Pain/Related Conditions

Question 1

Non-opioid analgesics: Acetaminophen

Answer 1

-reduces pain (analgesia) and fever (antipyretic) but does not provide anti-inflammatory effect, does not inhibit thromboxane (no effect on platelets)
–> peds dose: 10-15 mg/kq q 4-6H, infant sus: 160mg/5mL

Combos: Acetaminophen
+. hydrocodone (Norco, Vicodin, Lortab)
+ Oxycodone (Percocet, Endocet)
+ Codeine (Tylenol #2,3,4)
+ Tramadol (Ultracet)
+ Butalbital/Caffeine (Fioricet)
+ Diphenhydramine (Tylenol PM)

Question 3

Acetaminophen Overdose*

Answer 3

MAX DOSE: 4000 mg/day and 325 mg/rx dosing unit

Antidose for APAP is N-acetylcysteine (oral or Acetadote IV)
–> restores intracellular glutathione
-available in both oral and IV formulation

The Rumack-Matthew nomogram uses the serum acetaminophen level and the time since ingestion to determine whether hepatotoxicity is likely & the need for NAC

Question 4

NSAIDs and the Ductus Arteriosus *

Answer 4

before birth, the DA connects the pulmonary artery to the aorta, allowing oxygenated blood to flow to the baby, bypassing the immature lungs
**do NOT use NSAIDs in the 3rd trimester of pregnancy- can prematurely close the DA

–> IV NSAIDs (Indomethacin, Ibuprofen) can be used within 14 days after birth to close a patent DA

Question 5

Non-selective NSAIDs

Answer 5

-Ibuprofen (advil, motrin): ped 5-10mg/kg/dose q6-8h

-Idomethacin (Indocin, Tivorbex): PDA closure, higher risk for CNS & GI toxicity

-Naproxen (Aleve): 200 mg Q8-12H [ + esomeprazole (Vimovo) for GI protection, + sumatriptan (Treximet) for migraine]

-Ketorolac (Toradol): indicated as a cont of IV or IM ketorolac, max combined duration = 5 days, SE: acute renal failure, liver failure

Question 6

COX 2 selective NSAIDs

Answer 6

*inc risk of MI/stroke: avoid with CV risk

-Celecoxib (Celebrex): highest COX 2 selectivity, CI w/ sulfa allergy, SE: lower GI, renal complications,

-Diclofenac (voltaren): [ + misoprostal (Arthrotec) - replaces gut-protective prostaglandins to dc GI risk- avoid in females of childbearing potential)

-Meloxicam (mobic)

Question 7

Salicylate NSAIDs: Aspirin

Answer 7

(Bufferin, Ecotrin- EC, Durlaza ER)
BBW: NSAID hypersensitivity, risk of Reye’s syndrome, severe skin reactions
–> if used ASA w/ ibuprofen, take ASA 1 hr before or 8 hrs after ibuprofen

[ non-acetylated salicylates: Magnesium salicylate (Doans) - for back pain ]

Question 8

Opioid Boxed Warnings*

Answer 8

-addiction, abuse and misuse can lead to overdose and death
-respiratory depression, which can be fatal
-use of any opioid w/ benzos or other CNS depressants (including alcohol), can increase the risk of death
-Kadian, Embeda, Zohydro and Nucynta ER do not consume with alcohol
-accidental ingestion/exposure of even one dose in children = fatal
-crushing, dissolving, or chewing of the long acting products can cause the delivery of a potentially fatal dose
-life-threatening neonatal opioid withdrawal with prolonged use during pregnancy

Question 9

Common Opioids: Codeine

Answer 9

–> C-II
-Codeine + APA (Tylenol #2,3,4) = C III –> used as antitussive (anti-cough) - codeine cough syrups are C V

BBW:
-ulta rapid metabolizers of codeine (CYP450 2D6 polymorphisms) = OD/death
-CI in children < 12 y/o

Question 10

Common opioids: Fentanyl

Answer 10

(Duragesic, Sublimaze) - C-II
Patch: 12, 25, 50, 75, 100 mcg/h, change patch Q 3 days

-for chronic pain management only:
–> not for opioid naive patients
–> pts who have been taking morphine 60 mg daily or equiv for at least 7 days can be converted to a patch

-effects can be seen 8-16 hrs after application, some may need to be removed prior to MRI
-apply to hairless skin and press in place for 30 secs,
-dipose by flushing down the toilet

Question 11

Common Opioids: Hydrocodone

Answer 11

C-II
–> Hydrocodone + APAP (Norco, Lorcet, Lortab, Vicodin) = IR
–> Hydrocodone ER (Zohydro, Hysingla ER, Vantrela ER)

BBW: CYP3A4 inhibitors = can cause cause fatal overdose

Question 12

Common opioids: Hydromorphone

Answer 12

(Dilaudid) - C-II
**safety issues: POTENT; start low, convert carefully
–> satarting dose: 0.2-1 mg IV Q 2-3 hrs
-caution with 3A4 inhibitors, use lower doses initially

Question 13

Common Opioids: Methadone

Answer 13

(Dolophine, Methadose) - C-II
-approved for heroin detox (used more for pain)
-should be prescribed by those who know the requirements for safe use
-variable 1/2 life: 15-55 hrs
-risk of QT prologation, can be aggravated if dosed incorrectly
-can decrease testosterone, reduce sexual function in men
-serotonergic

Question 14

Common Opioids: Meperidine

Answer 14

(Demerol) C-II
-not for chronic pain: short acting, toxic metabolite, not for elderly
-renally cleared metabolite (normeperidine) that is lipophilic/ toxic if accumulated

SAFETY ISSUES: renal clearance, CNS toxicity –> seizures

Question 15

Common Opioids: morphine

Answer 15

(MD Contin, Kadian) C-II
K: can open and sprinkle on apple sauce

Question 16

Common opioids: Oxycodone

Answer 16

(Oxaydo, RoxyBond, Roxicodone) C-II
CR: Oxycontin
ER: Xtampa
+ APA = Endocet, Percocet

Safety issues: abuse/misuse, do not use with 3A4 inhibitors

Question 17

Opioid dosing conversions *

Answer 17

Morphine:
–> IV: 10 mg
–> PO: 30 mg

Hydromorphone:
–> IV: 1.5
–> PO: 7.5

Oxycodone:
–> PO: 20 mg

Hydrocodone:
–> PO: 30 mg

Question 18

Morphine-type allergy*

Answer 18

-the common drugs in the same chemical class that cross-react w/ each other have COD or MORPH in the name
-codeine
-hydrocodone
-oxycodone
-morphine
-hydromorphone
-oxymorphone
-bupenorphine
-heorin

opioid allergy symptoms: difficulty breathing, severe drop in BP, serious rash, swelling of face, lips, tongue, larynx

–> if true allergy options are: fentanyl, meperidine, methadone, tapentadol

Question 19

Opioid induced constipation *

Answer 19

-stimulants (Senna, biscodyl) or osmotic (PEG) laxatives are the typical 1st line, with or w/o stool softner

-if those dont work, can use OIC’s : Methylnaltrexone (Relistor), Naloxegol (Movantik), Naldemedine (Symoroic), Lubiprostone

Question 20

Centrally acting analgesics: Tramadol

Answer 20

(Ultram) C-IV, + APAP (Ultracet)
Warnings: seizure risk, serotonin syndrome, avoid with 2D6 inhibitors
SEs: dizziness, nausea, consitpation, loss of appetite, flushing, insomnia,

Question 21

Centrally acting analgesics: Tapentadol

Answer 21

(Nucynta) C-II
-seizure risk
-serotonin syndrome risk
-dizziness, drowsiness, nausea but less GI side effects than opioids

Question 22

Opioid overdose management*

Answer 22

-Narcan (nasal spray): onset of action is slower than injection, a single-use nasal spray is 4 mg admin in 1 nostril, repeat doses in alternating nostrils may be needed

-Naloxone (injection): generic formulation provided in multiple size vials, separate syringe will be needed, may need to repeat doses q 2-3 mins until emergency medical assistance arrives

Question 23

Common adjuvants for pain management

Answer 23

A. Anti-epileptic drugs: Gabapentin (Neurontin), Pregabalin (Lyrica), Carbamazepine

B. Antispasmodics (muscle relaxants) w/ analgesic effects: Baclofen (Lioresal), Cyclobenzaprine (Fexmid), Tizanadine (Zanaflex)

C. Antispasmodics (muscle relaxants) that work via sedation: Carisoprodol (Soma), Methocarbamol (Robaxin)

Question 24

Topical Adjuvants for pain control

Answer 24

-Lidocaine (Lidoderm) - up to 3 patches on body, can cut patches
-Capsaicin (Zostrix)
-Methyl salicylate (BenGay, IcyHot)

Question 25

Common Migraine Triggers*

Answer 25

1: Hormonal changes in Women -estrogen fluctuations -use progestin-only contraceptives in migraines with aura 2: Foods: beer, red wine, aged cheese, chocolate, aspartame, MSG, salty foods, processed foods 3: Stress: major cause of migraine 4: Changes in wake-sleep pattern: too much or too little sleep, including jet lag 5: Changes in the Environment: barometric pressure or weather changes

Question 26

Acute Migraine tx: triptans

Answer 26

-serotonin receptor type 1B and 1D agonists -Rizatriptan (Maxalt-MLT) : 6 yrs+ -Sumatriptan (Imitrex) : may be repeated once after 2 hrs -Zolmitriptan (Zomig ZMT) 12 y/o+ -Sumatriptan/naproxen (Treximet): abortive, must be in original container (> 12 y/o+) CI: cerebrovascular disease, cardiovascular disease, (stroke, TIA, MI, uncontrolled HTN) Warnings: inc BP, serotonin syndrome SEs: paresthesias (numb/tingling), triptan sensations (neck and chest pressure) --> Frovatriptan & naratriptan: longer duration of action, slower onset of action

Question 27

Acute migraine tx: Triptan Formulations*

Answer 27

A. Tablets: all B. ODT: Rizatriptan (Maxalt), Zolmitriptan (Zomig) C. Nasal Spray: Sumatriptan --> no priming, i spray in ONE nostril (may repeat once after 2 hrs) D. Nasal Powder: Sumatriptan --> 1 spray into EACH nostril (repeat once after 2 hrs) E. SC injection: sumatriptan (may repeat once after 1 hr)

Question 28

Acute migraine tx: Ergotamine drugs

Answer 28

-Dihydroegotamine (DHE 45, Migranal) : IM/SC/IV, nasal spray - must prime 4 pumps -Ergotamine + Caffeine (Cafergot): tab, supp --> non selective serotonin agents, caise cerebral vasoconstriction, generally considered in pts who do not respond to triptans BBW: CI with potent CYP3A4 inhibitors (GPACMAN) CI: uncontrolled HTN, ischemic heart disease, angina, MI, peripheral vascular disease, pregnancy, use within 24 hrs of triptans or other ergotamine-type drugs Warnings: cardiovascular effects, cerebrovascular events, intense vasoconstriction, DDIs

Question 29

Acute migraine tx: CGRP antagonists

Answer 29

-helps to treat or prevent migraines from occurring (dec inflammation + vasodilation) --> Rimegepant (Nurtec ODT) - approved for both treatment and ppx --> Ubrogepant (Ubrelvy): can take second dose if first one does not offer relief

Question 30

Serotonin Receptor Agonist: Lasmiditan

Answer 30

(Reyvow)- schedule V -NO vasoconstriction, NO contraindications, SE: CNS depression -strong inhibitor of P-gp

Question 31

Prophylactic tx of migraines: Beta Blockers

Answer 31

-Propranolol (Inderal) -Metoprolol t (Lopressor) -Metoprolol S (Toprol XL) -Timolol Warnings: caused with asthma COPD SE: bradycardai, fatigue, hypotension, impotence

Question 32

Prophylactic tx of migraines: Anti epileptics

Answer 32

-Divalproex (Depakote), Valproic acid --> BBW: fetal harm, hepatic failure, pancreatitis --> SEs: weight gain, thrombocytopenia, inc ammonia, alopecia, N/V, -Topiramate (Topamax) --> Warnings: fetal harm, metabolic acidosis, nephrolithiasis, inc ammonia, open angle glaucoma, oligohidrosis (dec sweating) --> SE: weight loss, somnolence, cognitive impairment & reduced efficacy of oral contraveptives

Question 33

Prophylactic CGRP Antagonist

Answer 33

PO: -Atogepent (Qulipta) -Rimegapant (Nurtec) Parenteral: -Eptinezumab (Vyept) IV Q 3 mon -Ernumab (Aimovig) SC monthly -Fremanezumab (Ajovy) SC monthly or q 3 mon -Galcancezumab (Emgality) Sc monthly

Question 34

Drugs that can increase uric acid*

Answer 34

-aspirin, low doses -calcineurin inhibitors (tacrolimus, cyclosporine) -Diuretics (loop and thiazides) -Niacin -Pyrazinamide (tb drug) -select chemo therapies (tumor lysis syindrome causing) and pancreatic enzymes

Question 35

Acute Gout tx: NSAIDs

Answer 35

-Indomethacin (Indocin): 50 mg TID until pain is tolerable - then taper down -Naproxen (aleve) 750 mg x1, then reduce to 250 mg Q8H until attack resolved --> avoid in severe renal disease, cardiac disease, bleeding

Question 35

Acute gout tx: Colchicine

Answer 35

(Colcrys) --> flare tx: 1.2 mg at the first sign of flare, in 1 hr single 0.6 mg then 0.6 mg daily or BID (only if symptoms began within 36 hrs) --> Prophylaxis: 0.6 mg qd or BID (max 1.2 mg/day) SEs: loose stools, N/V, myelosuppression and neuromyopathy and death possible if overdosed! CI: with clarithyomycin (CYP3A4 inhib) and cyclosporine (P-gf sub) -myopathy and rhabdomyolysis if taken w/ a statin (do not take with gemfabazol)

Question 35

Gout Treatment Basics*

Answer 35

Asymptomatic hyperuricemia is NOT treated w/ drugs (only when attack has occured) Treat acute pain with anti-inflammatory drugs: --> Colchicine --> Steroids (including intra-articular injections) --> NSAIDs (often with a higher starting dose) Treat chronically to prevent future attacks: --> allopurinol or febuxostat If UA remains > 6 and pt is on tx, add: --> probenecid or lesinurad daily --> replace XOI with IV pegloticase (Krystexxa)

Question 36

Acute Gout tx: steroids

Answer 36

-steroids can be given PO,IM,Iv intra-articular or via ACTH (Corticotropin) which triggers endogenous glucocorticoid secretion --> Prednisone --> Methylprednisolone (Medrol) --> Triamcinolone -start high, then cut the dose down (taper) SEs: inc BG, BP, appetite -intra articular: localized joint damage

Question 37

Chronic gout tx: Xanthine Oxidase Inhibitors (XOI)

Answer 37

-blocks uric acid production, titrate to UA < 6 mg/dL --> Allopurinol (Zyloprim): 50-100 mg daily (lower doses for CKD- 50) -allopurinol hypersensitivity syndrome (AHS): severe rash, fever, eosinophilia, hepatitis & renal failure - test for HLA-B*5801 --> Febuxostat (Uloric) 40-80 mg qd, more $, may be safer in severe renal impairment, def risk for hypersen. rxn For both: monitor for liver damage, precipitation of acute attacks, nausea and skin rash

Question 38

Chronic gout tx: Uricosurics

Answer 38

-increase excretion of uric acid in the urine, require adequate renal function --> Probenecid --> Lesinurad (Zurampic)

Question 39

Chronic Gout tx: Recombinant Uricase

Answer 39

-converts uric acid to allantion, allows for excretion --> Pegloticase (Krystexxa) -IV q 2 weeks -anaphylaxis possible: pre-medicate with antihistamines and steroids -do not use in combination with allopurinal or febuxostat

Question 40

Tumor Lysis Syndrome

Answer 40

-due to cell lysis and purine released to the blood = converted to uric acid --> acute gout and electrolyte abnormalities --> allopurinol for prevention --> rasburicase (Elitek) for tx