Pain & Analgesic Drugs PDF

Pain & Analgesic Drugs Objectives  Learn terminology for the use of analgesic medication, pain assessment  Describe the role of analgesia and adjunct agents in managing a variety of pain  Identify prototype medications and select specifics to various classifications of analgesics  W...

Pain & Analgesic Drugs Objectives  Learn terminology for the use of analgesic medication, pain assessment  Describe the role of analgesia and adjunct agents in managing a variety of pain  Identify prototype medications and select specifics to various classifications of analgesics  Will develop an understanding of medication classifications including opioids, non-narcotics, NSAIDS, anti-inflammatory and related medications  Identify mechanism of action, pharmacokinetics, select dosages, indications, contraindications and cautions, interactions, and adverse effect of pain medications Pain Nociception Detection of noxious stimuli or stimuli that are capable of damaging tissue Pain `An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’ (J.J. Bonica 1917-1997) Pain Four processes: Transduction Transmission Perception Modulation Pain Who should assess the pain? Pain Assessment Tool - OUCH scale Pain Pain is a personal and individual experience everyone is different! Pain Acute pain Sudden in onset Usually subsides once treated Nociceptive stimulus, e.g. stepping on a nail, causes acute pain via activation of nociceptive pathways Pain `Good pain’ serves biological purpose What purpose? Injury may lead to chronic (persistant) pain Pain Chronic pain (usually more than 6 weeks and can be long lasting) Persistent or recurring Often difficult to treat  Mild, musculoskeletal pain  Deep pain  Neuropathic Pain  Chronic Pain of Indeterminate Cause Neuropathic pain  Defined as “pain induced by injury to or disease of the somatosensory system”  Resulting from nerve injury or infections of the nervous system  eg phantom limb pain, trigeminal neuralgia, shingles (postherpetic neuralgia), diabetic neuropathy  Develops slowly, outlasts healing of original injury  Allodynia, hyperalgesia, causalgia (burning) Other Forms of Pain chronic pain of indeterminate cause pain associated with psychiatric disorders e.g.depression Sources of Pain Somatic Cancer Superficial Breakthrough Visceral Phantom vascular  after amputation, still feel pain respiratory Neuropathic Referred Psychogenic occurs in area away Central from the real cause Factors that Affect Pain Tolerance Aspects that lower pain Aspects that raise pain tolerance tolerance Discomfort Relief of symptoms Insomnia Sleep Fatigue Rest, or paradoxically, physiotherapy Anxiety Relaxation therapy Fear Explanation/support Anger Understanding/empathy Boredom Diversional activity Sadness Companionship/listening Depression Elevation of mood Introversion Understanding of the meaning and significance of pain Social abandonment Social Inclusion Mental Isolation Encouragement to express emotions Medication for Pain ANALGESIC  Selectively blocks the sensation of pain without blocking other symptoms or loss of consciousness ANESTHETIC  Local anaesthetic blocks nerve conduction and all local sensations (including pain)  General anaesthetics cause loss of sensations and unconsciousness Medication for Pain Analgesia What does it do for the cause of pain? Analgesic Drugs: Opioids Chapter 31 Pain Opioids Work Here Site of Action of Opioids 1. higher centres to alter the psychological response to pain  pain can still be felt but produces less suffering  perception 2. reduce neurotransmitter release from terminals pain fibres in dorsal horn of spinal cord  modulation Opioids Opioids Drugs bind to opioid receptors  “opioids” covers all natural & synthetic forms Opioids Morphine-like action compounds bind to opioid receptors on nerve endings Opiate - any drug derived from opium, e.g. morphine, codeine  Opium – “juice” of the poppy (Papaver somniferum) Receptor Sites Properties of different opioid drugs due to: affinity and activation for different opioid receptor subtypes (also pharmacokinetic differences)  All opioid analgesics are full agonists or partial agonists at µ and/or k receptors  µ   Morphine Agonist Agonist Agonist Naloxone Antag Antag Antag Opioids Agonists examples? Agonists-Antagonists eg buprenorphine What are those? Antagonists Effect on analgesia? Opioid Receptors µ (mu) receptors analgesia  brain (cortex, medulla, thalamus, limbic system, amygdala) and spinal cord  (kappa) receptors analgesia  brain and spinal cord dysphoria and hallucinations Pharmacological Properties of Opioids 1. ANALGESIA ( and  receptors) 2. SEDATION and `MENTAL CLOUDING‘ 3. EUPHORIA and TRANQUILLITY ( and  receptors) involves central dopaminergic pathways 4. ANTITUSSIVE - depresses cough reflex by acting on a cough centre in the medulla 5. DEPRESSION OF RESPIRATORY CENTRE (-receptors) direct effect on brainstem respiratory centre 6. NAUSEA, VOMITING Stimulation of chemoreceptor trigger zone of the medulla 7. MIOSIS (PIN POINT PUPIL) ( and  receptors) excitatory action of the parasympathetic nerve innervating the pupil 8. TOLERANCE AND SERIOUS DEPENDENCE ( receptors) 9. CONSTIPATION ( and  receptors) increase GI muscle tone to point of spasm, increase tone of anal sphincter 10. POSTURAL HYPOTENSION inhibition of baroreceptor reflex 11. DILATION OF CUTANEOUS BLOOD VESSELS (WARM SKIN) may involve release of histamine and lead to sweating and itching 12. URINARY URGENCY BUT DIFFICULTY IN URINATION inhibits urinary voiding reflex 13. BILIARY COLIC AND EPIGASTRIC DISTRESS Tone  in sphincter of Oddi  tone in bile duct (increases pain of gall stones) Opioids Analgesics Morphine Methadone (longer action than morphine) Fentanyl Diamorphine (Heroin) Levorphanol Hydromorphone Oxycodone Codeine Opioid Analgesics: Indications Alleviate mild to moderate to severe pain depending on the opioid used often given with adjuvant analgesic agents to assist with pain relief Opioids: Other Indications Opioids are also used for: Cough centre suppression (codiene) Treatment of diarrhea (loperamide) Balanced anaesthesia (fentanyl) Opioid Analgesics - Morphine Morphine  Acute and chronic pain Other analgesics compared to morphine “the standard” equianalgesic doses of other opioids Opioid Analgesics - Morphine Morphine primarily on mu (m) opioid receptors  brain and spinal cord IV, IM, SC, PO, intrathecal Opioid Analgesics - Morphine Metabolism: t ½ = 2 - 4 hours extensive liver metabolism  inactivation  first pass metabolism  consequence for dosing po vs IV/IM?  consequences of liver disease? Pregnancy/breast feeding risk exists for physical dependence  crosses placenta  enters breast milk Pharmacological Properties of Morphine 1. ANALGESIA ( and  receptors) 2. SEDATION and `MENTAL CLOUDING‘ 3. EUPHORIA and TRANQUILLITY ( and  receptors) involves central dopaminergic pathways. 4. ANTITUSSIVE - depresses cough reflex by acting on a cough centre in the medulla 5. DEPRESSION OF RESPIRATORY CENTRE (-receptors) direct effect on brainstem respiratory centre. 6. NAUSEA, VOMITING Stimulation of chemoreceptor trigger zone in area postrema of the medulla. 7. MIOSIS (PIN POINT PUPIL) ( and  receptors) excitatory action of the parasympathetic nerve innervating the pupil. 8. TOLERANCE AND SERIOUS DEPENDENCE ( receptors) 9. CONSTIPATION ( and  receptors) increase colonic tone to point of spasm, increase tone of anal sphincter. 10. POSTURAL HYPOTENSION inhibition of baroreceptor reflex 11. DILATION OF CUTANEOUS BLOOD VESSELS (WARM SKIN) may involve release of histamine and lead to sweating and itching 12. URINARY URGENCY BUT DIFFICULTY IN URINATION inhibits urinary voiding reflex. 13. BILIARY COLIC AND EPIGASTRIC DISTRESS. Tone  in sphincter of Oddi  tone in bile duct (increases pain of gall stones). Analgesics and Cancer Pain (Ch 32) Chronic Pain requires fixed schedule around-the-clock (ATC) treatment  opioids  NSAIDs  adjuvants Breakthrough Pain transient episodes of pain while chronic pain is controlled access to rescue medication Analgesics and Cancer Pain eg Sustained release morphine (MS Contin) Around The Clock (ATC) po administration  MS = morphine sulphate  Contin refers to continuous/sustained release Other analgesics when needed Including for breakthrough pain NSAIDs and adjuvant medications WHO Pain Management Ladder Figure 32.4 Cancer Pain - NSAIDs and Adjuvant analgesic agents NSAIDs the most common non-narcotic analgesic Adjuvants antidepressants eg amitriptyline (Elavil) antiseizure drugs eg carbamazepine glucocorticoids Morphine: Contraindications and Cautions Severe asthma or other respiratory insufficiency RESPIRATORY depression Hepatic dysfunction Elevated intracranial pressure (ICP) exacerbates condition Pregnancy Opioid Analgesics: Adverse Effects Respiratory depression #1 serious adverse effect CNS depression  possible coma Nausea and vomiting greatest on 1st dose, then decreases Constipation no tolerance development Opioid Analgesics: Adverse Effects Hypotension  dilation of peripheral arteries and veins (histamine release) Histamine release  itchiness, rash  dilation of peripheral arteries and veins Urinary retention Diaphoresis and flushing Pupil constriction (miosis) Opioid Analgesics: Interactions CNS depressants have cumulative effects eg Antipsychotics, antihistamines, sedatives (benzodiazepines, barbiturates) Ethanol (alcohol) Moderate Opioid Analgesics Codeine (3-methylmorphine) Oxycodone Buprenorphine Moderate Opioid Analgesics Codiene Less analgesia and respiratory depression liver metabolism to morphine (~10% of oral dose)  unpredictable effect antitusssive Moderate Opioid Analgesics Codiene often combined acetaminophen in Tylenol 1, Tylenol 2, Tylenol 3 acetylsalicylic acid in `222's or ‘292’ Moderate Opioid Agonists Oxycodone (Oxycontin or Percodan) metabolism required for activation abuse potential widely used in combination with acetaminophen (Percocet) Opioid Antagonists Naloxone (Narcan), naltrexone Used for complete or partial reversal of opioid-induced respiratory depression BUT what about the pain relief?  µ   Morphine Agonist Agonist Agonist Naloxone Antag Antag Antag Opioid Antagonists Naloxone Shorter half-life (~2 h) than morphine and some other opioids  Dosing effect? IV/IM/SC/nasal administration  IM or nasal in naloxone rescue kits Treating Opioid Addiction Methadone program Buprenorphine + naloxone (Suboxone) SL tablet Alternative to methadone Why use combination? Opioid Tolerance A common physiological result of chronic opioid treatment Which pharmacological effects show tolerance development? Result? Opioids: Physical Dependence State that develops in which an abstinence syndrome will occur if a drug is abruptly withdrawn Drug must be administered to maintain normal function Occurs with other unrelated drugs classes withdrawal symptoms specific to drug Opioids: Physical Dependence On abrupt discontinuation or when an opioid antagonist is administered Narcotic withdrawal Opioid abstinence syndrome Very unpleasant, but not dangerous! Withdrawal Sympoms  Anxiety, irritability, chills and hot flashes, joint pain, lacrimation, sneezing, rhinorrhea, diaphoresis, nausea, vomiting, abdominal cramps, diarrhea Opioids Physical dependence is NOT the same as addiction (substance dependence syndrome) Tolerance and physical dependence are both part of the body’s response to the presence of drug Opioid Analgesics: Implications Oral forms should be taken with food to minimize gastric upset Withhold dose and contact physician if there is a decline in the client’s condition or if VS are abnormal especially if respiratory rate is less than 12 breaths/minute Opioid Analgesics: Implications Respiratory depression may be manifested by: respiratory rate of less than 12 per minute dyspnea diminished breath sounds shallow breathing Opioid Analgesics: Implications Constipation  take with adequate fluid and fibre intake  stool softener (docusate) and/or stimulant (senna) daily Orthostatic hypotension  instruct to change positions slowly