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Pharmacology for PAIN: Prescribing Controlled Substances

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Pharmacology for PAIN: Prescribing Controlled Substances The Impact of Pain Pharmacology for PAIN: The National Center for Health Prescribing Controlled Statistics estimates that 32.8% of the U.S. population has persistent pain ~94 million U.S. residents have episodic or Substances persistent pain (1 in every 5 adults) Judith A. Kaufmann, Dr PH, FNP-BC Treatment for chronic pain rarely Robert Morris University results in complete relief and full functional recovery Of patients diagnosed with chronic pain and treated by a PCP, 64 percent report persistent pain two years after treatment initiation US Statistics: The Alarming Impact of Pain Facts Pain ranks low on medical tx priority Americans constitute 4.6% of world’s only 15% of primary care physicians report that they "enjoy" treating patients with chronic pain population-but consume ~ 80% of world’s Dahl et al., and Redford (2002) found that patients opioid supply said they fear dying in pain more than they fear death Americans consume 99% of world supply of hydrocodone Pain over the past 10 years has been designated the 5th vital sign Between 1999 and 2006, the number of people >age 12 using illicit prescription Pain is 3rd leading cause of absence pain relievers doubled from 2.6 to 5.2 from work million 2006 National Survey on Drug Use and Health (NSDUH) Are we the Pushers? Can we be found guilty? Since 1999, opioid analgesic poisonings on 55.7% of users obtained drugs from a death certificates increased 91% friend or relative who had been prescribed the drugs from 1 provider During same period, fatal heroin and cocaine poisonings increased 12.4% and 22.8% 19.1% of users obtained their drug directly respectively from 1 provider In 2008, 36,450 opioid deaths were 1.6% reported doctor shopping reported 3.9% reported purchasing drugs from a CDC, 2011 dealer Male:female ratio = 1.5:1 but death rate for females ia 20x higher than males 1 Is opioid abuse a recent Classifications of Pain phenomenon? Acute V. Chronic Pain relief and euphoric Acute pain has easily defined onset and is effects of opioids were transient well known to Sumerians • Occurs only between the time of tissue injury and and Egyptians (4000- tissue recovery 2000 BC) Chronic pain persists or recurs over extended Ancient Greeks first period of time and interferes with patient’s identified and used the functioning latex of immature seed • Associated with depression and dysfunction and capsules of the poppy diminished quality of life flower derived from opium • Much more complex and difficult to treat — (Papaver somniferum). Classifications of Pain Nociceptive pain Nociceptive V. Neuropathic Somatic nociceptive: originates in skin or skin structures Nociceptive: Primary sensory neurons • Stimulation of pain receptors (nociceptors) located Well localized to specific area in the body throughout the body • e.g., tendinitis, post surgical pain • Respond to noxious stimuli- thermal, mechanical, chemical Visceral nociceptive: originates in the internal Can be further subdivided into somatic and organs as a result of infiltration, compression, visceral pain stretching Difficult to localize and often referred to distant sites • e.g., MI pain, pancreatic pain, GB pain Both types of nociceptive pain respond to both non steroidal anti-inflammatories and opioids Chemical Mediators of Pain Chemical Mediators of Pain Initiate or perpetuate continuing stimulation of small pain conducting fibers Neurotransmitters: Acetylcholine and histamines Serotonin • Influences pain perception Polypeptides: Bradykinins, prostaglandins (PG), and substance P Blocking any of these substances minimizes pain signals and the perception of pain Targets for pharmacologic agents to control pain 2 “just don’t inhale…”: Cannabinoid Pain-Modulating receptors receptors and endogenous cannabinoids have Tolerance for pain varies person-person become a focus for research on pain regulation May be due to individual production of endogenous pain relieving substances Two cannabinoid receptors : • CB1-expressed in the brain, SC, and Enkephalins and endorphins • β-endorphin is the most important endogenous analgesic sensory neurons identified to date • CB1 receptors appear to be responsible Released by the pituitary in response to painful for the euphoric and anticonvulsive stimulus or stressor effects of cannabis Found in bloodstream and in specific neurons • CB2-expressed in non-neural tissue and Once released, β-endorphin stimulates inhibitory immune cells, including microglia neuronal receptors (opioid receptors) • Microglia: glial cells that acts as first line of active The mu (μ) receptor (an opioid receptor) inhibits the immune defense in the CNS transmission of pain signals to and from the higher • CB2 receptors appear to be responsible for brain centers the anti-inflammatory and possibly other These same μ receptors are stimulated by morphine- therapeutic effects of cannabis like drugs (opioids) Blocking the endocannabinoid Pain receptors and Their Biologic system: Lesson from Rimonabant Effects Receptor Biologic response to Stimulation Was in Phase III clinical trials for treatment MU (μ) Respiratory depression, physical of obesity depression, tolerance, constipation, Trials discontinued due to unexplained euphoria, miosis suicides in treatment group Kappa (κ) Spinal level analgesia and sedation Found that drug also blocked pleasure without respiratory depression, pupil center in the brain constriction (miosis) Sigma (σ) Vasomotor stimulation, psycomimetic effects, + miosis Neuropathic Pain Perception Pain There are two ways for nociceptive information to reach the CNS Originates from compression or injury to the neospinothalamic tract for "fast spontaneous peripheral nerve fibers or to the central pain" • Fast pain is felt within a .10 second of application of the pain nervous system stimulus • sharp, acute, prickling pain felt in response to mechanical and Describes as burning, shooting, electrical thermal stimulation • Aδ fiber (A delta-fibers) terminate on the dorsal horn of the • Can be dermatomal or non dermatomal in distribution spinal cord where they synapse with the dendrites of the neospinothalamic tract. E.g., post herpetic neuralgia, trigeminal neuralgia, paleospinothalamic tract for "slow increasing pain". diabetic neuropathy • Slow pain is transmitted via slower type C fibers • neurons terminate throughout the brain stem (thalamus, Less responsive to analgesics or anti- medulla,pons and midbrain inflammatories • Slow pain is stimulated by chemical stimulation poorly localized May require antidepressants, anticonvulsants described as an aching, throbbing or burning pain 3 When nociceptors become sensitized (ie, more responsive), their thresholds are reduced, thus causing hyperalgesia (ie, hypersensitivity to pain) The CNS discards more than 99% Bradykinin, histamine, leukotrienes, of all incoming signals as prostaglandins, serotonin, and K+ that are often irrelevant released near damaged or dying cells sensitize nociceptors. K+ activates the nociceptors. Substance P is also released from nociceptors through an axon reflex causing hyperalgesia, vasodilatation and increased capillary permeability Glutamate may be co-released with substance P from C-fibre terminals The gate-control hypothesis of pain Structural Brain Changes Pain transmission is suppressed by signals in thick myelinated Short term opioid use has been associated afferents with gray matter changes in patients with Pain sensation is enhanced by signals in thin afferents chronic pain Inhibitory interneurons(in dorsal LONG TERM gray matter changes horn of the SC) perform the gate- correlated with the dose of morphine after control through a special type of only one month of use pre-synaptic inhibition called primary afferent depolarization Changes persisted an average of 4.7 months (PAD), and the receptors on the after drug stopped cell body of the secondary neuron • Younger, et al., 2011 is the gate Recommended Order of Treatment for Pain Severity of Pain Agents Comments Mild to Moderate Acetaminophen, Maximum doses should be ASA, NSAIDs used before proceeding to opioids Opioid Analgesics Moderate to Severe Codeine, Usually prepared in hydrocodone, combination with non- oxycodone, opioid analgesics BLACK BOX WARNING: Use Cautiously. propoxyphene Side effects limit dosing Can lead to “pain in the …” for the Severe Morphine, MSO4 is the gold standard oxycodone, in all patients ~ including provider hydromorphone, the elderly fentanyl, meperidine 4 General Overview Analgesic Effects Bind with one of four opiate receptors Analgesic effects associated with binding to μ Opioid analgesics are: and κ receptors • Full agonists= morphine, hydrocodone, Associated with unexplained loss, hydromorphone, fentanyl, methadone, misplacement codeine, oxycodone • Partial agonist-antagonist =pentzocine (Talwin) Frequently the drug of choice for dogs Can precipitate withdrwawal • Weak agonist= Tramadol (Ultram) Drugs most often flushed down the toilet Activation of μ opioid receptors is associated with analgesia and undesired effects Difficult names for patients to recall Respiratory depression, euphoria, mydriasis, • Kaufmann, et al., 1988-2012 sedation, nausea, tolerance Agonist activity at the opiate μ- or κ-receptor can result in analgesia, initial miosis followed by mitosis, and/or decreased body temperature Opioids are classified by their ability to stimulate (agonist) or block (antagonist) Opioid Action opioid receptors Opiate agonists alter perception of
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