Musculoskeletal drugs

Pentosan Polysulfate

By M. Younus, BVSc, MVSc, SKUAST-K

Pentosan Polysulfate (heparin-like, semi-synthetic polysaccharide)

  • Commonly called as PPS.
  • FDA approved drug under the brand name Zycosan for use in osteoarthritis in horses.
  • Considered as disease modifying drug.

MOA:

  • PPS stimulates glycosaminoglycan synthesis in damaged joints and cartilages thereby increases proteoglycan content with in them.
  • PPS increases hyaluronic acid synthesis within joints.
  • PPS increases blood flow to Joints.
  • It also inhibits action of proteolytic enzymes, and scavenging of free radicals.
  • Pentosan polysulfate sodium may also modulate cytokine activity.

Effects:

  • Remodeling of damaged cartilages.
  • Increasing viscosity of joint and tendon sheath fluid
  • Repair of damaged Joints.
  • Mild anticoagulant with anti-inflammatory, fibrinolytic and hypolipidemic effects.

Side effects:

  • Inflammation , pain and neck muscle cramping at injection site.
  • Prolonged coagulation parameters.
  • Short duration vomiting or diarrhea, and abnormal bleeding in dogs.

Species:

  • Dog and Horse.

Indication:

  • For the control of clinical signs associated with osteoarthritis (OA) in horses and dogs.

Dose:

  • 3mg/kg IM once weekly for 4 weeks then once monthly thereafter in horses.
  • 3mg/kg S/C once weekly for 4 weeks in dogs.

Contraindication:

  • Post Surgery.
  • Clotting or bleeding problems.
  • Autoimmune disease.

Brands:

  • Pentorse 10ml vial for canines (Swati spentose pvt. Ltd India)

Composition: Each ml contains 100mg. Pentosan Polysulfate.

  • Pentorse 6ml and 50ml vials for equines ( Swati spentose pvt. Ltd India).

Composition: Each ml contains 250mg Pentosan Polysulfate.

Bisphosphonates

By M. Younus, BVSc, MVSc, SKUAST-K

Bisphosphonates

  • Non nitrogenous bisphosphonates are approved for horses.

Drugs:

1.Clodronate

2.Tiludronate disodium

MOA:

  • Bisphosphonates Inhibit enzyme that utilizes pyrophosphate.
  • Bisphosphonates bind with ca ions in the bone and get metabolized in the osteoclast.
  • The metabolized product replace ATP and thus osteoclast die due to lack of energy.
  • Bisphosphonates reduce the release of nitric oxide and cytokinin from macrophages.
  • Bisphosphonates Inhibit the secretion of matrix metalloproteinases by inducing interleukin-1 in chondrocytes /synovial cells.

Effects:

  • The net effect is inhibition of bone resorption and pain relief.
  • Anti inflammatory effect in chronic laminitis.

Side effects:

  • Transient colic is the main complication that occur with in 2-4 hrs. of treatment and last up to 90 minutes.
  • Increased frequency of urination .
  • Decreased appetite.
  • Rigid neck.
  • Fever.
  • Hyperkalemia ,hyperglycemia and hypercalcemia.
  • Reaction at injection site.

Species:

  • Horses.

Dose:

Clodronate:

  • 1.8mg/kg IM (at three sites) at 3-6 months intervals.

Tiludronate:

  • 1mg/kg IV infusion slowly for about 90 minutes.

Indication:

  • Navicular disease.
  • Bone pain.

Contra indication:

  • Simultaneous use of NSAIDS.
  • Renal disease.
  • Allergic to drug.
  • Hypercalcemia and hyperkalemia.
  • Not recommended in Horse less than 4years of age.
  • Should not be used in pregnant and lactating Mares.

Brands:

  • Tildren 500mg inj vial ( Bimeda-MTC Animal Health Inc ) offered by GNH India.

Composition: Each vial contains 500mg tiludronate.

  • Osphos 15ml inj vial ( Dechra Ltd) offered by GNH India.

Composition: Each ml contains 60mg Clodronate.

Dantrolene

By M. Younus, BVSc, MVSc, SKUAST-K

Dantrolene ( peripheral SK muscle relaxant)

MOA:

  • Dantrolene blocks release of calcium ions from sarcoplasmic reticulum of skeletal muscles thereby inhibits excitation contraction coupling.
  • No discernible effect on cardiac and pulmonary muscles.

Effects:

  • Skeleton muscle relaxation.

Side effects:

  • Sedation, dizziness, lethargy, and other signs of CNS depression.
  • Muscle weakness has been reported in dogs.
  • Other side-effects include increased urinary frequency and hypo-tension.

Species:

  • Dog, Cat, Pig and Horse.

Indication:

  • Malignant hyperthermia.
  • Muscle spasticity.
  • Post anesthetic Myopathy in horse.
  • Prevention of tying up in horse.
  • Porcine stress syndrome .
  • Urethras spasticity in cat and dog.

Dose:

  • 2-4mg / kg empty stomach 30 minutes before exercise in horse.
  • 3.5mg / kg PO in pig.
  • 1-5mg/kg PO 8hrly. in dog.
  • 0.5-2mg/kg PO BD in cat.

Contra indication:

  • Cardiopathy.
  • Pulmonary disease.

Brands:

Available as human brands:

  • Dantrolene sodium 5O cap(Par Pharmaceutical India).

Composition: Each capsule contains 50mg Dantrolene.

  • Dantrium 60ml inj vial(Par Pharmaceutical India).

Composition: Each vial contains 60mg Dantrolene.

Guaifenesin

By M. Younus, BVSc, MVSc, SKUAST-K

Guaifenesin ( SK muscle relaxant).

  • Approved for Horse.

MOA:

  • Guaifenesin binds GABA activated specific inhibitory neurotransmitter receptor sites in the brain and spinal cord.
  • Selectively blocks polysynaptic reflexes in the spinal cord, reticular formation, and subcortical areas of the brain.
  • Depress impulse transmission in the internuncial neurons of the spinal cord without impairing breathing.

Effects:

  • Skeletal muscle relaxation.

Species:

  • Horse

Indications:

  • Used for skeletal muscle relaxation.

Dose:

  • 3mg/kg PO OD .

Contraindication:

  • Horse recieving physostigmine.
  • Close angle Glaucoma in Dog.
  • Hypotension.
  • Prostrate enlargement.

Brands:

Available as human brands in India.

  • Barkiet tablet ( Sanzyme Private Limited India).

Composition: Each tab contains 200mg Guaifenesin.

Methocarbamol

By M. Younus, BVSc, MVSc, SKUAST-K

Methocarbamol (a carbamate).

  •  Centrally acting muscle relaxant.
  • Approved by FDA for treatment of SK muscle spasms.

MOA:

  • Methocarbamol inhibits  acetylcholinesterase at synapses in the autonomic nervous system, neuromuscular junction, and central nervous system.
  •  Methocarbamol thus block spinal polysynaptic reflexes, decreases nerve transmission in spinal and supraspinal polysynaptic pathways, and prolongs the refractory period of muscle cells. 
  • Methocarbamol has been found to have no effect on contraction of muscle fibers, motor end plates, or nerve fibers.

 Effects:

  •  Skeletal muscle relaxation.
  • Reduces skeletal muscle muscle rigidity and provide relief from muscle pain.

Side-effects:

  • Excessive salivation.
  • Emesis.
  • Muscular weakness and ataxia. 

Drug combinations:

  • Methocarbamol+ Paracetamol.
  • Methocarbamol+ Diclofenac.
  • Methocarbamol+ Paracetamol +Diclofenac.

Species: 

  • Dog , Cat and Horse.

Indication:

  • Adjunct to therapy of acute inflammatory and traumatic conditions of the skeletal muscle  ligamentous sprains and strains. 
  • Muscular spasms , myositis, fibrositis, bursitis, synovitis.
  • Intervertebral disc syndrome, compressive myelitis, spinal cord injury where cord remains intact.
  •  Muscular spasm prior to or following surgical procedures.
  • Strychnine poisoning and tetanus.
  • Tying up syndrome.

Dose:

Injection form:

  •  40 mg/kg  in dogs and cats.
  • 4-20 mg/kg  for moderate conditions till effect in  horses.
  • 20-50mg/kg  for severe conditions (tetanus) till effect  in horses.

Tablet form:

  • 120mg/kg in divided doses followed by 60 or 120 mg/kg  each  day.

Note:

  • In horses, the half-life is only 60–90 minutes and may need frequent administration.

Contraindication:

  •  Pregnancy except if potential benefits overweigh the possible hazards.
  • Caution is necessary for injection form in  renal impairment because of the presence of polyethylene glycol-300 in the vehicle, as it increases pre-existing acidosis and urea retention.
  •  Hypersensitivity to drug.

Brands:

  • Robaximol 100ml injection – Montreal Veterinary Products Inc (offered by GNH India).

Composition: Each ml contains100mg Methocarbamol.

  • Robaxin-V 100ml injection (Zoetis USA).

Composition: Each ml contains100mg Methocarbamol.

  • Robaxin-V  500 mg Methocarbamol tablet (Zoetis USA).

Composition: Each ml contains 500mg Methocarbamol.

Human brands in India:

  • Robinax 10ml injection (Khandelwal  India).

Composition: Each ml contains 100mg Methocarbamol.

  • Robinax 500mg Methocarbamol tablet (Khandelwal  India).

Composition: Each tab contains 500mg Methocarbamol.

HA(Hyaluronic acid)

By M. Younus, BVSc, MVSc, SKUAST-K

Hyaluronic acid-HA ( glycosaminoglycan)

  • HA is a nonsulfated, unbranched polysaccharide of alternating disaccharide units of N-acetylD-glucosamine and D-glucuronic acid.
  • Synthesized by chondrocytes and synoviocytes.
  • Main component of synovial fluid and extracellular matrix of cartilage.
  • Exogenous HA remains in the joint for a few days and the clinical therapeutic effects of persists between 5 and 13 weeks or more after injection.

MOA:

  • Hyaluronic acid generates an appropriate environment for cell migration and proliferation, and confers viscoelastic properties to these tissues.
  • Joints with OA have lower concentration and molecular weight of HA.
  • Exogenous supply of HA with desired molecular weight restores the concentration of HA.

Effects:

  • Regeneration of damaged joints.

Side effects:

  • Joint infection, pain following injection, and skin pigment.

Species:

  • Dog and horse.

Dose:

  • 5mg-12.5mg total dose depending on body weight intra articular weekly to monthly for 1-5 doses in dogs .
  • 47mg total dose for medium to large joints in horse.
  • Prepare the site aseptically under deep sedation.
  • Use appropriate sized needle attached to a syringe for entry into the joint cavity and aspiration of joint fluid is confirming needle with in the joint.
  • While the needle is maintained in the joint, the syringe is replaced with a 2nd syringe loaded with drug to be injected.
  • Injection should be smooth and without resistance.
  • Keep horse at rest for at least two days before resuming normal work.

Indication:

  • Osteoarthritis.

Contraindication:

  • Hypersensitivity.

Brands:

  • Hayalun 90- 3ml gel syringe( Vedall Pharma India)

Composition: 30mg Hyaluronic acid in 2ml

PAAG(2.5% Polyacrylamide gel)

By M. Younus, BVSc, MVSc, SKUAST-K

PAAG ( non-toxic and non-immunogenic biocompatible polymer injectable hydrogel).

  • Non-particulate, stable, homogenous gel similar to sodium hyaluronate gel in overall structure and tissue compatibility.
  • Composition : 97.5% sterile water and 2.5% cross-linked polyacrylamide.

MOA:

  • PAAG fills the joint space , reduces friction and provides mechanical support to the joint.

Effects:

  • Lubrication and reduction in joint friction.
  • Cushion like effect and regeneration of joint.

Side effects:

  • Swelling,pain and lameness if injected into periarticular space.

Species:

  • Horse

Dosage and Administration:

  • Under Standard aseptic site preparation , 2.5% PAAG is injected into the articular space using 18 to 20 gauge needles.
  • Before using 2.5% PAAG, lameness must be abolished or significantly improved by intra-articular anesthesia.
  • Give rest for 2-3 days, then walking for a week, and then low impact exercise with a gradual returning to full exercise over 2-3 weeks.
  • Gradual improvement is seen between 1-3 weeks.
  • Consider a second dose at 5-6 weeks post initial injection if lameness is not eliminated.

Indication:

  • Osteoarthritis including chronic osteoarthritis.

Contraindication:

  • Don’t administer into periarticular space as it may cause swelling and pain.

Brands:

  • Noltrex 2.5ml gel( Bioform India).
  • Arthramid Vet 2.5% iPAAG( Contura vet USA).

Alendronate ( bisphosphonate)second generation bisphosphonate and synthetic analog of pyrophosphate with bone anti-resorption activity.Administer on an empty stomach with water only. Food reduces absorption by 60%.MOA:Al Alendronate binds to and inhibits the activity of geranyltranstransferase (farnesyl pyrophosphate synthetase), an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signalling proteins, which is important in the process of osteoclast turnover. As a result, osteoclast activity is inhibited and bone resorption and turnover are reduced.Alendronate inhibits osteoclastic bone resorption, which helps manage conditions related to bone degradation and excessive calcium. It also inhibits angiogenesis, cancer cell division, and osteoclastogenesis, and induces apoptosis of osteoclasts.Side effects:Esophageal irritation or ulcers: Encourage drinking water post-dosing to minimize risks.Gastrointestinal issues: Vomiting, inappetence, or anorexia.Muscle and bone pain.Hypocalcemia: Monitor calcium levels, particularly in patients receiving long-term treatment.Osteonecrosis (rare, but reported in cats with prolonged use).Indication:Cats:Treatment of idiopathic hypercalcemia.Management of feline tooth resorption.Dogs:Management of bone pain caused by osteolytic conditions (e.g., bone tumors or osteosarcoma).Adjunct therapy for hypercalcemiaDose:Dogs:Hypercalcemia 0.5–1 mg/kg PO every 24 hours on an empty stomachBone pain (e.g., osteosarcoma) 10 mg/dog PO once dailyOsteosarcoma management (extra-label) 2 mg/kg PO once daily on an empty stomach.Cats:Idiopathic hypercalcemia 5–10 mg/cat PO weekly. Increase to 30 mg/cat PO if well toleratedTooth resorption 9 mg/kg PO twice per weekContraindication:Avoid use in animals with esophageal disease (e.g., esophagitis or stricture).Use cautiously in patients with renal insufficiency; avoid use in renal failure.Avoid concurrent use with calcium-containing supplements or medications, as they reduce alendronate’s bioavailability.Hypersensitivity to bis

phosphonates is a contraindication.

pyridostigmine and Neostigmine for Myesthenia gravis in dogs

Glucosamine and chondroitin sulphate for osteoarthritis in dogs.