Drugs for Pain, Headache, and Anesthesia Chapter 9 Drugs for Pain, Headache, and Anesthesia © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Topics Anatomy and Physiology of Pain and Sensation Headache Anesthesia Analgesic and Anesthetic Antagonists Herbal and Alternative Therapies © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation About Pain Is a physiological response to stimuli and is usually associated with tissue damage Peripheral nervous system Detects temperature, touch, and pain Is also responsible for the five senses Sensation Heat, cold, pressure, or chemical stimulus is perceived by sensory receptors and nerve endings in the peripheral nervous system Signals travel up the spinal cord to the cerebral cortex and sensation is perceived © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Anatomy of the Nervous System Pain alerts the body to harmful injury or inflammation © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Inflammation Causes the release of arachidonic acid, which is acted upon by the enzyme cyclooxygenase to form prostaglandins Prostaglandins Are chemical triggers for pain and cause local redness and swelling Are pyrogens (substances that produce fever) Acute pain Response involves the sympathetic nervous system Pulse increases, blood pressure rises, breathing speeds up, muscles tense, and pupils dilate Other responses: altered stomach and bowel functions, impaired immune response, and water retention © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation The Inflammation Process: Acute Pain Inflammation or harmful injury causes a cascade of events Some pain medications treat pain and fever by inhibiting prostaglandin production © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Chronic Pain Lasts longer than 3 months Produces a compensatory response involving depression and behavioral adaptation over time Causes feelings of hopelessness, sleep disturbances, lack of facial expression, isolation, fatigue, anger, and physical inactivity Usually coexists with other conditions © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Somatic and Visceral Pain Somatic pain Occurs from injury to the body frame, such as to bones and muscles Visceral pain Occurs from problems with internal organs, such as the kidneys or intestines Symptoms include nausea, vomiting, and sweating Patients may also describe the pain as originating somewhere else in the body (referred pain) An example is pain in the left shoulder and arm that accompanies a heart attack © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Neuropathic Pain Occurs from damage to nerve tissue itself Symptoms include tingling, burning, or stabbing pain in the area of injury Often involves the sciatic nerve in the legs, the trigeminal nerve in the face, and the peroneal nerves in the feet May not respond to typical analgesics Other agents (antidepressants or anticonvulsants) that alter nerve signal transmission are used © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Sympathetically Mediated Pain Is associated with nerve overactivity Patient feels pain when no obvious stimulus exists Phantom limb pain Patient feels pain in a missing limb Treat with nerve-blocking agents Impact of Pain Can hugely impact a patient’s quality of life and health Pain treatment involves good assessment, along with realistic and appropriate expectations for treatment © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain Mild pain Is managed with OTC analgesics (drugs that treat pain) Moderate to severe pain Requires prescription medications; many are narcotics Narcotic analgesics Are natural (e.g., codeine, morphine) or synthetic drugs with morphine-like activity Are controlled substances Opiates Can cause dependence, leading to addiction Produce euphoric effects that mimic endorphins, which help the body deal with pain over-the-counter (OTC) © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Tolerance and Dependence Tolerance Is a process whereby the body becomes less sensitive to the effects of a drug over time Requires higher and higher doses to produce the same therapeutic effects Dependence Can be both physiological (physical) and psychological (emotional) May need medical assistance to stop therapy Tapering (reducing doses over time) may avoid or minimize withdrawal symptoms © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Physiological Dependence The body becomes used to the effects of a drug over time and physically adjusts When drug use stops, uncomfortable and sometimes life-threatening withdrawal symptoms occur Many drugs besides narcotics can cause this, such as blood pressure medications Psychological Dependence The euphoric effects and relief a patient feels when analgesia for pain occurs It does not always lead to addiction © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Addiction Is a compulsive behavioral disorder in which the patient becomes preoccupied with drug use Addicts No longer take the drug as instructed Display decreased general function and ability to participate in normal life Alter normal behavior to get more of the drug and may see multiple prescribers and pharmacies Will likely need counseling and medical treatment © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Addressing Addiction Fear of addiction is a major barrier to adequate pain control Technicians Can help patients to understand tolerance and dependence effects in opiate drug use Some patients believe tolerance and dependence are addiction, so they resist appropriate therapy Can alert pharmacists when psychological dependence and addiction may be developing Important for patient safety © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Acetaminophen Indications: mild pain and fever Especially good for pain with headache or OA and for children who have pain or fever Indications (other): in combination with opiates for moderate to severe pain Achieves synergistic therapy Smaller doses needed and fewer side effects occur than by using either agent alone Mechanism of Action: inhibits prostaglandin production in the CNS osteoarthritis (OA) central nervous system (CNS) © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Acetaminophen (continued) Is not an anti-inflammatory (unlike NSAIDs) Routes: oral Side Effects: stomach upset and excitation Cautions Can cause liver toxicity if taken in high doses (4 g a day) or used chronically at daily maximum dose levels If regular alcohol use, total daily dose should be limited to 2 g due to possible serious liver damage Take in the lowest doses possible for short-term use nonsteroidal anti-inflammatory drugs (NSAIDs) © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Aspirin Indications: mild to moderate pain and fever; especially useful for pain with inflammation such as OA Indications (low dose): stroke and heart attack prevention Indications (other): in combination with opiates for moderate to severe pain through synergistic therapy Mechanism of Action: inhibits cyclooxygenase, the enzyme that converts arachidonic acid to prostaglandins Routes: oral; also rectal Side Effects (common): GI irritation, erosion, and bleeding; headache; dizziness; and rash gastrointestinal (GI) © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Aspirin (continued) Side Effect (severe): aspirin toxicity, which includes ringing in the ears (tinnitus), dizziness, and confusion Cautions Do not use if at risk for bleeding, have gout, or ulcers Do not use if have asthma or are pregnant Do not use if have allergy to aspirin Do not use in children for fever or pain Associated with Reye’s syndrome Do not take with NSAIDs because it increases bleeding risk and decreases aspirin effectiveness © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Your Turn Question 1: A patient who has osteoarthritis in both knees is having difficulty sleeping, feels tired and hopeless, and is physically inactive. What could cause this to happen? Answer: The patient has chronic pain and is responding with depression and behavioral changes. Question 2: What is the reason aspirin should not be taken with NSAIDs? Answer: Aspirin taken with a NSAID can increase the risk of bleeding risk. In addition, the effectiveness of aspirin is decreased. © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: NSAIDs and COX-2 Inhibitors Indications: mild to moderate pain and fever Especially useful for pain with inflammation such as injuries and some forms of arthritis Indications (some NSAIDs): combined with opiates for moderate to severe pain through synergistic therapy Mechanism of Action (NSAIDs): inhibit cyclooxygenase I and II Mechanism of Action (COX-2 inhibitors): inhibit cyclooxygenase II cyclooxygenase-II (COX-2) © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Narcotic Analgesics Most are opiate derivatives similar in action to morphine Indications: moderate to severe pain; used alone or in combination with other analgesics Mechanism of Action: inhibit mu and kappa opioid pain receptors Indications (methadone): severe pain and drug abuse treatment Indications (tramadol): short-term treatment (five days or fewer) of moderate to severe pain Tramadol is used when side effects of opiates are intolerable or addiction potential is high intramuscular (IM) intravenous (IV) subcutaneous (SC) © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Narcotic Analgesics (continued) Routes: all are oral; some are IM, IV, SC, and IT Side Effects (common): sedation, dizziness, stomach upset, fatigue, headache, and constipation Side Effects (less common): changes in blood pressure and heart rate Side Effect (severe): respiratory depression, especially at high doses; tolerance to this effect may develop at higher doses Side Effects (other): dysphoria (not euphoria), nausea, and vomiting © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Narcotic Analgesics Cautions Causes drowsiness and fatigue Are controlled substances and have legal restrictions on handling and dispensing Do not use with alcohol Oxycodone (OxyContin) and oxymorphone (Opana) Are for chronic pain, especially for malignant pain Do not crush or chew extended-release form Tramadol Can lower seizure levels © Paradigm Publishing, Inc.

Anatomy and Physiology of Pain and Sensation Drugs for Pain: Neuropathic Pain Agents Neuropathic pain Does not always respond to conventional analgesics Gabapentin (anticonvulsant) and tricyclic antidepressants (such as amitriptyline and nortriptyline) Are often used for neuropathic pain Indications (long-term, take at bedtime): spinal cord injury, sciatica, trigeminal neuralgia, and diabetic peripheral neuropathy © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Headaches Are a specific type and location of pain that are very common and affect millions of patients in the U.S. Migraine Headaches Are characterized by a throbbing, unilateral pain in the head that impacts normal activity of life Possibly caused by cerebral surface blood vessels constricting and then rapidly dilating Serotonin, a potent vasoconstrictor and neurotransmitter, may be involved United States (U.S.) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Migraine Headaches (continued) Involve pain, nausea, vomiting, and/or sensitivity to light and sometimes to sound Occur with or without aura Involves vision disturbances, such as seeing halos, flashing lights, floating spots, or areas of darkness or blurriness Is part of the prodrome (early) phase of a migraine Is a warning for patients to seek immediate treatment Treatment Is acute pain medication and abortive therapies © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Migraine Headaches (continued) Prevention Avoid triggers such as certain foods, stress, sleep deprivation, medications, and environmental irritants Hormonal regulation during menstrual cycles and careful timing of preventive drug therapies Medication Overuse Headache Occurs in response to withdrawal from prolong use of acute headache medications Occurs when triptans are used more than 6 times a month and other analgesics used 3 or more times a day for 3–5 days a week © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Drugs for Acute and Migraine Headaches Headaches caused by stress, tension, or neuralgia Use non-narcotic or neuropathic pain medications Migraine Use acute abortive and chronic preventive treatments Preventive therapy is needed if 2–3 migraines a month Abortive treatment works best when started within minutes of the first symptoms Preferably during the prodrome or aura phase NSAIDs, ergotamine drugs, and corticosteroids are used if abortive therapies are not working © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Drugs for Migraine Headache: Triptans Indication: first-line abortive therapy Begin working in 15 minutes and last 2 to several hours If severe throbbing pain had already started triptans are not as effective Has limits on total number of doses or total dosage that patients can take every 24 hours Mechanism of Action: stimulate serotonin receptors to cause vasoconstriction of cerebral blood vessels Routes: all are oral; Zolmitriptan (Zomig) is also nasal; Sumatriptan (Imitrex) is also nasal and SC injection Selective Serotonin Receptor Agonists (Triptans) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Drugs for Acute Headache: Triptans (continued) Side Effects (common): dizziness, hot flashes, tingling, chest tightness, muscle aches, weakness, increased blood pressure, and sweating Side Effects (administered by injection): bruising sometimes occurs at the injection site Cautions Do not take if high blood pressure, heart disease, or angina Do not take with MAOIs; could cause serotonin syndrome Do not take with ergotamine monoamine oxidase inhibitors (MAOIs) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Drugs for Acute Headache: Combinations Combinations of non-narcotic analgesics and caffeine are used to treat mild migraine headaches Using analgesics from multiple classes attacks pain from different mechanisms due to synergistic drug therapy Caffeine is sometimes combined with other analgesics Improves pain control by constricting blood vessels, but to a lesser extent than triptans Barbiturate products are controlled substances that are sometimes used for migraines Examples: butalbital and butorphanol © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Drugs for Acute Headache: Combination Agents (continued) Routes: all are oral, except butorphanol is nasal, IM and IV Cautions (barbiturates, opiates) Causes drowsiness and dizziness Do not take with alcohol Produce tolerance and dependence; may be habit forming Recommend limited and short-term use Caution (combination products with aspirin): do not take if allergic to aspirin or NSAIDs © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Headache Drugs for Headache Prevention Indication (preventive drug therapy): migraine affecting normal life and occurring more than twice a month Drugs are taken daily or at regular intervals Includes Beta blockers Antidepressants (tricyclics and serotonin reuptake inhibitors) Anticonvulsants (valproic acid, topiramate, and gabapentin) Calcium-channel blockers (verapamil and nimodipine) NSAIDs © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Anesthesia About Anesthesia Indications: inhibits sensation and pain during procedures such as surgery, dental work, and colonoscopy General anesthesia Affects the entire body and loss of consciousness occurs Skeletal muscle relaxes, breathing and cardiac function slows, and blood pressure decreases Local anesthesia Affects a select part of the body Causes loss of pain, tactile sensation, temperature sensation No loss of consciousness © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Anesthesia About Anesthesia: Preanesthetic Medications Indications: short diagnostic procedures or to enhance relaxation, pain control, and amnesia Reduce patient anxiety and resistance to therapy Medications: midazolam (Versed), diazepam (Valium), and lorazepam (Ativan), and fentanyl in various forms Administration: systemical © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Anesthesia General Anesthetics Indications: surgery and other procedures requiring overall muscle relaxation to keep the patient still Cause loss of consciousness Nitrous oxide is the exception Indication (nitrous oxide): dental procedures Dosage Forms: inhaled and injectable Length of Effect: varies, usually only a few minutes Anesthesiologist or anesthetist administers and adjusts these medications throughout a procedure © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Anesthesia General Anesthetics (continued) Inhaled Anesthetics Storage: steel containers as compressed gas or liquid Administration: inhaled through a face mask Most reduce blood pressure and renal function; concomitant IV fluids given to counteract this effect Technicians do not handle these products Injectable anesthetics Administration: continuous infusion Technicians in surgical satellites prepare these agents © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Anesthesia General Anesthetics (continued) Side Effects: nausea, vomiting, decreased blood pressure, and reduced renal function Coadministration (during procedures): antiemetic medications and IV fluids counteract side effects Cautions: do not use with seizure disorders Caution (rare, life-threatening): malignant hyperthermia Body temperature rises suddenly and rapidly with heart arrhythmias, difficulty breathing, and muscle rigidity Technicians stock and maintain dantrolene to treat malignant hyperthermia; check expiration date © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Anesthesia Local Anesthetics Indications: dental work, stitches, and sutures Dosage forms: topical, injection, and IV Mechanism of Action: depress first the nerve activity of small axons, then that of larger myelinated nerve fibers Esters are short-acting drug molecules metabolized by local tissue Amides are longer-acting drug molecules metabolized by the liver Side Effects: allergic reaction, skin rash, swelling at the application site, and CNS excitation, and cardiac arrhythmias Caution: consult with prescribers if have seizure disorders © Paradigm Publishing, Inc.

Analgesic and Anesthetic Antagonists Naloxone (Narcan) Is an opiate receptor antagonist that counteracts opioid pain and preanesthetic medications Indications: reverse opiate effects in overdoses Flumazenil (Romazicon) Is a benzodiazepine receptor antagonist Indications: reverse excessive sedation, speed recovery of consciousness in overdoses, and manage overdose of benzodiazepines Both agents given in the emergency or operating rooms © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Your Turn Question 1: A patient has occasional migraine headaches. She would like a medication to quickly stop her migraines before they become severe. What is the physician likely to prescribe? Answer: The physician is likely to prescribe a triptan because they are the first-line drug therapy for aborting migraines. Question 2: A patient has a deep cut that will not stop bleeding. The cut will require some stitches. What type of anesthetic will likely be used before the procedure begins? Answer: A local anesthetic will be applied before the cut is stitched up. © Paradigm Publishing, Inc.

Herbal and Alternative Therapies Caffeine Is a CNS stimulant Used in combination with other analgesics for headache, fatigue, and drowsiness Capsaicin Is a chemical derived from cayenne peppers Used as a topical treatment for pain Feverfew Is a plant product Used for migraine pain, menstrual cramps, and arthritis © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Summary Non-narcotic medications such as aspirin, acetaminophen, or NSAIDs are the first-line treatment for pain Narcotic medications are used for moderate or severe pain; they can promote tolerance and dependence Triptans are the mainstay of abortive migraine treatment General anesthesia involves a loss of consciousness and is either intravenous or inhaled Local anesthesia results in a loss of sensation in a specific area of the body and is topical or injected © Paradigm Publishing, Inc.