Topic 5: Central Nervous System I Pharmacology PDF

Topic 5: Central Nervous System I PHARMACOLOGY.  Objectives 1. Define acute pain and persistent (chronic or long-term) pain and 7. Define anaesthesia and describe the basic differences between contrast the signs, symptoms, and management of acute and persistent...

Topic 5: Central Nervous System I PHARMACOLOGY.  Objectives 1. Define acute pain and persistent (chronic or long-term) pain and 7. Define anaesthesia and describe the basic differences between contrast the signs, symptoms, and management of acute and persistent general and local anaesthesia. pain and cancer pain. 8. List the most commonly used general and local anaesthetics and 2. Describe pharmacological and nonpharmacological approaches for the associated risks. management and treatment of acute, persistent pain, cancer pain and 9. Discuss the differences between depolarizing neuromuscular blocking pain experienced in terminal conditions. drugs and nondepolarizing blocking drugs and their impact on the 3. Discuss the use of nonopioids, nonsteroidal anti-inflammatory drugs patient. (NSAIDs), and opioids and miscellaneous drugs in the management of 10. Compare the mechanisms of action, indications, adverse effects, acute and persistent pain, cancer pain, and special pain situations. routes of administration, cautions, contraindications, and drug 4. Identify examples of drugs classified as nonopioids, nonsteroidal anti- interactions of general anaesthesia and local anaesthesia, and of drugs inflammatory drugs, opioids, and miscellaneous drugs. used for procedural sedation. 5. Briefly describe the mechanisms of action, indications, dosages, routes of administration, adverse effects, toxicity, cautions, contraindications, and drug interactions of nonopioids, nonsteroidal anti-inflammatory drugs (see Chapter 49), opioids and miscellaneous drugs. 6. Briefly describe the specific standards of pain management as defined by the World Health Organization and the Canadian Pain Society.  Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage A personal and individual experience Whatever the patient says it is Exists when the patient says it exists Nociception (1 of 2) Pain results from stimulation of sensory nerve fibres called nociceptors. These receptors transmit pain signals from various body regions to the spinal cord and brain. Nociceptive pain: Somatic Visceral Pain Threshold VS Tolerance Threshold: Level of stimulus needed to produce the perception of pain A measure of the physiological response of the nervous system Tolerance The amount of pain a person can endure without it interfering with normal function Varies from person to person Subjective response to pain, not a physiological function Varies by attitude, personality, environment, culture, ethnicity Classification of Pain by Onset and Duration Acute pain Persistent pain (chronic pain) Sudden onset Persistent or recurring Limited, has an end Lasts 3 to 6 months More difficult to treat Tolerance  Reduces dose of analgesic Application of cold required and minimizes Cognitive techniques adverse effects Distraction Possibly alters ascending Relaxation strategies nociceptive input or stimulates descending pain Self-management Nonpharmacological modulation mechanisms Therapy for Pain Massage Exercise Transcutaneous electrical nerve stimulation (TENS) Heat therapy Three-Step Analgesic Ladder Medication Therapy for Pain: Analgesic Ladder Mild pain 1–3 on a scale of 0–10 “Step 1” medications Nonopioid analgesics (Aspirin and other salicylates, other nonsteroidal anti- inflammatory drugs [NSAIDs], and acetaminophen [Tylenol]) Ceiling effect: Increasing the dose beyond an upper limit provides no greater analgesia No tolerance or physical dependence Many available without a prescription Medication Therapy for Pain: Analgesic Ladder (Cont.) Mild to moderate pain 4–6 on a scale of 0–10, or Mild but persistent despite nonopioid therapy “Step 2” medications Mu: morphine, oxycodone, hydromorphone, methadone Opioid agonists (morphine) Antagonists (naloxone) Mixed agonist naloxone (pentazocine, butorphanol) should not be used because they bind as agonists on the mu receptor. Medication Therapy for Pain: Analgesic Ladder (Cont.) Moderate to severe pain 4–10 on a scale of 0 to 10, or When step 2 medications do not produce effective pain relief “Step 3” medications Most are mu-receptor agonists Potent No analgesic ceiling Can be delivered via many routes  Nonopioid Analgesics: Acetaminophen (Tylenol®) Analgesic and antipyretic effects Little to no anti-inflammatory effects Available over the counter (OTC) and in combination products with opioids  Acetaminophen: Mechanism of Action Similar to that of salicylates Blocks pain impulses peripherally by inhibiting prostaglandin synthesis Indications: Mild to moderate pain Fever Inability to take aspirin products Acetaminophen: Dosage 1 2 3 4 Maximum daily dose for Inadvertent excessive Be aware of the *Note: As of the date of healthy adults is 4 g/day, doses may occur when acetaminophen content writing of this text, but Health Canada is different combination of all medications taken Health Canada had not considering lowering* drug products are taken by the patient (OTC and yet made this decision. 2 000 mg for older adults and together. prescription). those with liver disease  Acetaminophen: Contraindications and Interactions Should not be taken in the presence of following: Drug allergy Liver dysfunction Possible liver failure Dangerous interactions may occur if taken with alcohol or other drugs that are hepatotoxic.  Acetaminophen: Toxicity and Managing Overdose Even though available OTC, lethal when overdosed Overdose, whether intentional or resulting from chronic unintentional misuse, causes hepatic necrosis: hepatotoxicity. Long-term ingestion of large doses also causes nephropathy. Recommended antidote: acetylcysteine regimen  Synthetic drugs that bind to the opiate receptors to relieve pain Mild agonists: codeine, hydrocodone Strong agonists: morphine, hydromorphone Opioid Drugs hydrochloride, oxycodone, meperidine, fentanyl, methadone Meperidine: not recommended for long- term use because of the accumulation of a neurotoxic metabolite, normeperidine, which can cause seizures.  Opioid Analgesics: Mechanism of Action Three classifications based on their actions: Agonists: Bind to an opioid pain receptor in the brain and cause an analgesic response (reduction of pain sensation) Agonists–antagonists : Bind to a pain receptor and Cause a weaker pain response than full agonists Antagonists (nonanalgesic)  Opioid Analgesics: Indications Mainly used to alleviate moderate to severe pain Often first line agents analgesic in immediate post operative setting Often given with adjuvant analgesic drugs to assist primary drugs with pain relief Balanced anaesthesia Opioids are also used for: Cough centre suppression Treatment of diarrhea  Known drug allergy Severe asthma Use with extreme caution in patients with the Opioid Analgesics: following: Respiratory insufficiency Contraindications Elevated intracranial pressure Morbid obesity or sleep apnea Paralytic ileus Pregnancy  Central nervous system (CNS) depression Leads to respiratory depression Most serious adverse effect Opioid Nausea, vomiting, constipation, biliary tract spasm Analgesics: Urinary retention Adverse Effects Hypotension, palpitations, flushing Itching, rash, wheal formation Pinpoint pupils indicating a possible overdose  A common physiological result of chronic opioid treatment Opioids: Opioid Tolerance State of adaptation Result: larger dose is required to maintain the same level of analgesia  Physiological adaptation of the body to the presence of an opioid Opioids: Physical Dependence Opioid tolerance and physical dependence are expected with long-term opioid treatment and should not be confused with psychological dependence (addiction).  Addiction: a pattern of compulsive drug use Opioids: characterized by a continued craving for an Psychological opioid and the need to use the opioid for Dependence effects other than pain relief  Alcohol Antihistamines Opioid Barbiturates Analgesics: Benzodiazepines Interactions Promethazine Monoamine oxidase inhibitors Others Codeine Sulphate Codeine sulphate Natural opiate alkaloid (Schedule I) obtained from opium Less effective Ceiling effect More commonly used as an antitussive drug Gastrointestinal (GI) disturbance  Naturally occurring alkaloid derived from the opium poppy Drug prototype for all opioid drugs; Morphine Schedule I controlled substance Sulphate Indication: severe pain Oral, injectable, and rectal dosage forms; also extended-release forms Dilaudid Hydromorphone (Dilaudid®): very potent opioid analgesic; Schedule I drug 1 mg of intravenous (IV) or intramuscular (IM) hydromorphone is equivalent to 7 mg of morphine. Fentanyl Synthetic opioid (Schedule I) used to treat moderate to severe pain Parenteral injections, transdermal patches (Duragesic Mat®), sublingual effervescent tablet (Fentora®) Naloxone Hydrochloride (Narcan®) Pure opioid antagonist Drug of choice for the complete or partial reversal of opioid-induced respiratory depression Indicated in cases of suspected acute opioid overdose Failure of the drug to significantly reverse the effects of the presumed opioid overdose indicates that the condition may not be related to opioid overdose.  Analgesics: Nursing Implications Before beginning therapy, perform a thorough history regarding allergies and use of other medications, including alcohol, health history, and medical history. Obtain baseline vital signs, intake and output as well as respiratory rate. Assess for potential contraindications and drug interactions.  Analgesics: Nursing Implications Perform a thorough pain assessment, including pain intensity and character, onset, location, description, precipitating and relieving factors, type, remedies, and other pain treatments. Level of pain is now considered a “fifth vital sign.” Rate pain on a 0–10 or similar scale.  Analgesics: Nursing Implications Be sure to medicate patients before the pain becomes severe, so as to provide adequate analgesia and pain control. Pain management includes pharmacological and nonpharmacological approaches; be sure to include other interventions as indicated.  Analgesics: Nursing Implications Patients should not take other medications or OTC preparations without checking with their physicians. Instruct patients to notify physician about signs of allergic reaction or adverse effects.  Opioid Analgesics: Nursing Implications Monitor for therapeutic effects. Decreased perception of pain Decreased severity of pain Increased periods of comfort Improved activities of daily living, appetite, and sense of well-being Decreased fever (acetaminophen)  Drugs that reduce or eliminate pain by depressing nerve function in the central nervous system (CNS) and peripheral nervous system Anesthesia: A state of reduced neurological function Anaesthetics Two types General anaesthesia: complete loss of consciousness and loss of body reflexes, including paralysis of respiratory muscles. Local anaesthesia: no paralysis of respiratory function; elimination of pain sensation in the tissues innervated by anaesthetized nerves  Drugs that induce a state in which the CNS is altered to produce varying degrees of: General Pain relief Anaesthetics Depression of consciousness Skeletal muscle relaxation Reflex reduction  Inhalational anaesthetics Volatile liquids or gases that are vaporized in oxygen and inhaled General Parenteral anaesthetics Anaesthetics Administered intravenously (2 of 2) Adjunct anaesthetics Drugs that enhance clinical therapy when used simultaneously with another drug Balanced anaesthesia  Varies according to drug For all anaesthetics, potency varies directly with lipid solubility. Mechanism of Fat-soluble drugs are stronger anaesthetics than water-soluble drugs. Action of Nerve cell membranes have a high lipid content, as does the blood– brain barrier. General Lipid-soluble anaesthetic drugs can therefore easily cross the blood– brain barrier to concentrate in nerve cell membranes. Anaesthetics Overall effects: Orderly and systematic reduction of sensory and motor CNS functions Progressive depression of cerebral and spinal cord functions  General anaesthetics are used during surgical procedures to produce unconsciousness. skeletal muscular relaxation. Indications visceral smooth muscle relaxation. Rapid onset; quickly metabolized Also used in electroconvulsive therapy treatments for severe depression  Vary according to dosage and drug used Adverse Sites primarily affected: Heart, peripheral circulation, liver, kidneys, Effects respiratory tract Myocardial depression is commonly seen.  Malignant hyperthermia Occurs during or after volatile inhaled general anaesthesia or use of the neuromuscular blocking drug (NMBD) succinylcholine Sudden elevation in body temperature (greater Adverse than 40°C) Effects Tachypnea, tachycardia, muscle rigidity Life-threatening emergency Treated with cardiorespiratory supportive care and dantrolene sodium (skeletal muscle relaxant)  Toxicity and management of overdose In large doses, anaesthetics are potentially life threatening. Cardiac and respiratory arrest are ultimate Adverse causes of death in cases of overdose. Administered in a controlled environment Effects General anaesthetics: interactions Antihypertensives: increased hypotensive effects β-Blockers: increased myocardial depression 43 Intravenous administration use for both general anaesthesia and moderate sedation Rapid onset of action ketamine Low incidence of reduction of hydrochloride cardiovascular, respiratory, and bowel (Ketalar®) function Adverse effects: disturbing psychomimetic effects, including hallucinations Contradicted with known drug allergy 44 “Laughing gas” Only inhaled gas currently used as a general anaesthetic Nitrous Oxide Weakest of the general anaesthetic drugs Used primarily for dental procedures or as a supplement to other, more potent anaesthetics 45 Parenteral general anaesthetic Used for the induction and maintenance of general anaesthesia propofol Sedation for mechanical ventilation in CCU settings (Diprivan®) Lower doses: sedative–hypnotic for moderate sedation Use with caution in patients who are hemodynamically unstable. 46 Fluorinated ether Widely used Rapid onset and rapid elimination Especially useful in outpatient surgery Sevoflurane settings Nonirritating to the airway Greatly facilitates induction of an unconscious state, especially in pediatric patients 47 Also called conscious sedation and moderate sedation Does not cause complete loss of consciousness and does not normally cause respiratory arrest Procedural Combination of an IV benzodiazepine (e.g., Sedation midazolam) or propofol and an opiate analgesic (e.g., fentanyl or morphine) Propofol also commonly used Anxiety and sensitivity to pain are reduced, and the patient cannot recall the procedure. 48 Also called regional anaesthetics Used to render a specific portion of the body insensitive to pain Interfere with nerve impulse transmission to specific areas of the body Do not cause loss of consciousness Local Topical Anaesthetics Applied directly to skin or mucous membranes Creams, solutions, ointments, gels, ophthalmic drops, powders, suppositories Parenteral Injected intravenously or into the CNS by various spinal injection techniques 49 Spinal or intraspinal Intrathecal Epidural Infiltration Types of Local Nerve block Anaesthesia Topical Peripheral nerve catheter attached to a pump containing the local anaesthetic: ON- Q PainBuster® pump 50 Benzocaine Cocaine hydrochloride Types of Local Dibucaine hydrochloride Anaesthesia Lidocaine Prilocaine Tetracaine hydrochloride 51 First, autonomic activity is lost. Then pain and other sensory functions are Drug Effects: lost. Last, motor activity is lost. Paralysis As local drugs wear off, recovery occurs in reverse order. (Motor, sensory, then autonomic activity are restored.) 52 Usually limited Adverse effects result if: Inadvertent intravascular injection Excessive dose or rate of injection Slow metabolic breakdown Adverse Injection into highly vascular tissue Effects Spinal headache”  70% of patients who either experience inadvertent dural puncture during epidural anaesthesia or undergo intrathecal anaesthesia.  Usually self-limiting  Treatment: bed rest, analgesics, caffeine, blood patch 53 Prevent nerve transmission in skeletal and smooth muscle, resulting in muscle paralysis Also paralyze the skeletal muscles required for breathing: the intercostal muscles and the diaphragm Neuromuscular Used with anaesthetics during surgery When used during surgery, artificial mechanical ventilation is Blocking Drugs required. (1 of 5) These drugs paralyze respiratory and skeletal muscles. Patient cannot breathe on his or her own. Do not cause sedation or pain relief. Patient may be paralyzed yet conscious. 54 When used during surgery, artificial mechanical ventilation is required. Neuromuscular These drugs paralyze respiratory and Blocking Drugs skeletal muscles. (2 of 5) Patient cannot breathe on his or her own. Do not cause sedation or pain relief. Patient may be paralyzed yet conscious. 55 Depolarizing drugs Nondepolarizing drugs Neuromuscular Short acting Blocking Drugs Intermediate acting (3 of 5) Long acting 56 Typical time course of NMBD-induced paralysis during a surgical procedure: Muscle weakness Neuromuscular Total flaccid paralysis: first fingers and Blocking Drugs eyes then limbs neck and trunk; finally, intercostal muscles and diaphragm (4 of 5) NMBDs do not cause sedation or pain relief. Recovery occurs in reverse order of paralysis. 57 Respiratory muscle paralysis occurs with Neuromuscular these drugs. Blocking Emergency ventilation equipment must be Drugs: Safety immediately available. 58 Succinylcholine (Quelicin®) Neuromuscular Works similarly to neurotransmitter Blocking Drugs: acetylcholine (ACh), causing depolarization Metabolism is slower than ACh, so as long as Depolarizing succinylcholine is present, repolarization Drugs (1 of 3) cannot occur. Result: flaccid muscle paralysis 59 pancuronium bromide Long-acting nondepolarizing NMBD Neuromuscular Used as an adjunct to general anaesthesia to facilitate endotracheal intubation and to Blocking Drugs: provide skeletal muscle relaxation during Depolarizing surgery or mechanical ventilation Drugs (2 of 3) Most commonly used for long surgical procedures that require prolonged muscle paralysis Available only in injectable form  Objectives 1. Define acute pain and persistent (chronic or long-term) pain and 7. Define anaesthesia and describe the basic differences between contrast the signs, symptoms, and management of acute and persistent general and local anaesthesia. pain and cancer pain. 8. List the most commonly used general and local anaesthetics and 2. Describe pharmacological and nonpharmacological approaches for the associated risks. management and treatment of acute, persistent pain, cancer pain and 9. Discuss the differences between depolarizing neuromuscular blocking pain experienced in terminal conditions. drugs and nondepolarizing blocking drugs and their impact on the 3. Discuss the use of nonopioids, nonsteroidal anti-inflammatory drugs patient. (NSAIDs), and opioids and miscellaneous drugs in the management of 10. Compare the mechanisms of action, indications, adverse effects, acute and persistent pain, cancer pain, and special pain situations. routes of administration, cautions, contraindications, and drug 4. Identify examples of drugs classified as nonopioids, nonsteroidal anti- interactions of general anaesthesia and local anaesthesia, and of drugs inflammatory drugs, opioids, and miscellaneous drugs. used for procedural sedation. 5. Briefly describe the mechanisms of action, indications, dosages, routes of administration, adverse effects, toxicity, cautions, contraindications, and drug interactions of nonopioids, nonsteroidal anti-inflammatory drugs (see Chapter 49), opioids and miscellaneous drugs. 6. Briefly describe the specific standards of pain management as defined by the World Health Organization and the Canadian Pain Society.