Capstone - Ex 3 Flashcards
How does inflammation cause pain? (peripheral)
Activates TRP channels
- PGs, bradykinin, cytokines, lipids
How is pain increased (centrally)?
Increased Abs through pain pathways to brain
- e.g. “wind up”
NSAIDs and Analgesia
MOA: dec PG synthesis and dec TRP activation
- COX inhibition
Local anesthetics and Analgesia
MOA: block APs
Ketamine and Analgesia
MOA: glutamate antagonist
- NMDA antagonist
Opioids and Analgesia
MOA: work at many synaptic sites (e.g. mu and kappa agonists)
A2 agonists and Analgesia
MOA: work postsynaptically on non-adrenergic neurons
Two classes of endogenous steroids produced in adrenal cortex - Corticosteroids
- Cortisol (glucocorticoid)
- zona fasciculata - Aldosterone (mineralocorticoid)
- zona glomerulosa
Glucocorticoid Summary
- production of inflammatory mediators
- dec PGs via phospholipase A inhibition
- WBC migration and fxn is suppressed
- Cell-mediated immunity is suppressed
NSAIDs
MOA: inhibit COX
- dec PG synthesis
Hydrocortisone (cortisol)
MOA: dec PGs via Phospholipase A inhibition
Use: topically for pruritus and inflammation assoc’d with allergy
Fludrocortisone
MOA: dec PGs via Phospholipase A inhibition
Use: systemically for cortisol and aldosterone replacement during adrenal insufficiency
Prednisone & methylprednisolone
MOA: dec PGs via Phospholipase A inhibition
Use: systemically for LONG-term management of allergy, chronic inflammation, and immunosuppression
Prednisone vs prednisolone
Prednisone:
- Pro drug that is metabolized to prednisolone
(Methyl)prednisolone:
- cats/horses have less conversion from prodrug to this
- hepatic failure has less conversion
Dexamethasone
MOA: dec PGs via Phospholipase A inhibition
Use: systemically for immediate relief of hypersensitivity and septic shock, long-term control of allergy, and immunosuppression
How can the adverse effects of long-term GC use be reduced?
Alternate-day therapy
Mitotane
MOA: eliminate or dec availability of adrenal steroids except aldosterone
- related to the insecticide DDT; cytotoxic
Use: hyperadrenocorticism (Cushing’s) or steroid-secreting tumors
How do NSAIDs effect pain and inflammation?
MOA: inhibit PG synthesis via blocking COX
Pain: PGs inc intensity and duration of firing from nociceptors - blocking them exerts analgesic effect
Inflammation: PGs dilate small arterioles which enhance edematous actions of histamine and bradykinin - blocking them exerts anti-edematous effect
What is the most-commonly reported adverse effect following NSAD therapy?
GI issues!!
Renal and hepatic toxicities are reported with much lower frequency
Species-specific activity and COX Selectivity
Cannot extrapolate between species!
E.g. Carprofen is COX2 selective in dogs, COX1 selective in horses, and may be more non-selective in horses
Which COX-selective drugs have less GI effects?
COX-2
Aspirin, ibuprofen are COX1 selective, which is why they have worse effects in dogs!
NSAIDs and Cats
Which are good?
Most are cleared via glucuronidation in the liver (cats aren’t good at this)
Meloxicam and piroxicam are better! metabolized by oxidation
What are the primary reasons NSAIDs are used in animals?
anti-inflammatory
Anti-pyretic
Analgesic
At what point in the nociceptive pathways do NSAIDs exert their predominant effect?
Nociceptors at TRP channels
What are the risks of NSAiDs and GC use concurrently
GI ulcers
What organ system is of most concern when giving an NSAID to adult cat
Kidney (esp with ahminoglycosides, ACEi, Beta-blockers, diuretics)
What are the pros and cons of using aspiring for chronic pain in the dog?
Pro: inexpensive, effective, easy to use
Con: GI, tolerance, blood thinning
Why do NSAIDs fail to control pain in some patients?
- pain not due to PGs (inflammation)
- pain is too strong/intense
- tolerance
- individual variation
What can you give with NSAID to enhance post-op analgesia?
opioids
Why do we choose NSAIDs over GC for post-op pain control?
NSAIDs don’t suppress immune function and fewer side effects
How do NSAIDs work?
Block COX and dec PGs
Why do we use opioids in animals?
Analgesia for severe pain and sedation
Why are clinically available opioids scheduled (controlled) by the DEA?
Misuse and abuse by humans
How common is opioid addiction in vet patients?
not common
General anesthesia vs Analgesia
GA:
- amnesia (loss of consciousness)
- analgesia (loss of pain)
- immobilization (mm relaxation)
Analgesia:
- loss of sensitivity pain
Tolerance and efficacy?
Higher tolerance, lower efficacy
Can pts develop tolerance to resp depressants or constipation effects of opioids?
Resp depression: patients develop tolerance quickly
Constipation: dogs tolerate well, other spp not so much
Can animals become dependent on opioids?
Yes, physically - their body no longer regulates nociceptive signals
How do we avoid withdrawal in patients?
Taper dose
MOA of endogenous/exogenous opioids - Nociceptive signals
MOA: Mu or kappa agonist –> opiates bind and hyperpolarize the membrane –> dec NT release
Why is the affinity of an opiod to the opiate receptor important to know?
affinity relates to DOA
Which opioid is difficult to reverse due to high binding affinity?
Buprenorphine - a partial mu agonist, binds with high affinity
Is butorphanol (potency = 5 ) more or less effective than morphine for the treatment of severe, acute pain in the dog? why?
Butorphanol - kappa agonist and mu antagonist
Butorphanol is less effective because its not a mu agonist (like morphine)
- only a partial agonist
- short DOA
Resp depression effects of butorphanol vs fentanyl
Butorphanol: ceiling effect
Fentanyl: lose dose - no effect; high dose - profound effect
opioids and GI motility in horses
DEC GI stasis!
How do high doses of hydromorphone affect body temperature in cats?
Cats = hyperthermia
other spp = hypothermia
MOA for analgesia with tramadol
Weak mu agonist, 5HT and NE reuptake inhibitor
How could you treat opioid-induced excitement in a dog?
Naloxone or sedative
Common way clients administer buprenorphine to cats
trans mucosal
Why is fentanyl administered as an IV infusion or a transdermal patch?
short DOA
What are some consequences of morphine-induced histamine release?
- vasodilation (hypotension)
- bronchoconstriction
- pruritus, sweating
Are opioids used to treat pain in animals with a hx of seizures?
Yes, not contraindicated in therapeutic doses
Seizures only seen with OD’s
Whats the predominant CV effect of hydromorphone in the dog?
Bradycardia
How would you characterize the sedative effects of opioids?
Drowsiness/sleepiness without amnesia (only in ill or old animals)
Which opioid is likely to induce vomiting in the dog and the cat?
morphine
*see vomiting with pre-meds
How can you completely reverse the effects of hydromorphone or butorphanol? what about buprenorphine?
Naloxone!
You cannot completely reverse bup - time and naltrexone can be attempted
What is the rationale for giving buprenorphine and meloxicam to a cat following dental sx?
Pain relief for 6-8 hours post-op with opioid
NSAID to reduce inflammation and pain
MOA of Diazepam
Benzodiazepines - enhance GABA inhibition
Is diazepam effective in young, healthy animals?
NO! its better used in old or ill animals
Why is diazepam combined with ketamine and xylazine to induce anesthesia in the horse?
muscle relaxation, anticonvulsant, sedation
Diazepam vs midazolam
Midazolam is water soluble and shorter acting
Flumazenil
Benzodiazepine antagonist - give it to reverse sedation/fear/anxiety/not waking up fast enough
Primary use of ACE
tranquilizer (anxiolytic)
Can you reverse Ace?
NO!!!
effects of Ace on CV
Depresses CV - vasodilation/hypotension = reflex tachycardia
How can you enhance sedative effects of ace in a dog or cat/
give opioids or alpha 2
Can you give ace in patients with hx of seizures?
Yes, hasn’t been proven to induce seizures BUT you can’t reverse ace so there is that risk
Alpha2 agonists MOA of analgesic and sedative effects
They inhibit excitatory NT release
Alpha 2 agonist effects on CV system?
BIG drop in CO, vasoconstriction/hypertension, reflex bradycardia
Alpha 2 agonist effects on resp system
Mild resp depression, increases CO2 threshold
Adv and dis-advantages of giving atropine with alpha2 agonists
Adv: counteracts bradycardia/hypotension
DA: doesn’t inc CO
- not advised to give anticholinergic with alpha2
How do you reverse dexmedetomidine?
yohimbine or atipamezole
what are the potential adverse effects of atipamezole?
profound hypotension, reflex tachycardia, excitement/pain
