non-opioid pharmacologic therapy for chronic pain in the pre-anesthetic patient amber dewey, np-c,...
TRANSCRIPT
![Page 1: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/1.jpg)
NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT
Amber Dewey, NP-C, MSN
April 10, 2015
![Page 2: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/2.jpg)
Objectives• Briefly discuss the current understanding of chronic pain,
as distinct from acute pain.• Discuss the various classes of non-opioid medications
used in the treatment of chronic pain, including mechanism of action, potential interactions with anesthetic agents, and potential concerns in the peri-operative patient.
![Page 3: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/3.jpg)
Plan• Chronic Pain: What is it?• NSAIDs and Acetaminophen• Muscle Relaxers• Calcium Channel Blockers and other anticonvulsants• Anti-depressant type medications• Topicals
![Page 4: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/4.jpg)
Pain• The 5th Vital Sign• … an unpleasant sensory and
emotional experience associated with actual or potential tissue damage, or described in terms of such damage.• International Association for the Study of
Pain, 1994
• The single most reliable indicator of the existence and intensity of pain and any resulting affective discomfort or distress is the patient’s self-report
![Page 5: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/5.jpg)
Chronic Pain• 100 million people in the U.S. have chronic pain
• More than diabetes, CHD and cancer combined
• Chronic pain does not “look” like acute pain• Cannot maintain the sympathetic outflow seen in acute pain
• Results in neural rewiring and upregulation of pain receptors (“wind-up”) – increased neuronal activity
• Hyper-reactivity of nervous and immune systems• Chronic pain can be a disease in itself
• IOM Document: Relieving Pain in America 2011
![Page 6: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/6.jpg)
![Page 7: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/7.jpg)
Mechanisms of Drug Interactions• Pharmacodynamic
• Overlapping or synergistic mechanisms of action or adverse effects
• Pharmacokinetic• Alterations in or competition for metabolic processes or excretion
![Page 8: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/8.jpg)
NSAIDs and Acetaminophen• Acetaminophen• Non-selective COX inhibitors
• Ibuprofen• Naproxen• indomethacin• nabumetone• Diclofenac• etodolac • Piroxicam
• Selective COX-2 inhibitors• Celecoxib• (Meloxicam)
![Page 9: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/9.jpg)
NSAIDs and Acetaminophen• Pharmacodynamics – inhibition of cyclooxygenase (COX),
rate-limiting step in the formation of prostaglandins.• Arachidonic acid is converted by COX to prostaglandins,
with multiple effects throughout the body• Prostaglandin H2 is converted to pro-inflammatory compounds• Prostaglandin E2 in the CNS is involved in hypothalamic set point
for thermoregulation (fever), and in reducing activation of the descending inhibitory serotonin pathways (pain)
• COX-1 is present in all tissues; COX-2 is preferentially expressed at sites of inflammation
![Page 10: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/10.jpg)
Acetaminophen• Not effective as an anti-inflammatory because is quickly destroyed
by high levels of peroxidase in inflamed tissues.• Thought to work primarily by inhibiting COX in the CNS – excellent
for pain and fevers. May also have an effect through endocannabinoid system and as NMDA receptor antagonist
• Pharmacokinetics: Hepatic metabolism – 3 routes• Glucuronide conjugation – 40-60%• Sulfate conjugation – 20-40%• Cytochrome P450 2E1 hydroxylation, then glutathione conjugation
• Propofol is eliminated primarily by glucuronidation and sulfation• Possibility for increased APAP toxicity, especially in patients with hepatic
impairment or cachexia
![Page 11: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/11.jpg)
NSAIDs• Aspirin – irreversible inhibition of COX• Other NSAIDs – reversible, although some have very long
half-lives (piroxicam – 50 hours)• Prostaglandin functions
• Renal – decrease tubular reabsorption• Platelets – increase clotting• Stomach – gastroprotective• Uterus – contraction/relaxation• CNS – hypothalamic thermostat• Inflammatory mediators
![Page 12: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/12.jpg)
NSAIDs• Most are highly protein bound, up to 99%• Metabolism is through various CYP 450 pathways and
glucuronidation• Toxicity in overuse
• Anion gap metabolic acidosis• Renal toxicity – acute renal failure, acute renal papillary necrosis
• Likely due to renal vasoconstriction
• Possible interactions• Other highly protein bound drugs – etomidate• Acidosis – increased potency of monoquaternary neuromuscular
blockers (rocuronium, vercuronium, tubocurarine)• Renal toxicity – drugs predominantly eliminated through renal
excretion (pancuronium)
![Page 13: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/13.jpg)
Muscle Relaxers• Cyclobenzaprine (Flexeril)• Tizanidine (Zanaflex)• Methocarbamol (Robaxin)• Baclofen• Carisoprodol (Soma)• Chlorzoxazone (Parafon Forte)• Metaxalone (Skelaxin)• Orphenadrine (Norflex)• Magnesium
![Page 14: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/14.jpg)
Muscle Relaxers• Act centrally and peripherally to reduce skeletal muscle
tone, depress spinal and supraspinal reflexes and inhibit ascending reticular formation
• Various mechanisms, mostly unknown exactly how they work
• Also provide an analgesic effect and usually some degree of sedation
![Page 15: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/15.jpg)
Muscle Relaxers – Mechanism of Action
• Baclofen – GABA-B agonist, causes hyperpolarization by increasing K+ conductance, reducing Ca2+ influx
• Tizanidine – central and peripheral alpha-2 agonist, inhibits release of excitatory amino acid neurotransmitters
• Magnesium – inhibits ACh release peripherally• Orphenadrine – NMDA and histamine receptor antagonist,
centrally acting• Cyclobenzaprine – has tricyclic antidepressant activity as
well as muscle relaxer• Carisoprodol – some action may be due to anxiolysis
(meprobamate is 1st metabolite)• Others – pretty much completely unknown
![Page 16: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/16.jpg)
Muscle Relaxers – Potential Interactions
• SEDATION – is a risk with all muscle relaxers. They are all sedating to some degree. There may be associated ataxia and confusion.• Abrupt discontinuation of centrally acting muscle relaxers is
generally contraindicated, due to potentially severe withdrawal effects
• Magnesium – may potentiate NMBDs, has been seen with vecuronium
• Tizanidine and etomidate – may be potentiation; both have alpha-2 agonist activity
• Intrathecal baclofen and etomidate – increased risk of seizure
• Dry mouth is often a problem with muscle relaxers, along with other anticholinergic effects.
![Page 17: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/17.jpg)
Anti-convulsants• Gabapentin (Neurontin)• Pregabalin (Lyrica)• Carbamazepine (Tegretol)• Oxcarbazepine (Trileptal)• Divalproex (Depakote)• Others
![Page 18: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/18.jpg)
Gabapentin and Pregabalin• Structurally related to GABA, but do not bind at GABA
receptor or work through the GABA-ergic system• Interact with alpha-2-delta-1 subunit of the voltage
dependent calcium channel on pre-synaptic neuron in the DRG
• Reduce calcium channel function => reduced release of neurotransmitters => reduced neuronal hyperexcitability
• Minimal effect on normal neuronal activity (pregabalin)• May also reduce glutamate synthesis (pregabalin)• Possible modulation of TRP channels, NMDA receptors,
protein kinase C, and inflammatory cytokines; stimulation of NE-mediated descending inhibition (gabapentin)
![Page 19: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/19.jpg)
Gabapentin and Pregabalin• Almost no protein binding• Almost no hepatic metabolism• Excretion is almost completely renal
• Half-life is prolonged in people with reduced kidney function• Can be given in dialysis patients, but reduce dose and give after
dialysis
![Page 20: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/20.jpg)
Gabapentin and Pregabalin• Most common adverse effects include sedation, dizziness,
ataxia, blurred vision, weight gain• May be associated post-operatively with respiratory
depression, headache• Abrupt discontinuation – may be increased risk of seizure
![Page 21: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/21.jpg)
Oxcarbazepine and Carbamazepine• Mostly used for trigeminal neuralgia• Mechanism of action likely due to blockade of Na
channels, reduction in repetitive firing of Na-dependent APs
• Possible involvement of Ca, K channels, possible decrease in DA and NE reuptake
• Stabilization of neuronal membranes
![Page 22: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/22.jpg)
Oxcarbazepine and Carbamazepine• Carbamazepine is a powerful inducer of CYP450 3A4• Oxcarbazepine also induces 3A4 and 3A5, inhibits 2C19,
but less than carbamazepine• Both undergo significant hepatic metabolism, both through
CYP450 system, then conjugation
![Page 23: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/23.jpg)
Oxcarbazepine and Carbamazepine• Sedation, ataxia, blurred vision, etc• Aplastic anemia, agranulocytosis – mostly carbamazepine,
but has been reported with oxcarbazepine• Hyponatremia• Abrupt withdrawal – increased risk of seizures
![Page 24: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/24.jpg)
Carbamazepine• Non-depolarizing NMBDs – reduced response, rapid
recovery – likely need higher dose, repeat dosing• Monitor closely!! • ? Increased clearance?• ? Decrease in affinity of nicotinic receptor for NMBD?• ? Increase number of nicotinic receptors?• ? Combination of above?• Literature suggests seen with vercuronium, pancuronium,
doxacurium, pipecuronium, rocuronium, cisatracurium• Not seen with atracurium, mivacurium
![Page 25: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/25.jpg)
Valproic Acid• Divalproex sodium – Depakote• There are other formulations• Mostly used with migraine• Mechanism of action is probably related to GABA-ergic
effects, possibly by inhibiting GABA degradation or reuptake; may also block Na channels
• Highly protein bound
![Page 26: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/26.jpg)
Valproic acid• Adverse effects
• Liver failure – highest risk in kids, has Boxed Warning• Thrombocytopenia, reduced platelet function, agranulocytosis• SIADH• CNS changes
• Increased risk of seizure with abrupt withdrawal
![Page 27: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/27.jpg)
Anti-depressants• Tricyclics
• Nortriptyline, amitryptyline, desipramine, imipramine
• Venlafaxine (Effexor)• Milnacipran (Savella)• Duloxetine (Cymbalta)
![Page 28: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/28.jpg)
Tricyclics• Serotonin and norepinephrine reuptake inhibition• Blockade of ion channels, reducing influx of Ca and Na• Interaction with adenosine and NMDA receptors• Blockade of alpha-1 and alpha-2 receptors - hypotension• Anti-histamine activity – sedation, weight gain• Muscarinic receptors – anticholinergic effects
• All have some activity at each site, but degree varies
![Page 29: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/29.jpg)
Tricyclics• 90-95% protein bound• Extensive CYP 450 metabolism, then glucuronidation
• Sedation, weight gain, dry mouth, blurred vision, delirium (especially in elderly), constipation, urinary retention
• Abrupt withdrawal – “discontinuation syndrome”
![Page 30: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/30.jpg)
Tricyclics• Potentially significantly increased sensitivity to
catecholamines• Sympathetic stimulation peri-operatively can lead to
hypertension and cardiac arrhythmias, post-operative confusion/delirium, ileus, urinary retention
• Avoid or use with caution: Epi, Norepi, atropine, pancuronium, ketamine, ephedrine, ketamine, meperidine
• Possibly increased seizure risk• Increased risk orthostatic hypotension, especially in
elderly
![Page 31: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/31.jpg)
Serotonin syndrome• Usually seen with multiple medications that increase
serotonin activity• Tramadol!• Agitation, confusion, increased motor activity,
hyperthermia, tachycardia, labile blood pressure, diarrhea. Seizures, rhabdomyolysis, renal failure, arrhythmias, coma and death may occur.
• Catch it early, or avoid altogether
![Page 32: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/32.jpg)
SNRIs• Venlafaxine, milnacipran, duloxetine• Serotonin and nortriptyline reuptake inhibitor
• Little to no anticholinergic, antihistamine or alpha receptor blockade
• Probably low risk in anesthesia
![Page 33: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/33.jpg)
Topical pain medications• Lidocaine ointment, cream, gel, patches• Diclofenac cream, gel, patches (NSAID)• Compounded topical preparations (multiple medications)• Capsaicin creams, patches
![Page 34: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/34.jpg)
Topical Pain Medications• Typically do not have much, if any, systemic absorption.
There may be very high tissue concentrations in the immediate area.
• If there is systemic absorption, pharmacodynamics, metabolism and excretion will be similar to oral forms of the medication.
![Page 35: NON-OPIOID PHARMACOLOGIC THERAPY FOR CHRONIC PAIN IN THE PRE-ANESTHETIC PATIENT Amber Dewey, NP-C, MSN April 10, 2015 amberld@earthlink.net](https://reader030.vdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9b964/html5/thumbnails/35.jpg)