[ALL] Lecture #2

Why does GI upset occur w/ COX inhibitor medications?

COX inhibitors are drugs that block the enzyme cyclooxygenase (COX), which is involved in producing prostaglandins. Prostaglandins help regulate inflammation, pain, and protect the stomach lining.

Ibuprofen (Advil, Motrin)

(PO & IV) (NSAID) (Reversible Non-Selective Cyclooxygenase Inhibitor-Propionic Acid Derivative)

MOA: Inhibition of

• COX-1 (Does not lead to protection against thrombotic events)

• COX-2 (leads to reduction in inflammation, pain, and fever.)

Indications:

• Rheumatoid arthritis (RA), osteoarthritis (OA), fever, dysmenorrhea, bursitis, and tendonitis.

Ibuprofen (Advil, Motrin) Adverse Effects

• GI related effects, including abdominal pain, N/V/D, ulcers leading to bleeding, and constipation.

• Renal impairment (because prostaglandins are needed for proper renal function)

• Increased risk for thrombotic events (stroke and MI)

• Very rarely, SJS

Ibuprofen (Advil, Motrin) Nursing Considerations

• Take w/ food, milk, or antacid. (due to GI upset)

• Patient education on bleeding and concurrent used w/ other blood thinners.

• Education on using the lowest possible effective dose for the shortest amount of time.

• No protection against myocardial infarction (MI) and stroke. (not as much compared to when taking aspirin—potency)

• Caution w/ renal impairment, monitor renal function. (Crt & BUN)

Keotrolac (Toradol)

(PO & IV) (NSAID-Reversible Non-Selective Cyclooxygenase Inhibitor)

MOA: Inhibition of

• COX-1 (Does not lead to protection against thrombotic events)

• COX-2 (leads to reduction in inflammation, pain, and fever.)

Indications:

Acute moderate to severe pain—a little bit stronger

• Postop patients

• Arthritis

• Chest tubes/fractures

Pain relief similar to morphine (opioid)—it’s that potent

Keotrolac (Toradol) Adverse Affects

-Similar to ibuprofen-

• GI related effects, including abdominal pain, N/V/D, ulcers leading to bleeding, and constipation.

• Renal impairment (because prostaglandins are needed for proper renal function)

• Increased risk for thrombotic events (stroke and MI)

• Very rarely, SJS

Keotrolac (Toradol) Nursing Considerations

• Alternative for severe pain management in patient unable to take opioids.

• Medication is only used up to five days total regardless of route used.

• No protection against MI and stroke. (so not really used in those cases)

• Caution w/ renal impairment, monitor renal function.

Celecoxib (Celebrex)

(PO) (Second Generation Selective Cyclooxygenase Inhibitor)

MOA: Inhibition of COX-2 (only) leading to reduction in inflammation and pain.

Indications:

• Osteoarthritis (OA), Rheumatoid Arthritis (RA), ankylosing spondylitis, juvenile idiopathic arthritis, acute pain, and dysmenorrhea.

**Reason some pts would get a med like this is that they have chronic pain and you're concerned about them getting an ulcer, so you give this med to get some additional stomach protection.

Celecoxib (Celebrex) Adverse Effects

• Common issues—dyspepsia and abdominal pain

• Increased risk for MI, cerebrovascular accident (CVA),and other cardiovascular (CV) related events from unimpeded platelet aggregation and increased vasoconstriction.

• Possible cross allergy w/ sulfa medications. (molecuule of the med has a sulfa componenet, so anyone allegric to sulfa should not take this med!)

• Renal impairment, although decreased risk w/ 2nd generation

Celecoxib (Celebrex) Nursing Considerations

• Decreased risk for GI related effects due to selectivity to COX-2 at therapeutic doses, but GI effects can still occur.

• No CV protection against MI and CVA; monitor and educate patient on signs/symptoms (s/s).

• Caution w/ renal impairment, monitor renal function.

Acetaminophen (Tylenol/Ofirmev)

(PO & IV) (CNS COX Inhibitor)

MOA: Reduces prostaglandin synthesis in the central nervous system (CNS).

Indications: Reduces fever and pain (no swelling)

Acetaminophen (Tylenol/Ofirmev) Adverse Effects

• Extremely rare at therapeutic doses, including anaphylaxis, SJS, & TEN (toxic epidermal necrolysis)—(very safe)

• Possible increased blood pressure w/ daily use.

• **Hepatotoxicity w/ excessive dosage and/or regular alcohol consumption (3 or more drinks)

Acetaminophen (Tylenol/Ofirmev) Nursing Considerations

• Assess alcohol consumption during patient interview. (for potential liver issues—hepatotoxicity)

• Educate on RUQ signs and symptoms, sources of acetaminophen, and safe 24-hour dosing.

(max 3,000 mg for those—who drink alcohol, are undernourished or have liver disease; max 4000- mg for those low-risk liver failure)

• Acetaminophen overdosing used in suicide attempts.

• Treat acetaminophen overdose w/ acetylcysteine (Acetadote) ASAP to prevent severe liver injury! (Drink it!)

What is the antidote for acetaminophen overdose?

Acetylcysteine (Acetadote)—(Drink it!)

Sulfasalazine (Azulfidine)

(PO) (Non-biologic (conventional) DMARD)

MOA: Uses 5-aminosalicylic acid to modulate local chemical mediators of inflammatory response, including leukotrienes.

Indications:

• Mono- or combination therapy for rheumatoid arthritis; Inflammatory bowel disease

Sulfasalazine (Azulfidine) Adverse Effects

• Most common-GI-related (N/V/D, anorexia, and abdominal pain)

• Also, dermatologic- pruritus, rash and urticaria; Rare SJS/TENS (sulfa-related)

• Most serious but rare- hepatitis and bone marrow suppression.

Sulfasalazine (Azulfidine) Nursing Considerations

• Recommend enteric formulation and divide daily dose, preferably after meals to minimize GI effects. (dissolves in the intestines!!)

• Periodic monitoring for hepatitis and bone marrow function every three months, or as clinically indicated. (LFT & CBC)

• Thoroughly assess for sulfa allergy and educate on serious dermatologic manifestations.

Etanercept (Enbrel)

(SQ) (Biologic DMARD—Tumor Necrosis Factor (TNF) Antagonist)

MOA: Inhibits inflammation through neutralization of TNF by preventing TNF interacting w/ natural receptors in synovium.

Indications:

• Moderate to severely active RA

• Off label use: W/ psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, juvenile arthritis

**Biologic meaning that it was specifically made for RA

Etanercept (Enbrel) Adverse Effects

• Mild AE at injection site (erythema, itching, swelling, pain)

• Opportunistic & serious infections (bacterial sepsis, invasive fungal infections, hepatitis B infection, and tuberculosis, w. risk increased in combination treatment)

• SJS & TENS

• Heart Failure

• Lymphoma and other malignancies

• Hematologic disorders

• Liver injury

• CNS demyelination

Etanercept (Enbrel) Nursing Considerations

• Screen for pre-existing conditions and infections—PPD. (e.g., TB will become active b/c this is an immunosuppressant!)

• Numerous drug interaction, particularly live vaccines (cannot take because the vaccine will give them the disease!)

• Monitor and educate on periodic monitoring and AE.

• Proper storage of auto-injectors, prefilled pens, and prefilled syringes in refrigerator and at room temperature when administering.

Rituximab (Rituxan)—from pain lecture

(IV) (Biologic DMARD—B-lymphocyte-Depleting Agent)

MOA: Monoclonal antibody that targets CD20 proteins to deplete positive B cells via cell lysis and apoptosis

Indications:

• Moderate to severely active RA

**Biologic meaning that it was specifically made for RA

Rituximab (Rituxan) Adverse Effects—from pain lecture

• Flu-like syndrome, especially during infusion.

• Infusion hypersensitivity reactions

—>Hypotension, hypoxia, MI, cardiogenic shock, bronchospasm

• Mucocutaneous reactions (SJS and TENS)

• Hepatitis B virus (HBV) reactivation

Rituximab (Rituxan) Nursing Considerations—from pain lecture

• Premedicate w/ IV glucocorticoid, antihistamine and acetaminophen.

• Treat severe reactions w/ glucocorticoids, epinephrine, and oxygen.

• Screen for HBV infection s/s.

• Monitor closely during infusion—start 50mg/hr; if inadequate response, titrate up to 400 mg/hr.

Abatacept (Orencia)

(IV & SQ) (Biologic DMARD—T-Cell Activation Inhibitor)

MOA: Selectively binds w/ receptors on antigen-presenting cells to prevent T cell activation to:

• Reduce T-cell proliferation

• Reduce production of interferon gamma, interleukins, and TNF.

Abatacept (Orencia) Adverse Effects

• Generally well-tolerated

• Most common—HA, URI, nasopharyngitis, and nausea

• Infusion reaction, including flushing, hypotension, and dyspnea.

• Increased risk for serious infections (PNA, cellulitis, bronchitis, diverticulitis, pyelonephritis, and UTI)

Abatacept (Orencia) Nursing Considerations

• Do not use live virus vaccine during treatment and for 3 months after stopping.

• Treatments may be periodic infusions, infusions transitioned to SQ therapy, or weekly SQ therapy only.

What is the first line for an acute gout attack?

NSAIDs—Indomethacin

Colchicine (Colcrys)

(PO) (Anti-inflammatory)

MOA: Inhibits leukocyte infiltration by disrupting microtubules required for cellular motility and cell division.

(sooo…bascially it stops white blood cells from causing inflammation, easing pain and swelling.)

Indications:

• Acute gouty attack

• Prophylaxis of future gout attacks

Colchicine (Colcrys) Adverse Effects

• Most characteristic—nausea, vomiting, **diarrhea and abdominal pain

• Myelosuppression

• Myopathy and rhabdomyolysis

Colchicine (Colcrys) Nursing Considerations

• Assess cardiac, renal hepatic, & GI function in older adult and debilitating patients.

• Monitor for new onset muscle pain and creatinine kinase levels, especially if on concurrent statin therapy for hyperlipidemia.

• Patient education to differentiate regimen for acute flares vs prophylaxis.

Allopurinol (Zyloprim)

(PO) (Xanthine Oxidase Inhibitor)

MOA: Inhibits xanthine oxidase enzyme to decrease uric acid production.

Indications:

• Chronic management of gout

• Nephrolithiasis

• Prevention of tumor lysis syndrome (TLS)

Allopurinol (Zyloprim) Adverse Effects

• Generally, well tolerated

• Mild GI reactions such as N/V/D and discomfort

• Neurologic effects, including drowsiness, headache, metallic taste,].

• Prolonged use—Cataracts

• Rare hypersensitivity syndrome

Allopurinol (Zyloprim) Nursing Considerations

• Monitor vision (due to cataracts) and educate patient on periodic examinations.

• Educate on place in therapy (attack vs. prevention)

• Increase fluid intake and avoid food triggers.

**Rx of gout flare up in the first 6 months of usage!

Probenecid

(PO) (Uricosuric)

MOA: Acts on renal tubules to inhibit reabsorption of uric acid—helps increase excretion of uric acid by the kidneys and reduce hyperuricemia.

Indications:

• Chronic management of gout

• Pharmacokinetic enhancer to prolong beta-lactam serum levels of cefoxitin or penicillin in gonococcal and neurosyphilis infections.

• Off label: cidofovir infusion nephrotoxicity prevention

Probenecid Adverse Effects

• Generally, well tolerated

• Mild GI effects, N/V and anorexia

• Possible renal injury from urate deposition

Probenecid Nursing Considerations

• Increase fluid intake to reduce risk of renal injury; monitor intake/output (I&Os).—to flush out the crystals!

• Educate on place in therapy (attack vs prevention); may exacerbate acute attacks.

• Periodic monitoring of renal function.

• Administer w/ food to minimize GI effects.

Pegloticase (Krystexxa)

(IV) (Recombinant Uric Acid Oxidase)

MOA: Converts uric acid to allantoin, which is water soluble and readily excreted by kidneys.

Indications:

• Indicated if patient not responsive to PO urate lower therapies.

**Last ditch effort!

Pegloticase (Krystexxa) Adverse Effects

• May experience gout flare initially.

• Anaphylaxis and infusion reactions can occur within 2 hours after infusion.

• Infusion reaction—urticaria, dyspnea, chest discomfort, erythema, and pruritus.

Pegloticase (Krystexxa) Nursing Considerations

• Premeditate w/ antihistamine, acetaminophen, and IV glucocorticoid, and monitor closely.

• Slow infusion rate to reduce symptom intensity of infusion reactions.

• Costly—$32,766.24 per dose. (Yikes!)

*May also cause a gout flare up intially

Migraine HA

• Typically, temporal

• W/ or w/o aura

• Photophobia (sensitivity to light) and visual changes may occur as well

• Throbbing sensation, inflammation, and vasodilation due to CGRP (calcitonin gene-related peptide) and 5-HT (5-hydroxytryptamine [serotonin]).

Tension HA

(most common)

• “Band-like”—tightness around forehead

• Daily stress = common risk factor for onset

Tension HA Management (Abortive)

• Acetaminophen

• NSAID

Tension HA Management (Prophylaxis)

• Amitriptyline (Elavil)

Cluster HA

• Around orbital-temporal area (one sided)

• Series of attacks

• May last 15 minutes to 2 hours

• No aura

• Felt ipsilateral ptosis (same side), congestion, rhinorrhea, and miosis

Cluster HA Management (Abortive)

• Sumtriptan (Imitrex)

• Oxygen 6-12 L at 100% FiO2 for 15-20 minutes

Sumatriptan (Imitrex)

(Enteral & Parenteral) (Serotonin Receptor Agonist)

MOA: Binds to receptors on intracranial blood vessels and causes vasoconstriction and diminishes perivascular inflammation. (This reduces swelling and pain signals, helping relieve migraines!)

(It affects all the blood vessels in the body, so pts w/ CAD or HTN are contraindicated!)

Indications:

• Acute treatment for moderate to severe migraine.

• Acute treatment for cluster headache.

• Off label use: Abortive therapy of cyclic vomiting syndrome.

(first-line)

Sumatriptan (Imitrex) Adverse Effects

• Well-tolerated but side effects are transient and mild.

—> Chest symptoms—Heavy arms and chest pressure

• Coronary vasospasm in patient w/ CV history (CAD, uncontrolled HTN, angina)

• Teratogenic

Sumatriptan (Imitrex) Nursing Considerations

• Educate on proper administration for migraine treatment.

• Educate patient to avoid triggers and recognize symptoms of aura that occur prior to onset.

• Avoid in patient w/ significant CV history.

• Educate on contraception due to risk of fetal harm.

Ergotamine (Ergomar)

(PO, Rectal & SL) (Alkaloids)

MOA: Selectively binds and activates serotonin receptors located on intracranial blood vessels, resulting in vasoconstriction and reducing the blood flow in cerebral arteries.

Indications:

• Second-line for migraine attacks in patient who have not responded to triptan.

Ergotamine (Ergomar) Adverse Effects

• Well-tolerated at therapeutic levels

• Can worsen N/V

• Risk of dependence

• Overdose resulting in ergotism (toxicity)

—> Effects includes muscle pain, paresthesia in fingers and toes, and extremities cold and pale.

• Contraindicated for those w/ hepatic or renal impairment, sepsis, CAD, peripheral vascular disease (PVD), uncontrolled HTN.

• Can cause fetal harm.

Ergotamine (Ergomar) Nursing Considerations

• Education for short vs. long term use.

• Ensure adherence to dosage and duration.

• Provide education on signs of overdose and instruct to seek immediate attention.

• Monitor for liver of kidney injury, CV history, and sepsis.

What is muscle spasticity?

It is like a charley horse that never ends (a contraction). Symptoms include: stiff rigid muscles, involuntary contractions or muscle spasms, and overactive reflexes.

Usually will see this in SCIs or Multiple Sclerosis

**Might see in stroke pts…

Baclofen (Lioresal)

(PO) (Centrally-Acting Muscle Relaxer for Spasticity)

MOA: Acts within spinal cord to suppress hyperactive reflexes involved in regulation of muscle movement; may mimic GABA on spinal neurons.

Indications:

• Multiple Sclerosis

• Spinal Cord Injury

Baclofen (Lioresal) Adverse Effects

• CNS depressant-like effects in initial treatment

—>Drowsy, dizzy, weakness, fatigue

• Constipation

• Urinary retention

• Withdrawal from abrupt cessation (so, Taper-off slowly!)

—>Visual hallucinations, paranoid ideations, seizures

Baclofen (Lioresal) Nursing Considerations

• Pre- and post- administration s/s assessment.

• Education of proper use and w/ non-pharmacological treatments.

• Additive CNS depression w/ other similar agents, including alcohol, opioids, or benzodiazepines. (more CNS depression)

• Worsening of pre-existing urinary retention and psychiatry conditions.

Cyclobenzaprine (Flexeril)

(PO) (Centrally-Acting Skeletal Muscle for Muscle Spasm)

MOA: Acts primarily within brainstem to reduce tonic somatic motor activity.

Indications:

• Localized muscle spasms, such as musculoskeletal injury

Cyclobenzaprine (Flexeril) Adverse Effects

• CNS depressant-like effects in initial treatment.

• Anticholinergic effects:

—> Urinary retention, constipation, blurred vision, dry mouth, photophobia.

• Dysrhythmias, including ST segment and conduction delay.

Cyclobenzaprine (Flexeril) Nursing Considerations

• Pre- and post- administration s/s assessment.

• Education on proper use and w/ non-pharmacological treatments, including physical therapy and heat therapy.

• Additive CNS depression w/ other similar agents, including alcohol, opioids, or benzodiazepines

• Education on non-pharmacological methods w/ managing anticholinergic effects, particularly in long-term use.

*Have pt take their first dose in the evening when b/c it might cause drowsiness.

Opioid analgesics primarily act on ______ receptors, some _______, not ________.

mu; kappa; delta

For opioid administration, you will always perform a…

pre- and post- administration assessment

T/F: Opioid administration is more effective if given around the clock (ATC) vs as needed (PRN) for the first 24 hours post-op.

True

Morphine

(PO & Parenteral) (Pure Agonist Opioid Analgesic (The Prototype))

MOA: Acts primarily on mu receptors to mimic endogenous opioid peptide actions.

Indications:

• Acute and chronic pain relief (moderate to severe pain)

• Myocardial Infarction (MI)

• Pre-op sedation

• Anxiety

Morphine & Fentanyl (Duragesic) Adverse Effects

• Respiratory depression and cough suppression

• Constipation, emesis, and urinary retention

• Sedation

• Orthostatic hypotension and increased intracranial pressure (ICP) secondary to autoregulatory cerebrovascular dilation.

• Physical dependence, euphoria, and potential for abuse

Morphine Nursing Consideration

• Tolerance, monitor possible physical dependence and abuse.

• Assess and reassess pain, respiratory status, and GI function.

• Manage constipation w/ increased fluid and fiber intake.

• Monitor use w/ other CNS depressants, anticholinergics, antihypertensives, etc.

• Provide ventilatory support and administer antagonist (naloxone) for toxicity.

What medication is used for opioid toxicity?

Narcan (Naloxone)

Fentanyl (Duragesic)

(IM, IV, Transdermal, & Nasal Spray) (Pure Agonist Opioid Analgesic)

MOA: High potency; acts primarily on mu receptors to mimic endogenous opioid peptide actions.

Indications:

• Acute and chronic pain relief

• Surgical analgesia

• Off label: uses of rapid sequence intubation & ICU sedation

Fentanyl (Duragesic) Nursing Considerations

• Transmucosal for breakthrough pain in patient w/ cancer & opioid tolerance only; monitor possible physical dependence and abuse; proper administration for transdermal patch.

• Assess & reassess pain, respiratory status, and GI function

• Most effective if administered ATC vs PRN

• Monitor use w/ other central nervous system (CNS) depressants, anticholinergics, antihypertensives, etc.

• Administer antagonists for toxicity (narcan).

Codeine

(PO tablet or Solution) (Moderate to Strong Opioid Agonist)

MOA: Acts primarily on mu receptors to mimic endogenous opioid peptide actions.

Indications:

• Mild to moderate pain

• Short-term symptomatic relief of cough

Codeine Adverse Effects

• Similar to morphine, but slightly lesser degree.

• Excessive sleepiness, breathing difficulty, lethargy, and poor feeding in infants from nursing mothers on codeine.

Codeine Nursing Considerations

• Same consideration as other opioids.

• Other formulations include those combined w/ other medications, including promethazine, guaifenesin, acetaminophen, or aspirin.

• Assess the patient’s benefits versus risks due to risk of abuse, misuse, and opioid addiction, leading to overdose and death.

Tramadol (Ultram)

(PO) (Opioid/Non-Opioid)

MOA: Pain relief is achieved through weak mu agonist activity and block of norepinephrine and serotonin reuptake for the treatment of moderate to severe pain.

Tramadol (Ultram) Adverse Effects

• Due to weak mu activity, risk for respiratory depression is low and rare.

• Common AE include sedation, dizziness, HA, dry mouth, and constipation.

• Serotonin syndrome if co-administered w/ agents that enhance serotonergic transmission.

Tramadol (Ultram) Nursing Considerations

• Abuse potential lower than pure opioid agents (Schedule IV, per DEA)

• Utilized in suicide attempts in combination w/ other CNS depressants (e.g. benzodiazepines, ETOH, etc.)

• Closely monitor and educate patient on use w/ SSRI, SNRI. Tricyclic, MAOI, and triptan medications. (These all increase serotonin!)

• Formulation also include combination w/ acetaminophen.

Methadone (Dolophine)

(PO, IM, & IV) (Long-Acting Pure Agonist)

MOA: Acts primarily on mu receptors to mimic endogenous opioid peptide actions.

Indications:

• Pain relief

• Maintenance treatment of opioid use disorder

• Short-term supervision of opioid withdrawal

Typical Opioid Withdrawal Symptoms

• Cold Shakes

• Chills and Sweating

• Fever-like symptoms

• Mood Swings

• Anxiety and Depression

• Bone Pain

• Vomiting

• Insomina

• Diarrhea

Methadone (Dolophine)

(PO, IM, & IV) (Long-Acting Pure Agonist)

MOA: Acts primarily on mu receptors to mimic endogenous opioid peptide actions.

Indications:

• Pain relief

• Maintenance treatment of opioid use disorder

• Short-term supervision of opioid withdrawal

Methadone (Dolophine) Adverse Effects

• Similar to morphine and fentanyl

• Prolonged QT interval and fatal dysrhythmias, including Torsades de pointes associated w/ higher doses. (The only difference!)

Methadone (Dolophine) Nursing Considerations

• Same considerations as morphine & fentanyl.

• Establish baseline ECG and monitor heart rhythm on telemetry as well as s/s indicative of heart rhythm change.

• Thorough history and assessment of opioid abuse prior to use for addiction to ensure proper methadone substitution dosing.

Buprenorphine/Naloxone (Suboxone)

(Buccal film, Injection, FL, flim, PO, Subdermal implant, and Transdermal Patch) (Agonist-Antagonist Opioid Analgesic)

MOA: Both agonist and antagonist action are mu receptors and antagonist action at kappa receptors. (Agonist at mu and Antagonist at kappa)

Indications:

• Acute and chronic pain relief

• Opioid use disorder & opioid withdrawal

Buprenorphine/Naloxone (Suboxone) Adverse Effects

• Mild respiratory depression

• Prolonged QT interval and fatal dysrhythmias

Buprenorphine/Naloxone (Suboxone) Nursing Considerations

• Same considerations as morphine & fentanyl.

• Establish baseline ECG and monitor heart rhythm on telemetry as well as s/s indicative of heart rhythm change.

• Thorough history and assessment of opioid abuse prior to use for addiction.

• Naloxone cannot readily reverse toxicity that has already developed.

Naloxone (Narcan)

(IV, IM, SQ, & Intranasal) (Competitive Antagonist)

MOA: Antagonist at opioid receptors that blockers opioid action. (Knocks opioid off receptor and takes over!)

Indications:

• Opioid overdose (respiratory depression, coma, etc.)

• Reversal of post-operative opioid effects

• Reversal of neonatal respiratory depression

Naloxone (Narcan) Nursing Considerations

• Will not see reversal if depression is caused by other agent (benzo, ETOH, etc), but can help rule out opioid etiology if no response after multiple doses.

• Due to short half-life, may need to repeat doses during overdose (e.g., 0.4 mg IV every 2-5 minutes while providing oxygenation and ventilatory support)

• Reversal of effects include onset of pain

• Other formulations can help w/ management of opioid-induced constipation and opioid addition.