PRESENTATION
BROCHURE
Chronic pain
in dogs Belén Ruano Puente
Chronic pain in dogs
Chronic pain
in dogs Belén Ruano Puente
P75350_Chronic_pain_Cover_SERVET.indd 3
26/10/17 12:51
AUTHOR: Belén Ruano Puente FORMAT: 17 × 24 cm. NUMBER OF PAGES: 128. NUMBER OF IMAGES: 50. BINDING: hardcover.
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The management of chronic pain in companion animals is an area in which there is a significant therapeutic void. In many cases professionals are unaware of the appropriate approach to manage chronic pain, despite the wide range of pharmacological, surgical and physical therapeutic options that act directly on the pain pathways. Recent discoveries in the area of pain pathways have opened many avenues for the management of chronic pain. The goal of this book is to present this new knowledge in the context of the small animal clinic.
Chronic pain in dogs
Presentation of the book In veterinary medicine, more so than in human medicine, pain was traditionally considered a side effect of the everyday conditions encountered of the clinic, and even considered normal in certain cases, certain diseases and in particular in animals of certain ages. This perspective on pain is more evident in cases involving animals of lesser sentimental value. In recent years, this sentimental value has increased; pets have become part of the family and, as such, the suffering of a pet is felt by the whole family. In the last two decades, neurology has evolved greatly thanks to advances in diagnostic imaging techniques and neurophysiology. Knowledge of the spinal cord, its complex control of sensations and its connection to higher structures, has created an exciting new field of research, which aims to understand the role of the nervous system in pain. It is becoming clear that there is no single type of pain and that each type has a different cause, and we have come to understand pain not merely as another symptom but as a cause of disease in itself. These neurological diagnostic systems are lacking in daily veterinary practice. However, in recent years pain studies have been conducted in different animals under carefully controlled laboratory conditions, and the resulting findings extrapolated to different species. This book aims to introduce the veterinarian to this new concept of pain and describes how pain is established in the organism and how to interpret it, identify it as a pathology in itself, and treat it as such. We will look at the pain pathways, the framework of pain control and the sophisticated therapeutic systems that are in continuous development. BelĂŠn Ruano Puente
Chronic pain in dogs
The author BelĂŠn Ruano Puente Degree in Veterinary Medicine specialising in pain and rehabilitation. Member of the Spanish Pain Society (SED), the International Association for the Study of Pain (IASP), and the Madrid Association of Companion Animal Veterinary Medicine (AMVAC).
hkeita/shutterstock.com
Head of the Pain and Rehabilitation Unit of the Pulso Animal Clinic (Manzanares el Real, Madrid). Pulso Animal is a group of professionals who, in their respective specialities and fields of expertise, seek to develop a method of treating animals with pain using an approach that considers all associated aspects and manifestations.
Communication services Website Online visualisation of the sample chapter. Presentation brochure in PDF format. Author’s CV. Sample chapter compatible with iPad.
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Chronic pain
in dogs BelĂŠn Ruano Puente
P75350_Chronic_pain_Cover_SERVET.indd 3
26/10/17 12:51
Table of contents 1. What is chronic pain?
3. Treatment of chronic pain
Introduction
Introduction
Nociception
Pharmacological therapy
Transmission Anatomy of nerve pathways
Transduction: neurotransmitters involved in chronic pain Cellular metabolic mechanisms of chronic pain
Perception and classification of chronic pain Pain modulation process Spinal control Supraspinal control Cortical control
Pain chronification
2. Diagnosis of chronic pain syndrome Introduction Stress Behavioural changes in states of continuous pain Diagnostic approach for a patient with pain Detailed anamnesis Physical examination Blood test Orientative analytical parameters
Complementary diagnostic techniques Thermography Techniques for assessing neurophysiological function
Pain scales used in animals
Anti-inflammatories Nonsteroidal anti-inflammatory drugs Corticosteroids
Opioids Mechanism of action of opioids Routes of opioid administration Opioids used in veterinary medicine
Antidepressants Tricyclic antidepressants Selective serotonin reuptake inhibitors Selective serotonin–noradrenaline reuptake inhibitors
Anticonvulsants Amantadine Growth factors Local anaesthetics Routes of administration Most commonly used drugs
α-adrenergic receptor agonists Medetomidine Dexmedetomidine
Cannabinoids Capsaicin Ketamine Routes of administration
Experimental drugs
4. Types of chronic pain Introduction Visceral pain Chronic pancreatitis Chronic renal failure Uraemic polyneuropathy Osteoarthritis: joint pain
Pain due to cancer Analgesic drugs in oncology Anti-inflammatories: NSAIDs and corticosteroids Analgesics Local anaesthetics Antiemetics Anticonvulsants NMDA receptor antagonists Bisphosphonates Other drugs
Geriatric pain Analgesic drugs in geriatric patients
Diabetic neuropathy Treatment of diabetic neuropathy
Joint pain Treatment of joint pain Joint stress stage Bone inflammation phase Bone reorganisation stage Degenerative stage
Radicular pain Treatment of radicular pain Corticosteroids Opioids Muscle relaxants NSAIDs Local anaesthetics Neurolytic agents Adjuvant analgesics Other therapies
5. Interventional therapies Introduction Ablative techniques Peripheral neurectomy Rhizolysis
Facet rhizolysis Cordotomy Dorsal root entry zone (DREZ) lesion
Decompression techniques Discolysis
Neuromodulatory techniques Neurostimulation Spinal infusion
Electrotherapy Transcutaneous electrical neurostimulation (TENS) Interferential currents Ultrasound Shockwave therapy Diathermy Neuromuscular therapy
6. Functional recovery of a painful limb Case descriptions Introduction Case 1 Shiba Golden Retriever, aged 14 years
Case 2 Terry A mixed breed, 30-kg dog with leishmaniasis
Case 3 Pepa Yorkshire Terrier, aged 5 years
Case 4 Admiral Labrador, aged 2 years
Case 5 Terry Golden Retriever, aged 10 years
Case 6 Miko Dachshund, aged 6 years
CHRONIC PAIN IN DOGS
Introduction It is important to be familiar with all therapeutic approaches currently used for the treatment of chronic pain, their efficacy, and their potential application in veterinary medicine. Many of these techniques involve the use of diagnostic imaging equipment and are thus very expensive (Fig. 1). Treatment of pain should be based on the following factors: Clinical history (previous medication). ■ Diagnosis of the pathology that may have caused the problem (inflammatory, infectious, oncological, traumatic, congenital, etc.) (Fig. 2). ■ Physical characteristics of the animal (age, character, renal and hepatic status, etc.). ■ Owner’s economic resources and attitude to the problem (very important). ■
It is essential to consider all these factors before establishing treatment. A comprehensive analysis of pain improvement, or the absence thereof, should be conducted. This should take into account the owner’s opinion, which should be as objective as possible.
Figure 1. Fluoroscopy equipment for radiofrequency treatment (ChaNaWiT, Shutterstock.com).
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Figure 2. Patient undergoing amputation. Adaptive muscle alterations resulted in osteoarthritis in the carpus and muscle contractures in the nonamputated limb, which, together with the pain in the stump, required permanent therapy.
Treatment of chronic pain
Clinically, the treatment of chronic pain remains in its infancy, given that most of the therapies used remain under study. Continual discoveries in the field of neurology are constantly changing the expectations associated with current therapies. Establishing an accurate prognosis is therefore difficult, particularly for veterinary surgeons, and the more polymodal the final treatment the more likely it will be successful.
Pharmacological therapy Analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, corticosteroids, and local anaesthetics are basic pharmacological tools used for the treatment of chronic pain. However, there are numerous adjuvant drugs that complement these basic agents, enhancing their effects and allowing for a reduction in the dose used, and therefore, in the associated side effects. The WHO has developed a schematic in the form of a ladder, in which each rung corresponds to the treatment recommended for pain of a given intensity (Fig. 3). In veterinary medicine the use of oral opioids (e.g. tramadol) is considered ineffective due to their metabolism by first-pass metabolism. Therefore, this rung should be modified, and alternative routes indicated, such as subcutaneous or topical administration, which are the only possible routes of administration by pet owners. In this book we will also discuss invasive and interventional techniques, the application of which is relatively rare in veterinary medicine due to the high cost of implantation processes and the need for patient cooperation. However, neuromodulatory techniques such as electrotherapy and manual physiotherapy
Figure 3. WHO pain ladder. 4
Potent opioids via other routes of administration (epidural) Invasive techniques (local anaesthetics) If pain persists
3
Potent opioids ± opioid analgesics ± adjuvants If pain persists
2
Weak opioids ± nonopioid analgesics ± adjuvants If pain persists
1
nonopioid analgesics ± adjuvants
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3
CHRONIC PAIN IN DOGS
can be added to the rungs of the aforementioned ladder. These approaches have been recently applied in veterinary medicine with great success and are well tolerated by patients and accepted by owners (Fig. 4). Here we will review the most effective drugs commonly used in small animals, discussing their current status in veterinary medicine and the relevant studies in human medicine. To do this, we must bear in mind that analgesic agents and their adjuvants have effects at different stages in the pain process, and that knowledge of these effects is important in order to prescribe an appropriate combination of drugs. Analgesics and adjuvants exert their effects at: ■ Nociceptors. ■ Primary sensory pathways. ■ The dorsal horn of the spinal cord. ■ Higher centres that mediate the control and reorganisation of nociceptive signals (thalamus, raphe nuclei, cortex). ■ Descending pathways. Some of these drugs can act at multiple levels. This lends them significant analgesic capacities, but is also associated with multiple side effects. The following is a list of the most commonly used drugs and therapies: ■ Anti-inflammatories (steroids and nonsteroids). ■ Pure analgesics (opioids). ■ Antidepressants. ■ Anticonvulsants. ■ NMDA modulators. ■ Growth factors. ■ Local anaesthetics. ■ α-adrenergic agonists. ■ Cannabinoids. ■ Chondroprotectors. ■ Ketamine. ■ Capsaicin. ■ Neurolytics (phenol extract of the Sarracenia purpurea plant). ■ Growth factors. ■ Experimental drugs. ■ Manual physical therapy. ■ Neuromodulation (electrostimulation) therapy. ■ Interventional therapy. Figure 4. Patient undergoing diathermy. ■ Surgical therapy.
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Treatment of chronic pain
These therapies do not have to be independent: they can be combined if a previous treatment is proving ineffective. To establish a solid starting point for diagnosis and treatment, the following should be noted: any history of previous infectious, chronic inflammatory, oncological, genetic, breed-specific, autoimmune, or traumatic processes.
In cases in which chronic pain is due to an established inflammatory process, treatment should be directed to control the cause (Fig. 5). Inflammation becomes chronic when: ■ The body’s response to the inflammatory process is ineffective. ■ The stimulus that triggered the inflammatory cascade persists or is repeated frequently. The agents or factors involved in chronic inflammatory processes can be bacterial, fungal, toxic, autoimmune, postural, mechanical, foreign bodies, etc. If the cause is not eliminated, proinflammatory agents remain active and cause neovascularisation and reorganisation of the affected tissues (e.g. degenerative osteoarthritis) through the formation of granulomas and fibrosis. This tissue response can affect the involved organ, resulting in complete functional impairment with important systemic consequences, which should be taken into account during diagnosis and treatment (Fig. 5). Two main drug types are used to interfere in the inflammatory process NSAIDs and steroids (cortisones).
Anti-inflammatories Anti-inflammatory drugs act by inhibiting the activity of cyclooxygenase and lipoxygenase. Cyclooxygenase type 1 (COX-1), which plays a physiological role in several metabolic pathways of the body, was the first subtype discovered (Fig. 6). Subsequent studies confirmed the existence of another variant, cyclooxygenase type 2 (COX-2), which is induced by inflammatory processes. Although it was initially thought that COX-2 inhibition did not result in the undesirable side effects associated with COX-1 inhibition, the former was also shown to regulate vascular tone and renal vascular flow (Fig. 7). Finally, researchers attempting to identify the origin of central analgesia discovered a third cyclooxygenase subtype (COX-3), which is active in the brain and to a lesser extent in the cerebellum and spinal cord, and controls fever and central pain (Fig. 8).
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CHRONIC PAIN IN DOGS
Figure 5. Evolution of the inflammatory process.
Cell damage
Altered cellular immunity
Release of phospholipids in response to the action of phospholipases Production of arachidonic acid
Oxygenation Action of cyclooxygenases
Action of lipoxygenases
Prostaglandins
Thromboxanes
PGI2: vasodilation and platelet aggregation PGD2 and PGE2: vasodilation PGF: bronchoconstriction
Leukotrienes
Intense plasma exudation
Haemostasis Platelet aggregation Vasoconstriction Bronchoconstriction These effects are very important for the production of bradykinin, the most potent endogenous algesic factor
INFLAMMATION
A wide variety of NSAIDs act on the different types of cyclooxygenases and lipoxygenases. Anti-inflammatory steroids include corticosteroids, which also inhibit the production of cyclooxygenase and lipoxygenase and modulate the production of macrocortin, an inhibitor of the enzyme phospholipase A2.
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Treatment of chronic pain
Figure 6. Characteristics of COX-1.
Constitutive enzyme (hormonal)
Can increase its production by 2–4 fold COX-1 Functions: regulates renal vascular flow, vascular tone, and bronchial tone, and protects the gastric mucosa
Location: platelets, vascular endothelium, gastric mucosa, intestine, kidney
Figure 7. Characteristics of COX-2.
Induced by genomic expression
3
Can increase its production by 10–20 fold COX-2
Functions: participates in immune and inflammatory processes Location: central nervous system, kidney, ovary, epithelial cells, synovial cells, chondrocytes, fibroblasts, and macrophages
Figure 8. Characteristics of COX-3.
Constitutive enzyme Concentration is inverse to that of peroxides COX-3 Functions: regulates fever and central pain Location: brain, endothelium of the choroid plexus, and to a lesser extent the cerebellum, spinal cord, heart, carotid arteries, and digestive system
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CHRONIC PAIN IN DOGS
Nonsteroidal anti-inflammatory drugs NSAIDs are the drugs of choice corresponding to the first rung of the pain ladder, given the fact that they can be used for long-term treatment. In studies of carprofen, analyses performed after 2 months of administration revealed no changes in total protein, albumin, urea, creatinine, alkaline phosphatase, or alanine-aminotransferase (ALT) levels. NSAIDs act by inhibiting the action of COX-1, COX-2, and COX-3 (paracetamol, dipyrone), and some also inhibit lipoxygenase. It has also been proposed that these drugs inhibit the nuclear factor NF-κB (salicylates). Carprofen is also thought to exert central effects: in vivo studies in animals have demonstrated that it has no effect on prostaglandin production. The specificity of each NSAID for COX-1 versus COX-2 is unclear, with different results obtained in vivo and in vitro, and contradictory findings reported by different research groups. Significant side effects have been reported in cardiovascular patients treated with recently developed specific COX-2 inhibitors (celecoxib). Moreover, COX-2 exerts a protective effect on the duodenal mucosa: a study conducted at the University of North Carolina reported perforation of the duodenum in dogs treated with specific COX-2 inhibitors. This enzyme is also found in the intra-renal vessels, at higher concentrations in dogs than in humans, where it prevents vasoconstriction in response to shock (Jones and Budsberg, 2000). It is also implicated in bone remodelling, healing of digestive ulcers, ovulation and implantation, and closure of the patent ductus arteriosus. In the kidney, prostaglandins have a regulatory effect on the reabsorption of water and salts, but renal side effects of NSAIDs are only observed in patients with pre-existing conditions (e.g. dehydration, arterial hypertension, or shock). Studies of meloxicam, carprofen, and tepoxalin have reported no renal side effects in patients with normal renal function (Table 1).
Meloxicam Inhibits COX-2 to a greater extent than COX-1. Completely absorbed following oral administration, with peak plasma levels observed at 6 hours. Efficacy has primarily been assessed in patients treated for joint problems (Johnston and Narbe, 2012). No effects on the production of chondrocytes, glucosaminoglycans, or collagen have been reported (Budsberg et al., 2013), although firocoxib shows greater efficacy for the treatment of joint pain. Can be administered topically for the treatment of joint pain.
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0.2 mg/kg at baseline; subsequently 0.1 mg/kg in 4-day cycles
4 mg/kg
1–2 mg/kg
5 mg/kg
1–2 mg/kg
2 mg/kg
1–2 mg/kg
4 mg/kg
10 mg/kg
Carprofen
Robenacoxib
Firocoxib
Deracoxib
Mavacoxib
Ketoprofen
Tolipanic acid
Tepoxalin
DOSE
Meloxicam
NSAID
Table 1. Characteristics of NSAIDs.
Selective for COX-1
COX-2
COX-2
380 times more selective for COX-2 than COX-1
140 times more selective for COX-2 than COX-1
1.75 times more selective for COX-2 than COX-1
12 times more selective for COX-2 than COX-1
COX SELECTIVITY
Every 24 hours
COX-LOX
3 days on / 4 days COX-2 off / 3 days on
Every 24 hours
Every 15–30 days
Every 24 hours
Every 24 hours
Every 24 hours
Every 24 hours
Every 24–48 hours
FREQUENCY
-
Hepatic
Hepatic
Hepatic
Hepatic
Hepatic
Hepatic
Hepatic
Hepatic
CLEARANCE
PO PO, SC
Renal (long-term) Do not administer for more than 3 consecutive days
PO
PO
N/A
Digestive
PO
PO
+
3–7 days
PO, SC
+
PO, SC, IV
PO, IM
+
N/A
ROUTES OF ADMINISTRATION
SIDE EFFECTS
++++
+
+++
+++
+++
++++
+++
++
+++
EFFECT ON OSTEOARTHRITIS
Treatment of chronic pain
3
37
CHRONIC PAIN IN DOGS
Carprofen This NSAID has a weaker inhibitory effect on prostaglandins, but exerts strong anti-inflammatory effects. Like firocoxib, few side effects have been reported. Oral carpfofen is well absorbed (90 %).
Firocoxib This drug selectively inhibits COX-2 (380 times greater affinity than for COX-1 in vitro). Peak plasma levels are observed at 1.25 hours. Owing to its analgesic efficacy, this NSAID is the anti-inflammatory of choice for the treatment of joint and muscle pain. Moreover, it showed a better safety profile and greater analgesic efficacy than carprofen in a double-blind study of 218 dogs with osteoarthritis (Pollmeier et al., 2006). Another comparative study (Drag et al., 2007) found that the analgesic activity of firocoxib was greater than that of carprofen, deracoxib, and meloxicam. An interesting 2011 study (Camargo et al.) found that when administered as part of a polymodal treatment, the postoperative analgesic activity of firocoxib was greater than that of butorphanol. Firocoxib administration to geriatric dogs at 5 mg/kg for 3 months causes few biochemical alterations (Joubert, 2009). Considering the high incidence of renal pathologies in geriatric dogs, this lack of biochemical changes is a good indicator of safety, and firocoxib is therefore considered an NSAID of choice based on its efficacy and safety profile. The long-term analgesic efficacy (52 weeks) of firocoxib was studied by Autefage et al., (2011). Firocoxib was administered at a dose of 5 mg/kg/day to 25 geriatric dogs with osteoarthritis, and efficacy measured based on improvement as reported by the owner, as well as effects on lameness and joint mobility. A marked improvement was observed after the first 15 days, with 96 % of dogs showing variable signs of improvement by 360 days. Analysis of hepatic and renal parameters during the treatment period revealed no alterations. Daily firocoxib administration at doses of 5 mg/kg, with monitoring of renal and hepatic activity, is thus considered effective for the treatment for osteoarthritis.
Acetylsalicylic acid This has a nonselective inhibitory effect on COX, but is more selective for COX-1 at very low doses. It inhibits PGE2 in blood, gastric mucosa, and synovial fluid and thromboxane B2 (TXB2) in blood. A peculiar aspect of its action is that it induces the formation of lipoxin A4, which has a protective effect on the digestive mucosa in cases of prolonged treatment. However, recent studies have shown that this effect is not exclusive to acetylsalicylic acid, and is also a feature of other NSAIDs.
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Treatment of chronic pain
Robenacoxib Peak plasma concentrations are achieved 50 minutes after the administration of 1–2 mg/kg. Its efficacy in the treatment of osteoarthritis is similar to or slightly greater than that of meloxicam.
Tepoxalin This drug acts on both cyclooxygenase and lipoxygenase, and therefore has an inhibitory effect on leukotrienes. It attenuates the massive proliferation of synoviocytes that occurs in osteoarthritis, an effect not observed in other NSAIDs (Sunaga et al., 2012).
Celecoxib Selective COX-2 inhibitor. In osteoarthritis patients, continuous treatment produces better results than intermittent treatment.
Metamizole NSAID with analgesic and antipyretic (inhibition of prostaglandin formation) properties and antispasmodic activity (via inhibition of prostaglandins and activation of the nitric oxide/cGMP pathway and potassium channels). Metamizole shows little anti-inflammatory activity, but diminishes the migratory capacity of neutrophils. It acts on cannabinoid and opioid receptors, activating the corresponding inhibitory pathways and thereby exerting its analgesic activity. The recommended dose is 15–25 mg/kg, administered subcutaneously, intravenously, or orally every 12 hours (Escobar et al., 2012; Ortiz et al., 2003).
Mavacoxib This NSAID has the ability to self-limit its rate of clearance and thus prolong its own activity. However, it should not be used without performing prior renal and hepatic analyses to avoid adverse effects (especially renal). Clinical doses are thought to result in mild COX-1 inhibition but marked inhibition of COX-2. Given the strong involvement of COX-2 in renal vascularisation, prolonged inhibition could result in a marked decrease in renal blood supply.
Paracetamol Paracetamol is an NSAID that inhibits COX-3, which is found in the central nervous system (brain), and has effects on both serotonergic and cannabinoid transmission. It also exerts antipyretic effects through its activity on the temperature-regulating centre in the hypothalamus, and strong analgesic activity via its action at opioid, serotonergic, and cannabinoid receptors. It has no anti-inflammatory activity.
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CHRONIC PAIN IN DOGS
Table 2. Results of haematological analyses of a patient who underwent treatment for 4 months with paracetamol and codeine.* GROUP Red blood cells
RESULTS
REFERENCE VALUES
Red blood cell count (× 106/μl)
PARAMETER
7.8
5.4–8.7
Haematocrit (%)
43.7
38.3–56.5
Haemoglobin (g/dl)
14.1
13.4–20.7
56
59–76
Mean corpuscular volume (MCV) (fl)
White blood cells
Platelets
Mean corpuscular haemoglobin (MCH) (pg)
18.1
21.9–26.1
Mean corpuscular haemoglobin concentration (CHCM) (g/dl)
32.3
32.6–39.2
RBC distribution width (RDW) (%)
29.7
13.2–19.1
Reticulocyte count (cells/μl)
33,540
10,000–110,000
Leukocytes (cells/μl)
5,300
4,900–17,600
Banded neutrophils (%)
0.4
-
Segmented neutrophils (%)
62.6
-
Lymphocytes (%)
30.2
-
Monocytes (%)
3.8
-
Eosinophils (%)
2.8
-
Basophils (%)
0.2
-
Banded neutrophils (cells/μl)
21
0–170
Segmented neutrophils (cells/μl)
3,318
2,940–12,670
Lymphocytes (cells/μl)
1,601
1,060–4,950
Monocytes (cells/μl)
201
130–1,150
Eosinophils (cells/μl)
148
70–1,490
Basophils (cells/μl)
11
1–100
Platelets (cells/μl)
330,000
143,000–448,000
-
8.4–13.2
Mean platelet volume (MPV) (fl) * Blood smear showed normal morphology.
Paracetamol is very effective in the treatment of chronic pain in dogs at doses of 10–15 mg/kg every 8 hours (Tables 2 and 3). It has a broad margin of safety; its metabolites are toxic at doses of over 100 mg/kg. Its toxicity can be reduced by administration in combination with ranitidine (50–120 mg/kg). Paracetamol is highly toxic in cats, in which it causes methaemoglobinaemia. As an analgesic it is highly effective when combined with opioids (codeine or hydrocodone: 0.22–0.5 mg/kg) for short periods (6 months). It can also be administered as part of a multimodal treatment approach for osteoarthritis together with NSAIDs such as carprofen, and even in combination with NSAIDs + opioids. Caution is recommended when administering paracetamol in combination with serotonergic agents (e.g. amitriptyline, fluoxetine, ondansetron, selegiline, tramadol) given the risk of serotonin syndrome. 40
Treatment of chronic pain
Table 3. Results of biochemical analysis of a patient who underwent treatment for 4 months with paracetamol and codeine.
The publishing strength of Grupo Asís RESULTS
REFERENCE VALUES
Total protein (g/dl)
PARAMETER
7.9
4.8–7.8
Albumin g/dl
2.6
2.7–4.1
Globulins (g/dl)
5.3
2.5–4.4
Albumin/globulin ratio
0.49
0.7–1.9
27
26–89
ALT (IU/l)
AST (IU/l) 110become one of the 16–89 Editorial Servet, a division of Grupo Asís, has reference publishing comTotal (mg/dl) sector worldwide. Hemolysed 0.01–0.31 panies in bilirubin the veterinary More than 15 years of experience in the publisCalcium (mg/dl) 11.2 8.2–11.9 hing of contents about veterinary medicine guarantees the quality of its work. With a wide Creatinine (mg/dl) 1.0 0.5–1.5 national and international distribution, the books in its catalogue are present in many diffeAlkaline phosphatase (IU/l) 58 13–105 rent countries and have been translated into nine languages to date: English, French, PorPhosphorus (mg/dl) 6.1 Russian and Chinese. 2.7–6.7 tuguese, German, Italian, Turkish, Japanese, Glucose (mg/dl)
36
60–120
Its identifying team Lipase (IU/l) characteristic is a large multidisciplinary 106 75–784formed by doctors and graduates in Veterinary Medicine and Fine Urea (mg/dl) 49 Arts, and specialised 21–59 designers with a great knowledge of the sector in which they work. Every book is subject to thorough technical and linguistic reviews and analyses, which allow the creation of works with a unique design Corticosteroids and excellent contents. Corticosteroids are recommended for the treatment of chronic pain caused by
3
chronic inflammation. They have both anti-inflammatory and analgesic effects, as
Servet the most renowned national and international authors theyworks act on with certain genes (induced specifically by corticosteroids) to modulate the to include the topics most demanded by veterinary in its catalogue. In addition to its own works, production of their protein products.surgeons One of these proteins, macrocortin, inhibits the companies production ofand cyclooxygenase and lipoxygenase phospholipase A2, blocking Servet also prepares books for the main multinational companies in the and thereby interfering with the inflammatory process. In this way, corticosteroids sector are among its clients. break the vicious cycle by which the inflammatory process induces central and peripheral sensitisation through the activation of silent receptors. For this reason, these drugs are considered effective for combined analgesic treatment of chronic processes. Several glucocorticoids are used in veterinary medicine, including prednisone, dexamethasone, budesonide, and long-acting corticosteroids.
Prednisone This is the precursor of prednisolone. In cats, the viability of prednisone, and its conversion to prednisolone, is limited. Anti-inflammatory effects are achieved at oral doses of 0.5–1 mg/kg/day in dogs and 1–2 mg/kg/day in cats.
Dexamethasone Dexamethasone is between 5 and 10 times more potent than prednisone and exerts its effects for 32 to 48 hours. It lacks mineralocorticoid activity and thus does not cause fluid retention. 41
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