Anesthesia Rounds 2 Flashcards
meloxicam vs robenacoxib
- COX 2 selectivity
Meloxicam is listed as COX-2 preferential inhibitor Robenacoxib is listed as COX-2 specific inhibitor
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Both are seen as more COX-2 selective than ketoprofen
meloxicam vs robenacoxib mehcanism of action
To compare these NSAID’s, you first need to review their mechanism of action. The primary mechanism of action of both is on the arachidonic acid pathway through the inhibition of the cyclooxygenase (COX) enzymes. However, inhibition of lipoxygenase (LOX), nuclear factor κ-B (NF-κB), and bradykinin can also contribute to the effects of NSAIDS. At least two isoforms COX have been identified, COX-1 and COX-2. COX-1 is seen as good and COX-2 is seen as bad, making the company terminology above make sense. However, the interaction of these drugs on these enzymes is not that specific and overall this is a simplification of COX.
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Overall, COX-1 is referred to as constitutive as it contributes to routine physiologic processes and homeostasis. But COX-1 is also up-regulated in inflammatory conditions and in the cerebral cortex as a component of the ascending pain pathways. COX-1 catalyzes the formation of prostaglandins that result in vasodilation, inflammation and pain, sensitization of nociceptors, and fever. It has gastroprotective effects such as increase mucous production, bicarbonate secretion, increase mucosal blood flow, and inhibition of acid secretion. In some species it also regulates renal blood flow. COX-1 products are also converted to thromboxane in platelets that result in platelet aggregation and vasoconstriction.
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COX-2 is referred to as inducible as it is up-regulated in many inflammatory conditions and some neoplastic tissues. Prostaglandins produced by COX-2 result in vasodilation, inflammation and pain, sensitization of nociceptors, and fever. COX-2 is constitutively expressed in the renal afferent vasculature of dogs and is primarily responsible for modulation of renal blood flow in dogs. COX-2 is up-regulated in healing GIT ulcers and is necessary for healing in the GIT. COX-2 products are also converted to prostacyclin which is primarily antagonistic to thromboxane. Prostacyclin results in vasodilation and inhibits platelet aggregation. Prostacyclin also sensitizes nociceptors. COX-2 is expressed in the dorsal horn of the spinal cord and is active in the propagation of the ascending pathways.
robenacoxib and meloxicam
Dosing Schedule and Route of Administration:
Generally a loading dose is given on Day 1 for both of these NSAID’s, then the consecutive daily doses are halved as a maintenance dose.
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During anesthesia with teaching, the loading dose may not be given on day 1. In addition, the NSAID may be withheld until the major portion of surgery is complete (ensuring that major complications such as hypotension or hemorrhage have not occurred). In general practice of healthy elective patients, pre-emptive analgesia with NSAIDs prior to anesthesia and surgery may be more typical.
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Robenacoxib PO or SC
Meloxicam PO, IV, or SC
robenacoxib for what age, weight?
Age: > 4 months of age
Dogs and cats> 2.5 kg
meloxicam for what age?
Age: > 3-4 months
NSAID contraindications
Cats and dogs are more prone to side effects with NSAIDs than people. They are listed as relative and absolute contraindications for use related to these side effects.
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Relative contraindication = geriatric
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Absolute contraindication = liver and kidney disease, dehydration, coagulopathy/bleeding, other NSAID or steroid use, vomiting, shock.
GI side effects of NSAIDs
- frequency
- mechanism
Gastrointestinal adverse effects account for up to 64% of the adverse effects reported in dogs for various NSAIDs in the literature. The GI adverse effects are primarily related to inhibition of COX-1 and resultant decreased gastroprotective effects.
Some NSAIDs also produce direct irritation of the GIT mucosa, but the primary GI adverse effects are due to COX-1 inhibition.
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Gastrointestinal adverse effects are associated with the use of any COX inhibitor regardless of whether it is a COX-2 selective or COX-1 sparing inhibitor. However, the incidences of adverse effects decrease with COX- 1 sparing inhibitors. Gastrointestinal adverse effects can range from gastritis and enteritis to ulceration and perforation. Unfortunately, clinical signs associated with the GIT (vomiting, diarrhea, anorexia, lethargy) are not always present prior to GI ulceration and perforation.
NSAID renal toxicity
- frequency
- mechanism
Renal adverse effects with NSAID use accounts for approximately 21% of the adverse effects in dogs. In cats, the incidence of renal toxicity is increasing and in literature reviews appears to be the highest concern. This is likely related to an increase in NSAID use in this species. In dogs, COX-2 is constitutively expressed in the renal vasculature and mediates renal vasodilation, and is up-regulated, maintaining renal blood flow during episodes of renal hypotension. In other species COX-1 is constitutively expressed in the renal vasculature, whereas COX-2 is up- regulated during hypotensive episodes and is important in the maintenance of renal blood flow. The expression of COX-1 and COX-2 in the feline renal vasculature has not been fully described. More renal related issues in cats are likely from the same renal blood flow issues in dogs, overdosage due to size estimation errors, and the fact that cats start with less nephron numbers as a species than dogs.
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The incidence of renal adverse effects is increased during conditions of renal hypotension such as anesthesia, hypovolemia, systemic hypotension, cardiovascular disease, shock, or concurrent administration of nephrotoxic drugs. Use of COX-2 selective NSAIDS does not result in a decrease in renal adverse effects due to the constitutive nature of COX-2 in canine renal vasculature. The use of NSAIDs in chronic kidney disease is not recommended.
hepatic toxicity of NSAIDs
- frequency
- causes
Hepatic toxicity with NSAID use in dogs account for approximately 14% of adverse effects in dogs. Hepatic toxicity can be from an overdose or idiosyncratic or non dose-dependent. Idiosyncratic toxicity often occurs during the first few days to weeks of treatment and has been reported with all of the NSAIDS used in veterinary medicine. NSAIDs are generally avoided with significant liver disease as reduced metabolism may lead to increased chance of toxicity or side effects in general.
NSAID issues with inhibition of platelet aggregation
- mechanism, which ones
Inhibition of platelet aggregation is an adverse effect associated with COX-1 selective NSAIDs such as aspirin, ketoprofen and flunixin in dogs. Of the NSAIDs, aspirin is the most likely drug to result in abnormal bleeding as it irreversibly inhibits thromboxane synthetase, essentially irreversible inactivating the platelet. Other COX-1 selective NSAIDs produce a reversible inhibition, meaning once the drug concentrations decrease, platelet function returns to normal.
cause of PVC under anesthesia in healthy case
In a healthy patient with a healthy heart, main differentials for this would be:
- pain or inadequate anlagesia,
- insufficient depth of anesthesia with excessive surgical stimulation,
- machine errors resulting in hypoxemia or hypercarbia - extreme changes in temperature
in a sick patient, possible causes of PVC under anesthesia
In a sick patient other considerations for this would be cardiac disease, electrolyte and acid base abnormalities, sepsis, and low oxygen delivery to tissues
PVC under anesthesia, treatment?
when is treatment indicated?
- lidocaine, dosed at 1/10th weight rule
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Treatment is indicated when multiple occur in a row or when one PVC is consistently noted/screen or every other screen. With each PVC, this cardiac contraction is not as strong and cardiac output will be lowered for this beat which will be noted as hypotension and could also develop into a more significant tachyarrhythmia.
causes of second degree AV block in healthy dog under anesthesia
From high vagal tone, (drug or surgical induced). We
tend to think of surgery as increasing sympathetic tone and thus mainly increasing HR, but you can see at maximal stimulation for an OHE or castration or intestinal or ocular traction, an increase in vagal tone, and thus a decrease in HR to a point that a bradyarrhythmia will be noted.
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- Drugs we use in anesthesia for premedication commonly result in bradycardia and potentially bradyarrhythmias.
- mainly alpha2-agonists, and pure u agonists
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- hypothermia adds to the vagal tone and incidence of bradycardia and bradyarrhythmias (and makes treatment less effective)
what drugs we use in anesthesia for premedication commonly result in bradycardia and potentially bradyarrhythmias.
- mainly alpha2-agonists, and pure u agonists
