Page 54 - VETcpd - Vol 1 - Issue 4

Drug Focus:Tramadol Hydrochloride

BackgroundTramadol hydrochloride is a synthetic product similar to codeine, licensed for use as an analgesic in humans for moderate to severe pain, including post-operative pain. WHO, the World Health Organisation, classifies it on their ‘analgesic ladder’ as sit-ting between the relatively weak NSAIDs (non-steroidal anti-inflammatory drugs) and the relatively strong morphine type opioids. In humans it is generally consid-ered effective, safe and well tolerated.

It is now listed (since June 2014) as a Schedule 3 Controlled Drug, under the Misuse of Drugs regulations 2001. Tramadol is exempt from Safe Custody regulations, however the RCVS advises that all Schedule 3 drugs are locked away. Although it does not need to be recorded in the Controlled Drugs Register, it is sub-ject to special prescription requirements. For further information go to www.bsava.com/Resources/BSAVAMedicinesGuide/ControlledDrugs.aspx

Currently tramadol is not licensed in any veterinary species, however it has become increasingly popular as an analgesic adjunct in canine (and feline) patients over the past few years. Unfortunately there is very little safety or efficacy data published in these species and most of the information available is anecdotal. Oral and injectable formulations are available.

Debbie Doyle MA VetMB MRCVSDebbie spent 5 years in general practice before going into industry and specialising in the area of pain management. She published a text book on the subject in 2006, commissioned by Elsevier Ltd.

From 2004 to 2007 Debbie was elected Secretary of the British Veterinary Orthopaedic Association and currently works as a free-lance veterinary writer.

E-mail: debs.grant@btinternet.com

Tramadol hydrochloride is not licensed in any veterinary species. Therefore it should only be used according to the Prescribing Cascade. For further guidance go to: www.vmd.defra.gov.uk/pdf/vmgn/VMGNote13.pdf

The majority of information available about the safety and efficacy of tramadol in dogs and cats is anecdotal

60% of tramadol activity is due to serotonin and noradrenalin reuptake inhibition40% of tramadol activity is due to mu-opioid receptor agonism

Mode of Action (Fox 2010)Tramadol is a centrally acting analge-sic with both opioid and non-opioid mechanisms of action. The drug comprises of two independently acting enantiom-ers, both of which are required for full analgesic activity: • R-enantiomer - inhibits noradrenalin

reuptake, which provides 40% of the drug’s overall analgesic effect.

• S-enantiomer - acts as both a mu opioid receptor agonist and a serotonin (5-HT) reuptake inhibitor, producing 40% and 20% respectively of the drugs overall analgesic effect.

The combination of the two enantiom-ers is synergistic, i.e. they produce a greater effect than the additive effect of each enantiomer used alone. There is no evidence of any COX (cyclo-oxygenase) inhibition by tramadol.

Interestingly, a study in human patients with knee osteoarthritis demonstrated that both tramadol and its active metabo-lite penetrate into joint fluid, significantly reducing synovial fluid levels of sub-stance P (Bianchi, Broggini, Balzarini et al 2003). Substance P is involved in potentiating nociceptive signals arising from inflamed joints. The study found not only did tramadol significantly reduce the intensity of joint pain, but the data also suggested that the activity of tramadol might also involve the modula-tion of inflammatory mediators (Bianchi, Broggini, Balzarini et al. 2003).

MetabolismTramadol undergoes extensive hepatic metabolism and the metabolites produced are hugely variable between individuals. At least 32 different metabolites have been identified in dogs (Fox 2010). Laboratory studies (Fox 2014), demonstrated that approximately 16% of tramadol is demeth-ylated to O-desmethyl-tramadol (M1 demethylated metabolite) in dogs, which appears to have a much greater binding affinity for mu-opioid receptors than the parent drug. Therefore it’s likely the metabolite is providing a significant anal-gesic effect. However, the M1 metabolite

VETcpd - Pharmacology Peer Reviewed

For Anaesthesia and analgesia referrals: vetindex.co.uk/anaesthesia

®

16th Edition

VetIndex 2014 Th

e year

ro

un

d g

uid

e to v

eterin

ar

y pro

du

cts, su

pplies an

d ser

vic

es

The year round guide to veterinary

products, supplies and services

2014

www.vetindex.co.uk

Rossdales equine Hospital & diagnostic centRe

Exning, Newmarketsurgery, medicine, reproduction and clinical diagnostics for local practice and referral services

tel: 01638 577754

Rossdales equine pRacticeBeaufort Cottage Stables, High Street, Newmarket

local practice ambulatory service and out-of-hours telephone servicetel: 01638 663150

BeaufoRt cottage laBoRatoRies

High Street, Newmarket

clinical pathology

tel: 01638 663017

visit our website at www.rossdales.com

20th Edition

®

Plus

The best nutritional supplement, providing antioxidants, probiotics,

prebiotics, enzymes, vitamins, minerals, phytonutrients

and so much more, as nature intended

www.petplus.info 01633 612595

Promotes and maintains whole body health including periodontal,

intestinal, cardio-vascular, skin & joint health, immunity & energy

Bob Partridge Dipl. EVDC

European Veterinary Specialist in Dentistry

is pleased to offer dental training, practice seminars,

advice, assistance and referral services for:-

Dental Cases, Facial Trauma, Neoplasia,

Complex Extractions, Orthodontics, Tooth

Fractures, Crowns, Oral Clearance, Imaging.

SpecOakBeck Veterinary Hospital

Harrogate, HG1 3HU

01423 - 561414

Actively Supporting you and

your Client Relationship

Full article available for purchase at www.vetcpd.co.uk/modules/