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Anesthesia-Pain-Treatment

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sihirlifil's version from 2017-05-09 11:35

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Pre-emptive analgesia =Administration of analgesics before noxious stimulus (possible in elective sx cases)
What does pre-emptive analgesia do? (biochemically)Prevents central sensitization
Reduces/eliminates preipheral sensitization (Ideally noxious stimulus never reaches CNS!)
Do you still need to use analgesics post-op if you use pre-emptive analgesics?YES! But pain is more easy to control
Part of a balanced anesthetic protocol
What is multimodal analgesia?Combination of different drug classes as part of balanced anesthesia
Targets multiple sites in the pain pathway
Additive/Synergistic effects
Lowers the dose required for other drugs
Minimizes potential side effects (b/c you have to use less of other drugs, which have dose-dependent SEffx)
Drugs that reduces the MAC (4)Fentanyl CRI
(Dex)medetomidine CRI
Ketamine CRI
Lidocaine CRI (50% Iso MAC reduction in horses!!!)
The 4 pillars of balanced anesthesia:Opioids
Non-steroidal anti-inflammatory drugs (NSAIDs)
Local anesthetics
Adjunctives
Which drug types are listed for Opioids? (4)Pure μ agonists (Morphine, fentanyl...)
Partial μ agonists (Buprenorphine)
κ agonist, μ antagonist (Butorphanol)
Antagonists (Naloxone, naltrexone)
Which drug types are listed for NSAIDs? (4)Non-selective COX-2 (aspirin, ketoprofen, ketorolac, phenylbutazone, flunixine)
COX-2 preferential (Meloxicam, carprofen, etodolac, tolfenamic acid)
COX-2 selective (Robenacoxib, cimicoxib, mavacoxib, firocoxib)
Atypical NSAIDs (Metamizole, paracetamol)
Which drug types are listed for Local anesthetics? (2)Esters (cocaine, procaine...)
Amides (Lidocaine, bupivacaine, ropivacaine, mepivacaine, prilocaine)
Which drug types are listed for Adjunctives? (5)Ketamine
α2 agonists
Tramadol
Gabapentin
Lidocaine CRI (also a LA!)
Opioids are used to treat...?"Symptom" pain
Acute pain (breakthrough in chronic pain e.g. cancer)
How do opioids work?Bind to opioid receptors --> G-protein coupled, activates 2nd messengers --> Close inward Ca2+ channel, stimulate outward K+ channel --> membrane hyperpolarization
What are the opioid receptors?μ (OP3)
κ (OP2)
δ (OP1)
μ (OP3) does?Analgesia, miosis, euphoria, respiratory depression, inhibits GI motility
κ (OP2) does?Analgesia, sedation, miosis (not as potent analgesic, better sedative)
δ (OP1) does?Analgesia, respiratory depression
Where are opioid receptors found?All over body! (Distribution is species-dependent)
Brain (esp. periaqueductal gray, reticular formation)
Spinal cord (substantia gelatinosa/Lamina II) Organs
Peripheral tissues, nociceptors (joints, cornea)
Recuvyra is?Basically fentanyl in a special vehicle (transdermal delivery) which is much quicker than patches
Drug properties of RecuvyraOnset of action 2-4 hours
Duration of action 96 hours (super long)
Special applicator, octylsalicylate = penetration enhancer
Reversible (naloxone)
Restrictions for RecuvyraONLY FOR DOGS >2kg!!
NSAIDs are used to treat...?"Source" of nociception
How do NSAIDs work? (general)Inhibit prostaglandin synthesis (main contributor in peripheral sensitization)
MAINLY PERIPHERAL ACTION (but some central via COX-3)
COX-2 converts _____ to _____Arachidonic acid --> Prostanoids (PGE2, PGI2)
COX-1 converts _____ to _____Arachidonic acid --> Prostanoids (TXA2, PGF)
Thromboxane A2 is responsible for?Platelet aggregation (thats why aspirin reduces risk of myocardial infarction! reduces TXA2)
Functions of prostaglandins (5)Renal blood flow regulation (big problem with NSAIDs in cats!)
Gastric mucosa blood flow (problem in dogs)
GIT mucus production (problem in dogs)
Duodenal bicarbonate secretion
Turnover mucosal cells
What is COX-3?Splice of COX-1 (works centrally)
COX-2 is has effects with healing of... (2)Ulcers, bone
COX-2: Inducible isoform in injured tissue =Upregulation
Where are prostaglandins during inflammation?Nociceptor level (leads to primary hypersensitization)
COX-2: prostacyclin effects?Antagonistic to TXA2 (i.e. inhibits platelet aggregation)
Vasodilation
In what special thing has COX-2 been identified?Carcinomas
Non-selective COX-2 means?COX-1 & COX-2 inhibition
COX-2 preferential means?Greater suppression of COX-2 than COX-1 (COX-1 sparing)
COX-2 selective means?Virtually no suppression of COX-1 at therapeutic doses ('coxibs')
NSAID propertiesHighly protein bound (= long duration of action! 12-24 hours; Mavacoxib up to 1 month!)
Hepatic metabolism (CYP450)
Mostly biliary excretion, some kidney
Narrow safety margin
Do NSAIDs have antagonists?NOPE
Whats the deal with NSAID products for cats?Very few licensed products
Why do cats struggle with NSAIDs?Low glucuronidation capacity- risk of accumulation and toxicity
The best NSAID for a cat is...Meloxicam! Metabolized by oxidation, not glucuronidation in liver
Advantages of NSAIDs (4)Long duration of action (need owner compliance!)
No CV or resp side effects!!
No behavioral side effects
Not a controlled drug (i.e. easily available)
Side effects of NSAIDS (5)GIT irritation/ulcers (especially dogs)
Impairment of renal perfusion (interferes with autoregulation of afferent arteriole)
Increased risk of bleeding
Premature closure of ductus arteriosus
Phenylbutazone: Idiosyncrasy (shetland pony)
Why wouldn't you want to give an NSAID to pregnant animal?Ductus arteriosus can close early- heart starts to work as if fetus was born already
What is one example of a beneficial use of NSAID?Endotoxemia- Flunixine (horse)
If you're giving NSAIDs long term, what do you want to do?Use lowest effective dose
Contraindications of NSAIDs (10)Hypovolemia
Hypotension
Dehydration
Impaired renal & liver function
Gastric ulcers
Vomiting & diarrhea
Thrombocytopenia
Coagulopathies
Coadministration with corticosteroids
Pregnant/Neonate/Lactating
What kind of drugs are Metamizol (Dipyrone) and Paracetamol (Acetaminophen)?Atypical NSAIDs
What is "atypical" about atypical NSAIDs? (Metamizol, Paracetamol)NO ANTI-INFLAMMATORY ACTIVITY (but antipyretic)
What are both atypical NSAIDs useful for? (Metamizol, Paracetamol)Spasmolytic (colic horses)
What is Metamizol useful for?Visceral pain (pancreatitis, colic, cystotomies...)
What is Paracetamol useful for?PK in dogs/horses, laminitis pain, headache (CSF tap, craniotomy)
Mechanism of action for Metamizol?COX-3 (central)
Endocannabinoidergic
*Opioidergic*
Mechanism of action for Paracetamol?COX-3 (central)
Endocannabinoidergic
*Prostaglandin H2 Synthetase*
*Serotoninergic pathway activation*
Potential side effects of Metamizol (3)Agranulocytosis, vomitus, salivation
Special consideration for paracetamol?TOXIC IN CATS!!! (even though there are still published doses)
Adjunctive analgesics are...Drugs with analgesia as a "side effect"; 4th pillar of balanced anesthesia
What class of drug does Ketamine belong to?Dissociative anesthetic (used as analgesic in SUBANESTHETIC DOSES)
Ketamine: Mechanism of actionNMDA-receptor antagonism in spinal cord & brain, some action at opioid receptors
Ketamine: IndicationsPrevent/reduce central sensitization (=WIND-UP)
Somatic pain**
Neuropathic pain
How do you administer ketamine?IV as bolus/CRI, Intermittent SubQ bolus, (epidural)
Side effects of Ketamine (6)Dysphoria
Hypersensitivity to noise
Accumulation (cats)
Cat: eyes stay open (use lube)
Ataxia (horse)
Subanesthetic doses in horse: Norketamine metabolite after 90 minutes!
What must you do if using ketamine during large animal surgery?Stop admin 30 minutes before the end of surgery
Does Ketamine reduce the MAC?Yep
Warning for ketamine?NEVER USE ALONE! causes muscle rigidity (use with benzos, α2 agonists)
α2 agonist: drugs in order of least selectivity --> most (and what does that mean?Xylazine, detomidine, romifidine, medetomidine, dexmedetomidine (= most analgesia)
Where are α2 receptors located?Dorsal horn, locus coeroulus
How do you administer α2 agonists?CRI, incremental IM in cattle
Special side effect of α2 agonists in horses?Ataxia
Side effects of α2 agonists (6)Dose-dependent CVS
Dose-dependent respiratory
Reduce GI motility
Diuresis
Hyperglycemia
Reduced perfusion (GI patients?)
Do α2 agonists reduce the MAC?Yeah
Systemic lidocaine is useful for?Visceral analgesia (routine in colic, rumenotomy...)
Anti-inflammatory
Reduce hyperalgesia
Neuropathic pain
Special things about systemic lidocaine?Antiarrhythmic (Class Ib)
Prokinetic
Toxin & free radical scavenger
Does systemic lidocaine reduce the MAC?YES! Especially horses (50% w/ Iso!!)
How is Tramadol formulated?Racemic mixture: + and - derivative
+ = weak μ agonist, SSRI
- = SNRI via α2 receptors
Is tramadol safe?Yes (even long-term)
How does tramadol work?Interferes with inhibitory control (decreases frequency of action potential from nociceptors --> SC --> cortex)
What's special about tramadol metabolites?26 identified in dogs!!
The metabolite is the active compound (2-3x more potent than tramadol)
What are the 2 main tramadol metabolites?O-Desmethyltramadol (M1)
N-Desmethyltramadol (M2)
Which metabolite of tramadol predominates in: Horse/Dog/Cat?Horse: M2 >M1
Dog: M2>M1 (also M5)
Cat: M1! ((Cats are also more prone to opioid-mediated side effects)
How is tramadol eliminated?90% kidney, 10% feces
How is tramadol administered?Mainly PO (slow IV, IM, epidural)
What's the problem with tramadol administration?Tastes bitter (can mix with syrup or marshmellows)
Side effects of tramadol (7)Sedation
Nausea
Excitement/Dysphoria/Euphoria (cats)
Horse: colic
Horse IV: trembling, ataxia, fasciculations
Cats: respiratory depression at high doses
(May reduce seizure threshold in pediatric)
Does tramadol reduce the MAC?Yesss (Sevo in cats and dogs)
NEVER combine tramadol with which drugs? Why?MAO inhibitors (Selegiline)
SSRI (Fluoxetine)
Tricyclic antidepressants (Clomicalm)
LEADS TO SEROTONIN SYNDROME! excessive serotonin in blood (tremor, rigidity, myoclonus, seizure, hyperthermia, salivation, death)
Gabapentin: mechanism of action?GABA-analogue but DOESNT ACT AT GABA RECEPTOR! Blocks presynaptic Ca2+ channels at afferent nerve, reduces glutamate and substance P release
Synergistic with opioids
How do you administer gabapentin? PO ONLY!
What kind of drug is gabapentin?Antiepileptic
Indications of gabapentinChronic pain
Neuropathic pain
Hyperalgesia
Allodynia
Laminitis, cancer, osteoarthritis
Gabapentin metabolismLiver --> excreted via kidneys
Side effects of gabapentin (4)Sedation
Muscle weakness
Fatigue
Dogs: weight gain with chronic administration
Non-pharmacologic modalities of pain management (7)Remove the cause!
Weight optimization
Acupuncture
Physiotherapy
Nutrition management
Thermal modification
Reduce stress (TLC <3)
Multimodal balanced anesthesia: what happens when you give a bolus of Lidocaine/Ketamine/Opioid, then continue giving CRI?Reach steady-state plasma levels, then continue to maintain even though you're only infusing a small amount
Multimodal balanced anesthesia: Epidural duration of action with opioid? with local anesthetic?Morphine: 24 hours! (also covers post-op)
Bupivicaine: 12 hours
Multimodal balanced anesthesia: extra considerations when using NSAIDs?Monitor kidney perfusion via Doppler (blood pressure) & maintain BP with fluids
Multimodal balanced anesthesia: what should you consider when using gabapentin pre-op?Give well before pre-med (can only be given PO, and want nothing in the stomach during surgery)
Multimodal balanced anesthesia: what is a rescue drug?e.g. Tramadol- use if current management becomes inadequate (evaluate first with objective pain scale)
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