Week 7: ADHD, Neuro Pain Flashcards
Mechanisms of Pain
Nociceptive
a, stimulation
*bradykinnins, K+, prostalglandins, histamine, leukotreines, seretonin, substance P, etc.
b.transmission
*a delta fibers: sharp localized pain-myelinated
*C fibers-unmyelinated -dull ache
Perception
Modulation
*endogenous opiate system (enkephlins, dynorphins, beta endorphines) and mu, delta, and k receptors
*NMDA receptors decrease effects of opioids
*seretonin, NE, GABA, neurotensin
CDC guideline for prescribing opioids for chronic pain
- recommend non pharm and non opioid treatments prior to opioids ; if opioids used, combine with non-opioids as appropriate
treatment goals should be established before initiating therapy. continue opioid only if improvement function/pain more than risks to patient
providers should weigh the potential risks versus benefits and discuss them w. patients when initiating opioids. pts should aldo be monitored periodically during treatment
neuropathic pain .
Pain caused by a lesion or disease of the somatosensory nervous system.
neuropathic pain is a clniical description (NOT) a diagnosis
characteristics of nervous system damage
increased nerve cell firing
AND/OR
decreased inhibition of neuronal activity in central structures uaually due to deafferentation
AND/OR
intact circuitry at the central level but a gain in response (sensitization) such that normal sensory input is amplified and sustained
Presentation / assessment of neuro. pain
spontaneous transmission
*continous (burning,throbbing,aching,shooting)
*intermittent (episodic, paroxysmal). shooting,stabbing,orelectric shock-like
hyperalgesia
increased pain from a stimulus that normally provokes pain
allodynia
*pain de to a stimulus that does not normally provoke pain
neuropathic pain general treatment principles
trt directed at reducing/stabilizing nervous system activity
drugs effective in 1 or more neuropathis syndromes are reasonable choices for neuropathies
onset of action: may be days to weeks
*dont expect this to act like an prn med for headache”
NEUROPATHIC PAIN TREATMENT
Tricyclic AD(TCA’s)
examples:
advantages:
disadvantages
dosing
examples: secondary (nortriptyline, desipramine)
tertiary (amitrityline, imipramine (crosses BBB)
advantages:
*most data
once daily dosing
concaminnant insomnia, depression’
disadvantages
delayed onset
anti-ach, cardiotoxicity
dosing
25 mg hs, max 150mg/day
trial: at least 6-8 weeks, 2 weeks @ max dose
NEUROPATHIC PAIN TREATMENT
SNRI
examples:
advantages:
disadvantages
dosing
examples:duloxetine, venlafaxine, DRIZALMA (only fda approved duloxetine DR capsule to be opened and sprinkled)
advantages:duloxetine fda approved in PDN, fibromyalgia
concamminant depression
side effect profile
disadvantages
risk of seretonin syndrome +/- interacting meds
duloxetine CI in hepatic impairment. severe end stage renal diseaSE (<30mL/min)
dosing:
D-30 mg 1x day, max 60 mg 2xday
v- 37.5 1-2xday, max 225 mg/day
NEUROPATHIC PAIN TREATMENT
SNRI
Milnacipran (Savella)
indication: fda approved fibromyalgia in 2009
37% pf subjects report ~50% decreased in pain
MOA: SNRI-3:1 NE:5HT
nmda receptor binding
lacks histaminic and muscarinic activity
pro:well tolerated, can improve fatigue
cons: bid
HTN
dosing: start 12.4 faily, titrate over 1 week to 50 mg bid
max 100mg bid
NEUROPATHIC PAIN TREATMENT
alpha 2 delta ligands
aka gabapentinoids
modulates hyperexcited nuerons by
…
*binds to presynaptic neurons at the a2 delta subunit of voltage gated calcium channels
drug binding reduces calcium influx into presynaptic terminals
decreased calcium influx reduces excessive release of excitatory neurotransmitters (eg. glutamate, substance P, noradrenaline
NEUROPATHIC PAIN TREATMENT
Gabapentin
examples:
advantages:
disadvantages
dosing
examples:
advantages:
low incidence of DI’s and ADRs
FDA approved for post herpatic neuropathy
disadvantages
mild cns depression,
significant toxicity
renal dosing
*Crcl: >60 mL/min: no dose adj. needed
Crcl: 30-59 total dose range 400-1400 mg/day PO in evenly divided doses
*CRcl>15-29 mL/min: total dose range 200-700 mg/day PO given in one daily dose
*Cecl=15 mL/min: total dose range 100-300 mg/day PO given in one daily dose at 100, 125 , 150, 200, or 300 mg
Crcl <15: reduce daily dose in proportino to crcl (e.g crcl=7.5 mL/min recieve 1/2 dose of pts. w. crcl 15mL/min recieve)
dosing
NEUROPATHIC PAIN TREATMENT
gabapentin products and dosing
gabapentin oral capsule, tablet, and solution
300 mg 3x/day start
lower in renal impairment-100mg 2-3x/dau
max 3600 mg/day
variable onset of action
gabapentin oral tab ER (Gralise 300 mg tab)
once daily eveneing meal
titrate to 1800 mg/day
gabapentin enacarbil oral tab ER (Horizant)
twice daily x3 days, then 2 tabs twice daily.
max 1200 mg/day
NEUROPATHIC PAIN TREATMENT
Pregablin
examples:
advantages:
disadvantages
dosing
examples:
advantages:
low incidence on DIs and ADR
concaminant anxiety
fda indicated in PDN, PHN and fibro.
disadvantages
DEA schedule V-dependency, euphoria
mild CNS depression, significant in toxicity
renal insufficiency
dosing
150 mg/day start: divided doses either 2x or 3x a day
lower in renal impairment
titrate q 3-7 days by 150 mg/day if tolerated.
max 600 mg/day
NEUROPATHIC PAIN TREATMENT
TRamadol
examples:
advantages:
disadvantages
dosing
examples:
advantages:
moderate pain (weak mu agonist),
less resp. depression
abuse potential
secondary moa of inhibiting reuptake of NE ans 5HT
disadvantages
DI: carbamezapine, quinidine, TCA, SSRIs
se: dizziness, GI, constipation, seizure risks
dosing
NEUROPATHIC PAIN TREATMENT
Tapentadol (Nucynta)
examples:
advantages:
disadvantages
dosing
indication: neuropathic pain associated w. peripheral neuropathy
examples:
advantages:
mu agonist
NE reuptakr inhibition
no active metbaolites
disadvantages
DEA schedule II
dosing
50mg, 75mg, 100mg
q4-6 hrs
1st dose load may repeat once 1 hr after dose
NEUROPATHIC PAIN TREATMENT
Capsaicin
examples:
advantages:
disadvantages
dosing
EXAMPLE: cApsaicin
depletes and prevents reaccumulation of substance p in peripheral sensory neurons
fda approved
application issues
longterm use
otc products can advertise use in arthritis pain, btu can be used in other neuralgias too
NEUROPATHIC PAIN TREATMENT
available forms of Quetenza
Capsaicin 8% topical patch (PHN-RX only)
pretreat w. local anesthetic to treatment area plus 1-2 cm of surrounding area
use up to 4 patches per application ; patches should be applied for 60 min and repeated no more frequently then q3 months as needed
medicated 0.025% patch
zostrix neuropathy 0.25% topical cream
capsaicin topical cream (0.025-0.1%)
NEUROPATHIC PAIN TREATMENT
Lidocaine
indication:
onset:
duration:
dosing
indications: PHN, topical anesthesia (skin mucous membranes, stomatitis)
onset: 5-10 min
duration: variable
how supplied
rx(patch 5%, viscous soln 2%)
otc (up to 4%)
NEUROPATHIC PAIN TREATMENT
medical cannabis
studies found a “significant, but clinically small, reduction in mean numerical rating scale pain scores”
Very general Tratment approach to neuropathic pain and considerations
first line drugs
1.SNRI’s
2.TCA’s
3. Gabapentinoids
consideration: can be used for all neuropathic pain conditions
second line drugs
1.tramadol
2.capsaicin 8% patches
3. lidocaine patches
considerations: tramadol indicated for all. capaicin and lidociane indicated for peripheral neuropathic conditions.
lidocaine has high tolerability and safety
third line drugs
1.strong opioids
2.botulinum toxin
Painful Diabetic Neuropathy (PDN)
patho
damage to peripheal nerves causes hyperexcitability and spontaneous impules
abnormal electrical connections
coupling of sympathetic and aferent neurons and abnormal release of substance Pfrom A fibers
persistent nerve stimulation acivates NMDA receptors
Painful Diabetic Neuropathy
tratment
- increase NE and 5HT increase pain supression induced by the descending inhibitory pathways
- TCAs
also monoamine reuptake, nmda blockade and sodium channel interferance. - SNRI
*duloxetine and venlafaxine
4.a2 delta ligands*gabapentin and pregablin
General proposed treatment algorithm for PDN
PDN
1. Depending on CI’s and co morbidities…can use
a. A2 delta agonists (Pregablin or gabapentin)
*usually first line
b.SNRI’s
c.TCA’S
2.if pain is inadequately controlled and depending on contra-indications a.can use combo therapy.
a.optimize dose of monotherapy and provide adequate duration of therapy
b.add agent from class of drug w. distinctly different pharmacology
ex: if started on a2d ligant, add SNRI or TCA
if onSNRI, add a2d ligand
- if pain is still inadequately controlled
*opioid agonist as monotherapy, followed by combo therapy if pai ncontroll is inadequatey
Post herpetic neuralgia (PHN)
ractivation of varicella-zoster virus
(shingles)
distribution along dermatomes
ften causes PHN d/t sensory nerve damage, causing reduced neurite densities