Lecture 4 1/28/25 Flashcards
What are the characteristics of NSAIDs?
-most common OA treatment
-palliate clinical signs
-anti-inflammatory
-do not halt OA progression
-can have serious side effects
-different modes of action for different NSAIDs
Which NSAIDs are approved for use in dogs?
-galliprant
-firocoxib/previcox
-deracoxib/deramaxx
-robenacoxib/onsior
-carprofen/rimadyl
-meloxicam/metacam
-etodolac/etogesic
What are the characteristics of grapiprant?
-inhibitor of PGE2 EP4 receptor
-prostaglandin receptor antagonist that binds with high affinity
-does not inhibit production of prostanoids
-well tolerated even at high doses
What are the characteristics of firocoxib?
-COX-2 inhibitor with unique COX-2 binding
-highly selective
-38% bioavailability
-oral absorption variable; food delays absorption
-half life of 7.8 hrs
-hepatic metabolism
-do not give to puppies < 7 months of age at doses greater than 5 mg/kg; bad side effects
What are the characteristics of deracoxib?
-controls post-op pain and inflammation
-controls pain and inflammation associated with OA
-COX-2 inhibitor with unique COX-2 binding
-highly selective
What are the characteristics of robenacoxib?
-controls post-op pain and inflammation
-used in cats following orthopedic surgery and spay/neuter
-used in dogs following soft tissue surgery
-cats must be >/= 5.5 lbs and >/= 6 months of age
-dogs must be >/= 4 months of age
-only allowed for use up to 3 days
What is the clinical pharmacology of robenacoxib?
-median blood Tmax of 0.5-1 hr
-mean blood half-life of 0.4-1.7 hrs
-accumulates at site of inflammation
-elimination via biliary route
What are the characteristics of carprofen?
-arylpropionic acid class
-reversible COX inhibitor
-90% absorbed
-reaches peak in blood conc. in 1-3 hrs
-half life of approx. 8 hours
-over 99% bound to plasma protein
-biotransformation by liver; eliminated in feces and urine
-inhibits COX-2 more than COX-1
-GI and idiosyncratic side effects
What are the characteristics of meloxicam?
-useful in hip dysplasia and other forms of OA
-some COX-2 selectivity
-peak conc. at 7.5 hr
-formulated as a syrup
What are the characteristics of etodolac?
-effective inhibitor of PGE2 synthesis by chondrocytes and synoviocytes
-improves lameness of hip dysplasia
-causes GI irritation/ulceration
-NOT recommended for use by Dr. Millis
What are the benefits of slow-acting disease-modifying OA agents/chondroprotective agents?
-positive effect on cartilage matrix synthesis
-positive effect on hyaluronan synthesis
-inhibitory effect on catabolic enzymes in OA joints
What are the anabolic effects of polysulfated glycosaminoglycans?
-stimulates chondrocytes
-inhibits metalloproteinases
-inhibits products of complement activation
-inhibits enzymes released from leukocytes
-inhibits prostaglandin E2 and toxic oxygen radical synthesis
-binds to proteoglycans, collagen, and other proteins
-stimulates synthesis of collagen, proteoglycans, and hyaluronic acid by chondrocytes and synoviocytes
What are the characteristics of adequan?
-injectable preparation of highly sulfated GAGs
-made from bovine tracheal cartilage
What is the pharmacology of adequan?
-maximum blood conc. in 20-40 min. after IM injection
-reaches maximum conc. in the joints 24-48 hrs after injection and decreases over 48 to 96 hrs
-distributes to many tissues and body fluids, such as articular cartilage, synovial fluid, and skeletal muscle
-low molecular weight; synovial membrane is not a significant barrier from blood to synovial fluid
-highest uptake in superficial layers of cartilage; lowest uptake near subchondral layer
-predilection for inflamed/diseased tissue
-prolongs blood clotting times
What are the characteristics of hyaluronic acid?
-major component of synovial fluid
-non-sulfated GAG made from rooster combs or bacterial culture
-interacts with aggrecan monomers in articular cartilage
-may restore viscosity of synovial fluid
What are the effects of hyaluronic acid?
-scavenging of oxygen-derived free radicals
-direct inhibition of WBC and enzyme chemotaxis
-reduces nitric oxide production in the meniscus and synovium
-stimulates HA synthesis by fibroblasts and synovial cells
What are the characteristics of tramadol?
-may be useful for treating chronic pain in combo with other treatments
-technically not an opioid but is controlled
-does not work well for OA pain
What are the characteristics of NMDA receptor antagonists?
-adjunctive drugs to improve control of pain
-central sensitization of pain receptors is mediated in part by activation of NMDA receptors
-reduces CNS hyperresponsiveness and allows other analgesics to function more effectively
What are the characteristics of amantadine?
-most common oral NMDA receptor antagonist
-may be given on a continual basis if needed; often given for 7-14 days
-elimination almost exclusively via the kidneys
-side effects are rare; include agitation and diarrhea
What are the characteristics of gabapentin?
-anti-convulsant with purported adjunctive analgesic action
-mechanism of action unclear; may involve inhibition of post-synaptic neuron firing
-used for many forms of chronic pain; best for neuropathic pain
-metabolized by liver and excreted by kidneys
-side effects include sedation and weight gain
What are the characteristics of weight control?
-#1 goal in lifelong OA management is achieving proper weight
-many dogs with joint dz are obese at presentation and remain obese
-obesity is clearly associated with progression of OA and symptom severity
Which nutritional supplements are used in the treatment of OA?
-omega-3 fatty acids
-glucosamine
-chondroitin sulfate
-avocado soybean unsaponifiables
-undenatured type II collagen
What are the characteristics of nutraceuticals?
-oral nutritional supplements
-do not necessarily undergo clinical testing to demonstrate efficacy
-have beneficial effects on cartilage matrix synthesis, HA synthesis by the synovial membrane, and catabolic enzymes
-may alter the biology of arthritis
What are the characteristics of PUFA supplements?
-competitively inhibit the conversion of arachidonic acid to eicosanoids by inhibiting cyclooxygenase and lipoxygenase
-decrease membrane AA levels, decreasing substrates to synthesize eicosanoids
-form eicosapentaenoic acid
-gives rise to 3-series PGs and 5-series leukotrienes which are weakly inflammatory
What are the characteristics of eicosapentaenoic acid?
-anti-inflammatory
-anti-aggregatory
-vasodilatory
What are the characteristics of arachidonic acid?
-pro-inflammatory
-pro-aggregatory
-thrombotic
What are the characteristics of glucosamine?
-amino monosaccharide used in the synthesis of disaccharide units of glycosaminoglycans and proteoglycans
-form side chains of core proteins of aggrecan of articular cartilage and the repeating disaccharide units of HA
What are the benefits of glucosamine?
-may have cyclooxygenase-independent, anti-inflammatory properties
-may inhibit cartilage degradation
-may stimulate glycosaminoglycan, proteoglycan, and collagen synthesis by chondrocytes and fibroblasts
-may scavenge oxygen-derived free radicals
-stimulates HA synthesis; used by synoviocytes to produce HA
What are the characteristics of chondroitin sulfates?
-glycosaminoglycans
-4- and 6-sulfated forms are components of articular cartilage
-typical sources include bovine trachea, nasal septum, and shark cartilage
-affinity for synovial fluid and cartilage
What are the benefits of chondroitin sulfate?
-stimulates synthesis of GAGs
-inhibits degradative enzymes
-reduces pain while improving function
-increases HA
-decreases collagenase
What are the characteristics of undenatured type II collagen?
-facilitates oral tolerance to antigens
-may stem systemic T-cell attack on joint cartilage
-effectively deactivates killer T-cell attack
What are the physical rehabilitation options for OA?
-heat
-cold
-extracorporeal shock wave therapy
-TENS
-therapeutic ultrasound
-therapeutic laser
-therapeutic exercises
-aquatic therapy
What are the major clinical objectives of cold therapy?
-decrease pain
-curb edema
What are the clinical objectives of heat therapy?
-decrease pain
-increase extensibility
Which modality is one of the most effective for OA?
extracorporeal shockwave treatment; similar effect levels to NSAIDs
What are the characteristics of therapeutic laser for OA?
-potentially useful
-may provide results
-non-invasive
-no reported side effects when used properly
What are the guidelines for exercise in the arthritic patient?
-performed only after correction of major risk factors
-initial exercise program consists of several short periods interspersed with rest periods throughout day
-space exercise periods evenly
-want low impact exercises
What are the biologic modalities for OA?
-platelet-rich plasma
-interleukin receptor antagonist protein
-stem cell therapy
-prolotherapy
-botulinum toxin
When do biologic modalities work best?
when there is still cartilage to protect
Which treatment options should be attempted first?
-weight loss
-NSAIDs
-exercise/lifestyle modifications
-adequan
-nutraceuticals
-omega-3 fatty acid diets
-other analgesics
Which treatment options are considered second level?
-cryotherapy/thermotherapy
-physical rehab
-aquatic therapy
-extracorporeal shockwave
-TENS
-laser
-ultrasound
-acupuncture
-herbs
Which treatment options are considered third level?
-platelet rich plasma
-stem cells
-intra-articular injections
-surgery
-cartilage transplant
