Mai Nguyen Mercer University COPHS Doctor of Pharmacy Candidate 2012 October 27, 2011 Preceptor: Dr....

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Mai Nguyen Mercer University COPHS Doctor of Pharmacy Candidate 2012 October 27, 2011 Preceptor: Dr. Ali Rahimi

Transcript of Mai Nguyen Mercer University COPHS Doctor of Pharmacy Candidate 2012 October 27, 2011 Preceptor: Dr....

Mai NguyenMercer University COPHS

Doctor of Pharmacy Candidate 2012October 27, 2011

Preceptor: Dr. Ali Rahimi

During the past two decades, the under-treatment of acute pain has been widely recognized as an important issue in health care.

Estimated that only ¼ of surgical patients in the US received adequate relief of acute pain.

Why there has been little progress in the treatment of acute postoperative pain is still unclear but the causes might be multifactorial.

Mechanisms

Incision pain differs in its mechanism from other inflammatory or neuropathic pain.

Thought to be mediated by: Sensitization of Aδ-fiber and C-fiber nociceptors Conversion of mechanically insensitive or silent Aδ

nociceptors to mechanically sensitive fibers after incision

Increased lactate concentrations and low pH in skin and muscle wounds after incision

Increase in prevalence and rate of spontaneous activity of spinal dorsal horn neurons

Predictors of Postoperative Pain Preoperative pain Anxiety Young Age Obesity Surgical fear Type of surgery and duration

Thought that early identification of predictive risk factors will help in development of effective pain management programs.

Acute Opioid-Induced Hyperalgesia (OIH) Paradoxical response to opioids in which patients who

receive opioids could actually become to painful stimuli leads to hyperalgesia rather than analgesia.

Caused by the upregulation of pronociceptive pathways within the central and peripheral nervous systems. ▪ Activation of glutamate and N-methyl-D-aspartate (NMDA) receptors

Distinctly different from analgesic tolerance to opioids, which results from desensitization of antinociceptive pathways. ▪ Although both will ultimately result in an increase in opioid requirements.

Occur in low, high, and maintenance doses of opioids Reported treatment of acute OIH:

▪ α2 agonists, COX-2 inhibitors, NMDA receptor antagonists (mostly studied)

more sensitive

Genetics-based Pain Therapy Determination of a patient’s genotype to

personalize pain therapy.

CYP2D6 OPRM1 PTGS2 SCN9A Over-expression: ↑ metabolism of tramadol and morphine

Under-expression: inhibit the prodrug activation of codeine to morphine

Mutation at 118AG leads to reduction in μ-opioid receptor expression and signaling

Associated with differences in individual responses to COX-2 inhibitors

Production of ABCB1 (glycoprotein) - identification of patients susceptible to respiratory depression induced by opioids.

Mutation reported in individuals with complete inability to sense pain

Persistent Postsurgical Pain (PPP) Diagnosed when pain persists beyond expected healing

period associated with tissue injury and inflammation and other causes for pain have been excluded▪ 2 months or longer after most surgical procedures

Many common operations (mastectomy, hernia repair, coronary artery bypass surgery, amputation) are associated with incidence of PPP of up to 30-50%.

Risk factors: perioperative pain, old age, female sex, obesity, depression, duration of disability (time to return to work)

Prevention of PPP: COX inhibitors, α2 agonists, gabapentin, NMDA antagonists, and steroids

Common routes of admin

Probable MOA

Potential SEs

Local anesthetics (bupivacaine, lidocaine)

EA/SA, PNB/C, SC, TR

Inhibition of sodium channel

Hypotension, systemic toxicity – seizures, cardiac dysrhythmias, cardiac arrest

Opioids (fentanyl, morphine)

EA/SA, IV, SC, TR μ-receptor agonist Sedation, N/V, respiratory depression

Paracetamol PO, IV Uncertain Hepatic toxicity and liver failure at high doses, hypersensitivity

NSAIDs (Celebrex, ibuprofen, ketorolac)

PO, IV Inhibition of cyclo-oxygenase

GI irritation, platelet inhibition, renal insufficiency or failure

Gabapentinoids (gabapentin, pregabalin)

PO Inhibition of voltage-gated sodium channels

Sedation, peripheral edema

α2 agonists (clonidine, dexmedetomidine)

PO, IV α2 –receptor agonist

Sedation, hypotension, bradycardia

EA/SA = epidural/spinal, PNB/C = peripheral nerve block/catheter, TR = transdermal, SC = subcutaneous

Extended-release local anesthetics Currently, researchers are developing local

anesthetics encapsulated in various biodegradable agents (liposomes, lipospheres, polyglycolic acid microspheres, and hydrogels), which when degraded will allow the gradual release of anesthetics.

None of formulations are currently available.

Extended-release epidural morphine DepoDur® is an extended-release formulation

of epidural morphine, which is enclosed in microscopic lipid-based particles.▪ Provides postoperative pain relief for 48 hours

after a single dose▪ Typical duration of epidural morphine is 12 to 24 hours.

▪ Increased incidence of respiratory depression when compared with IV patient-controlled analgesia with morphine.

Iontophoretic transdermal delivery of fentanyl Traditional transdermal formulation of fentanyl is not

recommended for routine treatment of acute or postoperative pain in opioid-naïve patients▪ Partly because it can take about 6-12 hours to obtain analgesic

plasma fentanyl concentrations after application

IONSYS™ uses low-intensity direct current (iontophoresis) to allow for a more rapid transfer of fentanyl from the patch into the skin and local circulation.▪ Allows the patient to activate a demand dose of 40 μg of fentanyl

with a lockout interval of 10 mins ▪ Withdrawn voluntarily from market due to technical challenges.

Peripherally acting μ-opioid receptor antagonists Opioids used to treat acute pain can exacerbate

postoperative ileus. Peripherally acting μ-opioid receptor antagonists

(methylnaltrexone and alvimopan) have been developed to avoid the adverse effects of opioids on postoperative ileus while providing analgesia.

Some concern with alvimopan in its association with a raised incidence of MI in one study.

Role of these agents in treatment of acute pain has yet to be established, but they might be of benefit to patients who have postoperative paralytic ileus.

Acupuncture Review incorporating 15 randomized controlled trials

noted a significant decrease in opioid consumption, risk of opioid-related SEs (eg, nausea), and postoperative pain intensity with adjunctive use of perioperative acupuncture.

TENS Relaxation therapy Massage Hypnosis Listening to music

Associated with reduction of pain and opioid requirement when used as adjunctive therapy

Postoperative pain remains incompletely controlled in some settings and the reasons why are not entirely clear.

Development of newer and more effective analgesic agents and techniques provide superior analgesia with a reduction in persistent pain states and improve patient outcomes.