Chapter 11- analgesic drugs

Overview

 Pain management is a crucial aspect of nursing care across various settings and patient
populations.
 Pain is a primary reason for healthcare visits, contributing to 78% of emergency
department visits in Canada annually.
 Conditions requiring pain management include surgical/diagnostic procedures, arthritis,
diabetes, multiple sclerosis, cancer, and AIDS.
 Pain causes suffering and economic burdens due to workplace productivity loss,
compensation claims, and healthcare expenses.

Pharmacological and Nonpharmacological Pain Management

 High-quality patient care requires knowledge of both pharmacological and

nonpharmacological pain relief strategies.
 This chapter focuses on pharmacological methods, specifically opioid analgesics.
 Box 11.1 provides examples of nonpharmacological approaches.

Analgesics and Classification

 Medications that relieve pain are called analgesics (painkillers).

 Analgesics are classified based on their chemical structure and mechanism of action.
 The primary focus is on opioid analgesics for moderate to severe pain.
 Adjuvant analgesics (adjuvants) are often added to opioid regimens.

Definition and Nature of Pain

 Pain is an unpleasant sensory and emotional experience linked to actual or potential

tissue damage.
 It is a personal and subjective experience, defined by the patient’s perception.
 Effective pain management requires an individualized approach, considering various
patient factors.

Mechanisms of Pain and Nociception

 Pain perception is complex and involves physical, psychological, and ethnocultural

aspects.
 Nociceptive pain serves a protective function and is divided into:
o Visceral pain (internal organs/smooth muscles)
o Somatic pain (skeletal muscles, ligaments, joints)
 Pain signals travel from nociceptors through the spinal cord to the brain.
 The pain threshold is the minimum stimulus required to produce pain.
 Genetic factors can influence variations in pain sensitivity.
Pain Receptors and Physiological Response

 Three primary receptors involved in pain perception:

o μ (mu) receptors (most crucial, located in the dorsal horn of the spinal cord)
o κ (kappa) and δ (delta) receptors (less critical but still involved)
 Pain perception and emotional well-being are linked to the number of μ receptors.
 The μ opioid receptor gene controls receptor quantity, influencing pain sensitivity.

Pain Threshold vs. Pain Tolerance

 Pain threshold: The physiological response of the nervous system to pain, relatively
uniform across individuals.
 Pain tolerance: The subjective amount of pain an individual can endure without
functional impairment.
 Pain tolerance is influenced by age, gender, culture, previous pain experiences, and
anxiety levels.
 Table 11.1 outlines factors affecting pain tolerance
o Conditions That Alter Pain Tolerance

-Pain Threshold & Conditions

o Lowered: Anger, anxiety, depression, discomfort, fear, isolation, persistent

pain, sleeplessness, tiredness
o Raised: Diversion, empathy, rest, sympathy, medications (analgesics,
antianxiety drugs, antidepressants)

Acute vs. Persistent Pain

 Pain can be classified based on onset and duration:

o Acute pain: Sudden onset, subsides with treatment (e.g., postoperative pain).
o Persistent (chronic) pain: Lasts 3-6 months or longer, often requiring increasing
drug dosages.
 Tolerance occurs when progressively higher doses of a drug are needed to achieve the
same effect.
 Table 11.2 compares acute and persistent pain, their characteristics, and associated
conditions.
Classification of Pain by Origin

 Vascular Pain: Originates from vascular or perivascular tissues, associated with

migraines.
 Referred Pain: Occurs when visceral nerve fibres synapse near subcutaneous nerve
pathways (e.g., cholecystitis pain referred to the back).
 Neuropathic Pain: Results from peripheral or CNS nerve damage, can be idiopathic.
 Phantom Pain: Occurs in amputated or paralyzed limbs, described as burning, itching,
tingling, or stabbing.
 Cancer Pain: Can be acute, persistent, or both; caused by tumor pressure, metastases,
hypoxia, fractures, muscle spasms, or treatment side effects.
 Central Pain: Associated with CNS damage due to trauma, tumors, inflammation, or
diseases like cancer, diabetes, stroke, and multiple sclerosis
 Gate Control Theory

 The concept of pain has evolved over time, influenced by prevailing scientific
knowledge.
 The most well-described theory of pain is the Gate Control Theory
 This theory explains how somatosensory afferents function as a “gate” that modulates
pain signals from the periphery to the brain.
 The theory states that pain perception is influenced by a gating mechanism in the dorsal
horn of the spinal cord, which regulates the transmission of sensory impulses.

Four Processes of Nociceptive Pain

1. Transduction
o Transformation of mechanical, chemical, or thermal stimuli into electrochemical
energy.
o Tissue injury triggers the release of prostaglandins, bradykinin, serotonin,
substance P, histamine, and potassium.
o Pain medications (e.g., NSAIDs for prostaglandins, antidepressants for serotonin)
target these mediators.
o The activation of nociceptors at the distal ends of sensory nerve fibres
generates action potentials.
o These impulses travel through sensory nerve fibres and activate pain receptors in
the dorsal horn of the spinal cord.
o The gate mechanism determines whether pain impulses are transmitted to higher
brain centres or blocked.
o If the gate permits sufficient impulses to reach the cerebral cortex, the sensation
of nociceptive pain is perceived.
2. Transmission
o Involves the propagation of pain impulses along nociceptive fibres.
o Two main types of nociceptive fibres:
 A-delta fibres (myelinated) → Fast transmission, sharp and localized pain.
 Mechanonociceptors: Respond to intense mechanical stimulation.
 Polymodal A-delta fibres: Respond to mechanical, thermal, and
chemical stimuli.
 C fibres (unmyelinated) → Slow transmission, dull and aching pain.
o Pain signals ascend through the anterolateral quadrant of the spinal cord via
the spinothalamic tract.
o Neurotransmitters (glutamate, substance P) facilitate impulse transmission from
nociceptors to dorsal horn neurons.
o The thalamus integrates nociceptive signals before relaying them to cortical
structures for perception.
o Gate Control Mechanism:
 A-fibres activation → Closes the gate, inhibiting pain transmission.
 C-fibres activation → Opens the gate, allowing pain transmission.
 The brain modulates the gate through descending nerve fibres, influencing
pain perception.
 3. Perception
o A subjective experience influenced by psychological, emotional, and behavioural
factors.
o Pain perception varies among individuals despite identical stimuli.
o μ (Mu) receptors in the dorsal horn are critical for pain sensitivity.
 Higher number of μ receptors → Reduced pain sensitivity.
 Lower number or absence of μ receptors → Increased pain sensitivity.
4. Modulation
o A neural mechanism that regulates pain transmission.
o Involves descending pain pathways from the brainstem to the spinal cord.
o Neurotransmitters involved in modulation:
 Endogenous opioids (enkephalins, endorphins)
 Serotonin (5-HT), norepinephrine (NE), GABA, neurotensin
o These substances bind to opioid receptors, inhibiting pain transmission by closing
the spinal cord gates.
o Endorphins (derived from “endogenous morphine”) are released in response to
pain or prolonged exertion (e.g., runner’s high).

-Pain Relief Mechanisms Related to the Gate Control Theory:

 Massage and counterirritation techniques (e.g., applying liniments) reduce pain

perception.
 Large-diameter A-fibres carry pain-modulating impulses, closing the gate and
reducing small fibre pain transmission.
 This principle underlies physical therapy techniques, transcutaneous electrical nerve
stimulation (TENS), and acupuncture.

Treatment of Pain in Special Situations

 ~20% of Canadians experience persistent pain.

 Pain is often misunderstood and undertreated.
 Patients with conditions like cancer, AIDS, sickle cell anemia may also have acute pain
crises.
 Acute pain management differs from persistent pain in medication type and dosage.

Routes of Drug Administration

 Common routes: Oral, IV, IM, subcutaneous, transdermal, rectal.

 Patient-Controlled Analgesia (PCA):
o Allows self-administration of opioids via a pump.
o Effective in reducing total opioid use.
o Common PCA opioids: Morphine sulfate, fentanyl.

Multimodal Pain Management

 Holistic approach: Combines pharmacological & nonpharmacological treatments.

 Goals:
o Pain reduction.
o Improved function & quality of life.

Cancer Pain Management

 Main priority: Patient comfort, not addiction prevention.

 Opioid tolerance:
o Occurs within one week of opioid use.
o Patients require higher doses over time due to tumor burden.
o Physical dependence is common but addiction is rare.
o Withdrawal symptoms occur if opioids are suddenly stopped.
 Preferred routes: Oral, IV, subcutaneous, transdermal, rectal (IM injections avoided due
to bruising & erratic absorption).

Controversy of Placebos

 Placebo effect:
o Triggered by endorphin activation & patient trust.
 Ethical concerns:
o Requires deception, making it unethical.
o Rarely used today.

Pain Management in Opioid-Dependent Patients

 Challenges:
o Clinicians hesitate to prescribe opioids.
o Patients often need higher doses due to opioid tolerance.
 Preferred drugs:
o Long-acting opioids (e.g., methadone, extended-release oxycodone).
 Genetic factors:
o Variations in cytochrome P450 enzymes affect opioid metabolism.
o Patients who report poor pain control should not be viewed with suspicion.
 Ethical priority:
o Pain control takes priority over concerns about addiction.
o Drug-seeking behavior (e.g., prescription forgery, doctor/pharmacy shopping) is a
legal issue.
o Community pharmacists help detect & report abuse.

Breakthrough Pain & Adjuvant Therapy

 Breakthrough pain:
o Occurs between doses of long-acting opioids.
o Treated with PRN (as-needed) immediate-release opioids.
o Increasing breakthrough doses may indicate the need for dose adjustment.
 o Crushing/chewing extended-release opioids is dangerous → Risk of overdose &
death.
 Adjuvant drugs (reduce opioid dosage & side effects):
o NSAIDs (e.g., ibuprofen).
o Antidepressants (e.g., amitriptyline).
o Antiepileptic drugs (e.g., gabapentin, pregabalin).
o Corticosteroids.
o Antiemetics & laxatives (to manage opioid side effects like nausea &
constipation).

Neuropathic Pain Management

 Opioids are often ineffective.

 Common causes:
o Diabetic neuropathy.
o Postherpetic neuralgia (shingles).
o Trigeminal neuralgia.
o AIDS-related nerve damage.
o Surgical nerve damage (e.g., post-thoracotomy pain).
 Symptoms:
o Allodynia: Pain from normally non-painful stimuli (e.g., light touch).
o Hyperalgesia: Exaggerated pain response.
o Burning, tingling, numbness, electrical sensations.
 Common adjuvant drugs:
o Amitriptyline (antidepressant).
o Gabapentin, pregabalin (anticonvulsants).

WHO Analgesic Ladder for Cancer Pain

 Standard framework for pain management, especially in opioid tolerance.

 Three-step approach:
o Step 1: Non-opioids (NSAIDs, acetaminophen, tramadol) ± adjuvants.
o Step 2: Weak opioids (e.g., codeine) ± non-opioids & adjuvants.
o Step 3: Strong opioids (e.g., morphine, fentanyl) ± non-opioids & adjuvants.
 Goal: Complete pain relief.
Opioid Drugs

Classification:

Opioids are categorized into:

 Mild agonists: e.g., codeine, hydrocodone bitartrate.

 Strong agonists: e.g., morphine, hydromorphone hydrochloride, oxycodone, meperidine,
fentanyl, methadone.

Meperidine Considerations

 Not recommended for long-term use due to the neurotoxic metabolite normeperidine.
 Restricted in hospitals because of risks such as:
o Neurotoxicity
o Delirium (especially in older adults)
o Serotonin syndrome

Opiate Agonist–Antagonists

 Example: Pentazocine.
 Associated with analgesic ceiling effect (higher doses do not enhance analgesia).
 Useful for patients who have not previously been exposed to opioids.
  Suitable for non-escalating, moderate to severe pain.

Administration Considerations

 IM injections are discouraged due to:

o Bruising and bleeding risks.
o Discomfort from injection.
 Preferred routes:
o IV
o Subcutaneous (e.g., via butterfly catheter)
o Oral
o Transdermal

 The synthetic pain-relieving drugs currently known as opioid analgesics originated from
the opium poppy plant. Natural opioids containing or derived from opium are known as
opiate analgesics

Chemical Structure

 Opioid analgesics: Strong pain relievers.

 Can be classified by:
o Chemical structure
o Action at specific receptors
 Three clinically useful natural alkaloids:

1. Morphine (pain reliever)

2. Codeine (pain reliever)
3. Papaverine (smooth muscle relaxant)

 Chemical classes:
o Morphine-like drugs
o Meperidine-like drugs
o Methadone-like drugs

Mechanism of Action and Drug Effects

 Agonists: Bind to opioid pain receptors in the brain → cause analgesia.

 Agonist–Antagonists (Partial Agonists): e.g., pentazocine
o Bind to opioid receptors but produce weaker pain relief.
o Affect κ (kappa) and μ (mu) receptors.
o Used for opioid-addicted patients and obstetric analgesia (less sedation risk).
 Antagonists: e.g., naloxone
o Bind to opioid receptors but do not relieve pain.
o Reverse effects of agonists and agonist–antagonists.
 Main opioid receptors:
 o μ (mu)
o κ (kappa)
o δ (delta)
o μ (mu) is the most important for analgesia.
 Equianalgesia: Process of calculating equivalent pain relief for different opioid
drugs/routes.

Indications

 Used for moderate to severe pain relief.

 Effects vary based on:
o Specific drug
o Receptor affinity
o Chemical structure
 Surgical Use:
o Fentanyl, sufentanil, alfentanil → combined with anesthetics.
o Used for pain relief and anesthesia balance.
 Postoperative Pain Management:
o Fentanyl injection → rapid onset, short duration.
o Fentanyl transdermal patches:
 For long-term pain management.
 Not for postoperative or short-term pain.
 Commonly Used Opioids:
o Morphine, meperidine, hydromorphone, oxycodone → postoperative and other
pain.
o Hydromorphone and morphine (injectable) → first-line in post-op settings.
o Meperidine → declining use due to toxicity concerns. Only immediate release
dosage forms both oral and injectable
o Oxycodone:
 Immediate-release: oral tablet, capsule, liquid (lasts ~4 hours).
 Sustained-release (OxyContin): long-acting (up to 12 hours).
 Replaced by OxyNeo to prevent abuse.
o MS Contin: sustained-release morphine (8-12 hours). The MS stands for the salt
name= morphine sulphate

Cough Suppression

 Opioids suppress the medullary cough center.

 Codeine: Most commonly used opioid for cough.
 Hydrocodone: Also used in cough suppressants, either alone or in combination
 CNS depressant effects → risk of sedation.
 Dextromethorphan (non-opioid) is an alternative to avoid sedation.

-Opioids reduce GI motility, leading to constipation from their anticholinergic effects (a side
effect that can be beneficial for diarrhea control).

Examples of opioid-containing antidiarrheals:

o Paregoric (opium/belladonna tincture)

o Diphenoxylate/atropine (Imodium)
Contraindications

Opioid analgesics are contraindicated in individuals with:

 Known drug allergy – Patients who report an allergy should be carefully assessed to
determine if it is a true allergic reaction or a pharmacological side effect.
o Codeine allergy – Many patients mistakenly identify nausea as an allergic
reaction.
o Morphine allergy – Often reported due to itching, which results from histamine
release rather than a true allergic reaction.
 Severe asthma – Due to the risk of respiratory depression and airway obstruction.

Conditions Requiring Extreme Caution

While not absolute contraindications, opioid analgesics must be used with extreme caution in
patients with:

 Respiratory insufficiency – Especially if resuscitative equipment is unavailable, as

opioids can cause respiratory depression.
 Elevated intracranial pressure (e.g., severe head trauma)
 Morbid obesity or sleep apnea
 Myasthenia gravis
 Paralytic ileus (bowel paralysis)
 Pregnancy

Adverse Effects

Opioids exert their effects on multiple organ systems, leading to various adverse effects.

Central Nervous System (CNS) Effects

 Euphoria – Opioids with high μ-receptor affinity and rapid onset of action (e.g., fentanyl,
heroin) produce intense euphoria, increasing misuse potential.
 CNS Depression – The most serious adverse effect, which may lead to respiratory
depression and ultimately death if untreated.
 Individual Variability – Patients respond differently to opioids, and some may experience
severe respiratory compromise despite cautious dosing.

Histamine Release Effects

 Itching (pruritus) – Frequently reported with morphine use due to histamine release, not
an allergic reaction.
 Rash – Can occur due to histamine-mediated vasodilation.
 Hemodynamic Changes – Histamine release leads to peripheral vasodilation, causing:
o Flushing – Common with natural opiates.
o Orthostatic Hypotension – Can increase fall risk, especially in elderly patients.
 Chemical Class Variability –
 o Natural opiates (e.g., morphine) release the most histamine.
o Synthetic opioids (e.g., meperidine) cause the least histamine release.

Respiratory System Effects

 Respiratory Depression – The leading cause of opioid overdose deaths, resulting from
suppression of the brainstem respiratory centers.
o High-Risk Patients – Those with pre-existing respiratory conditions such
as asthma, COPD, and sleep apnea are more susceptible.
o Sedation-Dependent – The degree of respiratory depression correlates with the
level of sedation.
 Prevention Strategies –
o Using short-acting opioids without active metabolites.
o Careful dose titration to balance pain relief and respiratory function.

Gastrointestinal (GI) Effects

 Nausea and Vomiting – Caused by opioid stimulation of the chemoreceptor trigger zone
(CTZ) in the CNS.
 Constipation – The most common GI side effect, resulting from:
o Decreased peristalsis.
o Increased water absorption from intestinal contents.
o More pronounced in nonambulatory (bedridden) patients.
o Often requires laxatives for management.

Genitourinary (GU) Effects

 Urinary Retention – Results from:

o Increased sphincter tone (due to sympathetic overstimulation), leading to
increased bladder outlet resistance.
o Decreased bladder sensation (due to parasympathetic inhibition).
o Management may include:
 Opioid agonist–antagonists
 Opioid antagonists
 Cholinergic agonists (e.g., bethanechol)

Immune System and Hypersensitivity Reactions

 True Anaphylaxis – Extremely rare, even with intravenous opioid administration.

 Histamine-Mediated Reactions –
o Some patients experience flushing, itching, or localized wheal formation at
injection sites.
o These are not true allergic reactions but are caused by histamine release
Toxicity and Management of Overdose

 Naloxone and Naltrexone:

o Both are opioid antagonists that bind to and occupy opioid receptors (μ, κ, and δ).
o Competitive antagonists with a strong affinity for these receptor sites.
o Reverse opioid-induced adverse effects such as respiratory depression.
o Used in the management of opioid overdose and less commonly for opioid
addiction.
 Opioid Antagonists (Reversal Drugs):
o Naloxone is the most commonly used opioid antagonist for overdose reversal.
o Naltrexone is used less frequently, often for opioid addiction treatment
 Management of Opioid Overdose

 Respiratory Depression:
o The most serious adverse effect associated with opioids.
o If mild, stimulating the patient may reverse hypoventilation.
o If unsuccessful, ventilatory assistance (bag and mask, or endotracheal intubation)
may be required.
o Naloxone administration may be necessary for severe respiratory depression.
 Administration of Naloxone:
o In the case of suspected opioid overdose, naloxone must be given, regardless of
withdrawal symptoms.
o Naloxone kits are available in most Canadian pharmacies and walk-in clinics.
o Kits come with information on overdose signs (e.g., altered mobility, speech,
consciousness, respiratory depression, constricted pupils) and how to administer
naloxone (nasal spray or injectable).
 Take-home Naloxone Kits:
o Available in Canada with guidance on overdose recognition and administration.
o Widely used by first responders (paramedics, firefighters) and the general public
to reverse overdoses.
o Used to prevent death from opioid overdose when immediate medical assistance
is unavailable.

Withdrawal Symptoms

 Withdrawal and Opioid Dependence:

o When naloxone is administered to an opioid-tolerant patient or if an opioid is
discontinued abruptly, withdrawal symptoms (abstinence syndrome) may occur.
o Withdrawal can happen in as little as two weeks of opioid therapy in opioid-naive
patients.
o Gradual dosage reduction (tapering) is preferred to minimize withdrawal severity.
 Onset and Duration of Withdrawal Symptoms:
o Short-acting opioids (e.g., codeine, hydrocodone, morphine, hydromorphone):
Withdrawal symptoms appear within 6-12 hours, peak at 24-72 hours, and subside
within 7-10 days.
o Long-acting opioids (e.g., methadone, transdermal fentanyl): Withdrawal
symptoms may not appear until 24 hours or more after discontinuation and may
be milder.

Respiratory Depression Management

 Mild Hypoventilation:
o Stimulating the patient may be enough to reverse mild hypoventilation.
 Severe Respiratory Depression:
o If respiratory depression is severe, ventilatory support (e.g., bag and mask,
endotracheal intubation) may be required.
o Naloxone may also be used to reverse severe respiratory depression.
  Careful Titration of Naloxone:
o Careful titration of naloxone to avoid over-reversal and opioid withdrawal.
o Naloxone effects typically last 1 hour; with long-acting opioids, respiratory
depression may recur, requiring additional naloxone doses.

Interactions

 Drug Interactions:
o CNS Depressants: Co-administration of opioids with alcohol, antihistamines,
barbiturates, benzodiazepines, promethazine, and other CNS depressants can lead
to additive respiratory depressant effects.
o MAO Inhibitors: Combining opioids (e.g., meperidine) with monoamine oxidase
inhibitors (e.g., selegiline) may result in severe respiratory depression, seizures,
and hypotension.

Laboratory Test Interactions

 Increased Serum Levels:

o Opioids can cause abnormal increases in the serum levels of:
 Amylase, alanine aminotransferase (ALT), alkaline phosphatase, bilirubin,
lipase, creatinine kinase, and lactate dehydrogenase.
 Decreased Urinary 17-Ketosteroid Levels:
o Opioid use can decrease urinary 17-ketosteroid levels.
 Increased Urinary Alkaloid and Glucose:
o Opioid use can increase urinary alkaloid and glucose concentrations.

Dosages

o For the recommended initial dosages of selected analgesic drugs in opioid-naive patients,
see the Dosages table on p. 181. Drug pharmacokinetics for selected drugs are provided
in the Drug Profiles box.
Drug Profiles

Opioid Agonists

Morphine Sulphate

 Naturally occurring alkaloid derived from the opium poppy.

 Drug prototype for all opioids.
 Classified as Schedule I controlled substance.
 Indicated for severe pain, high abuse potential.
 Available in oral, injectable, and rectal dosage forms.
 Extended-release forms: MS Contin, M-Eslon®, Kadian®, Avinza®.
 Potentially toxic metabolite: morphine-6-glucuronide.
 Accumulation of metabolite more likely in patients with kidney impairment.
 Other opioids, like hydromorphone and fentanyl, may be safer for patients with kidney
insufficiency.
 Hydromorphone is 5-8 times more potent than morphine. 1 mg of hydromorphone equals
7 mg of morphine (IV, IM, or subcut).
 Epidural forms can cause increased intracranial pressure and CNS depression, especially
with multiple injections or other CNS depressants. Only administer with an
anesthesiologist's order.

Codeine Sulphate/Phosphate

 Natural opiate alkaloid (Schedule I) obtained from opium.

 Similar pharmacokinetics and pharmacodynamics to morphine.
 About 10% of a codeine dose metabolized to morphine in the body.
 Less effective as an analgesic, with a ceiling effect (higher doses do not increase the
response).
 Primarily used as an antitussive in cough preparations.
 Combined with acetaminophen for mild to moderate pain and cough.
 Causes GI upset; often mistaken as an allergy by patients.
 Metabolized in the liver via the enzyme CYP2D6, converting to morphine.
 Genetic polymorphism in some individuals can prevent proper metabolism.
 Ultra-rapid metabolizers convert codeine to morphine faster, increasing opioid adverse
effects.
 Codeine use in children under 18 has been linked to morbidity and mortality, leading to
Health Canada’s recommendation against its use in pediatric patients
Fentanyl

 Synthetic opioid (Schedule I).

 Used to treat moderate to severe pain.
 High potential for misuse or abuse.
 Available as parenteral injection, transdermal patch, and sublingual tablet.
 Injectable form commonly used in perioperative and Critical Care Unit settings for
sedation during mechanical ventilation.
 Sublingual form requires drug to remain under the tongue for at least 5 minutes for
efficacy.
 Oral bioavailability is negligible, so not taken orally.
 Potent analgesic: 0.1 mg IV fentanyl is equivalent to 10 mg IV morphine.
 Transdermal patch effective for long-term control of persistent pain, especially cancer-
induced pain.
 Not for use in opioid-naive patients or for acute pain relief.
 Patch requires 6–12 hours to reach steady-state pain control; changes every 72 hours.
 Fentanyl patch safety warnings: Only for opioid-tolerant patients with persistent or
cancer pain. Deaths from respiratory arrest have occurred in non-opioid-tolerant patients.
 Patients are considered opioid tolerant – taking at least 60 mg of oral morphine daily or at
least 30 mg of oral oxycodone daily or at least 8 mg of oral hydromorphone daily or
equianalgesic dose of another opioid
 Patch risks: Do not cut or expose to heat (e.g., sauna, heating pad), as this accelerates
drug diffusion.
 Dispose of used patches properly to avoid misuse

Meperidine Hydrochloride (Demerol)

 Synthetic opioid analgesic (Schedule I).

 Must be used cautiously in older adults, patients needing long-term analgesia, or those
with kidney dysfunction.
 Poor oral bioavailability, variable IM absorption, short half-life (3–4 hours).
 Active metabolite: normeperidine, which can accumulate and cause neurotoxicity,
resistant to naloxone, making overdose dangerous.
 Due to risk of normeperidine neurotoxicity and poor risk-benefit profile, use of
meperidine has decreased, and it has been removed from stock in many agencies.
 Not recommended for long-term pain treatment, but can be used for acute pain in
postoperative settings or for acute migraine headaches.
 Available in tablet and injectable forms, but oral meperidine is being phased out from
many hospital formularies by ISMP Canada.
  Safe practices are recommended when prescribing parenteral meperidine, including using
safer alternatives for analgesia

Methadone Hydrochloride (Metadol)

 Synthetic opioid analgesic (Schedule I).

 Opioid of choice for detoxification treatment in methadone maintenance programs for
opioid addiction.
 Agonist–antagonist opioids (e.g., pentazocine) should be avoided in patients addicted to
heroin or those in methadone maintenance, as they can induce withdrawal symptoms.
 Recently, renewed interest for use in severe persistent pain (e.g., neuropathic and cancer-
related pain) requiring long-term opioid treatment.
 Methadone dosing for pain differs from dosing for opioid dependence due to opioid
tolerance.
 Readily absorbed through the GI tract, with peak plasma concentrations occurring at 4
hours for single dosing.
 Unique half-life of 24–36 hours, longer than its duration of activity, due to tissue binding
(liver, kidneys, brain).
 Accumulates in tissues with repeated doses, allowing for 24-hour dosing.
 Eliminated via the liver, making it a safer choice for patients with kidney impairment.
 Recent concerns about the prolonged half-life contributing to unintentional overdoses and
deaths.
 May cause cardiac dysrhythmias.
 Available for oral use in liquid form.
 Prior to May 2018, methadone could only be prescribed by healthcare providers with an
exemption under the Controlled Drugs and Substances Act (Canada). This regulatory
restraint was removed, and now methadone can be prescribed by authorized providers
under certain conditions: for patients under their direct care and when methadone is
required for the condition being treated

Opioid Agonist–Antagonists

 Classification: Schedule I.
 Mechanism of Action: Bind to the μ receptor, competing with other substances. Can act
as competitive antagonists (no action) or partial agonists (limited action).
  Risk Profile: Lower risk of misuse and addiction compared to full opioid agonists.
However, their antagonistic effects can induce withdrawal symptoms in opioid-dependent
patients.
 Contraindications: Not to be used in patients with hypersensitivity reactions to these
drugs.
 Therapeutic Indications:
o Used for short-term pain control, such as after obstetrical procedures.
o Can be used in patients with a history of opioid addiction to prevent
overmedication and reduce post-treatment addictive cravings.
o Combination of buprenorphine hydrochloride and naloxone (Suboxone) used for
in-office addiction treatment.
 Limitations:
o Not suitable for long-term pain management (e.g., cancer or persistent lower back
pain).
o Not to be used with full opioid agonists as they may reduce analgesic effects and
cause withdrawal symptoms in opioid-tolerant patients.
 Adverse Reactions: Similar to opioid adverse effects but with a lower incidence of
respiratory depression.
 Available Drugs:
o Buprenorphine transdermal patch (Butrans).
o Butorphanol tartrate.
o Nalbuphine (Nubain).
o Pentazocine (Talwin).
o Buprenorphine hydrochloride in combination with naloxone (Suboxone) for
enhanced opioid antagonism.
 Dosage Forms: Available in various dosage forms, including transdermal patches,
injectable, and combination formulations

Opioid Antagonists

- Opioid antagonists produce their antagonistic activity by competing with opioids for CNS
receptor sites

Naloxone Hydrochloride

 Classification: Pure opioid antagonist.

 Mechanism of Action: Works as a blocking drug to opioids, with no agonist (morphine-
like) properties. Does not produce analgesia or respiratory depression.
 Therapeutic Indications:
o Primary drug of choice for the complete or partial reversal of opioid-induced
respiratory depression.
o Used in cases of suspected acute opioid overdose.
o If naloxone does not significantly reverse the effects of suspected opioid
overdose, it suggests the condition may not be opioid-induced.
  Adverse Reactions:
o Opioid withdrawal syndrome, especially with abrupt over-reversal in opioid-
tolerant patients.
 Available Forms: Injectable and nasal spray.
 Contraindications: Known hypersensitivity to naloxone

Naltrexone Hydrochloride (ReVia)

 Classification: Opioid antagonist.

 Therapeutic Indications:
o Adjunct for maintaining an opioid-free state in former opioid addicts.
o Used in the psychosocial treatment of alcoholism.
o Reversal of postoperative opioid-induced respiratory depression.
 Adverse Reactions:
o Nausea and tachycardia, particularly from reversal of opioid effects.
 Contraindications:
o Known drug allergy.
o Hepatitis or liver dysfunction/failure.

Oxycodone Hydrochloride

 Classification: Opioid analgesic (Schedule I).

 Mechanism of Action: Structurally similar to morphine, with comparable analgesic
activity.
 Therapeutic Indications:
o Severe pain requiring long-term opioid treatment.
o Available in combination with acetaminophen (Percocet) and with aspirin (Ratio-
Oxycodone).
o Immediate-release (Oxy IR) and sustained-release (OxyNeo) formulations.
o Combination with naloxone (Targin) for dual therapeutic effect: naloxone reduces
opioid-induced constipation without affecting the analgesic effect.
 Adverse Reactions:
o Common opioid-related side effects (e.g., constipation, drowsiness).
 Contraindications:
o Opioid-tolerant patients should be monitored for signs of over-reversal when
naloxone is included.
 Hydrocodone Bitartrate (Schedule I)

 Mechanism of Action: A somewhat weaker opioid compared to oxycodone, often used

for moderate to severe pain.
 Therapeutic Indications:
o Available in tablet and syrup forms.
o Commonly combined with phenyltoloxamine (Tussinex) as a controlled-release
resin for enhanced antitussive effect
Nonopioid and Miscellaneous Analgesics

 Acetaminophen (Tylenol):
o Most widely used nonopioid analgesic.
o Over 4 billion doses sold annually in Canada, 15% of which are prescription
products.
o Available in combination with other medications (e.g., codeine, caffeine).
 NSAIDs:
o Includes aspirin, ibuprofen, naproxen, celecoxib (Celebrex), and others.
o Used for pain management, especially with inflammatory conditions like arthritis.
o Have significant anti-inflammatory effects in addition to analgesic effects.
 Miscellaneous Analgesics:
o Includes tramadol, transdermal lidocaine, and capsaicin.
o Capsaicin is a topical product that works by decreasing substance P, a pain signal.
o Available over the counter and used for muscle, joint, and nerve pain.

Mechanism of Action and Drug Effects:

 Acetaminophen:
o Similar to salicylates, blocks peripheral pain impulses by inhibiting prostaglandin
synthesis.
o Lowers body temperature by acting on the hypothalamus, causing vasodilation
and increased peripheral blood flow.
o Does not have anti-inflammatory effects (controversial) unlike NSAIDs.
o Not associated with cardiovascular effects, platelet effects, GI irritation, or acid-
base changes seen in NSAIDs.

Indications

 Mild to moderate pain and fever.

 Substitution for aspirin for patients who cannot tolerate or are contraindicated for aspirin.
 Antipyretic of choice in children and adolescents with flu to prevent Reye’s syndrome
(rare but extremely serious condition that causes swelling in the brain and liver)

Contraindications

 Known drug allergy.

 Severe liver disease.
 Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency.

Adverse Effects

 Acetaminophen is generally well-tolerated.

 Possible: Rash, nausea, vomiting.
 Less common but severe: Blood disorders (e.g., anemias), kidney issues with light-to-
moderate alcohol intake, and hepatotoxicity
Toxicity and Management of Overdose

 Acetaminophen Overdose:
o Can cause liver necrosis, the most serious acute toxic effect.
o Acute ingestion of 150 mg/kg (7-10 grams) or more may result in liver toxicity.
o Acute hepatotoxicity is usually reversible with acetylcysteine; long-term toxicity
may be permanent.
 Maximum Daily Dose:
o Standard maximum daily dose for healthy adults: 4,000 mg.
o Health Canada considering lowering maximum daily dose and adjusting
labelling/packaging for safety.
 Special Considerations:
o For patients with advanced age or liver dysfunction, a daily dose limit of 2,000
mg may be necessary.
o Caution with combination products (e.g., hydrocodone + acetaminophen) due to
potential excessive dosing.
 Management of Overdose:
o Serum acetaminophen concentration should be measured at least 4 hours after
ingestion.
o If concentration is unavailable, assume toxicity and start treatment with
acetylcysteine.
o Acetylcysteine is most effective within 10 hours of overdose.
o Dosage regimen: 140 mg/kg oral loading dose, then 70 mg/kg every 4 hours for
17 doses, often administered intravenously.
o If oral dose is vomited within 1 hour, repeat the dose.

Interactions

 Alcohol:
o Persistent heavy alcohol use increases risk of liver toxicity from acetaminophen.
o Maximum recommended daily dose for alcohol users: 2,000 mg.
o Warn patients who regularly consume alcohol not to exceed the recommended
acetaminophen doses.
 Other Drugs:
o Interactions can occur with phenytoin, barbiturates, warfarin, isoniazid, rifampin,
beta blockers, and anticholinergic drugs, among others

Drug Profiles

Acetaminophen

Acetaminophen (Tylenol) is an effective and relatively safe nonopioid analgesic used for mild to
moderate pain relief. Acetaminophen is provided in oral and rectal dosage formulations.
Acetaminophen is also a component of several prescription combination drug products, including
with oxycodone (Endocet, Percocet).
Tramadol Hydrochloride (Ultram)

 Classification: Miscellaneous analgesic with dual mechanism of action.

 Mechanism:
o Weak bond to μ (mu) opioid receptors.
o Inhibits reuptake of norepinephrine and serotonin.
 Indication: Moderate to moderately severe pain.
 Absorption: Rapidly absorbed; food does not affect absorption.
 Metabolism/Excretion: Metabolized in liver to active metabolite (O-dimethyl tramadol);
excreted via kidneys.
 Adverse Effects:
o Serious: Seizures and serotonin syndrome.
o Seizures may occur with both normal and excessive dosages, especially in
patients on tricyclic antidepressants, SSRIs, MAO inhibitors, and other drugs
lowering seizure threshold.
o Other: Drowsiness, dizziness, headache, nausea, constipation, and respiratory
depression.
 Contraindications:
o Known drug allergy (including potential cross-reactivity with opioids).
o Acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids, or
psychotropic drugs.
 Formulations: Oral dosage forms, including combination with acetaminophen
(Tramacet), extended-release (Durela, Ravilia, Zytram XL).
 Similar Drug: Tapentadol hydrochloride (Nucynta) — μ agonist and norepinephrine
reuptake inhibitor, classified as a scheduled opioid

Lidocaine, Transdermal (EMLA)

 Classification: Topical anesthetic and cardiac antidysrhythmic.

 Indication: Post-herpetic neuralgia (pain following shingles).
 Mechanism: Provides local pain relief by acting topically on skin.
 Application:
o Up to 3 patches can be applied to large painful areas.
o Patches should not be worn longer than 12 hours/day to avoid systemic toxicity
(e.g., cardiac dysrhythmias).
 Adverse Effects:
 o Minimal systemic effects; localized redness, edema, or unusual skin sensations at
the site.
o Reactions are typically mild and resolve in minutes to hours.
 Contraindications: Apply only to intact skin without blisters.
 Pharmacokinetics: Patch provides pain relief for 4 to 12 hours, with continuous dosing.
 Disposal: Used patches must be disposed of securely to prevent harm to children or pets.

Nursing Process

 Pain can be acute or persistent and affects patients across all settings and age groups.
 Pain is a complex and multifaceted issue requiring thorough assessment and
individualized intervention.
 Medical associations, healthcare organizations, and professional nursing bodies have
developed guidelines for pain assessment and management (e.g., Canadian Guideline for
Opioid Use, WHO guidelines for cancer pain, Registered Nurses Association of Ontario’s
guidelines).

Assessment:

A comprehensive and individualized assessment is essential for effective analgesia, focusing on:

 Pain Characteristics: Type, intensity, location, onset, duration, quality (e.g., stabbing,
dull ache, throbbing), and precipitating factors.
 Comfort: The level of physical and psychological ease experienced by the patient.
 Health and Medication History:
o Allergies to nonopioids, opioids, and other related substances.
o Drug-drug or drug-food interactions.
o History of alcohol or drug use, including substance abuse.
o Laboratory test results indicating liver and kidney function.
 Pain Intensity: Assess pain using pain scales such as Numeric Pain Intensity Scale (0-
10), Verbal Rating Scale, and FACES Pain Rating Scale.
 Factors Impacting Pain:
o Physical: Age, gender, pain threshold, health status, disease processes.
o Emotional, Spiritual, and Cultural: Reactions to pain, pain tolerance, fear,
anxiety, stress, societal influences, religious and cultural beliefs.
o Older Adults: Nonverbal cues and family/caregiver input may be necessary,
especially if the patient has physical or cognitive impairments.

Assessment Tools:

 Numeric Pain Intensity Scale: Patients rate pain from 0 to 10.

 Verbal Rating Scale: Descriptive words (e.g., mild, severe).
 FACES Pain Rating Scale: Uses facial expressions to help patients communicate pain
levels.
 Brief Pain Inventory: A multidimensional tool to assess pain location and impact on
function, especially for persistent pain.
 System-Focused Nursing Assessment:

 Neurological: Orientation, alertness, sensory and motor abilities, reflexes.

 Respiratory: Respiratory rate, rhythm, depth, breath sounds.
 GI: Bowel sounds, patterns, constipation, diarrhea, nausea, vomiting, abdominal
discomfort.
 GU: Urinary output, discomfort, urinary retention.
 Cardiac: Pulse rate, rhythm, blood pressure, dizziness, syncope.
 Vital Signs: Blood pressure, pulse rate, respirations, temperature, and pain level
(considered the fifth vital sign).
o Acute pain can elevate sympathetic responses (e.g., increased blood pressure,
pulse, and respiratory rate).

Considerations:

 Assessment must account for age, cognitive status, and pain-related factors (e.g., impact
on daily living, sleep patterns, depression, anxiety, quality of life).
 Ensure appropriate tools for age and cognitive status (e.g., large-print tools for older
adults).
 Pain re-assessment: Before, during, and after interventions, as well as during activity and
rest

Nonopioids

 Acetaminophen:
o Check for allergies, pregnancy, breastfeeding
o Contraindicated in severe liver disease, G6PD deficiency
o Cautious use with blood disorders, kidney, or liver toxicity
o Risk of inadvertent overdose with combination products
o Monitor for poisoning: weak pulse, dyspnea, clammy extremities
o Long-term use increases liver damage risk
o High doses cause liver dysfunction, nausea, jaundice, vomiting
o Children at high risk of liver dysfunction with overdose
 NSAIDs (Ibuprofen, Aspirin, COX-2 Inhibitors):
o Monitor kidney and liver function
o Assess for GI issues (ulcers)
o Aspirin:
 Contraindicated in children/adolescents (Reye’s syndrome)
 Can cause bleeding and ulcers
 Tramadol:
o Not recommended for those 75 years or older
 Lidocaine Transdermal:
o For postherpetic neuralgia
o Assess herpetic lesions and skin
o Keep away from children and pets
o Avoid use in young, small, or debilitated patients
 o Monitor liver function

Opioids

 General Assessment:
o Monitor vital signs due to CNS depressant effects
o Assess respiratory function: rate, rhythm, depth, breath sounds
o Check for head injury (masking intracranial pressure symptoms)
o Monitor neurological status: consciousness, sedation, sensory, motor
o Assess GI and GU function: bowel sounds, patterns, intake/output
 Concerns:
o Sphincter of Oddi spasms affecting bile flow
o Monitor kidney/liver function to prevent toxicity
 Neurological Disorders:
o Opioids may worsen or mask symptoms (Alzheimer’s, MS, stroke)
o Alternative pain management may be needed
 Age Considerations:
o Increased sensitivity in older adults and children
o Opioid use may be contraindicated based on age
Opioid Agonist–Antagonists

 Assessment:
o Monitor vital signs: focus on respiratory rate and breath sounds.
o These drugs have opioid agonist effects; similar assessment to opioids applies.
o Effective analgesics with CNS-depressant effects.
o Subject to analgesic ceiling effect.
o Monitor for potential opioid misuse; concurrent use with opioids may reverse
analgesia and induce withdrawal.
o Age Consideration: Not recommended for patients under 18 years of age.

Opioid Antagonists

- used mainly in reversing respiratory depression secondary to opioid overdosage.

o Naloxone may be used in patients of all ages, including neonates and children.
o Assess and document vital signs before, during, and after the use of the antagonist
so that the therapeutic effects can be further assessed and documented and the
need for further doses determined.
o may not work with just one dosing and that repeated doses are generally needed to
reverse the effects of the opioid

Implementation

Once the cause of pain has been diagnosed or other assessment and data
gathering have been completed, begin pain management immediately and
aggressively, according to the needs of each individual patient and situation.
 - Pain management is varied and multifaceted and needs to incorporate
pharmacological and nonpharmacological approaches .
- Negotiate with patients by integrating religious ceremonies and
traditional healing practices into pain care, rather than imposing
Western cultural approaches.
- Pain management strategies must also include consideration for the
type of pain and pain rating as well as pain quality, duration, and
precipitating factors, and interventions that help the pain

1. Individualize a plan of care based on the patient as a holistic and cultural

being
2. Manage mild pain with the use of nonopioid drugs such as acetaminophen,
tramadol hydrochloride, and NSAIDs
3. Manage moderate to severe pain with a stepped approach, using opioids.
Other analgesics or types of analgesics may be used in addition to other
categories of medication (see pharmacology discussion).
4. Administer analgesics as ordered but before the pain gets out of control.
5. Always consider the use of nonpharmacological comfort measures such as
homeopathic and folk remedies, exercise, distraction, music or pet therapy,
massage, and transcutaneous electrical stimulation. Although not always
effective, these measures may prove beneficial for some patients. See
Patient Teaching Tips for more information regarding analgesics.

Nonopioid

Give as ordered or as indicated for fever or pain

 Acetaminophen
o Give as ordered and within the recommended dosage range to avoid liver damage
and acute toxicity.
o Patients must read labels of other OTC medications containing acetaminophen to
avoid excessive intake and identify potential drug interactions.
o Educate patients on the signs of acetaminophen overdose: bleeding, loss of
energy, fever, sore throat, and easy bruising due to hepatotoxicity. These
symptoms should be reported immediately.
o Report any worsening or change in the nature or characteristic of pain.
o If given as a suppository, moisten it with cold water for easier insertion, using
water-soluble lubricating gel if needed.
o Tablets may be crushed if necessary.
o Adults taking more than 4,000 mg/day are at risk of acute hepatotoxicity. More
than 15g may be fatal.
 oLiver damage from acetaminophen can be minimized with timely acetylcysteine
dosing.
o Warn patients about acetylcysteine’s foul taste and odor (like rotten eggs). It is
better tolerated when mixed with a drink (cola or flavored water). Using a straw is
recommended to minimize contact with the mouth. It can be given via nasogastric
tube or intravenously if necessary.
 Tramadol:
o May cause drowsiness, dizziness, headache, nausea, constipation, and respiratory
depression.
o Assist with ambulation to reduce fall risk if dizziness, blurred vision, or
drowsiness occur.
o Educate the patient on injury prevention: dangle feet before full ambulation,
change positions slowly, and ask for assistance.
o Avoid tasks requiring mental clarity and alertness while on tramadol and other
analgesics, particularly opioids.
o Increase fluids and fiber to help prevent constipation.
o For nausea, offer flat cola, ginger ale, or dry crackers to alleviate symptoms

Opioids

Medication Administration

 Administer opioids after verifying the "rights" of medication administration (refer to

Chapter 1).
 Double-check the health care provider's order and confirm the last dose before
administering another dose.
 Monitor vital signs frequently, especially respiratory rate. A respiratory rate of 10
breaths/min (some protocols may use 12 breaths/min) may indicate respiratory depression
and should be reported to the health care provider.
 Adjust the drug dosage, frequency, or route if respiratory depression occurs, or
administer an antidote (opioid antagonist).
 Always have naloxone available, especially with IV or parenteral opioid dosage forms
(e.g., PCA, epidural).
 Naloxone reverses CNS depression, including respiratory depression, but also reverses
analgesia.

Monitoring Parameters

 Urinary output: should be at least 720 mL/24 hours.

 Bowel sounds: monitor for decreased peristalsis, which may require dietary changes or
the use of stool softeners.
 Pupillary reaction: pinpoint pupils may indicate overdose.
 Administer opioids before pain reaches its peak for optimal effectiveness.

Route of Administration
 Oral dosage forms are preferred unless nausea or vomiting is present.
 Taking the medication with food may reduce GI upset.
 If nausea/vomiting persists, an antiemetic may be ordered to be taken with the opioid.
 Essential safety measures: keep bedside rails up, use bed alarms, and ensure the call
bell/alarm is within reach to prevent falls and injury.

CNS Depression and Fall Risk

 Opioids cause CNS depression, leading to confusion, altered sensorium, hypotension,

altered motor function, and an increased risk of falls, especially in older adults.

Withholding and Adjusting Doses

 Withhold opioid doses and contact the healthcare provider if the patient's condition
worsens or if vital signs are abnormal, especially if the respiratory rate falls below 10
breaths/min.

Transdermal Opioid Delivery (e.g., Fentanyl)

 Transdermal patches (e.g., fentanyl) are available in two types:

o Reservoir system: Contains multiple layers with a gel/liquid drug reservoir.
Worn for 3-4 days.
o Matrix system: Slimmer, more comfortable, and worn for up to 7 days with more
constant drug levels. Free of alcohol to prevent skin irritation.
 Apply patches to clean, non-hairy areas and rotate sites to prevent irritation.
 Dispose of old patches properly.
 Monitor for potential contact dermatitis and notify healthcare provider if it occurs.
 Encourage the use of a pain journal for tracking the effectiveness of pain control at home.

Intravenous (IV) and Parenteral Opioid Administration

 Follow guidelines for dilution and infusion rates.

 Monitor equipment closely, as pumps may not be 100% reliable.
 Track PCA dosing amounts and times carefully.
 Monitor the IV needle site for complications and document any adverse effects.
 Pay attention to onset, peak, and duration of action, as each opioid has unique
characteristics. IV opioids have the most rapid onset.

Naloxone Administration

 Naloxone (opioid antagonist) reverses opioid overdose or opioid-induced respiratory

depression.
 Administer 0.4 to 2 mg IV undiluted over 15 seconds or as directed.
 In case of reconstitution, use 0.9% NaCl or 5% dextrose injection.
 Emergency resuscitative equipment should be nearby in case of respiratory or cardiac
arrest.
Opioid Agonist–Antagonists

Pharmacology and Mechanism of Action

 Agonist–Antagonist Drugs: These medications bind to opioid receptors in the brain,

producing both agonist (pain-relieving) and antagonist (blocking other opioid effects)
actions. When administered alone, they act as effective analgesics by binding with opioid
receptors.
 When Combined with Other Opioids: If given concurrently with other opioids,
agonist–antagonist drugs can block the action of the opioid, leading to the reversal of
analgesia. This may precipitate withdrawal symptoms in individuals dependent on
opioids.

Clinical Considerations

 Assessment and Monitoring: When administering agonist–antagonist drugs, close

monitoring of vital signs (especially respiratory rate) is essential. Patients should be
assessed for signs of sedation, dizziness, constipation, and urinary retention.
 Emphasize Communication with Patients: Patients should be instructed to report any
dizziness, sedation, constipation, or urinary retention. It is also important to educate the
patient that combining these drugs with other opioids could lead to withdrawal and
reduced pain relief.

Adverse Effects

 Similar to Opioid Agonists: As these drugs share adverse effects with full opioid
agonists, be vigilant for symptoms such as dizziness, sedation, and gastrointestinal issues
like constipation. Always review these with the patient.
Opioid Antagonists

- Opioid antagonists must be given as ordered and be readily available, especially when the
patient is receiving PCA with an opioid, is opioid naive, or is receiving continuous doses
of opioids. Several doses of these drugs are often required to ensure adequate opioid
agonist reversal (see earlier discussion). Encourage patients to report any nausea or
tachycardia.

General Considerations for Pain Management:

Ongoing Knowledge Base:

o It is essential to maintain an up-to-date understanding of all forms of analgesics

and pain management protocols.
o Focus should be on specific drugs, the management of mild to moderate pain,
severe pain, and pain in special circumstances, such as cancer pain.
o Regular review of the WHO’s three-step analgesic ladder is crucial for managing
cancer pain.

Pain Assessment and Early Treatment:

o Thorough pain assessment is critical in determining the most effective treatment

plan.
o Pain should be treated before it becomes severe, underlining the importance of
recognizing pain as the fifth vital sign.
o Pain lasting more than 12 hours a day requires individualized analgesic doses and
is best managed with around-the-clock dosing to maintain steady-state levels of
the medication.
o Scheduled dosing prevents drug troughs and reduces the risk of escalating pain.

Titration and Dosage:

o Pain relief is not one-size-fits-all; dosage needs to be titrated based on individual

patient needs.
o Aggressive titration may be required for difficult pain cases or cancer pain.
o For patients with severe or metastatic pain, increasingly higher doses may be
necessary, with opioids like morphine often required.
o The goal is to achieve a patient-rated pain level of less than 4 on a 1-10 scale.

Combination Therapy:

o If pain is not controlled by monotherapy, additional drugs or adjuvants may be

needed to enhance analgesic efficacy.
 NSAIDs: For analgesic and anti-inflammatory effects.
 Acetaminophen: Primarily for analgesic effects.
  Corticosteroids: Provide mood elevation, anti-inflammatory, appetite
stimulation, and antiemetic effects.
 Anticonvulsants: For neuropathic pain.
 Tricyclic Antidepressants: For neuropathic pain and opioid-potentiating
effects.
 Neuroleptics: For persistent pain syndromes.
 Local Anesthetics: For neuropathic pain.
 Hydroxyzine Hydrochloride: For mild antianxiety, sedative,
antihistamine, and antiemetic effects.
 Psychostimulants: To reduce opioid-induced sedation when opioid
dosage adjustments are ineffective.
o Refer to Table 11.11 for drugs contraindicated in cancer pain

Dosage Forms and Routes:

o Oral Administration: Preferred but may not always be viable due to patient
tolerance.
o Rectal Dosage Forms: Safe, inexpensive, and effective, especially useful in cases
of nausea or altered mental status. Not suitable for patients with diarrhea,
stomatitis, or low blood cell counts.
o Transdermal Patches: Provide extended pain control. Not for rapid titration and
should only be used once stable analgesia is achieved. Long-acting forms of
morphine or fentanyl may be delivered via transdermal patches when prolonged
pain control is needed.
o Injectable Routes: IV or subcutaneous infusions may be necessary, particularly
in hospice or cancer care settings.
o Patient-Controlled Analgesia (PCA) Pumps: Offer a patient-controlled method
for opioid delivery through IV, subcut, or intraspinal routes and may be used in
home care or hospice.
o Intrathecal or Epidural Routes: Require expertise and are available only from
specific home health care agencies for in-home care. Primarily used for
intractable pain.
o Transnasal Dosage Forms: Approved only for butorphanol tartrate, which is not
generally recommended.

Fast-Acting Rescue Drugs:

 o A fast-acting rescue drug should be ordered and readily available for patients with
cancer pain or those with special pain management needs.

Individualization of Treatment:

o Treatment plans must be tailored to the individual patient, taking into account
their unique needs and responses to treatment.
o The key to effective pain control is a personalized approach, including careful
selection of drugs and routes of administration.

Evaluation

 Positive Therapeutic Outcomes of Acetaminophen:

o Decreased symptoms, including reduced fever and pain.
o Monitor for adverse reactions:
 Anemia
 Liver problems (hepatotoxicity)
o Report patient complaints of abdominal pain or vomiting to healthcare provider.
 Monitoring Nonopioid Analgesics (e.g., Tramadol), Opioids, and Mixed Opioid
Agonists:
o Monitor frequently for both therapeutic effects and adverse effects.
o Therapeutic Effects:
 Increased comfort periods.
 Decreased pain reports.
 Improved activities of daily living, appetite, and sense of well-being.
o Adverse Effects:
 Nausea, vomiting, constipation, dizziness, headache.
 Blurred vision, decreased urinary output, drowsiness, lethargy.
 Sedation, palpitations, bradycardia, bradypnea, dyspnea, hypotension.
 When to Contact Healthcare Provider:
o If vital signs change, patient condition declines, or pain persists.
o Immediate action required for:
  Respiratory depression (e.g., rate <10 breaths/min, dyspnea, diminished
breath sounds, shallow breathing).
 Monitoring for Respiratory Depression:
o Observe for signs like a respiratory rate of less than 10 breaths per minute,
dyspnea, or shallow breathing.
 Review of Pain Management Effectiveness:
o Evaluate the effectiveness of multimodal and nonpharmacological approaches to
pain management.