Gout And Pain (Opioids, Opiates) Flashcards
Allopurinol
Zyloprim
Colchicine
Colcrys, Gloperba, Mitigare
Febuxostat
Uloric
Buprenorphine/Naloxone
Bunavail, Suboxone, Zubsolv
Codeine
Tylenol with Codeine
Fentanyl Transdermal
Duragesic, Ionsys
Hydrocodone
Norco, Lorcet, Vicodin, Zohydro ER, Hysingla ER
Methadone
Dolophine
Morphine
MS Contin, Avinza, Kadian
Oxycodone
Oxycontin
Tramadol
Ultram
Therapeutic Class - Allopurinol
Xanthine oxidase inhibitor, antigout
Therapeutic Class - Colchicine
Antigout
Therapeutic Class - Febuxostat
Xanthine oxidase inhibitor, antigout
Therapeutic Class - Buprenorphine/Naloxone
Opioid Partial Agonist and Antagonist combination, C-III
Therapeutic Class - Codeine
Opioid
Therapeutic Class - Fentanyl Transdermal
Opioid analgesic
Therapeutic Class - Hydrocodone
Opioid analgesic
Therapeutic Class - Methadone
Opioid analgesic
Therapeutic Class - Morphine
Opioid analgesic
Therapeutic Class - Oxycodone
Opioid analgesic
Therapeutic Class - Tramadol
Opioid analgesic
Controlled Substance Shedule
CII: Codeine, Fentanyl Transdermal, Hydrocodone, Methadone, Morphine, Oxycodone
CIII: Buprenorphine/Naloxone, Codeine + Acetaminophen TABLETS
CIV: Tramadol
CV: Codeine + Acetaminophen LIQUID
Dosage Forms - Allopurinol
Tablet: 100 mg, 300 mg
Dosage Forms - Colchicine
Tablet: 0.6 mg
Capsule: 0.6 mg
Oral Solution: 0.6 mg/5 mL
Dosage Forms - Febuxostat
Tablet: 40 mg, 80 mg
Dosage Forms - Buprenorphine/Naloxone
SL Tablet: 0.7/0.18, 1.4/0.36, 2/0.5, 2.9/0.71, 5.7/1.4, 8.6/2.1, 11.4/2.9
SL Film: 2/0.5, 4/1, 8/2, 12/3
Buccal Film: 2.1/0.3, 4.2/0.7, 6.3/1
Dosage Forms - Codeine
Tablet: 15, 30, 60
W/ APAP: 300/15, 300/30, 300/60
Elixir (APAP/Codeine): 120/12
Dosage Forms - Fentanyl Transdermal
Transdermal Patch (mcg/hr): 12.5, 25, 50, 75, 87.5, 100 Transdermal Iontophoretic System: 40 mcg/actuation
Dosage Forms - Hydrocodone
Tablet (w/ APAP): 2.5/325, 5/325, 7.5/325, 10 mg/325 mg
ER Tablet (24-hr, abuse-deterrent): 20, 30, 40, 60, 80, 100, 120 mg
ER Capsule (12-hr, abuse-deterrent): 10, 15, 20, 30, 40, 50 mg
Oral Elixir, Solution (w/ APAP per 15 mL): 7.5/325, 10/325
Dosage Forms - Methadone
Tablet: 5 mg, 10 mg
Soluble Tablet: 40 mg
Oral Solution: 5 mg/5 mL, 10 mg/5 mL, 10 mg/1 mL
Dosage Forms - Morphine
Tablet: 15 mg, 30 mg
ER Tablet: 15, 30, 60, 100, 200 mg
ER Abuse-Deterrent Tablet: 15, 30, 60, 100 mg
Capsule (24 hr): 10, 20, 30, 40, 45, 50, 60, 75, 80, 90, 100, 120, 200 mg
Oral Solution (mg/mL): 10/5, 20/5, 20/1, 100/5
Rectal Suppository: 5 mg, 10 mg, 20 mg, 30 mg
Dosage Forms - Oxycodone
IR Tablet: 5, 10, 15, 20, 30 mg
ER Tablet (12-hr Abuse-Deterrent): 10, 15, 20, 30, 40, 60, 80 mg
Capsule: 5 mg
12-hr Abuse-Deterrent: 9, 13.5, 18, 27, 36 mg
Oral Solution: 5 mg/5 mL
Oral Solution Concentrate: 100 mg/5 mL
Dosage Forms - Tramadol
Tablet: 50 mg, 100 mg
ER Tablet: 100, 200, 300 mg
ER 24-Hour Capsule: 100, 150, 200, 300 mg
Oral Solution: 5 mg/5 mL
MOA - Allopurinol
Decreases the uric acid content by inhibiting xanthine oxidase, which is the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid
MOA - Febuxostat
Decreases the uric acid content by inhibiting xanthine oxidase, which is the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid
MOA - Colchicine
Unknown. Thought to interrupt the cycle or monosodium urate crystal deposition in join tissues and therefore interrupts the inflammatory response that initiates and sustains an acute attack.
Inhibits urate crystal deposition, which is enhanced by low pH in the tissues, likely by inhibiting oxidation of glucose and subsequent lactic acid production in leukocytes
MOA - Buprenorphine/Naloxone
Mu receptors are responsible for analgesia, respiratory depression, miosis, decreased GI motility, and euphoria. In the CNS, it promotes analgesia and respiratory depression by decreasing brain stem respiratory centers’ response to carbon dioxide tension and electrical stimulation. It also decreases gastric, biliary, and pancreatic secretion, induces peripheral vasodilation, and promotes opioid-induced hypotension due to histamine release.
Buprenorphine:
a) Mu-opioid receptor partial Agonist
b) Kappa-opioid receptor ANTAgonist
Naloxone: Mu-opioid receptor ANTAgonist (causes opioid withdrawal when injected parenterally;
used as an abuse deterrent)
MOA - Codeine
3-methylmorphine that functions as a phenanthrene opioid, analgesic activity through conversion to morphine
MOA - Tramadol
Mu agonist and weak inhibitor of serotonin and norepinephrine reuptake
MOA - Hydrocodone
Unknown but opioid analgesic with antitussive properties
MOA - Oxycodone
Pure mu agonist
MOA - Morphine
Pure mu agonist
MOA - Fentanyl Transdermal
Phenylpiperidine opioid agonist with predominant effects on mu opioid receptor 50-100x more potent than morphine
MOA - Methadone
Binds to opiate receptors in CNS therefore inhibiting ascending pain pathways, changing perception to pain and producing generalized CNS depression.
Phenylethylamine opioid agonist that is qualitatively similar to morphine but chemical structure is unrelated to alkaloid-type structures of opium derivatives
Analgesic activity of (R)-methadone is 8-50x (+ a tenfold higher affinity for opioid receptors) that of (S)-methadone
FDA-Approved Indications - Allopurinol
- Gout, mild: 100-300 mg/day up to 800 mg
- Gout, moderate-severe: 400-600 mg/day up to 800 mg
- Hyperuricemia, tumor lysis syndrome (adults): 600-800 mg/day in 2-3 divided doses
- Nephrolithiasis and prophylaxis due to calcium stones: 300 mg/day in 1-3 divided doses
FDA-Approved Indications - Febuxostat
- Hyperuricemia in patients unable to tolerate or inadequately treat will allopurinol: 40 mg QD (up to 120 mg)
FDA-Approved Indications - Colchicine
- Gout, acute: 1.2 mg at first sign of flare, can add 0.6 mg in 1 hour (max: 1.8 mg over 1 hour)
- Gout, prophylaxis: 0.6 mg QD to BID (MDD = 1.2 mg, or at onset of diarrhea)
- Familial Mediterranean Fever (can adjust dose in 0.3 mg increments/day)
a) Children 4-6 years: 0.3-1.8 mg QD
b) Children 6-12 years: 0.9-1.8 mg QD
c) Adults: 1.2-2.4 mg QD
FDA-Approved Indications - Buprenorphine/Naloxone
- Opioid use disorder (>16 years): 12-16 mg (buprenorphine component) QD sublingually, titrate to response [typical dosing rage: 4-24 mg/day]
FDA-Approved Indications - Codeine
- Pain: 15-60 mg q4h PRN; w/APAP 300-1000 mg (MDD APAP = 4000 mg)
FDA-Approved Indications - Tramadol
- Pain, chronic, moderate to moderately severe:
a) IR: 50 mg a4-6h PRN (MDD = 400 mg)
b) ER: 100 mg QD (MDD = 300 mg)
Converting IR:ER is 1:1 - round down to the nearest 100 mg
FDA-Approved Indications - Hydrocodone
- Pain, severe: 10 mg q12h, titrate to response
FDA-Approved Indications - Oxycodone
- Pain, chronic, moderate to severe (opioid naïve patient):
a) IR: 5-15 mg q4-6h PRN
b) ER: 10 mg q12h PRN
FDA-Approved Indications - Morphine
- Acute pain in hospitalized patients with low risk of respiratory depression: 10 mg q4h PRN (max 30 mg q4h)
- Chronic pain, moderate to severe:
a) IR: 10-20 mg q12h, titrate to response (use IR formulations to calculate patient’s morphine requirement)
b) ER: dosed q12-24 hours
FDA-Approved Indications - Fentanyl Transdermal
- Pain, chronic (moderate to severe): >2 years old, opioid-tolerant, with pain than cannot be managed by other meals
a) Transdermal fentanyl dosage based on patients 24-hour ORAL morphine requirement
b) Replace patch q72hr, can replace q48 if uncontrolled pain
FDA-Approved Indications - Methadone
- Pain, chronic (moderate-severe) opioid-naïve patients: 2.5 mg q8-12h, may titrate to response
- Drug detoxification, opioid abuse: 15-30 mg q8h (usual range 80-120 mg/day) - when used for treatment of opioid addiction (detoxification or maintenance), can only be dispensed by certified opioid treatment programs
Off-Label Uses - Allopurinol
- Nephrolithiasis prophylaxis due to uric acid stones: 300 mg/day in 1-3 divided doses
Off-Label Uses - Colchicine
- Amyloidosis: 0.6 mg BID
- Behcet syndrome: 0.6 mg BID-TID
- Constipation: 0.6 mg q30min until diarrhea onset
- Pericarditis:
a) Adults > 70kg: 0.6 mg BID
b) Adults < 70kg: 0.6 mg QD
Off-Label Uses - Codeine
- Cough: 7.5-120 mg/d in divided doses
Off-Label Uses - Tramadol
- Restless leg syndrome:
a) IR: 50 mg QHS
b) ER: 100 mg QHS
Kinetics - Allopurinol
Absorption: F = 80-90% Distribution: Vd = 1.6-2.43 L/kg Metabolism: hepatic (78%) and RBC Elimination: renal 80%; T1/2 parent = 2 hours; T1/2 active metabolite = 15-25 hours Hepatic Dose Adjustment: none Renal Dose Adjustment: a) 30-60mL/min: 50mg QD b) 15-30mL/min: 50mg every other day c) 5-10mL/min: 50mg 2x/week d) <5mL/min: 50mg once weekly
Kinetics - Colchicine
Absorption: F = 45%
Distribution: Vd = 5-8 L/kg; 39% protein bound
Metabolism: Partial CYP3A4/5, P-gp substrate
Elimination: renal 40-65%; T1/2 = 26-32 hours
Hepatic Dose Adjustment: severe, hepatic failure - once every 2 weeks
Renal Dose Adjustment: <30mL/min: only once every 2 weeks
Kinetics - Febuxostat
Absorption: F > 49%
Distribution: Vd = 50L; 99% protein bound
Metabolism: numerous enzymes
Elimination: renal 50%; T1/2 = 5-8 hours
Hepatic Dose Adjustment: caution if severe
Renal Dose Adjustment: <30mL/min: max 40mg/day
Kinetics - Buprenorphine/Naloxone
Absorption: F = 15% (buprenorphine); 3% (naloxone)
Distribution: Vd = 97-187 L (buprenorphine)
Metabolism:
a) Buprenorphine: hepatic, major CYP3A4 substrate
b) Naloxone: hepatic via glucuronidation
Elimination: renal 30%; T1/2 = 33 hours (buprenorphine) 6 hours (naloxone)
Hepatic Dose Adjustment: caution
Renal Dose Adjustment: none
Kinetics - Codeine
Absorption: well absorbed
Distribution: Vd = 2.6 L/kg; 7-25% protein bound
Metabolism: prodrug activated by CYP2D6 to morphine; 2D6 substrate
Elimination: renal ~100%; T1/2 = 2-4 hours
Hepatic Dose Adjustment: AVOID chronic use in hepatic impairment
Renal Dose Adjustment:
a) 10-50mL/min: 75% of dose
b) <10mL/min: 50% of dose
Kinetics - Fentanyl Transdermal
Absorption: F = 92%
Distribution: Vd = 6 L/kg; 80-85% protein bound
Metabolism: extensive hepatic, CYP3A4 substrate
Elimination: renal 75%; T1/2 = 20-24 hours
Hepatic Dose Adjustment: none
Renal Dose Adjustment: <10mL/min: 50% dose reduction
Kinetics - Hydrocodone
Absorption: well absorbed
Distribution: unknown
Metabolism: prodrug activated to hydromorphone by CYP2D6; then CYP3A4 substrate
Elimination: renal 26%; T1/2 = 8 hours
Hepatic and Renal Dose Adjustment: severe - start with < 10 mg dose
Kinetics - Methadone
Absorption: F = 85%
Distribution: Vd = 3.6 L/kg; 85-90% protein bound
Metabolism: hepatic, CYP2B6 and 3A4 substrate; moderate 2D6 inhibitor
Elimination: renal 10-20%; T1/2 = 48-60 hours
Hepatic Dose Adjustment: none
Renal Dose Adjustment: none
Kinetics - Morphine
Absorption: F <40%; food slows rate but not extend of absorption
Distribution: Vd = 1.6 L/kg; 20-36% protein bound
Metabolism: hepatic by glucuronidation
Elimination: renal 90%; T1/2 = 15 hours
Hepatic Dose Adjustment: Severe impairment, extend dosing interval or lower starting dose
Renal Dose Adjustment:
a) 10-50mL/min: decrease dose by 25%
b) <10mL/min: decrease dose by 50%
Kinetics - Oxycodone
Absorption: F= 60-87%, food enhances absorption
Distribution: Vd= 2.6L/kg,
45% protein bound
Metabolism: Hepatic, CYP3A4 substrate
Elimination: renal 20%; T1/2 = 3-4 hours (IR); 5-18 hours (ER)
Hepatic Dose Adjustment: titrate w/ caution
a) IR: initiate lose dose;
b) ER: initiate at 1/3-1/2 usual dose
Renal Dose Adjustment: <60mL/min: reduce starting dose
Kinetics - Tramadol
Absorption: a) IR: F= 75% b) ER: F= 70% w/ variable food effect Distribution: Vd= 3L; 20% protein bound Metabolism: Hepatic via CYP3A4 and 2D6 Elimination: Renal 30%; T1/2 6 hour Hepatic Dose Adjustment: Moderate or severe, IR: 50mg PO q12h; AVOID ER Renal Dose Adjustment: <30mL/min, IR: extend interval to q12h (MDD: 200 mg); AVOID ER
Drug Interactions - Allopurinol
- Didanosine = AVOID
- Azathioprine = reduce azathioprine dose by 1/3 or avoid use
- Cyclophosphamide = monitor for toxic effects
Drug Interactions - Febuxostat
- Substrates for xanthine oxidase
- Contraindicated with azathioprine or mercaptopurine
- Caution with didanosine, theophylline
Drug Interactions - Colchicine
- Lipid-lowering agents (fibrates, statins) = AVOID
2. CYP3A4 inducers/inhibitors = monitor
Drug Interactions - Buprenorphine/Naloxone
- CYP3A4 inducers/inhibitors = monitor and consider dose adjustments
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = monitor
Drug Interactions - Codeine
- CYD2D6 inhibitors = AVOID
- Opioid agonists/antagonists = AVOID d/t withdrawal
- CNS depressants (opioids, alcohols) = AVOID
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = AVOID
- SSRIs, SNRIs, TCAs, Triptans = counsel when takin in combination with
Drug Interactions - Fentanyl Transdermal
- CYP3A4 inducers/inhibitors = consider dose increase w/inducers, avoid w/strong or moderate inhibitors
- Opioid agonist/antagonist = AVOID d/t withdrawal
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines
- Beta-blockers and calcium channel blockers = AVOID
- MAOIs = AVOID
- SSRIs, SNRIs, TCAs, Triptans = counsel when taken in combination with
Drug Interactions - Hydrocodone
- CYP2D6 inhibitors = monitor and consider dose increase
- CYP3A4 inducers/inhibitors = monitor and consider dose increase w/inducers; avoid with strong inhibitors; caution with moderate inhibitors and consider dose decrease
- Opioid agonist/antagonist = AVOID d/t withdrawal
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = AVOID
- MAOIs = AVOID
- SSRIs, SNRIs, TCAs, Triptans = counsel when taken in combination with
Drug Interactions - Methadone
- CYP2B6 inhibitors/inducers = monitor
- CYP2D6 substrates = AVOID
- CYP3A4 inducers/inhibitors = monitor
- Opioid agonists/antagonists = AVOID d/t withdrawal
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = AVOID
- MAOIs = contraindicated
- SSRIs, SNRIs, TCAs, Triptans = counsel when taken in combination with
- Amiodarone, agents that prolong QT interval = AVOID
- Didanosine = separate use by 1-2 hours
Drug Interactions - Morphine
- Opioid agonist/antagonists = AVOID d/t withdrawal
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = AVOID
- MAOIs = contraindicated
- SSRIs, SNRIs, TCAs, Triptans = counsel when taken in combination with
Drug Interactions - Oxycodone
- CYP3A4 inducers/inhibitors = caution
- Opioid agonists/antagonists = AVOID d/t withdrawal
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = AVOID
Drug Interactions - Tramadol
- CYP2D6 inhibitors = consider dose decrease
- CYP3A4 inducers/inhibitors = consider dose changes
- Opioid agonists/antagonists = AVOID d/t withdrawal
- Barbiturates, benzodiazepines, muscle relaxants, phenothiazines = AVOID
- MAOIs = contraindicated
- SSRIs, SNRIs, TCAs, Triptans = counsel when taken in combination with
Allopurinol in Pregnancy/Lactation
Pregnancy: caution
Lactation: compatible
Colchicine in Pregnancy/Lactation
Pregnancy: compatible
Lactation: probably compatible
Febuxostat in Pregnancy/Lactation
Pregnancy: caution
Lactation: possibly toxic
Buprenorphine/Naloxone in Pregnancy/Lactation
Probably compatible
Codeine in Pregnancy/Lactation
Contraindicated
Fentanyl Transdermal in Pregnancy/Lactation
Pregnancy: risk
Lactation: compatible
Methadone in Pregnancy/Lactation
Pregnancy: risk
Lactation: compatible
Morphine, Hydrocodone, Oxycodone, and Tramadol in Pregnancy/Lactation
Risk
Black Box Warning - Febuxostat
Increased risk of death (cardiac, all-cause)
Black Box Warnings - Codeine
- Serious risks of misuse, abuse, addiction, overdose, and death
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Hepatotoxicity
- Neonatal opioid withdrawal
- Accidental Ingestion
- Children who are CYP2D6 ultra-rapid metabolizers
Black Box Warnings - Fentanyl
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Respiratory Depression
- CYP3A4 interactions
- REMS
- Accidental Ingestion
- Transdermal not for use post-operatively; fatalities in children; formulations not interchangeable; fever; care with disposal
Black Box Warnings - Hydrocodone
- Serious risks of misuse, abuse, addiction, overdose, and death
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Respiratory Depression
- Hepatotoxicity
- Neonatal opioid withdrawal
- CYP3A4 interactions
- REMS
- Accidental Ingestion
Black Box Warnings - Methadone
- Serious risks of misuse, abuse, addiction, overdose, and death
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Respiratory Depression
- Neonatal opioid withdrawal
- REMS
- Accidental Ingestion
- QTc prolongation; conditions for use in opioid addiction; CYP interactions
Black Box Warnings - Morphine
- Serious risks of misuse, abuse, addiction, overdose, and death
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Respiratory Depression
- Neonatal opioid withdrawal
- REMS
- Accidental Ingestion
- Medication errors
Black Box Warnings - Oxycodone
- Serious risks of misuse, abuse, addiction, overdose, and death
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Respiratory Depression
- Neonatal opioid withdrawal
- CYP3A4 interactions
- REMS
- Accidental Ingestion
- Medication errors with oral solution
Black Box Warnings - Tramadol
- Serious risks of misuse, abuse, addiction, overdose, and death
- Concurrent use with benzodiazepines/CNS depressants/ethanol
- Respiratory Depression
- Neonatal opioid withdrawal
- REMS
- Accidental Ingestion
- CYP2D6, drug interactions, errors
Contraindications - Colchicine
Patients with renal and/or hepatic failure
Contraindications - Codeine
Avoid use in < 12 years of age or aged 12-18 years post-op after tonseillectomy
Contraindications - Fentanyl Transdermal
Avoid in acute or post-operative pain, bronchial asthma, mild or intermittent pain, opioid non-tolerant patients and paralytic ileus
Contraindications - Hydrocodone
Avoid in paralytic ileus, respiratory depression, severe asthma
Contraindications - Methadone
Avoid in bronchial asthma, paralytic ileus, respiratory depression, hypercarbia
Contraindications - Morphine
Avoid in acute or severe asthma, paralytic ileus, respiratory depression, GI obstruction, concurrent use or within 14 days of MAOI
Contraindications - Oxycodone
Avoid with asthma, paralytic ileus, respiratory depression, hypercarbia
Contraindications - Tramadol
Avoid with paralytic ileus, respiratory depression, bronchial asthma, age < 12 years, hypercapnia, current MAOI use or use within the last 14 days
Adverse Effects - Allopurinol
Common: none
Less common: Rash, maculopapular eruption, acute attacks of gout with initiation
Rare but serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, thrombocytopenia, granulomatous hepatitis, hepatotoxicity, immune hypersensitivity reaction, renal failure
Adverse Effects - Colchicine
Common: D/N
Less common: vomiting
Rare but serious: agranulocytosis, rhabdomyolysis
Adverse Effects - Febuxostat
Common: none
Less common: rash, nausea, elevated LFTs, arthralgia
Rare but serious: ECG abnormalities, hypersensitivity, stroke, mood changes, drug reaction rash with eosinophilia and systemic symptoms
Adverse Effects - Buprenorphine/Naloxone
Common: Vasodilation, sweating, headaches, insomnia, constipation, GI distress, opioid withdrawal, dizziness
Less common: Dyspnea, respiratory depression, glossodynia
Rare but serious: Stevens-Johnson syndrome, physical dependence, tolerance, elevated liver functions tests, seizures
Adverse Effects - Codeine
Common: Nausea, vomiting, constipation, somnolence
Less common: Pruritus, euphoria, dizziness
Rare but serious: Stevens-Johnson syndrome, GI bleeding, elevated liver functions, thrombocytopenia, physical dependence, tolerance, respiratory depression, serotonin syndrome, adrenal insufficiency, decreased sex hormones
Adverse Effects - Fentanyl Transdermal
Common: Application site reactions, sweating, constipation, GI distress, confusion, headache, anxiety, urinary retention, fatigue
Less common: Arrhythmias, chest pain, dyspnea, respiratory depression upper respiratory tract infection
Rare but serious: Stevens-Johnson syndrome, physical dependence, tolerance
Adverse Effects - Hydrocodone
Common: Constipation, GI distress, somnolence
Less common: Rash, respiratory depression, euphoria, pruritus
Rare but serious: Stevens-Johnson syndrome, physical dependence, tolerance, respiratory depression, serotonin syndrome, adrenal insufficiency, decreased sex hormones
Adverse Effects - Methadone
Common: Constipation, GI distress, hypotension, dizziness, sedation
Less common: Diaphoresis, physical dependence, tolerance
Rare but serious: Respiratory depression, arrhythmias, Stevens-Johnson syndrome, QTc prolongation, serotonin syndrome, adrenal insufficiency, hypogonadism
Adverse Effects - Morphine
Common: Constipation, nausea, vomiting, hypotension, dizziness, sedation, diaphoresis, headaches, depression, xerostomia
Less common: Dyspnea, urinary retention, edema, pruritis
Rare but serious: Cardiac arrest, physical dependence, respiratory depression, serotonin syndrome, adrenal insufficiency, decreased sex hormones
Adverse Effects - Oxycodone
Common: Constipation, GI distress, sedation, sweating, pruritus
Less common: Asthenia, dyspnea, hypotension, euphoria, nausea, vomiting
Rare but serious: Cardiac arrest, respiratory depression, physical dependence, tolerance, severe hypersensitivity, serotonin syndrome, adrenal insufficiency, decreased sex hormones
Adverse Effects - Tramadol
Common: Constipation, GI distress, dizziness, sedation, edema, sweating, pruritus, headaches, flushing
Less common: Dyspnea, xerostomia, depression, orthostatic hypotension
Rare but serious: Cardiac arrest, physical dependence, tolerance, seizures, pancreatitis, suicidal ideation, anemia, serotonin syndrome, adrenal insufficiency, decreased sex hormones
Drug Monitoring - Allopurinol
Efficacy: Resolution of signs of gout, serum uric acid measured 48 hours after therapy
Toxicity: LFTs, renal function, CBC
Drug Monitoring - Colchicine
Efficacy: Resolution of gout s/sx
Toxicity: CBC, Alk Phos at baseline & periodically, s/sx of agranulocytosis or myotoxicity, renal & hepatic function
Drug Monitoring - Febuxostat
Efficacy: Reduction in uric acid levels < 6mg/dL, decrease in gout attacks
Toxicity: LFTs baseline & periodically, s/sx of CV events, s/sx of hypersensitivity or severe skin reactions
Drug Monitoring - Buprenorphine/Naloxone
Efficacy: UDS(-) for illicit drugs, relief of s/sx associated with narcotic addiction
Toxicity: Severe skin rash, excessive drowsiness, decreased breathing, severe constipation
Drug Monitoring - Codeine
Efficacy: Decreased pain
Toxicity: LFTs, SCr
Chronic use: severe skin rash, black tarry stools, excessive drowsiness, yellowing of eyes & skin, change in urination
Drug Monitoring - Fentanyl Transdermal
Efficacy: Relief of pain
Toxicity: Severe skin rash, excessive drowsiness, decreased breathing, HR, severe constipation, chest pain, inability to urinate, constipation
Drug Monitoring - Hydrocodone
Efficacy: Relief of pain
Toxicity: Seek medical attention if severe skin rash, excessive drowsiness, decreased breathing, severe constipation, black tarry stools or yellowing of eyes or skin
Drug Monitoring - Methadone
Efficacy: Relief of pain, relief of s/sx associated with opioid addiction
Toxicity: Seek medical attention if severe skin rash, excessive drowsiness, decreased breathing, severe constipation, chest pain or dizziness; vital signs. Consider ECG if on other QTc prolonging agents
Drug Monitoring - Morphine
Efficacy: Relief of pain
Toxicity: Excessive drowsiness, decreased breathing, severe constipation, chest pain, dizziness , vital signs
Drug Monitoring - Oxycodone
Efficacy: Relief of pain
Toxicity: Excessive drowsiness, severe skin rash, decreased breathing, severe constipation, chest pain, dizziness. Monitor vital signs, specifically RR and BP
Drug Monitoring - Tramadol
Efficacy: Relief of pain
Toxicity: Excessive drowsiness, decreased breathing, severe constipation, chest pain, dizziness, signs of tolerance. Monitor vital signs
Counseling and Pearls - Allopurinol
Counseling: Take at after meals to lessen gastric irritation. Adequate hydration to prevent kidney stones. Avoid alcohol and caffeine. Seek medical attention if s/sx of myelosuppression, agranulocytosis or SJS occur.
Pearls: Not for acute treatment therefore patient adherence is crucial. Full effect can take 2-6 weeks. Recommend slow dose titration.
Counseling and Pearls - Colchicine
Counseling: Ensure patient is aware of proper dosing strategy for gout flares (dosing to symptom relief or onset of ADR, particularly diarrhea)
Pearls: Medication guide required for dispensing. A natural alkaloid found in plants like the autumn crocus and glory lily
Counseling and Pearls - Febuxostat
Counseling: Take at without food. Recommend weight loss and limitation of alcohol to reduce gout attacks. Seek medical attention for severe mood swings, rashes or abnormal heartbeat.
Pearls: More effective in lowering uric acid levels but caused higher LFT levels than allopurinol. Associated with greater risk of CV-related death and all cause death. May need prophylactic therapy with NSAID or Colchicine for the first 6 months of initiation due to an increase in gout flares.
Counseling and Pearls - Buprenorphine/Naloxone
Counseling: Use a stool softener and/or laxative to prevent constipation. Avoid driving and tasks requiring motor coordination due to drowsiness. Avoid alcohol and other CNS depressants. Do not crush or swallow tablet. Place tablet(s)/film under the tongue until it dissolves. If a second film is needed, place on the opposite side from the first film. For buccal film, press and hold firm by finger against moist cheek for 5 seconds, do not use more than 2 buccal films at a time. If a second film is needed, place on the opposite cheek.
Pearls: Monitor for signs of diversion. Concurrent use with opioids with precipitate withdrawal symptoms. There is a ceiling effect which limits the analgesic properties. Sublingual film and tablet strengths are NOT interchangeable. Do not substitute within products. REMS program. Additional counseling and psychosocial support is recommended. Not recommended for treatment of dependence on long-acting opiates or methadone but useful for withdrawal of short-acting opiates and heroin.
Counseling and Pearls - Codeine
Counseling:
If using chronically, laxative is recommended to prevent constipation. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol.
Pearls: Caution in elderly as they are more sensitive to effects. Caution with other CNS depressants due to additive effects. Avoid use with benzodiazepines. Tolerance and physical dependence may occur; avoid abrupt discontinuation. Oral solution has 7% alcohol. Has a liquid formulation combination with guaifenesin for cough.
CYP2D6 gene interaction
Multiple genes - ultra-rapid metabolism
Lack functional genes - do not metabolize codeine to morphine
Counseling and Pearls - Hydrocodone
Counseling: Use stool softener and/or laxative to prevent constipation. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol and CNS depressants.
Pearls: Caution in elderly. Avoid use with benzodiazepines. Tolerance and physical dependence may occur do not abruptly stop. If using with APAP, do not exceed > 3 grams of APAP/day
Counseling and Pearls - Methadone
Counseling: Use motility-promoting laxative to prevent constipation. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol and CNS depressants. Seek medical attention if SOB or extremely drowsy. Breast-feeding women should monitor child for signs of sedation & respiratory depression.
Pearls: Tolerance and physical dependence may occur do not abruptly stop. High patient variability therefore careful initiation and titration dosing. Fatal respiratory depression has occurred with the highest risk at initiation and with dosage increases. For oral administration only. Do not chew or swallow table for suspension-dissolve in liquid and drink. Keep away from children and pets. Should avoid use with benzodiazepines. Medication guide required at dispensing. REMS requirements.
Counseling and Pearls - Fentanyl Transdermal
Counseling: Use laxative to prevent constipation. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol and CNS depressants. Apply to clean, dry skin. Skin breaks may increase absorption. Remove old patch when new one applied. Febrile patients may have increased absorption. Monitor carefully
Pearls: Not for acute pain. Caution in elderly, due to increased sensitivity for ADR. Tolerance and dependence can occur, avoid abrupt discontinuation. REMS requirements. Also available as injectable, nasal spray, oral liquid, buccal film, buccal tablet, and sublingual tablet. Substantial differences exist in the pharmacokinetic profile of fentanyl products. Do not convert patients on a mcg-per-mcg basis from one fentanyl product to another fentanyl product; the substitution of one fentanyl product for another fentanyl product may result in a fatal overdose. Do not cut patch. Contraindicated in opioid-naïve patients; use limited to opioid tolerant patients. Avoid concomitant use with benzodiazepines, alcohol or other CNS depressants. Absorption from patch is delayed 12-24 h after patch placement due to depot effect in the outer layer of skin. Skin depot also results in lingering presence of drug in serum after patch removal.
Counseling and Pearls - Morphine
Counseling: Use stimulant laxative to prevent constipation. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol and CNS depressants. ER products should not be crushed or chewed as it will release the total morphine dosage at once and increase the risk of respiratory depression. ER capsule can be opened and sprinkled on soft food but must be swallowed whole and not chewed.
Pearls: Avoid use with benzodiazepines. Tolerance and physical dependence may occur do not abruptly stop. 20mg/mL concentration is only for opioid-tolerant patients. REMS requirements. ER products should not be used in children. Fatal respiratory depression has occurred but commonly at dose start or change. Avinza cannot be administered with alcoholic beverages or ethanol-containing products.
Counseling and Pearls - Oxycodone
Counseling: Use laxative to prevent constipation. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol and CNS depressants.
Pearls: Significant drug of abuse. Tolerance and physical dependence may occur do not abruptly stop. ER products cannot be crushed or chewed because it will release total oxycodone dose and increase risk of respiratory depression. ER products should not be used in children. Keep in safe space away from children. Do not use with benzodiazepines. REMS requirements. Preferred to be used in combination with APAP due to beneficial pain management effect abuse potential.
Counseling and Pearls - Tramadol
Counseling: Use laxative to prevent constipation if used chronically. May cause drowsiness, avoid driving or other tasks requiring motor coordination. Avoid alcohol and CNS depressants. ER products cannot be crushed or chewed, but can be taken with or without food, but always take the same way to avoid absorption variability.
Pearls: Tolerance and physical dependence may occur do not abruptly stop. Tramadol related deaths have been reported in patients with histories of emotional disturbances, suicidal ideation/attempts, or misuse of tranquilizers, alcohol and other CNS-active drugs. Suspension and creams are available in compounding kits. Avoid use with benzodiazepines. Tramadol does not appear to produce significant respiratory depression or CV effects in most patients.
