Supportive Care for the Cancer Patient Flashcards
What are the pronociceptive mediators?
Cytokines
Interleukins
Chemokines
Prostanoids
Endothelins
Growth factors
Where does the generation of pain signals start?
PNS
What are the triggers of the pain cascade in cancer?
Tissue compromise
Invasion
Injury
*All from the tumor itself
Where are sensory neurons primary afferent fibers and cell bodies located?
Dorsal root ganglia (DRG)
What percentage of patients develop late radiation side effects?
5%
2-3 years after finishing
In what species is radiation induced pain more common?
Dogs
What does CIPN stand for?
Chemotherapy induced peripheral neuropathy
What is the pathophysiology of chemotherapy induced pain?
- Recruitment and activation of immune and glial cells –> production and release of pronociceptive mediators in the DRG and spinal cord
- Oxidative stress d/t mitochondrial dysfunction
- Increased activity of voltage-gated and ligand-gated ion channels
What is the prevalence of cancer related pain in humans?
33-64%
What tumor types are most likely to be associated with pain?
- Bone tumors
- CNS tumors
- GI tumors
- Inflammatory mammary carcinoma
- Genitourinary tract tumors
- Prostate tumors
- Intranasal tumors
- Invasive STS
- Invasive cutaneous tumors
- Liver and biliary tumors
- Disseminated intrathoracic and intraabdominal tumors
- Lung tumors (humans > animals)
Which NSAIDs are approved in the EU for long term musculoskeletal pain management in cats?
Meloxicam
Robenacoxib
What is a potential benefit beyond analgesic support with the use of piprant NSAIDs?
Grapiprant selective against EP4 prostaglandin PGE2 receptor antagonist – EP4 receptor implicated in cancer metastasis in murine models and EP4 activity promotes breast cancer progression
In what situation should acetaminophen be recommended as a frontline analgesic therapy in dogs?
Dogs with renal compromise
What is the reason why oral opioid administration in dogs is challenging?
High first pass effect – subtherapeutic plasma concentrations
Which oral opioid has shown predictable analgesia when administered subligually in cats?
Buprenorphine
Why is tramadol thought to be more efficacious in cats as opposed to dogs?
Cats produce active metabolite M1
Why is tramadol administration difficult in cats?
Highly aversive taste even in compounded formulations
What are signs of serotonin syndrome?
Altered mental status
- Agitation, restlessness, vocalization, confusion, seizures
Neuromuscular and autonomic dysfunction
- Abdominal pain, vomiting, diarrhea, salivation
- Muscle rigidity, tremors, ataxia, shivering
What drugs are contraindicated concurrently with tramadol?
Trazodone
Mirtazapine
What are the most common NMDA receptor antagonists in veterinary medicine?
Ketamine
Amantadine
When should amantadine be avoided in veterinary patients?
CHF
Hx of seizures
Patients on selegiline, sertraline, or tricyclic antidepressants
What anticonvulsant medications are the most effective for neuropathic pain in humans?
Gabapentin
Pregabalin
Which tricyclic antidepressant shows the most promise for pain control in cats and based on its use to treat what other chronic condition?
Amitriptyline
Used to treat interstitial cystitis
How does low dose lidocaine produce pain relief in cancer patients?
In pain states - aberrantly expressed sodium channels lead to hyperexcitability and ectopic activity in peripheral and central nerves encoding nociceptive information
Lidocaine – inhibits sodium channels
In which cancers in the human population are steroids shown to provide analgesia?
- Bone cancer
- Spinal cord compression
- Brain tumors
Which cancers in veterinary patients may corticosteroids provide analgesic benefit?
Ulcerated or inflamed mast cell tumors
Cerebral edema secondary to intracranial neoplasia
What is the mechanism of bone cancer-related pain?
- Dysregulated osteoclast activity
- Activation of nociceptors by prostaglandins, cytokines, and hydrogen ions released in resorptive pits
What is the mechanism of action of bisphosphonates?
Synthetic analogs of pyrophosphate and inhibit mevalonate pathway –> inhibition of osteoclast activity
What is an uncommon but severe side effect of bisphosphonates?
Mandibular osteonecrosis
Why is zoledronate preferred over pamidronate?
- Rapid infusion rate
- 100-fold greater anti-resorptive potencyW
What is a non-traditional palliative radiation therapy option which has reported improvement in lameness scores of 63% of dogs in a noncontrolled clinical trial?
Samarium Sm153 lexidronam
What is the primary palliative radiation therapy protocol utilized in dogs with osteosarcoma which showed clinically appreciable analgesia in 91% of dogs?
8 Gy x 2 on consecutive days (16 Gy total)
What is the median duration of pain relief associated with the standard pRT treatment for osteosarcoma?
2 - 3 mos (67 - 95 days)
Which chemokine and receptor are commonly involved with neuropathic pain?
CCL2 (chemokine) + CCR2 (receptor)
Increased levels of what protein have been described in inflammatory, neuropathic, and cancer models of pain and appears to induce long lasting pain in both animals and humans?
Nerve Growth Factor (NGF)
