Two peripheral effects of eicosanoids
vasodilation
Sensitization
How does peripheral sensitization by eicosanoids contribute to pain?
increases sensitivity to messengers (bradykinin, histamine)
and increases sensitivity to mechanical touch and pressure
Two effects of eicosanoids in the CNS?
increases activity of Ca channels
activates microglia
How do NSAIDs produce analgesia?
inhibition of cyclo-oxygenase (COX)
Inhibition of lipoxygenase (LOX)
Concerning inflammation, COX is responsible for production of which compounds
thromboxanes
prostaglandins
3 homeostatic/housekeeping duties of COX
1) protection of gastric mucosa (dilates vessels to bring nutrients & promotes mucus production)
2) protection of kidneys (dilation of renal vessels)
3) coagulation of platelets (thromboxane important for clots)
Which NSAIDs have COX-1 activity
ALL of them (some are just more selective for COX-2)
3 beneficial actions of NSAIDs
1) anti-pyretic (C)
2) analgesic (P&C)
3) anti-inflammatory (P)
3 primary side effects associated with NSAID use?
1) gastric irritation/ulceration (consider enterohepatic circulation)
2) renal damage/failure
3) prolonged clotting times
3 instances when NSAIDs would be contraindicated?
1) if patient already has evidence of gastric ulceration
2) if patient has insufficient renal blood flow (meds, dehydration, hypotension, CHF)
3) if patient has clotting abnormalities
labeled indication for Phenylbutazone
Horses–musculoskeletal pain
labeled indication for Flunixin
Horses–muculoskeletal and visceral pain
Cattle– pyrexia, inflammation
labeled indication for Carprofen
Dogs–post-op pain & osteoarthritis
labeled indication for Meloxicam
dogs–Osteoarthritis
Cats–post-op pain
labeled indication for Robenacoxib
Cats–surgical pain (up to 3 days)
What is a neuromuscular blocking agent? How is it different from other muscle relaxants?
it blocks nerve conduction at NMJ to provide complete paralysis
Work peripherally, not centrally
3 advantages of using NMBAs?
Immobility (for delicate surgeries where movement cannot occur)
Complete relaxation (penile relaxation)
Lower inhalant levels (good for patient’s with cardiovascular compromise)
5 disadvantages for NMBAs
1) mechanical ventilation required (diaphragm paralyzed)
2) Monitoring (extra intense)
3) Uncertainty/Variable duration
4) Residual weakness
5) side effects (depends on drug)
At what 4 locations does ACh function as a neurotransmitter?
1) nicotinic receptors
2) pre-ganglionic parasympathetic muscarinic receptors
3) post-ganglionic parasympathetic muscarinic receptors
4) pre-ganglionic sympathetic muscarinic receptors
2 types of NMBAs?
Depolarizing
Non-depolarizing
Describe how Depolarizing NMBAs work
mimic ACh, but aren’t as easily broken down so they work longer; lead to a persistent state of depolarization (rigid muscles) that is followed by relaxation after fatigue sets in
Describe how non-depolarizing NMBAs work
bind ACh but have NO ACTIVITY (just blocks ACh binding)–>gradual muscle relaxation
also decreases vesicle fusion, which decreases presynaptic release of ACh
A non-depolarizing NMBA used in vet med?
Atracurium
How is atracurium eliminated and why is it beneficial (2 reasons)?
via hoffman degradation (temp & pH based)
elimination is independent of liver/kidney function & allows for a more predictable offset
3 methods of NMBA reversal
elimination
indirect competitive antagonism
direct antagonist
Describe how acetylcholinesterase inhibitors can be used to antagonize NMBAs
indirect antagonism
they allow build up of ACh in the synaptic cleft, which will eventually outcompete the NMBA for binding spots
Predominant side effect seen when giving AChase inhibitor? How can it be prevented?
increase in muscarinic (vagal) stimulation (i.e. bradycardia)
can give anticholinergic (i.e. atropine, glycopyrrolate)
What device is used to monitor paralysis with NMBAs?
peripheral nerve stimulator
Which peripheral nerve stimulation pattern is used most often clinically?
Train of four (4 twitches 0.5sec apart)
compare first and last twitch to assess depth
Where can a veterinarian find legal guidance for appropriate means of euthanasia?
State practice act (no guidelines in Al)
3 classifications of euthanasia methods?
acceptable
acceptable with conditions
unacceptable
What does it mean for a euthanasia method to be “acceptable”
it consistently produces humane death as a solo agent
Name 7 ways death is confirmed after euthanasia
lack of pulse lack of breathing lack of corneal reflex lack of response to toe pinch inability to heart respiration and heart beat via stethoscope graying of mucous membranes rigor mortis
the only acceptable solo sign to confirm death?
Rigor mortis
otherwise need to confirm at least 2
3 causes of death following acceptable euthanasia
hypoxia (direct or indirect)
direct depression of neurons
physical disruption of brain
When is intra-organ (i.e. cardiac) injection of injectable euthanasia acceptable? Exception?
when patient is anesthetized;
cats can have intrahepatic when no under anesthesia
Most widely used injectable barbituate for euthanasia?
Sodium pentobarbital
Why would a barbituate be combined with a cardio-active agent?
it makes it less likely to be abused, lowering it to a schedule III (from schedule II)
General anesthesia and trained personnel allow for which drug to be an acceptable means of euthanasia?
potassium chloride
Two acceptable forms of euthanasia for dogs and cats?
Barbiturates
Non-barbiturate anesthetic (propofol, ketamine/xylazine)
Captive bolt is acceptable if combined with? (4)
adjunct agent:
1) pithing
2) exsanguination
3) potassium/magnesium salts
4) second shot
What is the only “acceptable” method of euthanasia of equines
Barbiturates
