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                  Naloxone

➢ Generic Name

• Naloxone

➢ Brand Name

• Bunavail, Evzio, Kloxxado, Narcan, Suboxone, Targin, Targiniq, Zubsolv

➢ Drug Classification

• CENTRAL NERVOUS SYSTEM AGENT; NARCOTIC (OPIATE) ANTAGONIST

➢ Mechanism of Action

• NARCAN (naloxone hydrochloride injection, USP), is a synthetic congener of oxymorphone. In structure it differs from oxymorphone in that the methyl group on the nitrogen atom is replaced by an allyl group. It is a competitive inhibitor of the µ-opioid receptor. Naloxone antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients.

➢Route of Administration

intravenous (IV)

intramuscular (IM)

subcutaneous (SC)

endotracheal

sublingual

intralingual

submental

nasal routes

➢Absorption

Onset: 2 min.
Duration: 45 min.
Distribution: Crosses placenta.
Metabolism: Metabolized in liver.
Elimination: Excreted in urine.
Half-Life: 60–90 min.

➢ Stock Dosage

Opiate Overdose
Adult: IV 0.4–2 mg, may be repeated q2–3min up to 10 mg if necessary
Child: IV 0.01 mg/kg, may be repeated q2–3min up to 10 mg if necessary

Postoperative Opiate Depression
Adult: IV 0.1–0.2 mg, may be repeated q2–3min for up to 3 doses if necessary
Child: IV 0.005–0.01 mg/kg, may be repeated q2–3min up to 3 doses if necessary

➢ Indication

• Intramuscular, intravenous, and subcutaneous injections are indicated for complete or partial reversal of opioid depression, diagnosis of known or suspected opioid overdose, and as an adjunct therapy in the treatment of septic shock. It reverses the effects of opiates, including respiratory depression, sedation, and hypotension.

➢ Contraindications

• NARCAN (naloxone) is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients in NARCAN (naloxone) .

➢ Side effects

Body as a Whole:
Reversal of analgesia
tremors
hyperventilation
slight drowsiness
sweating
CV:
Increased BP
tachycardia
GI:
Nausea
vomiting
Hematologic:
Elevated partial thromboplastin time

➢ Nursing interventions

Assessment & Drug Effects

Obtain baseline respiratory rate, depth, and rhythm and size of pupils before administering the drug.

Observe patient closely to be certain pain relief is achieved. Record relief of pain and duration of analgesia.

Assess for mentioned cautions and contraindications (e.g. drug allergy, respiratory dysfunction, myocardial infarction and CAD, hepatorenal dysfunction, etc.) to prevent untoward complications.

Conduct pain assessment with patient to establish baseline and evaluate effectiveness of drug therapy.

Perform thorough physical (CNS, vital signs, bowel sounds, urine output) to establish baseline status before beginning therapy, determine drug effectiveness and evaluate for any potential adverse effects.

Monitor laboratory results (liver function, kidney function) to determine need for possible dose adjustment and identify toxic drug effects.

Be alert to elevated pulse or respiratory rate, restlessness, anorexia, or drawn facial expression that may indicate need for analgesia.

Differentiate among restlessness as a sign of pain and the need for medication, restlessness associated with hypoxia, and restlessness caused by morphine-induced CNS stimulation (a paradoxic reaction that is particularly common in women and older adult patients).

Monitor for respiratory depression; it can be severe for as long as 24 h after epidural or intrathecal administration.

Have a narcotic antagonist and equipment for assisted ventilation readily available when administering this drug IV to provide patient support in case of severe reaction.

Monitor timing of analgesic doses. Prompt administration may provide a more acceptable level of analgesia and lead to a quicker resolution of the pain.

Provide non-pharmacological pain measures like breathing exercises, back rubs, and stress reduction to increase drug effectiveness and reduce pain.

Provide comfort measures (e.g. small, frequent meals for GI upset) to help patient tolerate drug effects.

Provide safety measures (e.g. adequate lighting, raised side rails, etc.) to prevent injuries.

Assess vital signs at regular intervals.

Encourage changes in position, deep breathing, and coughing (unless contraindicated) at regularly scheduled intervals.

Be alert for nausea and orthostatic hypotension (with light-headedness and dizziness) in ambulatory patients or when a supine patient assumes the head-up position or in patients not experiencing severe pain.

Monitor I&O ratio and pattern.

Observe patient closely; duration of action of some narcotics may exceed that of naloxone. Keep physician informed; repeat naloxone dose may be necessary.

May precipitate opiate withdrawal if administered to a patient who is opiate dependent.

Note: Narcotic abstinence symptoms induced by naloxone generally start to diminish 20–40 min after administration and usually disappear within 90 min.

Monitor surgical and obstetric patients closely for bleeding. Naloxone has been associated with abnormal coagulation test results. Also observe for reversal of analgesia, which may be manifested by nausea, vomiting, sweating, tachycardia.

Report any remaining signs of opioid-induced CNS depression such as euphoria, dysphoria, confusion, and hallucinations.

Be alert for any residual symptoms of respiratory depression, including decreased respiratory rate, confusion, bluish color of the skin and mucous membranes, and difficult/labored breathing. Monitor pulse oximetry and perform pulmonary function tests to document whether ventilation and respiratory function have returned to normal levels.

Assess blood pressure (BP) and compare to normal values. Report changes in BP, either a problematic decrease in BP (hypotension) or a sustained increase in BP (hypertension).

Assess heart rate, ECG, and heart sounds, especially during exercise. Report any rhythm disturbances or symptoms of arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.

Implement appropriate manual therapy techniques, physical agents, and therapeutic exercises to reduce pain and help wean patient off opioid analgesics as soon as possible.

Because of the risk of arrhythmias and abnormal BP responses, use caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (BP, heart rate, respiratory rate, fatigue levels), and terminate exercise immediately if any untoward responses occur

Monitor patient response to therapy (relief of pain, sedation).

Monitor for adverse effects (e.g. GI depression, respiratory depression, arrhythmias, etc).

Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.

Monitor patient compliance to drug therapy.

Patient & Family Education

Educate client on drug therapy to promote understanding and compliance.

Encourage the patient to report postoperative pain that emerges after administration of this drug to physician.

Instruct patient not to use of any OTC drug unless approved by physician.

Instruct patient not to smoke or ambulate without assistance after receiving drug. Bedside rails are advised.

Educate client to use caution or avoid tasks requiring alertness (e.g., driving a car) until response to drug is known since morphine may cause drowsiness, dizziness, or blurred vision.

Educate patient about the dangers of opioid overdose; encourage patient to adhere to proper dosing schedule.

Instruct patient to report other troublesome side effects such as severe or prolonged GI problems (nausea, vomiting).

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                Morphine Sulfate

➢ Generic Name

• Morphine sulfate

➢ Brand Name

• Astramorph PF, Avinza, DepoDur, Duramorph, Epimorph , Kadian, MSIR, MS Contin, Oramorph SR, Roxanol, RMS, Statex

➢ Drug Classification

• CENTRAL NERVOUS SYSTEM (CNS) AGENT; ANALGESIC; NARCOTIC (OPIATE) AGONIST

➢ Mechanism of Action

• Morphine-6-glucuronide is responsible for approximately 85% of the response observed by morphine administration. Morphine and its metabolites act as agonists of the mu and kappa opioid receptors. The mu-opioid receptor is integral to morphine's effects on the ventral segmental area of the brain. Morphine is a narcotic agonist-analgesic of opiate receptors which inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation; suppresses cough by acting centrally in medulla.

As a potent opioid, morphine has seemed to be the ideal analgesic. It has innate hemodynamic effects that are beneficial during MI. It decreases heart rate, blood pressure, and venous return, and it may also stimulate local histamine-mediated processes. Theoretically, this reduces myocardial oxygen demand.

➢Absorption

Onset: PO, 15-30 min; IV, <5 min

Duration: 4 hr (immediate-release)

Peak plasma time: PO, <60 min; PR, 20-60 min; SC, 50-90 min; IM, 30-60 min; IV, 20 min

Peak plasma concentration: PO, 20-40 ng/mL

➢Distribution

Protein bound: IV, 36%

Vd: IV, 1-4.7 L/kg

➢Metabolism

Metabolized in liver via conjugation with glucuronic acid

Metabolites: 6-Glucuronide, 3,6-diglucuronide, 3-glucuronide

➢Elimination

Half-life: 2-4 hr (immediate release); 11-13 hr (Kadian)

Excretion: Urine (2-12%), feces (7-10%)

➢ Route and Stock Dosage

PO Rect:  (Adults  ≥50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 30 mg every 3–4 hr initially  or  once 24-hr opioid requirement is determined, convert to extended-release morphine by administering total daily oral morphine dose every 24 hr (as  Kadian  or other ER capsules), 50% of the total daily oral morphine dose every 12 hr (as  Kadian, Morphabond, MS Contin ), or 33% of the total daily oral morphine dose every 8 hr (as  Morphabond, MS Contin ). Dose of ER capsules (not  Kadian ) should not exceed 1600 mg/day because of fumaric acid in formulation.

PO Rect:  (Adults and Children  <50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 0.3 mg/kg every 3–4 hr initially.

PO (Children  >1 mo): Prompt-release tablets and solution– 0.2–0.5 mg/kg every 4–6 hr as needed.  Controlled-release tablet– 0.3–0.6 mg/kg every 12 hr.

IM IV SC (Adults  ≥50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 4–10 mg every 3–4 hr.  MI– 8–15 mg, for very severe pain additional smaller doses may be given every 3–4 hr.

IM IV SC (Adults and Children  <50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 0.05–0.2 mg/kg every 3–4 hr, maximum: 15 mg/dose.

IM IV SC Neonates: 0.05 mg/kg every 4–8 hr, maximum dose: 0.1 mg/kg. Use preservative-free formulation.

IV SC (Adults): Continuous infusion– 0.8–10 mg/hr; may be preceded by a bolus of 15 mg (infusion rates vary greatly; up to 80 mg/hr have been used).

IV SC (Children  >1 mo): Continuous infusion, postoperative pain– 0.01–0.04 mg/kg/hr.

IV Neonates: Continuous infusion– 0.01–0.03 mg/kg/hr.

Epidural:  (Adults): Intermittent injection– 5 mg/day (initially); if relief is not obtained at 60 min, 1–2 mg increments may be made (total dose not to exceed 10 mg/day).  Continuous infusion– 2–4 mg/24 hr; may ↑ by 1–2 mg/day (up to 30 mg/day).

Epidural:  (Children >1 mo): 0.03–0.05 mg/kg, maximum dose: 0.1 mg/kg or 5 mg/24 hr. Use preservative-free formulation.

➢ Interaction
Drug-Drug

Use with  extreme caution  in patients receiving  MAO inhibitors  within 14 days prior (may result in unpredictable, severe reactions–↓ initial dose of morphine to 25% of usual dose).

Use with  benzodiazepines  or other  CNS depressants  including other  opioids,  nonbenzodiazepine sedative/hypnotics,  anxiolytics,  general anesthetics,  muscle relaxants,  antipsychotics, and  alcohol  may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.

Drugs that affect serotonergic neurotransmitter systems, including  tricyclic antidepressants,  SSRIs,  SNRIs,  MAO inhibitors,  TCAs,  tramadol,  trazodone,  mirtazapine,  5–HT3  receptor antagonists,  linezolid,  methylene blue, and  triptans  ↑ risk of serotonin syndrome.

Mixed agonist/antagonist analgesics, including  nalbuphine  or  butorphanol  and  partial agonist analgesics, including  buprenorphine , may ↓ morphine's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients. May ↑ the anticoagulant effect of  warfarin.

Cimetidine  ↓ metabolism and may ↑ effects.

IV morphine may ↓ levels and antiplatelet effects of  clopidogrel,  prasugrel, and  ticagrelor ; consider IV antiplatelet agent as alternative in patients with acute coronary syndrome if morphine concomitantly used.

➢ Indication

• Symptomatic relief of severe acute and chronic pain after nonnarcotic analgesics have failed and as preanesthetic medication; also used to relieve dyspnea of acute left ventricular failure and pulmonary edema and pain of MI.

➢ Contraindications

Hypersensitivity;

Some products contain tartrazine, bisulfites, or alcohol and should be avoided in patients with known hypersensitivity;

Acute, mild, intermittent, or postoperative pain (extended/sustained-release);

Significant respiratory depression (extended-release);

Acute or severe bronchial asthma (extended-release);

Paralytic ileus (extended-release).

Use Cautiously in:

Head trauma;

↑ intracranial pressure;

Severe renal, hepatic, or pulmonary disease;

Hypothyroidism;

Seizure disorder;

Adrenal insufficiency;

History of substance abuse;

Undiagnosed abdominal pain;

Prostatic hyperplasia;

Patients undergoing procedures that rapidly ↓ pain (cordotomy, radiation); long-acting agents should be discontinued 24 hr before and replaced with short-acting agents;

Geri:  Geriatric or debilitated patients (↑ risk of respiratory depression; dose ↓ suggested);

OB:  Lactation: Avoid chronic use; has been used during labor but may cause respiratory depression in the newborn; prolonged use of extended-release morphine during pregnancy can result in neonatal opioid withdrawal syndrome;

Pedi:  Neonates and infants <3 mo (more susceptible to respiratory depression);

Pedi:  Neonates (oral solution contains sodium benzoate which can cause potentially fatal gasping syndrome).

➢ Side effects

constipation,

nausea,

vomiting,

stomach pain,

diarrhea,

loss of appetite,

weight loss,

headache,

dizziness,

spinning sensation,

anxiety,

flushing (warmth, redness, or tingly feeling),

memory problems, or

sleep problems (insomnia or strange dreams).

Other adverse reactions include the following

CNS: Euphoria, insomnia, disorientation, visual disturbances, dysphoria, paradoxic CNS stimulation (restlessness, tremor, delirium, insomnia), convulsions (infants and children); decreased cough reflex, drowsiness, dizziness, deep sleep, coma, continuous intrathecal infusion may cause granulomas leading to paralysis.
CV: Bradycardia, palpitations, syncope; flushing of face, neck, and upper thorax; orthostatic hypotension, cardiac arrest.
GI: Constipation, anorexia, dry mouth, biliary colic, nausea, vomiting, elevated transaminase levels.
Urogenital: Urinary retention or urgency, dysuria, oliguria, reduced libido or potency (prolonged use).
Other: Prolonged labor and respiratory depression of newborn.
Hematologic: Precipitation of porphyria.
Respiratory: Severe respiratory depression (as low as 2–4/min) or arrest; pulmonary edema.

➢ Nursing interventions

Assessment & Drug Effects

Assess type, location, and intensity of pain prior to and 1 hr following PO, subcut, IM, and 20 min (peak) following IV administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% reduction in the patient's pain rating on a numerical or visual analogue scale or the patient reports satisfactory pain relief. When titrating doses of short-acting morphine, a repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal.

Patients on a continuous infusion should have additional bolus doses provided every 15–30 min, as needed, for breakthrough pain. The bolus dose is usually set to the amount of drug infused each hr by continuous infusion.

Patients taking extended-release morphine may require additional short-acting opioid doses for breakthrough pain. Doses of short-acting opioids should be equivalent to 10–20% of 24 hr total and given every 2 hr as needed.

High Alert: Assess level of consciousness, BP, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Subsequent doses may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use. Geri:  Assess geriatric patients frequently; older adults are more sensitive to the effects of opioid analgesics and may experience side effects and respiratory complications more frequently. Pedi:  Assess pediatric patient frequently; children are more sensitive to the effects of opioid analgesics and may experience respiratory complications, excitability, and restlessness more frequently.

Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Patients who receive morphine for pain rarely develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.

Assess bowel function routinely. Institute prevention of constipation with increased intake of fluids and bulk and with laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid-induced constipation.

Assess risk for opioid addiction, abuse, or misuse prior to administration. Abuse or misuse of extended-release preparations by crushing, chewing, snorting, or injecting dissolved product will result in uncontrolled delivery of morphine and can result in overdose and death.

Monitor blood pressure prior to administration.  Hold if systolic BP < 100 mm Hg or 30 mm Hg below baseline.

Monitor patient's respiratory rate prior to administration.

Reassess pain after administration of morphine.

Monitor for respiratory depression and hypotension frequently up to 24 hours after administration of morphine.

Place call light signal close to patient.  Accompany patient if need to get out of bed to minimize risk of falls.

Drug interactions:  CNS depression potentiated with other narcotics, alcohol, barbiturates, & benzodiazepines.

Drug interactions:  Anticholinergic effects potentiated with antihistamines, tricyclic antidepressants, and atropine–these can worsen constipation and urinary retention.

Drug interactions:  Hypotension can result if combined with anti-hypertensive drugs or vasodilators.

Treatment for overdose includes ventilatory support (manual ventilation with a bag-valve-mask resuscitator) and administration of an opiate antagonist (e.g., naloxone).

Tolerance, a condition requiring larger doses to achieve the same therapeutic effect, can result from prolonged use.

Physical dependence, resulting from prolonged use, may create the risk of withdrawal symptoms if drug is completely discontinued.

Avoid alcohol and other CNS depressants while under the influence of morphine.

Avoid tasks requiring alertness like driving and operating heavy machinery while under the influence of morphine.

Obtain baseline respiratory rate, depth, and rhythm and size of pupils before administering the drug. Respirations of 12/min or below and miosis are signs of toxicity. Withhold drug and report to physician.

Observe patient closely to be certain pain relief is achieved. Record relief of pain and duration of analgesia.

Be alert to elevated pulse or respiratory rate, restlessness, anorexia, or drawn facial expression that may indicate need for analgesia.

Differentiate among restlessness as a sign of pain and the need for medication, restlessness associated with hypoxia, and restlessness caused by morphine-induced CNS stimulation (a paradoxic reaction that is particularly common in women and older adult patients).

Monitor for respiratory depression; it can be severe for as long as 24 h after epidural or intrathecal administration.

Continue monitoring for respiratory depression for at least 24 h after administering of drug

Assess vital signs at regular intervals. Morphine-induced respiratory depression may occur even with small doses, and it increases progressively with higher doses (generally max: 90 min after SC, 30 min after IM, and 7 min after IV).

Encourage changes in position, deep breathing, and coughing (unless contraindicated) at regularly scheduled intervals. Narcotic analgesics also depress cough and sigh reflexes and thus may induce atelectasis, especially in postoperative patients.

Be alert for nausea and orthostatic hypotension (with light-headedness and dizziness) in ambulatory patients or when a supine patient assumes the head-up position or in patients not experiencing severe pain.

Monitor I&O ratio and pattern. Report oliguria or urinary retention. Morphine may dull perception of bladder stimuli; therefore, encourage the patient to void at least q4h. Palpate lower abdomen to detect bladder distention.

Patient & Family Education

Explain therapeutic value of medication prior to administration to enhance the analgesic effect.Avoid alcohol and other CNS depressants while receiving morphine.

Instruct patient how and when to ask for pain medication. Do not stop taking without discussing with health care professional; may cause withdrawal symptoms if discontinued abruptly after prolonged use. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx.

Instruct patient that it may cause drowsiness or dizziness. Caution patient to call for assistance when ambulating or smoking and to avoid driving or other activities requiring alertness until response to medication is known.

Advise patient that morphine is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.

Advise patient to change positions slowly to minimize orthostatic hypotension.

Caution patient to avoid concurrent use of alcohol or other CNS depressants with this medication.

Encourage patients who are immobilized or on prolonged bedrest to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.

Do not use of any OTC drug unless approved by physician.

Do not smoke or ambulate without assistance after receiving drug. Bedside rails are advised.

Use caution or avoid tasks requiring alertness (e.g., driving a car) until response to drug is known since morphine may cause drowsiness, dizziness, or blurred vision.

Limitations of use

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain

Not indicated for acute pain or as a PRN analgesic