20 – Miscellaneous Analgesic Drugs Flashcards
Nontraditional analgesic agents: are often classified as adjuvant analgesics to
- Potentiate effect of traditional analgesics
- Reduce dose and side effects of primary drugs
- *part of multimodal treatment plan
- *used to treat acute AND chronic (neuropathic) pain
Chronic pain
- Pain that has persisted beyond normal tissue healing time
- *without apparent biological value
What are the two components of chronic pain
- Inflammatory pain
- Neuropathic pain
Neuropathic pain is pain caused by a
- Disease or lesion which leads to damage or dysfunction of somatosensory (pain) system
Neuropathic pain can lead to
- Abnormal pain sensations
o Hyperalgesia
o Allodynia
Example of neuropathic pain in a cat post-amputation
- First: hiding and inappropriate urination
- Second: non mobility without falling over, very LETHARGIC
- *phantom limb pain
Phantom limb pain is
- A complex neuropathic pain syndrome
- *excessive pain conditions: allodynia and hyperalgesia
Phantom limp pain is associated with
- Direct nerve injury
- Central sensitization
- Changes in cortical recognition of pain and sensation
‘steps’ of phantom limp pain
- Excessive c-fiber firing
- Result in ongoing dorsal horn stimulation
- Stimulation of NMDA receptors
- Development of new sympathetic nerve fibers
Antiepileptic drugs: examples (2)
- Gabapentin
- Pregabalin
Gabapentin
- Treatment for seizures and neuropathic pain
- Structural analogue of GABA with little activity on GABA receptor
- *also acts on descending noradrenergic inhibitory system
- Dose and administration frequency vary among individuals
- High, but VARIABLE oral bioavailability
- NOT linear pharmacokinetics
Gabapentin blocks
- Calcium influx into presynaptic membrane by inhibition of voltage-gated calcium channels=decreased release of excitatory NTs
Gabapentin is available as
- Capsules
- Tablets
- Liquid
- *avoid formulations with xylitol (human formulations)
Gabapentin elimination half life
- 3-4hrs
- *need frequent oral dosing (3x/day)
- *work with client to find dose and administration frequency
Gabapentin dose range
- 3-20mg/kg BID-TID
- *6-8 hrs (12 hours showed POOR response)
What was the most common side effect of gabapentin that owners reported?
- *sedation
- ataxia
Take home message of gabapentin to minimize adverse events
- Start with lower dose that could be titrated up until a balance between sedation and efficacy is achieved
Gabapentin in humans
- May be good for acute pain
- Single dose reduced opioid consumption post op
Pregablin
- Similar structure to gabapentin, but has HIGHER oral bioavailability
o Potential more effective - Linear pharmacokinetics
Pregablin dose in cats and dogs
- Cats: 1-2mg/kig BID (sedation at 4mg/kg)
- Dogs: 4mg/kg BID
NMDA receptors location
- Dorsal horn of spinal cord
NMDA receptors are activated by
- Excitatory NTs (glycine and glutamate) during SUSTAINED nociception in dorsal horn
- *activations occurs mostly in maladaptive (chronic) and NOT in acute pain
NMDA receptors are key players in
- Central sensitization and wind-up
What drugs can antagonize NMDA receptors to produce ANITHYPERALGESIC effects?
- Amantadine
- Subanesthetic doses of ketamine
Ketamine
- Subanesthetic dose used for analgesia/antihyperalgesia
- NOT considered a stand-alone analgesic (part of multimodal)
- *used IV as a variable or constate rate infusion (CRI) for pain management in perioperative period
May also have effects on various receptors (4)
- Mu-opioid
- Muscarinic
- Monoaminergic
- GABA
Where is ketamine metabolized and excreted?
- Metabolized: liver
- Excreted: kidney
Inhalant sparing effects of ketamine allows
- Dose-dependent decreases of inhalant anesthetics PLUS reduction of side effects of inhalant anesthetics
Positives of ketamine
- Improved post operative analgesia
- Decreased opioid requirement
- *chronic pain management
What type of patients would you use ketamine for?
- Chronic pain
- Procedures causing severe pain
- As an adjuvant to opioid analgesics in perioperative analgesia
*can get BEAVIOURAL SIDE EFFECTS
Amandatine for treatment of
- Influenza virus A infection and Parkinson’s disease in humans
- Neuropathic pain
Amandatine is an antihyperalgesic and is used for MULTIMODAL PROTOCOLS to
- Enhance effects of NSAIDs, gabapentin and opioids
- Decrease central sensitization
Amandatine
- Good oral bioavailability
What are some examples of Serotonin and NE reuptake inhibitors?
- Tricycle antidepressants
- Amitriptyline (3-4mg/kg q 12h)
Tricyclic antidepressants (TCAs)
- Block reuptake of serotonin and NE in CNS=increases concentration in synaptic cleft=enhance descending INHIBITION of nociception
- Antagonize VG Na channels
- NMDA antagonist
TCA analgesic effects
- Occur more quickly and at LOWER doses than antidepressant effects
- *no clinical trials in vet med
What are the side effects of TCA?
- Sedation
- Excitability
- Vomiting
- Arrhythmias
- Increased appetite
- Weight gain
Acetaminophen (paracetamol)
- Analgesic and antipyretic effects, but WEAK anti-inflammatory activity
- *mechanism for analgesia is poorly understood
- *contraindicated in cats (hepatotoxicity or methmoglobinemia)
Antipyretic effects of acetaminophen are mediated by
- COX inhibition
Tetrahydrocannabinol (THC)
- Major psychoactive cannabinoid
Cannabidiol (CBD)
- Primary Non-psychoactive cannabinoid
Endocannabinoid system: receptors and ligands
- CB1 receptor
- CB2 receptor
- Endogenous ligands (endocannabinoids)
o Anandamide (AEA)
o 2-arachindonoyl glycerol (2-AG)
Endocannabinoid system: lipid signaling modulates
- *broad range of physiological processes and behaviours
o Pain
o Mood
o Appetite
o Emesis
o Neuronal activity
o Memory
o Immunity
CBD products
- Hemp based product
- *no quality control
o 60 different active compounds in cannabinoids
o THC must be less than 0.3%
o Contamination! - *used for anxiety, seizures, anorexia, vomiting, pain and sleep aid
CBD for canine osteoarthritis
- CBD oil for 4 weeks
- Owners blinded
- *decreased pain and increased activity
- *increased liver enzymes (alkaline phosphatase)
Current reality of CBD products
- Lots of uncertainties
- *need more scientific evidence
Nerve growth factor (NGF)
-Inflammatory mediator produced by tissue damage of osteoarthritis
- *interaction with tropomyosin kinase A receptor (TrkA)
- Key regulator in inflammatory and neuropathic pain
NGF is a key regulator in inflammatory and neuropathic pain: ‘mechanism’
- Elicits release of other inflammatory mediators
- Increases nerves sensitivity
- Causes phenotypic (physical and biochemical) changes in nerve
What are the phenotypic changes that NGF does to the nerve?
- Increased pain receptors, proinflammatory mediators and ion channels are produced
- Neurogenic inflammation (key component of osteoarthritis pain)
Anti-nerve growth factor monoclonal antibodies
- Free NGF can be captured
o Lower NGF available to bind to nociceptors
o Help normalized changes to nerve seen with chronic pain
o Reduce nerve sensitivity and alleviate OA pain
mAbs in general and anti-NGF mAbs
- Species-specific
- *very specific actions
- No significant adverse effects
- Single SC infection=potential pain relief for 4 weeks of pain relief
o May need see positive effects until 2 months (so be patient) - *non-narcotic, non-sedating
Solensia in cats
- Anti-NGF mAb
- Can sting when injected!
