Management of Pain. Agenda: Definitions Pathophysiology Analgesics

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1 C. Brian Warriner, MD, FRCPC Professor and Past Chair UBC Department of Anesthesiology, Pharmacology and Therapeutics

2 Agenda: Definitions Pathophysiology Analgesics Gases(N 2 O) Opiates NSAID s Acetaminophen Phencyclidine derivatives (NMDA antagonists) Alpha 2 -adrenergic agonists

3 Agenda (continued) Analgesics Local anesthetics combination therapy Modes of delivery Oral Rectal Systemic Neuraxial Modes of Delivery Case reports Obstetrics

4 Definition: Oxford Pocket Dictionary Strongly unpleasant bodily sensation such as is caused by illness or injury Mental suffering or distress Vulgar as in pain in the neck or other anatomical areas Great cares or troubles Verb (idiomatic) to pain

5 Descriptors: Sharp, crushing, burning, cramping, gassy, throbbing, cutting, aching, dull, deep, pinching, slashing, pin-point, continuous, spasm, tearing, lancing, knifing, etc

6 The Pain Team: (don t memorize the various health profesionals) The patient Nurses (nurse-clinician) Anesthesiologist Clinical pharmacologist Psychiatrist Pharmacist Psychologist Physiotherapist Occupational therapist Radiologist Neurosurgeon Social worker The family Pastoral care Obstetrical pain: patient, partner, coach, midwife, obstetrician

7 Incidence: Appears to be independent of race, culture, economic status 30% of adults have chronic pain at any given time 12% have severe pain 2% have disabling pain 80,000 British Columbians have disabling pain more common that cancer or heart disease

8 Pathophysiology of Pain

9 Pain neurotransmission simplified Nociceptive receptors in periphery respond to ph, ATP, and ligands to create afferent nerve conduction to dorsal root ganglia, dorsal horn of the spinal cord, brainstem, thalamus, hypothalamus, and cortex Modulation occurs at all levels and is mediated by opioid peptides, norepinephrine, glycine, and GABA

10 Opiates are drugs from natural sources, opioids are manufactured drugs Opiate/Opioid peptides inhibit synaptic transmission at several sites: betaendorphin, enkephalins, dynorphins. Opiate/Opioid receptors are mu, delta and kappa

11 Opiates/Opioids produce analgesia because of their actions in the brain, brainstem, spinal cord, and peripheral terminals of primary afferent nerves. Brain: Alter mood in response to pain Brainstem: stimulate release of inhibitory signals Spinal cord: inhibit primary afferent activity Peripheral sites: inhibit afferent response

12 Types of Pain: Acute severe but usually managed with opioids, NSAID s, acetaminophen, local anesthetics Transitional: not easily diagnosed, needs aggressive treatment to prevent transition to chronic Chronic: long-lasting, difficult to treat, personality changes, drug seeking

13 Complex regional pain syndromes: Previously called reflex sympathetic dystrophy Transitional to chronic in nature Can be initiated by relatively minor insults Peripheral sensitization resulting in allodynia and hyperalgesia Requires very aggressive team approach to therapy Can result in completely non-functional limb requiring amputation

14 Neuropathic pain: Injury to peripheral nerves and CNS can lead to functional and structural changes in the pathways Nerve regeneration after injury can produce a nidus of intense pain Flitting, shock-like pain Often very difficult to treat Are common in diabetics but can occur with no known cause

15 Classes of Drugs: Opiate/Opioid receptor agonists Non-steroidal anti-inflammatory drugs Tri-cyclic antidepressants Anti-convulsants NMDA receptor antagonists Alpha 2 -agonists 5HT 1 -agonists for migraine Gases(N 2 O)

16 Opioid receptor agonists: (do not memorize individual drugs but do know class characteristics) Morphine Heroin Meperidine Codeine Oxycodone Hydromorphone Fentanyl Sufentanil Remifentanil, alfentanil Methadone tramadol

17 Opiate/Opioid receptor agonists: Act on mu-receptors to produce both effects and side-effects brain, brainstem, spinal cord, and peripheral terminals Side effects: respiratory depression, nausea and vomiting, constipation, sedation, dizziness, euphoria, confusion, muscle rigidity, pruritus Physical and psychological dependence

18 Opiate/Opioid receptor agonists: Tolerance can develop quickly (in a matter of minutes with remifentanil) Morphine is the reference opioid used primarily for treatment of acute pain injury, surgery, acute abdomen, etc Primary metabolism is in liver and oral morphine is rapidly reduced by first-pass metabolism

19 Opiate/Opioid receptor agonists: Many dosage forms: Oral, transmucosal Inhalation Subcutaneous Intramuscular Intravenous (continuous, intermittent, PCA) Intra-thecal epidural

20 Opiate/Opioid receptor agonists: Codeine methyl-morphine rapidly converted to morphine by the liver effective orally and intramuscularly commonly used as antitussive and mild analgesic Heroin converted to morphine by liver no real therapeutic advantage over morphine addicted claim it produces more euphoria than morphine but studies inconclusive

21 Opiate/Opioid receptor agonists: Meperidine (Demerol) first synthetic opioid 1/10 th potency of morphine Less Sphincter of Vater spasm Fentanyl 100 times potency of morphine intermediate duration intravenous used primarily by anesthesiologists and ER physicians

22 Opioid receptor agonists: Sufentanil 1000 times potency of morphine intermediate duration used only by anesthesiologists Remifentanil 70 times potency of morphine very short duration of action - metabolized by ester hydrolysis in plasma given only by continuous intravenous infusion by anesthesiologists

23 Opiate/Opioid antagonists: naloxone very rapid reversal of opioid effects given IV by ER physicians and anesthesiologists Naltrexone longer acting antagonist used in treatment of both opioid addiction and alcoholism Virtually no action in absence of opiate/opioid

24 Non-steroidal antiinflammatories (do not memorize individual drugs but do know class characteristics) ASA and others of same class Ibuprofen is a relatively low potency, short acting example of the family Inhibit the action of cyclooxygenase enzymes (COX-1 and COX-2) and reduce the production of prostaglandins

25 NSAID s: Analgesia by reducing prostaglandin synthesis Reduce the recruitment of leukocytes which produce inflammatory mediators Directly inhibit the release of prostaglandins in the dorsal horn

26 NSAID s: Side effects: gastric hemorrhage, platelet dysfunction, renal toxicity Specific drugs: (do not memorize individual drugs but do know class characteristics) ASA relatively short acting, little negative effect upon kidney Acetaminophen reduces central prostaglandin synthesis no real anti-inflammatory effect no renal effects overdose can cause acute liver failure

27 NSAID s: Specific drugs: (do not memorize individual drugs but do know class characteristics) Ibuprofen relatively short acting Naproxen, ketorolac (systemic), diclofenac, and others relatively long acting all have negative renal and gastric effects likely also have cardiac effects COX-2 inhibitors were introduced with the expectation of fewer side effects (particularly gastric) but caused increased incidence of ischemic cardiac events and were withdrawn from the market

28 Antidepressants: (do not memorize individual drugs but do know class characteristics) Tri-cyclics Increase norepinephrine and serotonin activity in spinal cord Activate depressed chronic pain patients Diabetic neuropathy and post-herpetic neuralgia Amitriptyline, nortriptyline and imipramine

29 Anticonvulsants: (do not memorize individual drugs but do know class characteristics) Reduce neuronal excitability Gabapentin, carbamazepine Chronic pain management Diabetic neuropathy Trigeminal neuralgia Dizziness, somnolence, confusion, ataxia Pre-gabalin new member of this class fewer side effects heavily marketed

30 NMDA receptor antagonists: Reduce central sensitization due to increased NMDA Ketamine (phencyclidine relative) general anesthetic agent which, in small doses, is an effective analgesic addictive street drug (Special K) Used occasionally for labour analgesia and analgesia prior to surgery.

31 Alpha 2 -agonists: Clonidine Can be given orally or neuraxially Sedation, severe postural hypotension, very dry mouth Newer agent: dexmedetomidine very heavily marketed for ICU sedation

32 5HT 1 -agonists: (sumatriptan) For the treatment of migraine headaches Self-administered by syringe and needle Vasoconstriction and prevention of central sensitization Vasoconstriction can increase risks in other vascular beds such as the cardiac

33 Local anesthetics as an adjunct to opiates: Neuraxial analgesia Sub-arachnoid (spinal) Epidural loss of sensation, muscle weakness, hypotension Two families: esters and amides

34 Modes of delivery: (do not memorize individual drugs but do know class characteristics) Oral most drugs Rectal acetaminophen, NSAID s, ASA IM or IV opiates, ketorolac (NSAID) patient controlled analgesia (PCA) Neuraxial opiates, clonidine, local anesthetics Percutaneous fentanyl patch

35 Case 1: A 27 year old male is in a fight and appears in the ER with severe abdominal pain and evidence of internal damage. He asks for pain relief. What would you do?

36 PCA

37 Case 2: A 60 year old woman is admitted to the hospital with cancer of the lung. She requires a lobectomy. This is associated with very severe post-operative pain. What can be done to help?

38 Epidural

39 Case 3: A 62 year old woman complains of continuous nagging, aching pain over her back and legs. Neurological and musculoskeletal exam are essentially normal except for reduced range of motion of the back and lower limbs. How should her pain be managed?

40 Obstetrical Pain Each patient has a unique labour pain experience Labour pain is mediated from t 10 l 1 Intermittent, increasing in intensity, very severe Delivery pain is mediated from S 2,3,4 and tends to be continuous or nearly so

41 Downloaded from: Miller's Anesthesia (on 27 November :15 AM) 2005 Elsevier

42 Downloaded from: Miller's Anesthesia (on 27 November :15 AM) 2005 Elsevier

43 Obstetrical Pain Pain varies greatly from patient to patient and pregnancy to pregnancy Modes: Psycho-prophylaxis breathing, relaxation exercises Massage, baths, acupuncture Nitrous oxide demand valve respirator for period during contraction only effective analgesic but of only intermediate potency can cause sedation, confusion

44 Obstetrical Pain Modes: Intravenous narcotics: different effects on Mom and babe potential for respiratory depression in new born Ketamine effective in small doses but effect short-lived and larger doses can cause neuropsychiatric effects Intramuscular narcotics same problems as IV but longer lasting

45 Obstetrical Pain Modes: Epidural continuous infusion of local anesthetic (dilute) and opioid (usually fentanyl) can cause reduced muscle strength and loss of urge to push slows down early stages of labour but probably quickens entire labour time Various potential complications associated with the procedure

46 Recent Developments May, British Columbia 1 st province to include chronic pain as separate disease entity under the common heading of chronic diseases allows funding for research and specific payments for pain management) October, 2008 BC Pain Society approved by BC Legislature 2014 BC Government provides major funding for Pain Society

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