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Chapter 9
Drugs for Pain, Headache, and
Anesthesia
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Chapter 9
Topics
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Anatomy and Physiology of Pain and Sensation
Headache
Anesthesia
Analgesic and Anesthetic Antagonists
Herbal and Alternative Therapies
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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
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Anatomy and Physiology of Pain and Sensation
Anatomy of the
Nervous System
• Pain alerts the body
to harmful injury or
inflammation
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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
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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
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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
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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
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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
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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
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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
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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
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Anatomy and Physiology of Pain and Sensation
Physiological
Dependence
Psychological
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
• The euphoric effects and relief a patient
feels when analgesia for pain occurs
• It does not always lead to addiction
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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
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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
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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
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Anatomy and Physiology of Pain and Sensation
Drugs for Pain: Acetaminophen (continued)
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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
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Analgesic and Anesthetic Antagonists
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
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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.
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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
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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
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