg producing significant effects from 9 to 12 hours after administration, and 4 mg/kg producing significant effects from 10 to 16 hours after administration.

There are few studies assessing the effects of tramadol administration to clinical canine patients in controlled clinical trials. Only 1 study reports the effects of oral tramadol in a blinded study using positive and negative controls, and these were in patients with osteoarthritis. The incorporation of both positive and negative controls is important because an effect (perceived improvement) occurred in the placebo group using an owner-completed canine brief pain inventory questionnaire.2 However, significant improvement was noted in the positive control group (carprofen, 2.2 mg/kg twice a day) and tramadol (4 mg/kg 3 times a day) group compared with the placebo (administered 3 times a day). Plasma concentrations of carprofen and tramadol were measured 3 hours after the first dose and last dose (14 day). The plasma concentrations of carprofen were within the expected plasma concentrations. The plasma concentrations of tramadol were low (39.3 ± 35.3 ng/mL) 3 hours after the first dose and were significantly decreased 3 hours after the last dose (7.1 ± 8.8 ng/mL), and not even detected in 4 of 11 dogs, again suggesting decreased bioavailability with multiple doses. In comparison, the plasma concentrations of tramadol in humans after 100 mg by mouth peak at 308 ng/mL 2 to 3 hours after dosing. The plasma concentrations of ODM and DDM were not reported.

There are few studies assessing the effects of tramadol administration to clinical feline patients in controlled clinical trials. Only 1 study reports the effects of tramadol using a blinded study with negative controls and these were in patients after ovariohysterectomy. Treatment groups included placebo, the NSAID vedaprofen (0.5 mg/kg by mouth), tramadol (2 mg/kg subcutaneously [SC]), and the combination of tramadol and vedaprofen.22 Patients were evaluated with a composite pain scale. All of the patients receiving placebo and vedaprofen received rescue analgesia, 50% of the tramadol patients received rescue analgesia, and none of the vedaprofen and tramadol group received rescue analgesia. The composite pain scale was significantly lower for the combination of vedaprofen and tramadol from 1 to 56 hours after surgery, but not significantly lower in any of the other treatment groups for more than 1 time point compared with placebo.

Tramadol is overall well tolerated in dogs. Administration of single oral doses of 450 mg/kg was not fatal in an unstated number of dogs.1 Administration of 40 mg/kg per day to 8 dogs was well tolerated for 1 year, with mydriasis and reduced body weight observed. Adverse effects of tramadol overdose include restlessness, difficulty walking, salivation, vomiting, tremors, and convulsions. Anecdotal reports suggest that diazepam is effective in controlling tramadol-induced convulsions. Similar adverse effects are expected in cats with acute tramadol overdoses.

Adverse effects such as nausea and anorexia, and occasionally sedation, can occur in dogs with routine dosages of tramadol. According to the label, tramadol may also decrease the seizure threshold in humans and as such it would be best to avoid use in animals prone to seizures. Tramadol is bitter tasting and can result in profuse salivation and retching if the animal tastes the drug. Similar adverse effects are expected in cats with routine doses of tramadol.

A case series describing 3 postoperative dogs reported higher potential of GI adverse effects when tramadol was combined with deracoxib, an NSAID, than expected from an NSAID alone.23 There are not currently any contraindications listed for tramadol use with NSAIDs in humans. However, there is documentation of potential interactions with other drugs affecting serotonin reuptake, including selective serotonin reuptake inhibitors (eg, fluoxetine, paroxetine) and serotonin-norepinephrine reuptake inhibitors (SNRIs; eg, venlafaxine, duloxetine) increasing the risk of GI ulcers administered alone or in combination with NSAIDs.24 In addition, a case series in humans identified that patients prone to GI adverse effects of NSAIDs had a higher risk of GI perforation caused by tramadol administered alone.25 The mechanism of action is thought to be serotonin-enhanced gastric acid secretion through vagal stimulation. Another potential mechanism is decreased platelet aggregation caused by serotonin depletion within the platelets, because platelets do not synthesize serotonin and rely on transport to accumulate serotonin. On activation of platelets, serotonin is released, resulting in vasoconstriction and subsequent enhanced hemostasis. The risk of GI bleeding in humans administered drugs that inhibit serotonin reuptake and NSAIDs is decreased if acid-suppression therapy (eg, H2 antagonists such as famotidine or proton pump inhibitors such as omeprazole) is coadministered. Therefore it may be prudent to administer acid-suppression therapy to dogs and cats when tramadol is administered concurrently with an NSAID to decrease the risk of GI adverse effects.

The use of tramadol with other drugs that affect serotonin reuptake or metabolism should be avoided because of the risk of serotonin toxicity. Monoamine oxidase inhibitors (selegiline), tricyclic antidepressants (TCAs; eg, amitriptyline, clomipramine), selective serotonin reuptake inhibitors (fluoxetine, paroxetine), and SNRIs (venlafaxine) should not be administered concurrently with tramadol. Serotonin syndrome has been documented in dogs, with signs such as tremors, rigidity, myoclonus, seizure, hyperthermia, salivation, and even death.26

Because of the high concentrations of ODM in cats administered tramadol, opioid-mediated adverse effects can occur in this species. Sedation, mydriasis, dysphoria or euphoria, constipation, and vomiting can occur in cats.

There are some data supporting tramadol use in clinical veterinary patients, but more studies need to be conducted to confirm its efficacy and safety in dogs and cats. Dogs may benefit from tramadol administered 4 to 10 mg/kg by mouth 3 times a day. However, the long-term efficacy of tramadol may decrease with time. Cats may benefit from tramadol after surgery when combined with an NSAID. Other studies are needed to fully describe the potential uses of tramadol in dogs and cats.

Tramadol is not currently a Drug Enforcement Agency (DEA) scheduled drug [** James - it is now!! **]. However, numerous US states have enacted laws requiring special handling as a potential drug of abuse, including classifying it as a schedule IV (CIV) drug. Therefore any prescribers should check with their respective boards of pharmacy to determine current requirements for tramadol prescriptions. Tramadol has a moderate potential for diversion or misuse. The current cost of tramadol is low.

7. Tørring, M. L., Riis, A., Christensen, S., Thomsen, R. W., Jepsen, P., Søndergaard, J. and Sørensen, H. T. (2008), Perforated peptic ulcer and short-term mortality among tramadol users. British Journal of Clinical Pharmacology, 65: 565–572. doi: 10.1111/j.1365-2125.2007.03038.x

In this population-based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs.

8. Vet J. 2009 May;180(2):253-5. doi: 10.1016/j.tvjl.2007.12.011. Epub 2008 Mar 3.

Pharmacokinetic evaluation of tramadol and its major metabolites after single oral sustained tablet administration in the dog: a pilot study.

Giorgi M1, Saccomanni G, Lebkowska-Wieruszewska B, Kowalski C.

"The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog."

RE: Pain control in my elderly staffie

Aine Seavers — Sun, 15 May 2016 23:27:05 GMT

sure can, I will send you the reading list and there is a pain panel report that reviewed it- i think its a UK one that also was not impressed with it,let me see if i can find their report and then I can send you a bulk job, Glad to hear more and more vets getting concerned about the blanket use of this medication Aine

RE: Pain control in my elderly staffie

Will McMullan — Sun, 15 May 2016 20:38:26 GMT

I meant the tramadol receptors. I agree, I think it's crazy how much tramadol gets dispensed these days and I have switched completely to paracetamol and am trying to convince the rest of the practice.

RE: Pain control in my elderly staffie

Aine Seavers — Sun, 15 May 2016 06:24:00 GMT

I don't have an issue with this approach as the drug is being monitored and the patient care individualised -but so often its given with an NSAID and Tramadol gets all the credit when in fact no greater pain relief than the NSAID alone.

We are constantly told to practise eBM yet when one looks at Tramadol-one wonders how it came to be so popular with such little evidence. Pharmacology mates of mine don’t rush to embrace it and as a clinician I find very few have looked into this drug before they blanket used it-it seems to have gotten a free pass. It can be sedative and in some it causes spectacular orthostatic hypotension-which keeps you quiet and sleepy but is your pain well controlled?

A case series in humans identified that patients prone to gastrointestinal (GI) adverse effects of NSAIDs had a higher risk of GI perforation caused by tramadol administered alone. The mechanism of action is thought to be serotonin-enhanced gastric acid secretion through vagal stimulation. The advice is to add in a proton pump inhibitor (PPI)! So yet another drug. The use of a PPI in our pets in this instance, in my mind, would be a case of polypharmacy gone mad simply because a vet thought it would be EBM and a good thing to use tramadol in a dog.

So if Veterinary recommendations are that tramadol in dogs probably should not be used alone but combined with an NSAID – which brings us back to a heightened risk of gastrointestinal tract ulceration than if we didn’t use the Tramadol at all, so why bother to dispense it.

other concerns -, it lowers the seizure threshold for one,

What about drug interactions? Be really careful using Tramadol combined with drugs likes Clonicalm® (clomipramine hydrochloride) Reconcile- (Fluoxetine hydrochloride) Plavix®clopidrogel () that you don’t induce distressing serotonin syndrome. care with ondenestron,.

VCNA Small Anim Pract. 2013 Sep;43(5):1109-25. Pharmacokinetic studies in dogs have shown that dogs do not produce ODM as a substantial metabolite after tramadol administration; however, they do produce DDM.¹Therefore dogs are not expected to have substantial opioid effects after tramadol administration. Plasma concentrations of tramadol after administration of 10 mg/kg by mouth to dogs were slightly less than the plasma concentrations achieved in humans administered 100 mg single doses, but the concentration of ODM was 10 times less in dogs compared with humans. The elimination half-life of tramadol in dogs is more rapid (1.1 hours) compared with humans (5.6 hours). The production of DDM, which has an elimination half-life of 3.6 hours in dogs, may produce some opioid effects in dogs. Repeated doses of tramadol either decreased drug absorption or enhanced presystemic metabolism of tramadol in dogs, in which a 60% to 70% decrease in tramadol plasma concentrations resulted after just 8 days of treatment (20 mg/kg by mouth

RE: Pain control in my elderly staffie

Lindsey Edwards — Sun, 15 May 2016 01:56:27 GMT

There do seem to be tramadol responsive dogs which regain comfort and mobility when treated with repeated results if treatment repeated and regression as withdrawn. Treatment could be offered on trial basis and withdrawn if not responding?

RE: Pain control in my elderly staffie

Aine Seavers — Sun, 15 May 2016 00:35:36 GMT

For which one-the gabapentin or the Canine-specific pharmacology of Tramadol where only the intra-epidural use reference showed any real evidence of efficacy-I have many references for Tramadol-do you want the ones where it and nsaid showed to be no better than the nsaid alone so why combine ? let me know as I hate the use of Tramadol in dogs with a passion- cant extrapolate efficacy in humans and in cats to efficacy in dogs and when it comes to analgesia I need to know the drug i use has a significant chance of working in the majority of dogs so Tramadol not for me- there is a growing chorus of voices of vets really looking at how this drug is working and finding they can do much better for pain relief for dogs. Some of that work has seen drugs like Paracetamol come back into vogue and in terminal arthritic cases we have used that as well to good effect.

RE: Pain control in my elderly staffie

Laurence Webb — Sat, 14 May 2016 22:20:24 GMT

+1 for paracetemol/Pardale aonlgisde NSAIDs.

The harness sound worth investigating so something I will look at in the future so thanks for the info Aine.

RE: Pain control in my elderly staffie

Will McMullan — Sat, 14 May 2016 21:56:29 GMT

[quote user="Aine Seavers"]

Unlike Tramadol which fails in 50% or more of dogs who physically dont have the receptors to have Tramadol work, gabapentin much more likely to be effective.

[/quote]

Have you got a reference for this?

RE: Pain control in my elderly staffie

Aine Seavers — Sat, 14 May 2016 07:08:50 GMT

gabapentin, gabapentin and gabapentin with the Metacam. Unlike Tramadol which fails in 50% or more of dogs who physically dont have the receptors to have Tramadol work, gabapentin much more likely to be effective. As a tangent- the dogleggs site does a brilliant hygroma harness which i have used on a few staffies and St Bernards for elbow skin issues and the owners report the dogs much more stable on their front legs as the leather harness supports the elbows so don't adduct as much when standing and splint the limbs and also pad the elbows when sleeping so a non drug work around. The other drug you could use is Fosamax-again used this in staffies whose elbows were so painful the dog walked in backwards tilted back so wt on hind not fore legs as limping is a luxury a dog can't afford with front leg lamness due 67% front leg loading. But Fosamax needs special dosing care, i can send you the protocol privately later. That and massage-esp the Trigger points and myofascial planes getting some Bowen massage style always helps.

RE: Pain control in my elderly staffie

dachsie_4 — Thu, 12 May 2016 20:38:01 GMT

I have had good success with acupuncture in a retriever that just plain creeks underhand on all joints - had a flare up and settled well on pardale and gabapentin ....

RE: Pain control in my elderly staffie

Joyce Whitehead — Thu, 12 May 2016 19:45:45 GMT

There has been a thread before including this, here I think

https://www.vetsurgeon.org/uk/small_animal/f/9/t/11503.aspx?PageIndex=1

Ive only tried it once so not enough to be sure of the effect!

RE: Pain control in my elderly staffie

Edward Jones — Thu, 12 May 2016 18:58:03 GMT

Related to amantadine - has anyone come across using ketamine for chronic pain control with periodic injections of low doses?

RE: Pain control in my elderly staffie

Bob Russell — Thu, 12 May 2016 15:52:35 GMT

As we have that on the shelf, I will give it a go!

RE: Pain control in my elderly staffie

Joyce Whitehead — Thu, 12 May 2016 13:49:42 GMT

I have put a very elderly Labrador with totally shot elbows onto gabapentin with his previcox and Pardale, he is loads better, might be worth a try? I just have him 100mg bid and that was enough for a significant improvement.

RE: Pain control in my elderly staffie

Richard Carter — Thu, 12 May 2016 13:07:43 GMT

our end of road labradors and very elderly when nsaids have run their course go onto tramadol/ preds, sometimes with very surprising results. Often tramadol given at night to help sleep properly with preds in am so urination a bit under control by pm

RE: Pain control in my elderly staffie

Bob Russell — Thu, 12 May 2016 12:34:02 GMT

She has been on Pardale (additional to NSAI) and PLT's. The damage is too advanced for much beyond pain management. Was considering dusting off my acupuncture skills!

RE: Pain control in my elderly staffie

David Mills — Thu, 12 May 2016 12:32:51 GMT

Having seen the improvement in my mother's lab when onto plt then nsaids/roids I'd be adding in preds at a low dose.

Gabapentin and amantadine may be worth a try. Similarly paracetamol.

RE: Pain control in my elderly staffie

Will McMullan — Thu, 12 May 2016 12:09:00 GMT

You can try it. I don't think there is any evidence either way for it's efficacy but is used by some practicioners. Have you tried Pardale? Or switching to PLT? Or intra-articular steroid injections? Acupuncture? All have some advocates in the orthopaedic community.

Unfortunately too late for your staffie but we are probably only a few years away from a licensed anti-NGF antibody preparation that in early trials has been shown to have a big positive effect on lameness due to OA. I don't have a link to the trials but if it continues to develop in the same way we could be in for a bit of a paradigm shift in treatment of OA pain. Fingers crossed.