Chapter 63 Implanted Drug Delivery Systems for the Control of Chronic Pain Flashcards
KEY POINTS 1. Intraspinal therapy restricts drug effects to regions associated with the source of the nociceptive input. 2. Morphine and hydromorphone are well suited for intrathecal use in view of their hydrophilicity and slow absorption from the cerebrospinal fluid. Morphine, hydromorphone, and ziconotide are the first-line agents in intrathecal drug therapy. The inclusion of ziconotide as a first line drug is secondary to the randomized, double-blind placebo-controlled studies showing its
opioids analgesic
action
a spinal, as well as supraspinal, analgesic
action
descending system of pain inhibition
This pathway begins with projections from the frontal cortex and hypothalamus to the periaqueductal gray (PAG) of the midbrain. PAG fibers then project to the dorsal pons and the
posteroventral medulla, where projections then travel via the dorsolateral funiculus to terminate in the substantia gelatinosa of the spinal cord dorsal horn. These efferent
projections inhibit the second order ascending nociceptive neurons and thus inhibit pain transmission.
At the spinal level of antinociceptive processing, opiates
presynaptically diminish
primary afferent terminal excitability and inhibit substance P release.
Postsynaptically, opiates
act to
suppress excitatory amino acid–evoked excitatory postsynaptic potentials (EPSPs) in dorsal horn neurons.
Intraspinal pharmacotherapy for pain attempts to
largely restrict drug effects to regions associated with the
source of noxious input.
Advantages of Intraspinal opioids
Systemic side effects are minimized, and a much higher local analgesic concentration is achieved at its site of action, even at comparatively lower doses. Morphine and hydromorphone are particularly well suited for this application, because of their hydrophilicity and resulting slow absorption from the cerebrospinal fluid. As a result, analgesia from intrathecal morphine or hydromorphone not uncommonly lasts up to 24 hours.
Side Effects from Systemic Administration
of Oral, Parenteral, and Transdermal Narcotics
Central Nervous System Effects of Opiates
Analgesia Mydriasis Euphoria or dysphoria Nausea and vomiting Sedation Confusion Cough reflex depression Respiratory depression
Side Effects from Systemic Administration
of Oral, Parenteral, and Transdermal Narcotics
Peripheral Effects of Opiates
Decreased gastrointestinal tract motility Constipation Urinary retention Histamine release Pruritus Increased biliary duct pressure
Indications for Chronic
Intraspinal Analgesic Administration
Chronic pain with known pathophysiology
Sensitivity of the pain to the agent to be infused
Failure of maximal medical therapy (antiinflammatory
agents, antidepressants, nonnarcotic analgesics, and systemic narcotics.)
Favorable psychosocial evaluation
Favorable response to trial of intraspinal analgesic agents
Contraindications for Chronic
Intraspinal Analgesic Administration
Intercurrent systemic infection,
Uncorrectable bleeding diathesis,
Allergy to agent to be infused,
Failure of a trail of intraspinal analgesic agents,
acute psychotic illnesses and severe, untreated depression or anxiety
Obstruction of cerebrospinal fluid flow (relative)
Intraspinally Administered Drugs in the Treatment of Intractable Pain
Opiates
- Morphine
- Hydromorphone
- Fentanyl
- Sufentanil
- Dynorphin
- Beta-endorphin
- D-ala-D-leu-enkephalin
- Methadone
- Meperidine
Alpha-Adrenoceptor Agonists
- Clonidine
- Tizanidine
GABA B Agonists
- Baclofen
Intraspinally Administered Drugs in the Treatment of Intractable Pain
Naturally Occurring Peptides and their Analogues
- Somatostatin
- Octreotide
- Vapreotide
- Calcitonin
Intraspinally Administered Drugs in the Treatment of Intractable Pain
Local Anesthetics
- Bupivacaine
- Ropivacaine
- Tetracaine
NMDA Agonists
- Ketamine
Other Agents
- Ziconotide (SNX I I I)
- Midazolam
- Neostigmine
- Aspirin
- Droperidol
- Gabapentin
Nonallergic reactions to the infused agent, contraindication?
such as urinary retention or pruritus, most often occur only acutely after initial intrathecal exposure to the drug and
often resolve with time or respond to specific treatment. These reactions therefore do not represent absolute contraindications
to chronic intrathecal drug infusion
Percutaneous epidural catheter attached to
external pumps,
internalized passive catheters with reservoirs requiring percutaneous bolus drug administration, patient activated
mechanical systems, constant rate infusion pumps, and
programmable infusion pumps are all viable options.
generally regarded as an indicator of long-term efficacy
Pain relief in response to acute intraspinal analgesic agents
approaches to the trial of intrathecal narcotics
single versus multiple
injections, administration via lumbar puncture versus indwelling
catheter, epidural versus intrathecal routes, and bolus versus continuous infusion of the drug
The equianalgesic epidural dose is roughly
10 times that of an intrathecal dose.
epidural administration disadvamtage
may lead to greater systemic side effects, including constipation and urinary retention. These higher doses further increase the probability of developing tolerance. Also, the higher dose requirement with epidural infusion to reach equivalent subarachnoid concentration necessitates refilling pump reservoirs on a more frequent basis. Dural fibrosis possible
Question of increased tolerance
complication of epidural catheter placement
dural scarring, resulting in catheter failure caused by occlusion, kinking, or displacement.
intrathecal drug
administration carries the disadvantages of
potential CSF leak and postural spinal headaches, respiratory depression caused by supraspinal drug redistribution, and meningeal infection or neural injury.
major advantage of epidural administration
the theoretically lower risk of serious complication. epidural catheters can be placed at virtually any level, making it potentially
more useful for the treatment of upper body pain, Reduced risk of respiratory depression, spinal headache, neural injury
advantages of the intrathecal route including
the lower drug dosage requirements leading to increased intervals
between pump refills, the lower risk of catheter failure, and the infrequent occurrence of potential complications, suggest
this is the preferred route for intraspinal drug delivery, Less systemic effect, No dural fibrosis at tip of catheter, Possible to sample spinal fluid for culture diagnosis and drug levels
different methods to accomplish intraspinal drug delivery
percutaneous epidural catheters attached to external pumps,
internalized passive catheters and reservoirs requiring percutaneous
drug administration, patient activated mechanical systems, constant rate infusion pumps, and programmable infusion pumps.