20 – Miscellaneous Analgesic Drugs Flashcards
(52 cards)
1
Q
Nontraditional analgesic agents: are often classified as adjuvant analgesics to
A
- 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
2
Q
Chronic pain
A
- Pain that has persisted beyond normal tissue healing time
- *without apparent biological value
3
Q
What are the two components of chronic pain
A
- Inflammatory pain
- Neuropathic pain
4
Q
Neuropathic pain is pain caused by a
A
- Disease or lesion which leads to damage or dysfunction of somatosensory (pain) system
5
Q
Neuropathic pain can lead to
A
- Abnormal pain sensations
o Hyperalgesia
o Allodynia
6
Q
Example of neuropathic pain in a cat post-amputation
A
- First: hiding and inappropriate urination
- Second: non mobility without falling over, very LETHARGIC
- *phantom limb pain
7
Q
Phantom limb pain is
A
- A complex neuropathic pain syndrome
- *excessive pain conditions: allodynia and hyperalgesia
8
Q
Phantom limp pain is associated with
A
- Direct nerve injury
- Central sensitization
- Changes in cortical recognition of pain and sensation
9
Q
‘steps’ of phantom limp pain
A
- Excessive c-fiber firing
- Result in ongoing dorsal horn stimulation
- Stimulation of NMDA receptors
- Development of new sympathetic nerve fibers
10
Q
Antiepileptic drugs: examples (2)
A
- Gabapentin
- Pregabalin
11
Q
Gabapentin
A
- 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
12
Q
Gabapentin blocks
A
- Calcium influx into presynaptic membrane by inhibition of voltage-gated calcium channels=decreased release of excitatory NTs
13
Q
Gabapentin is available as
A
- Capsules
- Tablets
- Liquid
- *avoid formulations with xylitol (human formulations)
14
Q
Gabapentin elimination half life
A
- 3-4hrs
- *need frequent oral dosing (3x/day)
- *work with client to find dose and administration frequency
15
Q
Gabapentin dose range
A
- 3-20mg/kg BID-TID
- *6-8 hrs (12 hours showed POOR response)
16
Q
What was the most common side effect of gabapentin that owners reported?
A
- *sedation
- ataxia
17
Q
Take home message of gabapentin to minimize adverse events
A
- Start with lower dose that could be titrated up until a balance between sedation and efficacy is achieved
18
Q
Gabapentin in humans
A
- May be good for acute pain
- Single dose reduced opioid consumption post op
19
Q
Pregablin
A
- Similar structure to gabapentin, but has HIGHER oral bioavailability
o Potential more effective - Linear pharmacokinetics
20
Q
Pregablin dose in cats and dogs
A
- Cats: 1-2mg/kig BID (sedation at 4mg/kg)
- Dogs: 4mg/kg BID
21
Q
NMDA receptors location
A
- Dorsal horn of spinal cord
22
Q
NMDA receptors are activated by
A
- Excitatory NTs (glycine and glutamate) during SUSTAINED nociception in dorsal horn
- *activations occurs mostly in maladaptive (chronic) and NOT in acute pain
23
Q
NMDA receptors are key players in
A
- Central sensitization and wind-up
24
Q
What drugs can antagonize NMDA receptors to produce ANITHYPERALGESIC effects?
A
- Amantadine
- Subanesthetic doses of ketamine
25
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
26
May also have effects on various receptors (4)
- Mu-opioid
- Muscarinic
- Monoaminergic
- GABA
27
Where is ketamine metabolized and excreted?
- Metabolized: liver
- Excreted: kidney
28
Inhalant sparing effects of ketamine allows
- Dose-dependent decreases of inhalant anesthetics PLUS reduction of side effects of inhalant anesthetics
29
Positives of ketamine
- Improved post operative analgesia
- Decreased opioid requirement
- *chronic pain management
30
What type of patients would you use ketamine for?
1. Chronic pain
2. Procedures causing severe pain
3. As an adjuvant to opioid analgesics in perioperative analgesia
*can get BEAVIOURAL SIDE EFFECTS
31
Amandatine for treatment of
- Influenza virus A infection and Parkinson’s disease in humans
- Neuropathic pain
32
Amandatine is an antihyperalgesic and is used for MULTIMODAL PROTOCOLS to
- Enhance effects of NSAIDs, gabapentin and opioids
- Decrease central sensitization
33
Amandatine
- Good oral bioavailability
34
What are some examples of Serotonin and NE reuptake inhibitors?
- Tricycle antidepressants
- Amitriptyline (3-4mg/kg q 12h)
35
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
36
TCA analgesic effects
- Occur more quickly and at LOWER doses than antidepressant effects
- *no clinical trials in vet med
37
What are the side effects of TCA?
- Sedation
- Excitability
- Vomiting
- Arrhythmias
- Increased appetite
- Weight gain
38
Acetaminophen (paracetamol)
- Analgesic and antipyretic effects, but WEAK anti-inflammatory activity
- *mechanism for analgesia is poorly understood
- *contraindicated in cats (hepatotoxicity or methmoglobinemia)
39
Antipyretic effects of acetaminophen are mediated by
- COX inhibition
40
Tetrahydrocannabinol (THC)
- Major psychoactive cannabinoid
41
Cannabidiol (CBD)
- Primary Non-psychoactive cannabinoid
42
Endocannabinoid system: receptors and ligands
- CB1 receptor
- CB2 receptor
- Endogenous ligands (endocannabinoids)
o Anandamide (AEA)
o 2-arachindonoyl glycerol (2-AG)
43
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
44
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
45
CBD for canine osteoarthritis
- CBD oil for 4 weeks
- Owners blinded
- *decreased pain and increased activity
- *increased liver enzymes (alkaline phosphatase)
46
Current reality of CBD products
- Lots of uncertainties
- *need more scientific evidence
47
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
48
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
49
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)
50
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
51
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
52
Solensia in cats
- Anti-NGF mAb
- Can sting when injected!
