Pain Flashcards
1
Q
Nociceptive vs. Neuropathic pain
A
Nociceptive: tissue damage stimulates sensory nerves releasing substances (ex. prostaglandins, substance P, and histmaine) which can result from injury to internal organs to skin, muscles, bones, joints, or ligaments
Neuropathic: damage or malfunction of nervous system (ex. fibromyalgia, diabetic neuropathy, chronic HAs, certain drug-induced toxicities - ex. vinca alkaloids)
2
Q
Acute vs. chronic pain and General TX
A
Acute: begins suddenly, usually sharp and nociceptive in nature
Chronic: persistent pain for three or more months, can persist w/ visible injury (ex. crushed lumbar vertebrae) or w/o visible pain (ex. osteoarthritis, diabetic neuropathy)
-Subdivided into cancer pain or chronic non-cancer pain
General TX:
-Mild pain (1-3): non-opioid +/- adjuvant
-Mild/moderate pain (4-6): opioid for mild/moderate + non-opioid +/- adjuvant
-Severe (7-10): opioid for moderate/severe +/- non-opioid +/- adjuvant
**Non-opioids = APAP, NSAIDs
**Adjuvants = antidepressants, anticonvulsants, muscle relaxants
3
Q
Acetaminophen:
-Brand
-MOA
-ROA
-Administration
-Dosing
A
Brand: Tylenol, FeverAll, Ofirmev
MOA: not well defined, but through to involve inhibition of prostaglandin (PG) synthesis in the central nervous system, resulting in reduced pain impulse generation
-Effects: pain and fever, but NOT anti-inflammatory
ROA: PO, rectal suppository (FeverAll), IV (Ofirmev)
Administration:
-Avoid using “APAP” abbreviation
-Injection: concentration of 10mg/mL in 100mL vials - caution w/ dosing (order as mg NOT mL and doses should be prepared in pharmacy
-Infant’s and children’s suspension: 160mg/5mL - use dosing syringe or dosing cup
Dosing:
-Pediatrics (<12 yo): 10-15mg/kg Q4-6H (max: 5 doses/day)
-Adults: maximum dose <4000mg/day from all sources
4
Q
Acetaminophen:
-AVEs
-Warnings
-BBW
-DDIs
-Overdose
A
AVEs: generally well tolerated w/ PO administration
Warnings: severe skin rxns, renal imapirment
BBW: severe hepatotoxicity (can require transplant or result in death) w/ doses >4 grams/day or use multiple APAP-containing products)
-Risk of 10-fold dosing errors w/ injection
DDIs: avoid or limit alcohol (hepatoxocitiy), can be used w/ warfarin but if used chronically (>2 g/day) and can increase INR
Overdose: N-acetylcystiene (NAC, Acetadote): glutathione precursor administered IV or PO –> Rumack-Matthew nomogram uses the serum APAP level and time since ingestion to determine whether hepatotoxicity likely and the need for NAC
5
Q
Acetaminophen Combination Brands:
1. With hydrocodone
- With oxycodone
- With codeine
A
- Norco, Vicodin
- Endocet, Percocet
- Tylenol #3 or #4
6
Q
Acetaminophen Combination Brands:
1. With caffeine
- With aspirin + caffeine
- With caffeine + pyrilamine
A
- Excedrin Tension Headache
- Excedrin Extra Strength or Excedrin Migraine
- Midol Complete
7
Q
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): MOA
-Non-selective NSAIDs
-Selective NSAIDs
-ASA
A
MOA: COX-1 and COX-2 enzymes catalyze conversion of arachidonic acid to prostaglandins and thromboxane A2 (TxA2)
-Non-selective NSAIDs: inhibit COX-1 and COX-2
-Selective NSAIDs: inhibit COX-2 only –> less GI AVEs since COX-1 protects grastric mucosa
-ASA: irreversible COX-1 and COX-2 inhibitor –> antiplatelet
8
Q
NSAIDs: Class AVEs and recommendations
A
- Decreased renal clearance - caution or avoid in renal failure or additive nephrotoxic drugs
- Increased BP - caution in controlled HTN, avoid in uncontrolled HTN
- Nausea - especially with salicylates, can be minimized CF, switching to EC or buffered product, or changing to different NSAIDs
- Photosensitivity - avoid sun exposure, sunscreen, sun-protective clothing
- Premature closure of ductus arteriosus - avoid in 3rd trimester of pregnancy
9
Q
NSAID Class BBWs and recommendations
A
- GI risk: increased risk of GI bleeds/ulcerations - greatest risk: hx of GI bleed or taking systemic steroids, SSRIs, SNRIs
- CV risk: increased risk of MI and stroke –> avoid use in CVD or risk factors
- Coronary artery bypass graft (CABG) surgery: CI after CABG –> antiplatelet (ASA) recommended after
10
Q
NSAIDs: list drugs per their MOA and discuss the benfits/risks of each class
-Non-selective NSAIDs (inhibit COX-1 and COX-2)
-Selective NSAIDs (increased COX-2 inhibition)
-Salicylate NSAIDs (which ones are non-acetylated salicylates)?
A
Non-selective: have GI and CV risk and risk in post-operative CABG setting –> ibuprofen, indomethacin, naproxen, ketorolac, piroxicam, sulindac
-Others (less commonly used): meclofenamate, mefenamic acid, ketoprofen, fenoprofen, flurbiprofen, oxaprozin
Selective NSAIDs: lower GI risk, but increased MI/stroke risk (avoid in CV risk and avoid higher dose and longer duration in pts for risk of CV disease), same risk for renal complications –> celecoxib, diclofenac, meloxicam, etodolac, nabumetone
Salicyclate NSAIDs: aspirin/acetylsalicyclic acid
-Non-acetylated: salsalate, magnesium salicylate, choline magnesium trisalicylate, diflunisal, salicylate salts
11
Q
NSAID Brand Names:
1. Ibuprofen
- Indomethacin
- Naproxen
A
- Advil, Motrin, NeoProfen (IV for closing the PDA)
- Indocin
- Aleve, Naprosyn
12
Q
NSAID Brand Names:
1. Ketorolac
- Celecoxib
- Diclofenac patch
A
- Toradol
- Celebrex
- Flector
13
Q
NSAID: Brand Names
1. Diclofenac Gel
- Meloxicam
- Aspirin
A
- Voltaren
- Mobic
- Ascriptin, Bufferin, Ecotrin, Bayer
14
Q
NSAID Brand Names
1. Magnesium salicylate
- Naproxen + esomeprazole
- Naproxen + sumatriptan
A
- Doan’s Extra Strength
- Vimovo
- Treximet
15
Q
Non-selective NSAIDs:
1. Ibuprofen dosing for adults and children. When using OTC, limit self-TX to under ___ days.
- _________ is high risk for CNS effects and should be avoided in psych conditions. It also has higher GI AVEs.
- Dosing for OTC naproxen. Why might prescribers choose naproxen?
A
- -Pediatrics: 5-10mg/kg/dose Q6-8H (max: 40mg/kg/day)
-Adults (OTC): 200-400mg Q4-6H (max: 1.2 grams/day) –> Rx max dose of 3.2 g/day
-Limit self TX to <10 days
- Indomethacin
- 220mg (200mg naproxen = 220mg naproxen sodium salt) Q8-12H –> prescribers may choose naproxen since the dosing can be BID
16
Q
Non-selective NSAIDs:
1. __________ is sometimes used in those w/ reduced renal function and pts on lithium who require an NSAID.
- What are some risks associated w/ piroxicam?
A
- Sulindac
- High risk of GI toxicity and severe skin rxns –> used whn other NSAIDs have failed and may require PPI for GI protection
17
Q
Ketorolac:
-Administration considerations
-AVEs
-Warnings
-BBWs
A
Administration:
-Nasal spray: one spray in each nostril for those <65 yo –> one spray in ONE nostril for those >/=65 yo
-Prime nasal spray five times before use –> no additional priming needed for additional doses, D/C 24 hours after opening
-Usually used after surgery, never before
AVEs: HA, injection site pain (often given IM)
Warnings: increased bleeding, acute renal failure, liver failure, anaphylactic shock
BBWs:
-Max combined duration IV/IM and PO/nasal is 5 days in adults
-PO ketorolac: for short-term moderate/severe pain ONLY as continuation of IV/IM ketorolac
-NOT for intrathecal or epidural use
-Avoid in advanced renal disease or at risk for renal impairment due to volume depletion, hypersensitivity rxns to ketolorac or other NSAIDs, labor and delivery, use w/ ASA or NSAIDs
-Dose adjustments needed in >/=65 yo or <50kg
18
Q
Selective NSAIDs:
1. __________ has the highest COX-2 inhibition while the rest have some selectivity. Selective NSAIDs have lower risk for ______AVEs, same risk of _____AVEs, and increased risk of _______ AVEs.
2.__________ is CI in sulfonamide allergy.
A
- Celecoxib; GI; renal; CVD/MI/Stroke
- Celecoxib
19
Q
Selective NSAIDs
1. Diclofenac is combined with _______ under the brand name _________ which has a BBW warning to avoid in females of childbearing potential unless capable of complying with effective contraceptive measures. What is the purpose of this combo?
- What is the maximum total dose for topical diclofenac? What is dosing for OTC?
A
- Misoprostol; Arthrotec –> used to replace gut-protective prostaglandins to decrease GI risk, but due to increased uterine contractions can terminate pregnancy and cause cramping/diarrhea
- 32 grams/day for total body
-OTC: 2 grams QID (max: 8mg/day) for hands, wrists, or elbows; 4 grams QID (max: 16mg/day) for feet, ankles, or knees
20
Q
Salicylate NSAIDs:
-Drugs/Brands
-Dose of ASA (cardioprotective)
-Administration considerations
A
Drugs: aspirin (Ascriptin, Bufferin, Ecotrin, Bayer, Durlaza, Vazalore), salsalate, magnesium salicylate (Doan’s Extra Strength), choline mangensium trisaslicylate, diflunisal, salicylate salts
ASA dosing (cardioprotective): 81-162mg PO QD
Administration:
-To decrease nausea, use EC or buffered product or CF –> Ecotrin, Bufferin
-*PPIs may be used for GI protection w/ chronic use *
-Do NOT use Durlaza or Yosprala when immediate effect needed (ex. acute MI)
-Methyl salicylate popular OTC found in BenGay, IcyHot, Thera-Gesic, Salonpas
21
Q
Salicylate NSAIDs:
-AVEs
-Warnings
A
AVEs: dyspepsia, heartburn, bleeding, nausea
-Toxicity can cause tinnitus
Warnings:
-Avoid w/ NSAID hypersensitivity (past rxn w/ trouble breathing), nasal polyps, asthma
-Avoid ASA in children and teenagers w/ any viral infection (Reye’s Syndrome: somnolence, N/V, lethargy, confusion)
-Severe skin rxns (rare)
-GI ulceration and bleeding
-Avoid in 3rd trimester of pregnancy due to fetal harm
22
Q
NSAIDs: DDIs
A
- Additive bleed risk: steroids, SNRIs, SSRIs, antiplatelets, anticoagulants
- Caution using ASA w/ other ototoxic agents (ex. aminoglycosides, IV loop diuretics)
- Can increase levels of lithium and methotrexate
- Multiple NSAIDs should NOT be used together –> except in addition to low-dose ASA for cardioprotection (if using ASA and ibuprofen: take ASA one hour before or eight hours after ibuprofen)
23
Q
Define opioid-related terminology:
1. Physical dependence
2. Addition
3. Opioid use disorder (OUD)
A
Physical dependence: physical withdrawl symptoms when opioid stopped or dose is late/missed (ex. anxiety, tachycardia, shakiness, SOB)
Addiction: strong desire or compulsion to take drug despite harm, involving drug-seeing behavior (ex. exaggerating pain or physical impairment, RX forgery, doctor shopping)
OUD: problematic pattern of opioid use cuasing impairment or distress
24
Q
Define opioid-related terminolgoy
1. Tolerance
2. Opioid hyperalgesia
3. Break-through pain (BTP)
A
Tolerance: higher opioid dose needed to produce same level of analgesia that a lower dose previously provided
Opioid hyperalgesia: when dose is increased, pain becomes worse (try another different class of analgesic or another opioid)
BTP: sharp spikes of severe pain despite use of an ER opioid (must be treated w/ IR or fast-acting analgesic)
25
*Opioids:*
-MOA
-All opioids are CIIs except which ones?
MOA: mu receptor agonists within CNS to provide pain relief, but also cause euphoria and respiratory depression
-Full mu receptor opioid agonists: codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone
-Buprenorphine: partial mu-opioid agonist
C-III: buprenorphine, codeine/APAP
C-V: codeine oral solution in combo products (ex. cough syrups)
26
Opioids: class AVEs
-*Constipation*
-*N/V (especially w/ acute, high-dose use)*
-*Somnolence, dizziness/lightheadedness*
-*Seizures*
-Opioid-induced hyperalgesia,
-*Respiratory depression*
-Pruritus (especially in opioid-naive pts and morphine --> *can use Benadryl*)
27
*Opioids: class BBWs*
1. Addiction, abuse, and misuse leading to overdose and death
2. Respiratory depression which can be fatal --> use w/ BZD or other CNS depressants (including alcohol can increase this risk)
3. Accidental ingestion/exposure of even one dose in children can be fatal --> never give medication to anyone else including patches
4. Crushing, dissolving, or chewing long-acting products can deliver potentially fatal dose
5. Life-threatening neonatal opioid withdrawl can occur w/ prolonged use in pregnancy
6. Morphine ER capsules, Nucynta ER, oxymorphone ER, and hydrocodone ER capsules --> do NOT consume alcohol, can increase drug plasma levels leading to fatal overdose
28
*Opioid Brand Names:*
1. Fentanyl
2. Buprenorphine patch
3. Buprenorphine buccal film
4. Hydrocodone/APAP
1. Sublimaze, Duragesic
2. Butrans
3. Belbuca
4. Norco, Vicodin
29
*Opioid Brand Names:*
1. Methadone
2. Meperidine
3. Morphine ER
4. Hydromorphone
1. Methadose
2. Demerol
3. MS Contin
4. Dilaudid
30
*Opioid Brand Names:*
1. Morphine injection
2. Oxycodone IR
3. Oxycodone ER
4. Oxycodone/APAP
1. Duramorph, Infumorph
2. Roxicodone
3 OxyContin
4. Endocet, Percocet
31
Codeine:
-TX
-AVEs
-Warnings
-CIs
-BBW
TX: *antitussive*
AVEs: *high degree of GI AVEs including constipation*
Warnings: adolescents betwen 12-18 who are obese or have sleep apnea or severe lung disease and are at risk for breathing problems, breastfeeding
CIs: *do NOT use in children <12 yo for any indication and <18 yo following tonsillectomy/adenoidectomy surgery *
-FDA recommends avoiding cough and cold medicine for any child <18 yo
BBW: *respiratory depression and death in children found to be ultra-rapid metabolizers of codeine due to CYP2D6 polymorphisms after tonsillectomy and/or adenoidectomy*, use w/ CYP2D6 inducers or inhibitors should be carefully considered
32
Fentanyl Patch: Counseling
1. *Apply 1 patch Q72H (can be Q48H) - available in different strengths as mcg/hr*
2. Analgesic effect can be seen 8-16 hours after application - D/C all-around the clock opioids when patch applied
3. *Do NOT apply more than 1 patch at a time. Apply to hairless skin (cut hair short if needed)*
4. *Can be covered only with permitted adhesive film dressings BIoclusive or Tegaderm --> do NOT cover with heating pad* or any other bandage
5. Some patches need to be removed prior to MRI - refer to manufacturer
6. *Dispose of patch by flushing down toilet and keep away from children and pets*
33
Fentanyl:
-AVEs
-BBW
AVEs: hyperhidrosis (excessive sweating), dry mouth, asthenia, loss of appetite, *application site rxns/erythema (patch)*
BBW: potential for medication erros when converting between different dosage forms, *use w/ strong or moderate CYP3A4 inhibitors can result in increased effects and potentially fatal respiratory depression*, avoid exposing transdermal fentanyl extrenal heat
34
Fentanyl:
-Other formulation considerations beyond patch
-What are similar IV drugs?
Other formulations:
-*Patch and lozenge: NOT used in opioid-naive pts; a pt who has been using equivalent to morphine 60mg/day or more for at least 7 days can be converted to patch*
-Lozenge: cut off stick and flush unused/unneeded doses
-IV: short T1/2 --> boluses given Q1-2H, often given as CIV or PCA
-Transmucosal IR (lozenge, buccal tabs, SL): REMS program that requires documentatoin of pt's opioid tolerance w/ each prescription for cancer breakthrough pain
Similar IV drugs: alfentanil (Alfenta), *remifentanil* (Ultiva), sufentanil (Dsuvia)
35
Buprenorphine:
-Administration considerations
-AVEs
-Warnings
-BBW
Administration:
-Film: apply between gum and cheek tissue
-Butrans (patch): *can only be covered w/ Bioclusive or Tegaderm* (medical adherence coverings), do NOT expose to heat, *fold sticky sides together and flush down the toilet or put in disposal unit included in drug packaging*
AVEs: dizziness, sedation, HA, confusion, mental and physical impairment, diaphoresis, QT prolongation, respiratory depression (dose-dependent)
-Patch: *application site rxns* (pruritus, erythema, or rash), N/V, constipation, somnolence, dry mouth
Warnings: CNS depression, severe dental AVEs w/ buccal formulations
BBW (Butrans): QT prolongation (do NOT exceed one 20mcg/hr patch at a time)
36
Hydrocodone:
-Administration considerations
-AVEs
-Warnings
-BBW
Administration:
-Hydrocodone-containing cough and cold preparations NO longer indicated in children <18 yo
-ER: available in abuse-deterrent formulations, preferably avoid if breastfeeding
-*APAP component in IR: 325mg*
-Hysingla ER: QT prolongation in doses >160mg/day
AVEs: pruritus, dry mouth
Warnings (APAP + opioids): respiratory and/or CNS depression, constipatoin, hypotension, skin rxns (rare), caution in liver disease (avoid or limit alcohol intake), and in CYP2D6 poor metabolizers
BBW: *initiation of CYP3A4 inhibitors (or stopping inducers) can cause fatal overdose*
37
Hydromorphone:
-Dose for PO and IV
-Administration considerations
-AVEs
-BBW
*Dosing:*
-PO: 2-4mg Q4-6H PRN
-IV: 0.2-1mg Q2-3H PRN
Administration:
-*Potent (high risk of overdose)--> start low, convert carefully*
-Commonly used in PCAs and epidurals
-ER tablet: abuse-deterrent formulation (crush and extraction resistant --> CI in opioid-naive pt
-Two week washout required between hydromorphone and MAOIs
'
AVEs: pruritus, dry mouth, hyperhidrosis
BBW: *risk of medication error w/ high potency (HP) injection (use in opioid-tolerant pts only*: HP injection 10mg/mL more concentrated than standard - ex. 1mg/mL, 2mg/mL)
38
Methadone:
-Dosing consideration
-TX
-AVEs
-Warnings
-BBWs
Dosing consideration: *variable T1/2 making it hard to dose safely*
TX: heroin detox, pain
AVEs: hyperhidrosis
-Can *decrease testosterone* and contribute to sexual dysfunction
Warnings:
-Combination w/ other serotonergic drugs or MAOIs can increase risk of serotonin syndrome, also blocks reuptake of NE
-Caution in elderly and seizure hx
*BBWs:*
-Life-threatening QT prolongation and serious arrhythmias (ex. TdP) have occured w/ large, multiple daily doses and should be prescribed by professionals who know requirements for safe use
-Initiation of CYP450 inhibitors or stopping inducers can cause fatal overdose (major CYP3A4 substrate)
39
Meperidine:
-Administration considerations
-AVEs
-Warnings
Administration:
-*No longer recommended as analgesic*, avoid for chronic pain (if for acute pain, use short-term or single use)
-*Short duration of action* (pain controlled for a max of 3 hours)
AVes: hyperhidosis
Warnings: *renal impairment/elderly at risk for CNS toxicity (normeperidine is a metabolite renally cleared that can cause CNS toxicity including seizures), avoid with or within 2 weeks of MOAIs (serotonergic)*
40
Morphine:
-Administartion considerations
-AVEs
-BBW
Administration:
-Do NOT use MS04 or MS abbreviations for morphine or magnesium
-Do NOT crush or chew any ER products --> ER capsules can be opened and sprinkled on applesauce or soft food
-Renal impairment: start at lower dose or avoid morphine due to accumulation of active metabolite
AVEs: *pruritus (histamine-induced --> can use Benadryl)*, dry mouth, hyperhidosis
BBW: medication errors w/ oral soluation (note strength), appropriate staff and equipment needed for intrathecal/epidural administration
41
Oxycodone:
-Administration considerations
-AVEs
-BBW
Administration:
-Abuse-deterrent formulations: Oxaydo, OxyContin, Xtampza ER
-Xampza ER capsules can be opened and contents administered w/ soft food or through a gastric tube
-Avoid high fat meals w/ higher dsoes except re-formulated OxyContin
-Renal impairement: start at lower doses or avoid oxycodone due to accumulation of active metabolite
AVEs: *pruritus*, dry mouth, hyperhidrosis
BBW: *initiation of CYP3A4 inhibitors* or stopping inducers can cause fatal overdose, caution w/ oxycodone oral solution and oral concentrate (confusion between mg and mL and different concentrations)
42
Oxymorphone: Administration
1. *Take on an empty stomach*
2. Do NOt use w/ moderate/severe liver impairment --> use low doses in elderly, renal, or mild liver impairment due to higher drug concentrations
43
*Opioids: DDIs*
1. CNS depressants (increased risk of respiratory depression): alcohol, hypnotics, BZDs, muscle relaxants --> avoid alcohol in ALL opioids especially ER formulations
2. Increased risk of hypoxemia w/ underlying respiratory disease (ex. COPD, sleep apnea)
3. Methadone: caution in agents that worsen cardiac function or increase arrhythmia risk including QT prolongation, caution w/ other serotonergic drugs and those that worsen renal fxn
4. Hydrocodone, fentanyl, methadone, and oxycodone: CYP3A4 substrates --> avoid use w/ inhibitors
5. Serotonergic: methadone, meperidine, tramadol, tapentadol
44
Opioid: Conversions
1. When is it appropriate to consider switching to another opioid?
2. Conversions between IV/IM and PO morphine, hydromorphone, and oxycodone
3. Steps to the calculation
4. What are the exceptions to conversions?
1.
-Dose increased or interval shortened and pain relief NOT adequate
-Side effects are intolerable
-Drug unaffordable or not included on formulary
-Changing formulations from IV to PO
2.
-*Morphone: 10mg IV/IM, 30mg PO
-Hydromorphone: 1.5 IV/IM, 7.5mg PO
-Oxycodone: 20mg PO*
3.
-*Calculate total 24 hour dose of current drug
-Use ratio conversion to calculate dose of new drug
-Calcuate 24-hour dose of new drug and reduce dose by >/=25% for cross-tolerance (if the exam does NOT specify to reduce, calculate the equivalent dose and do NOT reduce)
-Divide for ther new drug's appropriate interval and dose
-Always have medication available for breakthrough pain while making changes (dosing ranges from 5-17% typically 10-15% of TDD baseline opioid dose typically Q1-2H PRN --> for elderly, 5% of TDD Q4H PRN)*
4.
-*Fentanyl patches: follow specific instructions given on exam --> use dosing table provided (remember to be aware of converting mcg --> mg and vice versa)
-Methadone: due to highly variable T1/2, separate conversion charts for pain specialists*
45
*Opioids: Side Effects*: In a true allergy (NOT itching or rash), switch opioid to a different chemical class. What are the drugs likely to cross-react?
-Common drugs in same chemical class that cross-react have cod or morph in the name (ex. codeine, hydrocodone, oxycodone, morphine, hydromorphne, oxymorphone)
-Buprenorphine: has norph instead of morph, but does cross-react
-Tramadol allergy likely to cross-react w/ tapentadol
-In morphine group allergy: fentanyl, meperidine, methadone, tapentadol
46
*Opioid: Side Effects*
1. Most side effects of opioids lessen overtime except _________. What drugs can be taken to alleviate this?
2. All oral opioids should be taken with food to lessen nausea except for ____________.
3. Which patients are at greater risk for respiratory depression?
1. Constipation; TX:
-First line: stimulant laxatives (ex. senna, bisacodyl) or osmotic laxatives (ex. PEG)
-After OTC laxatives failed: peripherally-acting mu-opioid receptor antagonists (ex. methylnaltrexone, naloxegol, naldemedine) or lubiprostone (Cl channel activator)
2. Oxymorphone
3. Hx of previous overdose, substance use disorder, using large doses (>/=50mg morphine or equivalent), use w/ BZDs/gabapentin/pregabalin, comorbid illnesses (ex. respiratory or psychiatric disease)
47
Peripherally-acting mu-opioid receptor antagonists (PAMORAs):
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
Drugs: *methylnaltrexone (Rellistor), naloxegol (Movantik)*, naldemedine (Symproic)
MOA: *inhibits opioid receptors in the gut to reduce constipation w/o affecting analgesia*
ROA: PO, injection (methylnaltrexone)
Administration:
-Stay close to toilet after injecting
-D/C all laxatives prior to use
TX: *opioid-induced constipation (OIC) - only for those who have failed OTC laxatives*
48
Peripherally-acting mu-opioid receptor antagonists (PAMORAs):
-AVEs
-Warnings
-CIs
AVEs: *abdominal pain*, flatulence, diarrhea, nausea, dizziness
Warnings: *risk of GI perforation* (rare: monitor for severe abdominal symptoms)
-Methylnaltrexone: use >4 months has NOT been studied, D/C if opioid D/C or if severe/persistent diarrhea
CIs: GI obstruction
-Naloxegol: do NOT use w/ strong CYP3A4 inhibitor (ex. grapefruit juice)
49
Tramadol:
-Brand
-MOA
-ROA
-Control schedule
Brand: Ultram, ConZip
MOA: *centrally acting analgesic (mu-opioid receptor agonist, inhibitor of NE and 5-HT reuptake)*
ROA: PO
Control schedule: *CIV*
50
Tramadol:
-AVEs
-Warnings
-CIs
-BBWs
AVEs: *dizziness, constipation, nausea, somnolence* or insomnia, dry mouth, pruritus, flushing, HA, asthenia
-Lowever severity of GI AVEs vs. strong opioids
-On Beers list: postmarketing reports of hyponatremia and SIADH
Warnings: *seizure risk* (avoid in seizure hx, head trauma), *serotonin syndrome (risk w/ serotonergic drugs or CYP2D6 or 3A4 inhibitors)*, CNS depression, *hypoglycemia*, respiratory depression (rare), avoid in suicidal pts, risk of serious breathing problems in 12-18 yo w/ obesity/sleep apnea/lung diseae, breastfeeding mothers should avoid due to increased risk of breathing problems in infants
CIs: *children <12 yo or children <18 yo following tonsillectomy/adenoidectomy, use w/ MOAIs within 14 days*
BBWs: *respiratory depression and death in children following tonsillectomy/adenoidectomy as ultra-rapid metabolizers (CYP2D6 polymorphism)*, use w/ CYP3A4 or 2D6 inhibitors should be carefully considered due to variable effects
51
Tapentadol:
-Brand
-MOA
-ROA
-Control Schedule
Brand: Nucynta, Nucynta ER
MOA: *centrally acting analgesic (mu-opioid receptor agonist, inhibitor of NE reuptake)*
ROA: PO
Control schedule: *CII*
52
Tapentadol:
-Comparison to tramadol
-AVEs
-Warnings
-CIs
Comparison to tramadol: *stronger analgesic*
AVEs: *dizziness, constipation, nausea, somnolence* or insomnia, dry mouth, pruritus
-Lower severity of GI AVEs vs. strong opioids
Warnings: *can increase seizure risk* (avoid in seizure hx or risk), *risk of serotonin syndrome* with other serotonergic drugs
CIs: use with MAOIs within 14 days
53
Opioid Overdose:
-S/Sx
-Steps in management
-Drugs used in TX
-Acute withdrawl symptoms
S/Sx: *extreme sleepiness, slow or shallow breathing, fingernails or lips turning blue or purple, extremely small "pinpoint" pupils, slow HR, and/or BP*
*Management:*
1. Call 911 and give naloxone (If question about whether to give naloxone, give naloxone)
2. If NOT breathing or struggling to breathe, support measures should be performed
3. After administering naloxone, monitor for signs of respiratory depression. Provide repeat doses if needed after 20-60 minutes.
*Two forms of nalaxone:*
-Nasal Spray: 3-4mg/spray (OTC, Narcan), 4-8mg/spray (RX, RiVive) --> spray in one nostril and may repeat Q2-3 minutes in altering nostrils until emergency medical assistance arrives (onset of action slower than injection)
-Injection: provided in multiple size vials, repeat Q2-3 minutes until emergency medical assistance arrive
Alternative to naltrexone: *nalmefene nasal spray or injection *
Acute withdrawl symptoms: *pain*, anxiety, tachypnea, agitatoin, diarrhea
54
Drugs used for opioid use disorder (OUD) and their considerations
1. Buprenorphine - *partial agonist at LOW doses, but antagonist at high doses; can be combined w/ naloxone (Suboxone: SL film, Zubsolv: SL tablet)*
-Sublocade (SC injection): pts must have been taking stable dose of transmucosal buprenorphine for 7 days prior to initiation
-Butrans (patch): apply weekly
2. Methadone* - can be for TX of pain and OUD
3. *Naltrexone (Vivitrol): opioid antagonist, blocking effects of alcohol and opioid*
-Tablet taken QD or injection Qmonth
-Do NOT initiate until pt is opioid free for at least 7-10 days (or longer for long-acting opioids)
4. *Lofexidine (Lucemyra): non-opioid alpha-2 adrenergic agonist that is NOT specifically indicated for OUT, but can help withdrawl symptoms who abruptly stop opioid use*
-Can reduce efficacy of PO naltrexone
-Paroxetine and other CYP2D6 inhibitors can increase risk of orthostatic hypotension and tachycardia
55
Gabapentin:
-Brand
-MOA
-ROA
-Administration considerations
Brand: *Neurontin*, Gralise, Horizant
MOA: anticonvulsant
ROA: PO
Administration:
-Take ER formulation CF
-IR, ER, and gabapentin enacarbil are NOT interchangeable
56
Gabapentin:
-TX
-AVEs
-Warnings
TX: Horizant -*postherapeutic neuralgia (PHN) and restless syndrome*
-Off-label for fibromyalgia, neuropathic pain, HA, alcohol use disorder, alcohol withdrawl
AVEs: *dizziness, somnolence, peripheral edema/weight gain*, ocular effects (diplopia, blurred vision), ataxis, nystagmus, tremor, dry mouth, mild anxiolytic (scheduled in some states)
Warnings: angioedema/anaphylaxis, multiorgan hypersensitivity (DRESS) rxns, suicidal thoughts or behaviors (all ASMs), increased seizure frequency if rapidly D/C in those w/ seizures, CNS depression (if possible, avoid other CNS depressants), if prescribed w/ opioid use lowest dose possible
57
Pregabalin:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
Brand: *Lyrica*
MOA: anticonvulsant
ROA: PO
TX: *fibromyalgia, postherapeutic neuralgia, neuropathic pain associated w/ DM and spinal cord injury*
AVEs: *dizziness, somnolence, peripheral edema/weight gain, mild anxiolytic (CV)*, diplopia, ataxia
Warnings: angioedema, hypersensitivity rxns, risk of suicidal thoughts or behvaior (all ASMs), increased seziure frequency if rapidly D/C in those w/ seizures, CNS depression (if possible, avoid other CNS depressants), if prescribed w/ opioid use lowest dose possible
58
Muscle Relaxants: Antispasmodics w/ analgesic effects
-Drugs/Brands
-ROA
-Administration considerations
Drugs: *baclofen (Lioresal), cyclobenzaprine (Amrix, Fexmid*, Flexeril - D/C), *tizanidine (Zanaflex)*
ROA: PO
Administration (baclofen, cyclobenzaprine): caution in elderly (start low, titrate carfeully), cyclobenzaprine caution in heart disease (can precipitate or exacerbate cardiac arrhythmias --> similar structure to amitriptyline)
59
Muscle Relaxants: Antispasmodics w/ analgesic effects
-AVEs
-CIs
-BBW
AVEs: excessive *sedation, dizziness, confusion, asthenia (muscle weakness)*
-Baclofen: nausea, HA, constipation, hypotension, seizures
-*Cyclobenzaprine: dry mouth, serotonergic (do NOT combine w/ other serotonergic agents)
-Tizanidizine (centrally-acting alpha-2 agonist): hypotension, dry mouth*, increased LFTs
CI (tizanidine): use w/ strong CYP1A2 inhibitors (ex. fluvoxamine, ciprofloxacin)
BBW (baclofen): abrupt withdrawl of intrathecal baclofen has resulted in severe effects (high fever, lethargy, reboud/increased spasciticity, muscle rigidity, rhabdomyolysis, leading to organ failure/death)
60
Adjuvant drugs for pain:
1. What are muscle relaxants that are considered antispasmodics that exert their effects through sedation?
2. _________ metabolizers will have increased Soma concentrations.
3. _________ anticonvulsant is approved for trigeminal neuralgia.
1. *Carisoprodol (Soma*, Vanadom), metaxalone (Skelaxin), *methocarbamol (Robaxin)*
-Rarely used: *dantrolene (Dantrium - for malignant hyperthermia)*, chlorzoxazone (Lorzone), orphenadrine
2. *CYP2C19 poor metabolizers*
3. *Carbamazepine*
61
Adjuvant drugs for pain:
1. What antidepressants are approved for neuropathic and musculoskeletal pain?
2. _________ is an SNRI approved for fibromyalgia ONLY and NOT depression.
3. Brand names for methyl salicylate and trolamine. What is the occassional risk w/ these agents?
1. *Amitriptyline*, desipramine (Norpramin), *duloxetine (Cymbalta*, Drizalma Sprinkle)
2. Milnacipran (Savella, Savella Titration Pack)
3. *methyl salicylate (BenGay, IcyHot, Salonpas*, Thera-Gesic), *trolamine (Aspercreme)* --> occasionally causes first to third-degree burns mostly in pre-existing neuropathic damage (D/C and seek medical attention if pain, swelling, or blistering occurs)
62
Lidocaine patch: Counseling
1. *Apply to painful area 1-3 patches/day and wear up to 12 hours/day (approved for PHN in shingles)
-Lidoderm (patches): do NOT apply more than three patches at one time*
2. *Can cut into smaller pieces before removing backing*
3. *When done w/ patch, fold in half and safely discard from children and pets*
4. Do NOT cover w/ heating pads or electric blankets
5. DO NOT use on broken, abraded, severely burned skin or skin with open lesions (can significantly increase amount absorbed)
63
Capsaicin:
-Brand
-MOA
-ROA
-Dosing
-Administration considerations
-AVEs
Brand: *Zostrix (OTC), Zostrix HP (OTC)*, Quetenza (RX)
MOA: decreases TRPV1-expressing nociceptive nerve endings which *decreases substance P*
ROA: topical
*Dosing:*
-Capsaicin 0.025% (Zostrix) or 0.075% (Zostrix HP) cream
-Apply TID to QID
Administration:
-Onset of pain relief takes 2-4 weeks of continuous application for OTC products and 1 week for Quetenza
-*Do NOT touch genitals, nasal area, mouth, or eyes after application. Wash hands after application (if treating hands, leave for 30 minutes then wash hands)*
-Qutenza: applied in HCP for PHN pain --> causes topical burning and requires pre-TX w/ lidocaine, applied for 1 hour and effect lasts for months
AVEs: topical burning which dissipates with continued use
64
Headaches:
-S/Sx of tension headaches
-S/Sx of migraines
-S/Sx of serious CDV, cerebrovascular, or infection events that require medical attention
Tension HA: pressure or tightness around head
Migraines: *chronic HA that lasts for hours or days that can cause N/V, sensitivity to sound/light*, are often on one side of head, and *may have auras* (sensory warnings: ex. flashes of light, blind spots, or tingling in arms/legs)
S/Sx pt needs medical attention: *fever, stiff, neck, rash, confusion, seizures, double vision, weakness, numbness, chest pain, SOB, aphasia (trouble speaking)
-"First or worst" HA*
65
Migraines:
-Pathophysiology
-Triggers
Pathophysiology: NOT well understood --> may be caused by increased neuronal activity (ex. imbalance of neurotransmitters including *5-HT* and/or activation of trigeminal nerve leading to release of *calcitonin gene-related petptide = CGRP)* that lead to neurogenic inflammation and vasodilation
Triggers: *stress, sensory stimuli (bright lights, sun glare, loud sounds, certain scents - unpleasant or not), changes in wake-sleep pattern, changes in environment (ex. weather, barometric pressure)*
-Common *food* offenders: alcohol (especially beer and red wine), aged cheese, chocolate, aspartame, overuse of caffeine, monosodium glutamate (MSG), salty foods, processed foods
-*Hormonal changes in women: fluctuations in estrogen --> continuous or extended cycles can help reduce, progestin-only or nonhormonal contraceptive recommended in migraine w/ aura to reduce stroke risk*
66
Migraines: Diagnosis
*At least five attacks (no set time - can be over years) where HA must meet the following*
1.* Last 4-72 hours*
2. Have 2 or more of the following: *unilateral location, pulsating*, moderate/severe pain, aggravated by routine physical activity
3. *One of the following occurs w/ HA: nausea and/or vomiting, photophobia, phonophobia*
67
Migraines:
-Nonpharmacotherapy TX
-Natural products
-Medication Overuse HA TX
Nonpharmacotherapy: *HA diary to identify triggers*, cold compresses, massage, acupuncture, transcutaneous electrical nerve stimulation (TENS) units, remote electrical neuromodulation (REN) devices
Natural products: *riboflavin (vitamin B2), magnesium, butterbur, feverfew*, peppermint (topically), and coenzyme Q10 have been used for prevention
Medication Overuse HAs: HA that occurs >/=15 days per month --> *limit acute HA treatment*
-If drug contains opioid or butalbital, slow taper needed
68
Migraines:
-Acute Drug TX
-Drugs to avoid in migraines and why
Acute Drug TX: try to limit to no more than 2-3 times/week
-*OTC options (mild/moderate):* APAP, ASA, ibuprofen, naproxen, combo products (ex. Excedrin migraine: ASA/APAP/caffeine) --> caffeine acts as vasoconstrictor
-RX options: *NSAIDs at higher doses or alternative options NOT available OTC, serotonin receptor agonists (triptans), CGRP receptor antagonist*, ergotamine drugs, lasmiditan
-Antiemetic can be considered in migraines w/ N/V
Avoid: *butalbital-containing products, opioids, tramadol, tapentadol --> decrease efficacy, abuse/dependence potential, and risk of rebound headache (MOH)*
-Last line if nothing else works
69
Triptans:
-MOA
-TX
-Triptans should NOT be taken for more than ______ days of the month to avoid medication overuse HA.
MOA: selective agonists for 5-HT1 receptor (1B/1D subtypes) to induce constriction of blood veseels, inhibiting neuropeptide release and decrease pain transmission
TX: *acute treatment at first sign of migraine*
MOH: no more than 10 days
70
*Which triptans come as: tablets, ODT, spray, powder, SC injection (prefilled syringe/vial vs/ autoinjector)?*
-ODT: rizatriptan (Maxalt-MLT), zolmitriptan (Zomig ZMT)
-Spray: sumatriptin (Imitrex), zolimitriptan (Zomig)
-Sumatriptan: also comes as powder (Onzetra Xsail), prefilled syringe/vial, and autoinjector (Imitrex STATdose System, Zembrace SymTouch)
71
Triptrans:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: *paresthesia (tingling/numbness),* dizziness, hot/cold sensations, chest pain/tightness, dry mouth, somnolence, nausea, unpleasant taste, vision loss
-*Triptan sensations (pressure or heaviness in chest or pressure in neck region) usually disipate after administration*
Warnings: *increased BP, serotonin syndrome,* cardiac and cerebrovascular events, arrhythmias, MOH, seizures (sumatriptan only), caution in hepatic or renal impairment (product specific)
CIs: *cerebrovasular disease (stroke/TIA), uncontrolled HTN, ischemic heart disease*, coronary artery vasospasm, peripheral vascular disease, hx of hemiplegic or basilar migraine, *use within 24 hours of another triptan or ergotamine-type medication*
DDIs:
-*Sumatriptan, rizatriptan, zolmitriptan: CI w/ MAOI within 14 days*
-*Caution w/ other sertonoergic drugs*
-Use w/ strong CYP3A4 inhibitors: electriptan CI, reduce dose of almotriptan
72
*Triptans: Administration considerations*
1. Which formulations are useful if nausea is present?
2. Which formulations work the fastest?
3. How many doses do nasal sprays contain?
1. ODTs, oral films, nasal sprays, injections
2. Nasal sprays, injections
3. ONE dose (do NOT prime) --> only goes in one nostril
73
*Triptans: Administration considerations*
1. Nasal powders are given in one nostril or both nostrils?
2. Injections are given ___(SC/IM) in the _________ or __________.
3. Doses can be repeated, but when should they NOT be repeated?
1. BOTH nostrils
2. SC; lateral thigh or upper arm
3 If the patient experiences NO relief..if partial relief, then take another dose
74
Triptans: Administration considerations
1. Sumtratriptan is typically given as one dose and can be repeated in two hours except which formulations?
2. The majority of triptans are also given as one dose and can be repeated in two hours except for _______ which can be repeated in four hours.
3. _________ has the longest T1/2 and both _________ and _______ are considered long-acting with slower onset. These can be chosen if HA is expected to last long or anticipated. All others are shorter T1/2 with faster onset.
1.
-*SC injection: can repeat in 1 hour (Zembrace SymTouch can be given 4 times/day)*
-Tosymra (spray): can repeat in 1 hour (other spray = Imitrex --> repeat in 2 hours)
2. Naratriptan
3. *Frovatriptan; Frovatriptan and Naratriptan*
75
*Triptans: Administration considerations*
1. Which drugs/formulations are approved in children >/=12 yo and >/=6 yo?
2. _______ should be protected from moisutre and dispensed in original container.
3 _______ contains phenylalanine and should NOT be used in phenylketonuria.
1.
-Children >/=6 yo: rizatriptan (tablets, ODT)
-Children >/=12 yo: almotriptan tablets, zolmitriptan nasal spray, RizaFIlm (rizatriptan ODT), Treximet (sumatriptan/naproxen)
2. Treximet
3. Maxalt-MLT ODT (rizatriptan)
76
Ergotamine Drugs:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
Drugs: *dihydroergotamine (Migranal*, Trudhesa D.H.E. 45), ergotamine (Ergomar), ergotamine/caffeine (Migergot, Cafergot)
MOA: *nonselective agonist of serotonin receptors, causing cerebral vasoconstriction*
ROA: *injection (SC, IM, or IV - DHE 45, nasal spray (Migranal),* SL tablet (ergotamine), tablet/suppository (Migergot, Cafergot)
Administration (nasal spray): *prime* by pumping four times, do NOT inhale deeply (to let drug absorb into skin of nose)
TX: *migraines not relieved w/ triptans*
77
Ergotamine Drugs:
-AVEs
-Warnings
-CIs
-BBW
AVEs: N/V; Nasal spray: rhinitis, dysguesia, local irritation
Warnings: *CV events (avoid in baseline risk), cerebrovascular events*, ergotism (intense vasoconstriction results in peripheral vascular ischemia and possible gangrene -presents as intense pain in arm or leg and cold), cardiac valvular fibrosis, MOH, *potentially serious DDIs*
CIs: *uncontrolled HTN, ischemic heart disease* (angina, MI), coronary artery vasospams, peripheral vascular disease, *pregnancy*, hemiplegic or basilar migraine, renal/hepatic impairment, sepsis, use w/ pressors/vasoconstrictive drugs, *use within 24 hours of serotonin agonists (triptans) or other ergotamine-type drugs*
BBW: *potent CYP3A4 inhibitors (PIs, macrolides) due to life-threatening peripheral ischemia*
78
Calcitonin gene-related peptide (CGRP) Receptor Antagonists:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
Drugs: rimegepant (Nurtec), ubrogepant (Ubrelvy), zavegepant (Zavzpret)
MOA: *inhibits CGRP from causing vasodilation and neurogenic inflammation*
ROA: *ODT (rimegepant)*, tablet (ubrogepant), nasal spray (zavegepant)
Administration:
-Safety of treating >8 migraines/month (ubrogepant, zavegepant) OR using >18 doses/month (rimegepant) has NOT been established
-Ubrogepant: can repeat dose if needed
TX:
-*Acute migraine: ubrogepant
-Prevention and TX of acute migraines: rimegepant*
79
Calcitonin gene-related peptide (CGRP) Receptor Antagonists:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: nausea, somnolence, taste disorder (zavegepant)
Warnings (rimegepant): hypersensitivity rxns including delayed serious rxns
CIs: do NOT use w/ strong CYP3A4 inhibitors (ubrogepant only, but caution in rimegepant)
DDIs (rimegepant and ubrogepant): major CYP3A4 substrates and minor P-gp substrates
-Moderate or weak CYP3A4 inhibitor or P-gp inhibitor: ubrogepant starting dose of 50mg
-Moderate or weak CYP3A4 inducer: ubrogepant starting dose of 100mg
-Avoid using second dose of rimegepant within 48 hours in pt taking moderate CYP3A4 inhbiitor or P-gp inhibitor
80
Lasmiditan:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-Warnings
Brand: Reyvow
MOA: *first-in-class serotonin agonist selective for 5-HT1F receptor subtype - does NOT cause vasoconstriction*
ROA: PO
Administration:
-*Since it does NOT cause vasoconstriction, NOT CI in CVD unike triptans or ergotamine drugs*
-Safety of treating >4 migraines/month has NOT been established
-*Schedule CV*
TX: *acute migraine*
AVEs: dizziness, fatigue, paresthesia
Warnings:
-CNS depression, including significant driving impairment (should NOT use if pt cannot wait at least 8 hours after dose to drive or operate heavy machinery) --> caution if taking other CNS depressants
-May cause serotonin syndrome w/ or w/o other serotonergic drugs
-May decrease HR (caution in drugs that decrease HR)
81
Migraine Prophylaxis:
1. When is prophylaxis indicated?
2. How long is the trial of prophylaxis?
3. An antihypertensive medication with the best evidence for prophylaxis is ______. What are alternatives?
1. *Has had 4 or more migraines/month, migraines decraese QOL*, if other acute TXs are ineffective/CI/not tolerated, or if pt requests
2. 2-6 months
3. *Propranolol; alternatives: other beta-blockers (timolol or metoprolol succinate/tartrate)*, lisinopril, or candesartan
-Propranolol XL is NOT FDA-approved for migraine prophylaxis
82
Migraine Prophylaxis:
1. What are some antiseizure medications used for prophylaxis?
2. Which CGRP receptor antagonists can be used for prophylaxis? How are they administered/dosing frequency?
3. What are other options besides antihypertensives, antiseizures, and CGRP receptor antagonists?
1. *topirimate (popular due to weight loss) and valproic acid*
2.
-*ONLY two PO antagonists given daily*: rimegepant, atogepant (prophylaxis only)
-*IV given Q3 months*: eptinezumab-jjmr (Vyepti)
-*SC monthly*: erenumab-aooe (Aimovig), galcancezumab-gnim (Emgality), fremanezumab-vfrm (Ajovy - *has higher dose that can be given Q3 months*)
3.
-*Antidepressants: TCAs (most evidence w/ amitriptyline), alternative: venlafaxine*
-*Botulinum toxin type A (Botox) injections for chronic migraines only* (>/=15 HA days/month)
-Extended cycle or continuous OCs or vaginal ring (if NO aura)
-NSAIDs or tripants w/ longer T1/2: frovatriptan preferred or naratriptan --> can be started prior to menses and continued for 5-7 days
-*Natural products: riboflavin (vitamin B2), magnesium, butterbur, feverfew*
83
Onzetra Xsail (sumatriptan nasal powder): Counseling
1. Open pouch and remove first nosepiece. Insert nospiece into device until you hear a click.
2. Press and release the white button to pierce the medication capsule.
3. Insert the nosepiece deeply into nose (first nostril). Rotate device to place mouthpiece into mouth.
4. *Blow into device w/ mouth for 2-3 seconds to deliver medication into your nose*. A vibration/rattling may occur.
5. Press the clear tab to remove the first nosepiece. Check the capsule to be sure medication is gone. Discard the first nosepiece.
6. Insert second nosepiece into device and repeat steps using second nostril.
84
Gout:
-Define
-Pathophysiology
-Risk Factors
Gout: *type of arthritis from buildup of uric acid (UA) crystals primarily in joints (often the metatarsophalangeal joint (MTP, the big toe) which can be asymptomatic or have sudden onset of pain and damage to joints, tendons, or other tissues*
Pathophysiology: *adenosine --> hypoxanthine --(Xanthine Oxidase)--> Xanthine --(Xanthine Oxidase)--> Uric Acid which is either degraded to allantoin vis uricase, renally excreted, or causes crystallization (gout attack)*
Risk factors: *male sex, obesity, excessive alcohol consuption* (particularly beer), HTN, CKD, lead intoxication, advanced age, *certain foods (organ meats, high-fructose corn syrup*; limit fruit juices, tablet sugar, sweetened drinks/desserts, salt, beef, lamb, pork, seafood with high purine content
85
*Drugs that increase uric acid*
-ASA (lower doses)
-Cyclosporin
-Diuretics (loops and thiazides)
-Niacin
-Pyrazinamide
-Select chemotherapy (w/ tumor lysis syndrome)
-Select pancreatic enzyme products
86
*Gout: Acute TX*
-Options: anti-inflammatory drugs (colchicine, steroids including intra-articular injections, NSAIDs often w/ high starting doses, interluekin-1 anatagonists reserved for refractory or intolerance to other TX)
-In severe: combinations of acute TX; inadequate response to NSAIDs, colchicine, or steroids: interluekin-1 antagonists
-If localized to 1-2 joints, intra-articular steroids (methylprednisolone) can help
-Non-pharm: ice to reduce inflammation
87
*Gout: Chronic TX*
-Asymptomatic hyperuricemia is NOT treated w/ drugs
-Chronic to prevent attacks: xanthine oxidase inhibitor (allopurinol preferred; alternative: febuxostat) --> slow titration (use NSAIDs, steroids, and/or colchicine can be used initially to prevent)
-If xanthine oxidase inhibitor (XOI) not working well enough and UA remains >6mg/dL: add on probenecid to daily XOI or replace XOI w/ IV pegloticase (Krystexxa)
88
Colchicine:
-Brand
-ROA
-Dosing for acute gout attacks
-Administration considerations
Brand: *Colcrys*, Gloperba, Mitigare
RO: PO
Dosing (acute gout attack): *1.2mg PO (two 0.6mg tablets) followed by 0.6mg in 1 hour (do NOT exceed 1.8mg in 1 hour* or 2.4mg/day) *starting within 36 hours of symptoms onset*
Administration considerations:
-Maintain adequate fluid intake
-*Wait 12 hours after treatment dose before resuming prophylaxis dosing*
89
Colchicine:
-AVEs
-Warnings
-CIs
-DDIs
AVEs:*N/D, myopathy, neuropathy* (dose-dependent), decreased vitamin B12
Warnings: *myleosuppression*, neuromuscular toxicity (including rhabdomyolysis), *myopathy risk* (if possibly do NOT use w/ cyclosporine, diltiazem, verapamil, gemfibrozil, or statins)
CI: do NOT use in combo w/ *P-gp or strong CYP3A4 inhibitor* w/ renal or hepatic impairment
DDIs:
-With moderate CYP3A4 inhibitors, max dose of 2 hours x1 then wait at least 3 days for next dose
90
Canakinumab:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
Brand: Ilaris
MOA: *interluekin-1 antagonist*
ROA: SC injection
Administration considerations:
-Must test for TB prior to initiation
-Avoid live vaccines
-Dosing varies per indication
TX: *refractory gout or pts w/ CI or intolerance to other medications*
AVEs: nasopharyngitis, serious infections
91
Allopurinol:
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: *Zyloprim, Aloprim*
-Duzallo: allpurinol + lesinurad (uricosuric)
MOA: *xanthine oxidase inhibitor to decrease uric acid production*
ROA: PO
Administration:
-Higher doses used for tumor lysis syndrome
-Take after a meal to reduce stomach upset (higher doses can be divided)
-Drink plenty of fluids
-*Due to high rate of gout attacks when beginning, use w/ colchicine or NSAID for first 3-6 months*
TX: *gout, tumor lysis syndrome*
92
Allopurinol:
-AVEs
-Warnings
-Monitoring
-DDIs
AVEs: *rash, gout flare, nausea*, diarrhea, increased LFTs
Warnings:
-*Hypersensitivity rxns (including SJS/TENs/DRESS): HLA-B*5801 testing prior to use if high risk (ex. Asian descent, African American) and do NOT use if positive*
-*Hepatoxicity*, bone marrow suppression, nephrotoxocity
Monitoring: CBC, LFTs, renal function
DDIs:
-*Increase concentration of mercaptopurine, active metabolite of azathioprine (caution w/ allopurinol)*
-Avoid w/ didanosine (XOIs can increase didanosine levels)
-*Avoid use w/ peloticase (increased risk of anaphylaxis)*
-Antacids decrease allopurinol absorption
93
Febuxostat:
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: Uloric
MOA: *xanthine oxidase inhibitor to decrease uric acid production*
ROA: PO
Administration: *due to high rate of gout attacks when beginning, use w/ colchicine or NSAID for first 3-6 months*
TX: *gout*
94
Febuxostat:
-AVEs
-Warnings
-CI
-BBW
-Monitoring
-DDIs
AVEs: rash, nausea, arthralgia, *increased LFTs*
Warnings: *hepatoxicity*, possible MI or stroke, gout flare, hypersensitivity, *serious skin rxns* (SJS/TEN/DRESS)
CI: do NOT use w/ mercaptopurine or azathioprine
BBW: *increased risk of CV death compared to allopurinol in pts w/ established CV disease (use should be limited to those who cannot tolerated allopurinol or if allopurinol is NOT effective)*
Monitoring: LFTs
DDIs:
-*Increase concentration of mercaptopurine, active metabolite of azathioprine (CI w/ febuxostat)*
-Avoid w/ didanosine (XOIs can increase didanosine levels)
-*Avoid use w/ peloticase (increased risk of anaphylaxis)*
95
Probenacid:
-MOA
-ROA
-TX
MOA: *uricosuric - inhibits reabsorption of uric acid in the kidneys, increasing uric acid excretion*
ROA: PO
TX: *gout
-Can be used to increase beta-lactam levels by decreasing beta-lactam renal excretion* (occassionally done w/ PCNs for neurosyphilis or other PCN-treated infections)
96
Probenacid:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: hypersensitivity rxns, hemolytic anemia
Warnings: decreased effectiveness w/ CrCl <30mL/min (ACR guidelines: do NOT use if <50mL/min), do NOT use w/ G6PD deficiency
CIs: do NOT use w/ ASA therapy, blood dyscrasias, UA kidney strones (nephrolithiaisis), children <2 yo, initiation in acute gout attack
DDIs:
-Reduces renal clearance of toher medications (do NOT use salicyclates concurently, others: methoxtrate, PCNs, cephalosporins, carbapenems)
-Decreasese efficacy of loop diuretics, but increases risk of loop diuretic toxicity
-*Avoid w/ pegloticase (anaphylaxis risk)*
97
Pegloticase:
-Brand
-MOA
-ROA
-TX
Brand: Krystexxa
MOA: *recombinant uricase that converts uric acid to allantoin which is excreted*
ROA: *IV*
TX: *refractory gout*
98
Pegloticase:
-AVEs
-Warnings
-CIs
-BBWs
AVEs: antibody formation, gout flare, infusion rxns, nausea, bruising, urticaria, erythema
Warnings: acute gout flares can occur upon initiation - an NSAID or colchicine should be given one week prior to infusion and continued for at least 6 months
CIs: *G6PD deficiency*
BBW:
-*Anaphylactic rxns (monitor and premedicate w/ antihistamines and steroids*; risk greastest if UA >6 mg/dL; *do NOT use in combo w/ allopurinol, febuxostat, or probenacid)*
-Life-threatening hemolytic reactions and methemoglobinemia may occur w/ G6PD deficiency
99
Opioid Potency Comparisons
**Personal card added -wasn't in NAPLEX book
Most potent: fentanyl
-Buprenorphine
-Levorphanol
-Oxymorphone
-Hydromorphone
-Phenazocine
-Methadone
-Oxycodone
-Morphine
-Hydrocodone
-Tapentadol
-Dihydrocodeine
-Tramadol
Least potent: Codeine
99
*Brands:*
1. Fiorinal = ________ + ______ + ________
2. Fironal with Codeine = _____ + ____ + ___ + ____
3. Fioricet = ________ + ______ + ________
3. Fioricet with Codeine = _____ + ____ +____+ ___
1. ASA + butalbital + caffeine
2. ASA + butalbital + caffeine + codeine
3. APAP + butalbital + caffeine
4. APAP + butalbital + caffeine + codeine
