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Therapeutics: musculoskeletal system

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Podcast: Therapeutics: musculoskeletal system

Drugs used in the diagnosis of musculoskeletal disease in the horse

  • Local anesthetics.
  • Sedatives.
  • Tranquillizers.
  • General anesthetics.

Local anesthetic agent

  • Very commonly used   Anesthesia: local - overview  .
  • Mechanism of action:
    • Prevent voltage-dependent increase in sodium ion conductance.
    • Block the initiation and propagation of action potentials.
    • Interrupt transmission between peripheral nociceptors and the cerebral cortex.
  • Regional blocks of specific peripheral nerves.
  • Local infiltration of tissues may block nerve endings, fibers and specific nerves.
  • Intrasynovial blocks:
    • Joints: pain receptors in synovium, joint capsule and subchondral bone.
    • Sheaths/bursa: where pain is perceived in these structures is less clear.
  • Not selective to pain fibers:
    • Block   →   suppressed pain, cold/warmth, touch/pressure.

Uses

Reactions

  • Local tissue reactions:
    • Inflammation if severe can   →    necrosis: more common and potentailly more severe with epinephrine (adrenaline)   Epinephrine  .
    • Allergic reactions: more common and potentailly more severe with esters, eg procaine   Procaine hydrochloride  .
    • Neurotoxicity: rare but increases with 200 ml or more used locally in short period.
    • Ataxia after more proximal regional blocks in limb?
  • Systemic reactions:
    • Inadvertent intravenous injections.
    • Overdosage and systemic absorption.
    • CNS toxicity is dose dependent: depression/sedation    →   excitement, muscle twitches and convulsions.
    • Cardiovascular reactions:
      • Bradycardia    →   and/or conduction disturbances.
      • Myocardial depression, peripheral vasodilation    →   hypotension.
      • Severe cases    →   cardiovascular collapse

Onset, elimination and duration

  • Determined by the physiochemical properties of agent:
    • Rate of onset of action is determined by the acidic dissociation constant (pKa).
    • The agents lipid solubility determines its potency (higher lipid solubility    →   increased potency).
    • The degree of protein binding determines the duration of action (higher longer).
  • Elimination:
    • Ester-linked agents, eg procaine hydrolysed in blood: half-life in minutes.
    • Amides, eg lidocaine and rest undergo hepatic metabolism: half-life in hours.
    • LA and metabolites detected in equine urine for prolonged periods.
  • Class 2 foreign substances by ARCI.

Specific drugs

  • Lidocaine (lignocaine)  Lidocaine  :
    • 2% solution + epinephrine   Epinephrine   (11-12.5 mg/ml).
    • pKa 7.8; rapid onset (4 min); intermediate potency; rapid tissue penetration; medium duration of action (60-150 min).
    • Rapid systemic absorption (peak 20-30 min).
    • Peak urine concentration: 60 min.
    • Half-life: 48 min.
    • Duration of action prolonged by adding epinephrine (vasoconstrictor):
      • Decreases rate of absorption.
      • Do not use in synovial structures.
      • Side effects: irritant, tissue necrosis, cardiac arrhythmias.
      • Lower limb blocks may    →   digital ischemia and local reactions.
      • Maximum use in one clinical exam period 200 ml.
  • Mepivacaine  Mepivacaine  :
    • 2% solution.
    • pKa 7.7; rapid onset (5-10 min); intermediate potency; rapid tissue penetration; medium duration of action (68-210 min).
    • Does not cause vasodilation and epinephrine is not required.
    • Diffuses rapidly into the systemic circulation (peak 60 min).
    • More highly protein bound than lidocaine (slightly increased duration of action).
    • Peak urine concentration (2 h); mepivacaine and metabolite (50 and 33 h).
    • Less tissue irritant and recommended for joints.
    • More expensive.
    • No effect on bone scintigraphy.
  • Bupivacaine  Bupivacaine hydrochloride  :
    • 0.5% solution.
    • pKa 8.16; moderate onset; high potency; moderate tissue penetration.
    • Longer duration of action (4-8 h):
      • Be careful about accumulated doses.
      • No new block until after previous one worn off.
    • Peak urine concentrations: 
      • 2 h post-intra-articular injection.
      • 4 h post-subcutaneous injection.
    • No effect on bone scintigraphy.
    • Maximum dose should not exceed 2 mg/kg.
    • Therapeutic pain relief ?diagnostic use.
  • Ropivacaine:
    • pKa 8.16; moderate onset; high potency; moderate tissue penetration; long duration of action.
    • S-isomer of bupivacaine.
    • Reduced cardiotoxic effects.
    • Similar duration of action.
  • Procaine  Procaine hydrochloride  :
    • pKa 8.9; moderate onset; low potency; slow tissue penetration; short duration of action.
  • Prilocaine:
    • Similar to lidocaine but less toxicity.

Sedatives

Tranquillizers

  • To allow safe examination in excitable/nervous horses: acetylpromazine   Cyclosporine  0.010.02 mg/kg IV.

General anesthesia

Drugs used in the treatment of musculoskeletal disease in the horse

Non-steroidal anti-inflammatory drugs (NSAIDs)

Analgesia

  • Osteoarthritis (OA):
    • 60% of lameness in horse related to OA   Musculoskeletal: osteoarthritis (joint disease)  .
    • In high motion joints NSAIDs   →    increased joint mobility:
      • Normal cartilage matrix homeostasis.
      • Decreased capsular/synovial fibrosis.
    • In low motion joints NSAIDs   →    decreased pain   →    continue exercise normally:
      • Maintains fitness.
      • Prevents secondary pain elsewhere due to gait changes.
      • Chronic use is very common.
    • Acute flare-ups of both types of OA.
    • Decreases inflammation of synovium/capsule in joint disease.
  • Trauma:
    • Judicious use in fractures.
    • Decreases pain    →   welfare implications.
  • Post-operative analgesia.
  • Decrease soft tissue inflammation:
    • Direct or secondary trauma.
    • Injuries to tendons/ligaments.
    • Muscle inflammation and pain.
    • Decreases excessive swelling and inflammation post-surgery.
  • Chondroprotection/chondrodestruction:
    • Area of intense research mainly in vitro:
      • Release of cytokines.
      • Production of cartilage proteoglycans.
    • No clear picture of role of NSAIDs in healthy or OA joints:
      • Some beneficial anabolic effects but some detrimental catabolic effects.
      • ? Neutral effect.
      • Mainly analgesic effect in treating OA in the horse.

Specific drugs

  • Aspirin  Acetylsalicylic acid  :
    • The oldest NSAID.
    • Very effective anti-thrombotic agent with dose dependent effects.
    • Analgesic and anti-inflammatory at higher doses but rarely used today.
    • Oral + intravenous forms available in some countries.
  • Phenylbutazone  Phenylbutazone  :
    • Oral and intravenous preparations (? intramuscular route).
    • Metabolized in liver and very highly protein bound.
    • Parenteral forms are often irritant:
      • Local tissue reactions intramuscularly.
      • Extravascular    →    perivascular inflammation + slough.
      • Occasional thrombophlebitis.
    • Care when using synchronously with other protein-bound drugs.
    • Synchronous feeding of hay delays absorption.
    • Toxicity is quite common at high doses.
  • Suxibuzone:
    • Derivative of phenylbutazone:
      • ? Any evidence suggesting higher efficacy.
      • ? More palatable.
      • ? Less ulcerogenic.
    • Do not give with other NSAIDs.
    • Care when using synchronously with other protein-bound drugs.
    • Synchronous feeding of hay delays absorption.
    • Same contraindications and toxicities as phenylbutazone.
  • Meclofenamic acid  Meclofenamic acid  :
    • Oral preparation.
    • Slow onset of action 36-96 h before clinical effects.
    • ? Better in laminitis.
  • Flunixin meglumine  Flunixin meglumine  :
    •  Available as oral (paste + granules) + parenteral intravenous injection (intramuscular injection is possible but has been associated with local reactions).
    • Rapid onset of action: 1h.
    • Anti-endotoxic at low doses.
    • Mainly excreted via the kidneys unchanged.
    • Synchronous feeding of hay delays and decreases absorption.
  • Carprofen  Carprofen  :
    • Intravenous and oral preparations (? intramuscular injections).
    • Weak anti-inflammatory agent.
    • Good analgesic.
    • Low incidence of side effects.
    • Useful in decreasing soft tissue swelling.
  • Ketoprofen  Ketoprofen  :
    • Intravenous injection (? intramuscular injection) (similar to carprofen).
    • Presence of inflammation alters pharmacokinetics:
      • Inflammatory loci serve as sequestration sites.
      • Therefore higher levels in inflamed joints.
    • Do not use in pregnant or lactating mares.
    • In neonatal foals increase dose and decrease dosing interval.
    • Potent analgesic + effective anti-inflammatory.
    • Efficacy in comparison to other NSAIDs?
      • Studies vary with models used:
        • Higher in chronic hoof pain.
        • Less in carpal synovitis cf phenylbutazone.
        • Equivalent to flunixin in various injuries/colic/endotoxemia.
  • Naproxen:
    • Intravenous or oral preparations (similar to ketoprofen).
    • Poorly absorbed and slow onset of action (days).
    • ? More effective in soft tissue injuries + myositis.
  • Vedaprofen  Vedaprofen  :
    • Oral gel (? intravenous preparation in Europe) - similar structure to carprofen/ketoprofen.
    • Can be used in pregnancy but not in lactating mares or foals <6 months.
  • Eltenac  Eltenac  :
    • Intravenous preparations.
    • Efficacy in studies equivalent to flunixin in carpal synovitis model.
    • ? Better at controlling swelling and edema.
    • ? Of use post-operatively.
    • Do not use in pregnant mares.
  • Meloxicam:
    • Intravenous and oral suspension preparations.
    • Eliminated in feces and urine.
    • Do not use in pregnant or lactating mares or in foals <6 weeks of age.
    • More COX-2 specific than other NSAIDs used in the horse.

Corticosteroids

  • All corticosteroids have a wide range of actions   Therapeutics: anti-inflammatory drugs  .
  • Wide variety of anti-inflammatory effects suppressing inflammation at a variety of levels.

Use in joints

  • Controversial:
    • Accelerate joint degeneration.
    • ? Negative affects on cartilage.
    • Steroid arthopathy.
  • ? The drugs or the way we use them:
    • Is it a dosage problem?
    • ? Negative effects only at high doses.
  • Low doses inhibit cartilage degradation.
  • ? Exercise during corticosteroid treatment is detrimental: clinical trials suggest that judicious use of exercise may be beneficial.
  • Major side effects also include:
    • Iatrogenic synovial sepsis - decreased dose of bacteria required (give i/a antibiotics concurrently).
    • No effect on bone in horse with commonly used agents.
    • Laminitis (no scientific studies of link anecdotal): be careful if previous laminitis or foot pathology.
    • Positive drug tests: variable with specific drug:
      • 4-5 d triamcinolone.
      • >3 weeks methylprednisolone.

Specific drugs

  • Methylprednisolone acetate (MPA)  Methylprednisolone  :
    • Rapid conversion from MPA to MP (active form).
    • Long acting: 3-35 days.
    • Affects:
      • Improves synovial membrane histopathology and synovial parameters.
      • Some detrimental effects on cartilage (carpus model).
      • But also reduces degradative enzymes.
      • Less effect on lameness than triamcinolone.
      • Some of the damage may be exacerbated by exercise: ? rest, ? hyaluronate.
    • Uses:
      • Predominantly used for OA, low motion joints, small tarsal joints, PIP joint.
      • Can be repeated when clinical signs recur.
  • Triamcinolone  Triamcinolone  :
    • Acetonide commonly used in UK.
    • Moderate-long acting.
    • In carpal chip animal model: 
      • Improved lameness and synovial fluid parameters.
      • Improved synovial and cartilage morphology.
      • ? Any detrimental effects on joint.
    • Widely used in joint disease therapy:
      • High motion joints, eg carpus, fetlock and DIP joint.
      • ? One-off treatment.

Deal with the primary problem.

  • Betamethasone  Betamethasone  :
    • Usually compounded esters of sodium phosphate and acetate.
    • Long duration of action.
    • No measured deleterious effects in normal exercised joints.

Clinical considerations

  • Dose used depends on clinical case:
    • Volume of joint.
    • Type of joint problem.
    • Number of joints.
  • Multiple joints can    →    excessive doses   →    ? laminitis.
  • Patient preparation and control are essential to reduce the risk of iatrogenic infection:
    • Are i/a antibiotics necessary?
    • Instruct owners to watch for signs of infection up to 2 weeks.
  • Best used in:
    • Low-motion joints.
    • Any joint where the primary problem has been resolved ? surgically.
    • Where the joint/horse is rested post injection (high-motion joints):
      • Rest and slow return to exercise over 14 days.
      • ? Increases duration of action.
      • ? Effect of treatment altered.

Exercising whilst on steroids without addressing a problem often accelerates the problem.

  • Use very short acting medications with minimal side effects.
  • ? Other medications, eg hyaluronate.   
  • ? PSGAGs any use.
  • Repeated injections:
    • Increased likelihood of i/a + ? systemic complications.
    • Look at alternative forms of therapy, eg NSAIDs, PSGAGs, physiotherapy.

Sodium hyaluronate (HA)  Sodium hyaluronate 

  • Glycosaminoglycan: pharmaceutical (intravenous and intra-articular injections) and nutraceutical (oral) preparations.
  • A normal component of articular cartilage synovial membrane and synovial fluid - decreased in osteoarthritis joints.
  • Specific role in joint disease treatment unclear:
    • There is no evidence in vitrothat it stimulates hyaluronic acid synthesis by synoviocytes.
    • ? Stimulates proteoglycan synthesis by equine chondrocytes.
  • Anti-inflammatory effects are mainly via steric hindrance:
    • Prevents inflammatory cell migration.
    • Reduces production of inflammatory mediators.
    • Protects cartilage matrix from inflammatory mediators/enzymes.
  • Increased lubrication.
  • Principle use in cases of acute synovitis (joints/sheaths).

Intra-articular preparations

  • Direct intrasynovial injections:
    • Joints, sheaths, bursae.
    • ? Most efficacious.
  • HA + concurrent i/a corticosteroids commonly used:
    • No published data on any additional benefit in horse.
    • Published work in man showed synergistic effect in some studies.
  • Risks of joint infection + flare.
  • Probably should be used every 7 days as in man for a series of 1-3 injections.
  • Use in tendons?

Intravenous preparations

  • Intravenous administration for multiple joint/sheath problems.
  • Unclear as to its efficacy.

Polysulfated glycosaminoglycans (PSGAGs)  Polysulfated glycosaminoglycan 

  • GAGs are the predominant matrix macromolecule in articular cartilage - reduced in osteoarthritis (OA).
  • PSGAGs are a semi-synthetic preparation of a form of GAGs:
  • Indicated for the treatment of OA in the early stages.
  • Exact mechanism of action is unknown:
    • Anti-inflammatory: 
      • Decrease levels of inflammatory mediators in diseased joints.
      • Inhibit effects of some degradative enzymes.
    • Anabolic - increased synthesis:
      • Endogenous hyaluronic acid in the joint.
      • Articular cartilage proteoglycans.
  • There is only one product with proven research/clinical efficacy licensed for use in the horse in Europe and the United States:
    • Intramuscular and intra-articular administration.
    • Intra-articular use has been associated with increased risks of iatrogenic synovial sepsis:
      • 250 mg/joint every 7 days for 3-4 treatments.
    • Intramuscular dose every 3-5days for minimum of 5-7 treatments.
    • Post-operative surgery: i/a single dose at 7 days post-operative.

Pentosan polysulfate  Pentosan polysulfate 

  • Ca* and Na pentosan polysulfate.
  • Used in humans and other species, including horse, for OA treatment but only licensed for use in the dog.
  • No pharmacological studies in the horse but anecdotal evidence:
    • Decreases joint effusion.
    • Decreases lameness.
  • Mode of action:
    • Inhibition of degradative enzymes.
    • Improves synthesis of HA/proteoglycans.
    • Increases subchondral bone blood flow.
  • Oral, intramuscular and intra-articular preparations.
  • Treatment of synovitis, capsulitis + mild osteoarthritis.

Biphosphonates

  • Inhibit osteoclastic reabsorption in bone: modulate bone remodeling.
  • Inhibit release of collagenase and proteoglycan degrading enzymes.

Tiludronate

  • Disodium tiludronate   Tiludronate  is approved for use in horses in Europe (used under Special Treatment License or Special Import Certificate):
    • Licensed use: 0.1 m/kg/day for 10 days by slow IV.
    • Off-license use: 1 mg/kg slow infusion in 1 l saline IV over 30-40 min.
    • Reassess in 6-8 weeks and repeat if insufficient response.
  • Intertarsal joint OA: 70% cases decrease in lameness.
  • Navicular disease:
    • Effective up to 6 months treatment.
    • Long-term clinical trial in progress.
  • Do not use in animals <3 years old, in lactating mares or horses with renal dysfunction.
  • Used in Europe for all sorts of OA condition - ? proof of efficacy - it does not alter biochemical properties of cartilage or soft tissue structures.
  • Clinical trials in progress.

Nutraceuticals

  • NAVNC defined it as: a non-drug substance that is produced in a purified or extracted form, administered orally to provide agents required for normal body structure and function with the intent of improving the health and well-being of animals.
  • Massive number of nutritional substances marketed:
    • Over 60 in USA.
    • Various claims for efficacy in joint disease: treatment and prophylaxis.
    • ? Part of the alternative therapy culture.
  • Generally contain variable amounts of:
  • There is no data from controlled/blinded clinical studies in horse re: efficacy in either treatment or prophylaxis.
  • Some compounds have positive affect on cartilage biology in laboratories.
  • Clinical data is poor and confused.
  • Content may not be the same as on label:
    • There is no formal monitoring.
    • 84% human product labels are wrong.
  • Controversial as to:
    • Extent of absorption from gut.
    • Bioavailability to joint.
    • Affects on cartilage health and repair after disease.
    • Disease modification.
    • Modification of symptoms of joint disease.
  • Often wild unsubstantiated claims are made in advertising.
  • Expensive.
  • ? Safety.
  • Unlicensed:
    • Very variable literature.
    • Very commercial market $50 million/year.
    • Placebo?
  • ? What the position is regarding their use and veterinary liability.

Glucosamine (GLN)

  • 3 commercial forms   Glucosamine  :
    • Hydrochloride and sulfate forms - ? most effective.
    • HCl salt more stable and twice as bioavailable.
  • Parenteral GLN does reach joint but at low levels (synovial only 10% of serum):
    • Does it affect non-articular tissue not cartilage?
    • ? High enough levels to affect cells in cartilage.
  • Chondroinductive and chondroprotective in in vitro tests.
  • ? 4-8 weeks before it is effective. 
  • Not toxic. 
  • Best used early in treatment.

Chondroitin sulfate (CS)

  • More difficult and expensive to produce   Chondroitin sulfate  .
  • Form and source of CS greatly affects its pharmacokinetics.
  • CS is orally absorbed in horse but may be enzymatically degraded.
  • Tropism for cartilage and synovial fluid:
    • Accumulates in plasma with multiple dosing.
    • Prolongs effect.
  • In vitro:
    • Increases synthesis proteoglycans.
    • *Reduces inflammatory/degradation enzymes.
  • GLN and CS combined products  most common - ? synergism.
  • Clinical cases: decreases lameness, increases flexion, increases stride length.

Others

  • Methylsulphonylmethane (MSM) metabolite of DMSO  Dimethyl sulfoxide  :
    • Unknown pharmacokinetics in horse ? broken down in gut.
    • Anti-inflammatory ? anti-oxidant ?
    • No controlled or clinical studies published for use in equine OA.
  • Polyunsaturated fatty acids:
    • ? Anti-inflammatory by stabilizing cell membranes.
    • No literature on use in horse.
  • Collagen hydrolysate:
    • Stimulates chondrocytes to produce increased collagenous matrix.
    • No literature on use in the horse.

Vitamins, minerals, trace elements

  • Vitamins C, D   Vitamin D3  , E   Vitamin E  , b carotene:
    • Se, Zn,  Mn, niacinamide, bioflavonoids Link: Nutrition: minerals.
    • ? Effectiveness.
  • Herbs:
    • Dope testing issues.
    • ? Effective.
    • ? Safe.

Autologous conditioned serum (ACS)

  • Specific inhibition of deleterious cytokines and mediators in joints.
  • Uses anti-inflammatories produced by homologous blood cells:
    • Blood from horse   →    syringe with special chromium sulfate glass beads.
    • Incubated 24 hrs - WBCs attach to beads   →    increased AI proteins.
    • Serum centrifuged, separated and collected.
    • Immediate use or aliquoted/frozen for later use.
  • Weekly i/a injections (3-5).
  • OA carpal model (no clinical case studies):
    • Decreases lameness up to 5 weeks.
    • Improved parameters of articular and synovial morphology.
    • ? Better in some joints than others.
  • Early OA treatment or ? post-operatively.

Platelet rich plasma (PRP)

  • 3 preparation methods:
    • Tube.
    • Buffy coat.
    • Apheresis.
  • Autologous serum: decreases costs and side effects.
  • Used in equine joint and soft tissue orthopedic injuries.
  • 3 injections into joint every 2-3 weeks.
  • Core injuries in tendon: 3 injections either peri-lesionally or intra-lesionally every 2-3 weeks.
  • Clinical trials in Spain: 
    • Decrease in lameness and effusion.
    • Increased tendon healing.
    • Surprisingly long lasting.

Future therapies

Tetracyclines

  • Minocycline and doxycycline have been used in arthritic disease in humans   Therapeutics: tetracyclines  :
    • Decrease joint pain.
    • Decrease cartilage erosion progression.

Gene therapy

  • Long-term administration of protein by genetically modified cells placed in joint.
  • Virus vectors:
    • Place gene sequence into host cell.
    • Modification   →    increased protein production.
    • Long-lasting effect: ? up to 6 months.
    • Decreases lameness and synovial effusion.
    • Reduces pathology in cartilage.
  • Problems with vector causing inflammation and damage:
    • Immune reaction on second injection.
  • Better vectors required.
  • Regulatory issues.
  • Public acceptance.

Antimicrobials

Treatment for joint sepsis

  • Parenteral use: either IV, IM; and oral.
  • Intra-articular agents.
  • Sustained-release preparations.
  • Regional perfusion.

Intra-articular antibiotics

  • Treatment of established infections.
  • Preventative measure during administration of other therapeutic/diagnostic agents.

There is no substitute for proper preparation.

  • Based on culture and sensitivity results   Bacteriology  or most likely organism.
  • Choose agents carefully: physical properties, toxic effects, mechanism of action, half-life:
  • All cause mild reactive synovitis.

Sustained release preparations

  • Result in high sustained levels of agent at site of infection: 
    • Reduced cost.
    • Less systemic side effects.
  • Must be minimally reactive, consistent elution, easily stored/prepared:
    • Polymethylmethacrylate (PMMA) bone cement - usually beads (small and spherical) in a mould.
    • + antibiotic powder/liquid - amikacin and gentamicin.
  • Some antibiotics have reduced action when bacteria are adhered to PMMA.
  • 30 days release: 150-250 mg/2 g cement up to 1-3 g/10 g.
  • Ceftiofur is released rapidly   →    early removal or replace beads.
  • Other antibiotics used include: penicillins   Therapeutics: beta-lactam antibacterials  , cephalosporins, erythromycin   Erythromycin  , potentiated sulfonamides   Therapeutics: sulfonamides  .
  • Placed in or close to:

Biodegradable materials

  • Beads formed from Plaster of Paris, polylactic acid and polycoglycolide:
    • 4-8 weeks elution latter 2, shorter for former.
    • High levels, rapidly and constantly.
    • Biodegradable and more biocompatible NOT REMOVED.
    • Osteoconductive/? osteoinductive.
  • Collagen-based delivery systems:
    • Membranes and sponges impregnated with gentamicin +/- other antibiotics.
    • Resorbed from 1 week to several months depending on where placed.
    • Increased rate of release + hemostasis.
    • Usually used in joints post lavage.
  • Amikacin-impregnated ferric hyaluronate implants:
    • High MIC concentrations over 5 days.
    • No serum levels.
    • Well tolerated by joint.
    • No adverse effects.

Regional perfusion

  • Saturation of areas of tissues of limbs with antibiotics   Joint: septic arthritis - adult  .
  • Maintained in target region by blocking exit with tourniquet:
    • Proximal and ? distal.
    • Esmarch bandage to collapse superficial vasculature.
  • Intramedullary cannulated bone screw   →    cortex of target bone.
  • Catheter   →    palmar/plantar, saphenous or cephalic veins.
  • Na/K penicillin   Penicillin G  , ampicillin   Ampicillin  , gentamicin   Gentamicin  , amikacin   Amikacin  have all been used successfully.
  • Others may induce vasculitis, eg enrofloxacin Enrofloxacin.
  • Dosages: 250-500 mg amikacin Amikacin; 100-300 mg gentamicin Gentamicin (50 mg foals).
  • Total volume: 60 ml (30 ml digit); foals 10-12 ml. 
  • Rate of flow: 2 ml/min (1 ml/min foot).

Analgesia

  • Many different groups of drugs are used to provide analgesia in the treatment of musculoskeletal conditions, eg opioids, NSAIDs   Anesthesia: analgesia - overview  , several of which can have adverse side effects in the horse.
  • Increasingly, drug combinations are being used which allow dose reduction of these drugs resulting in a decreased incidence of adverse side effects, eg alpha-2 agonists + opioids, ketamine   Ketamine hydrochloride  + local anesthetic infusions   Peri-operative lidocaine infusion: IV  ; alpha-2 agonists + NSAIDs. 
  • Ketamine can be used at sub-anesthetic doses via continuous intravenous infusion to produce analgesia. Either alone or in combination with lidocaine   Lidocaine  and morphine   Morphine  : morphine 0.05 mg/kg/min; lidocaine 1.4 mg/kg loading dose then 0.04 mg/kg/min and ketamine 10-20 mg/kg/min.
  • Low-dose ketamine injection either IM or IV (0.2 mg/kg) administered every 2 h is an effective intra-operative analgesic and may be effective in the conscious horse.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Hallowell G (2007) Equine pain managementVet Review 124, 23-28.

Other sources of information

  • Bertone J J & Horspool L J I (2004) Equine Clinical Pharmacology. Saunders, UK. ISBN: 0702024848.