Exam 1 - Orthopedics and Pain Mgmt. Flashcards
Sharp, dull, aching, throbbing…
Nociceptive Pain
Burning, tingling, shooting
Neuropathic Pain
What organ FXC is important to check before administering pain meds?
Liver and Renal FXC
Make sure they’re clearing drug apropriately
WHO Ladder Approach
Step 1 - Nonopioids (Acetaminophen and NSAIDs)
Step 2 - Opioids for mild to moderate pain
Step 3 - Opioid for moderate to severe pain
Where do drugs treat pain?
Inflammation of tissue
CNS
What drug prevents transmission of pain signal from periphery to CNS?
Lidocaine
COX1
Constituitive enzyme; produces gastric barrier to prevent ulcers from forming.
COX2
Inducible, upregulated when injury occurs.
*main focus
What drugs should you start with when you have somatic/visceral pain?
Start with NSAIDs, APAP, or corticosteroids +/- opioids.
What drugs should you use for neuropathic pain?
Opioids are useful, but not as helpful as they would be in broken bone, etc.
Use antidepressants, anticonvulsants, and baclofen.
Acetaminophen (Tylenol)
Good analgesic and antipyretic.
Poor anti inflammatory, does not work out in periphery. Has anticoagulant effects.
1st line: osteoarthritis and back pain.
Can be mixed with opioids for synergistic effects.
What is the IV form of acetaminophen?
Ofirmev
Good to use when patient can’t tolerate oral or rectal acetaminophen.
Ex: Neutropenic HemOnc patients.
“Opioid sparing drug” - lets you use less opioids. Less side effects, so can recover quicker post-op with this than an opioid.
Why don’t you give rectal drugs to neutropenic patients?
You might perforate their rectum and cause septicemia..
What do you worry about with overuse of Acetaminophen (Tylenol)?
Hepatic injury
Limit to 4g of Tylenol per day for normal patient.
Lower threshold for cirrhosis (3g/day).
Make sure you take into account all sources of acetaminophen.
NSAIDs
Work at site of inflammation by inhibiting synthesis of COX1 and COX2 to decrease prostaglandin synthesis.
How does asthma happen from NSAIDs?
NORMAL: Inflammation has membrane phospholipids that go to arachodonic acid to go to COX to produce prostaglandins, prostacyclin, and thromboxanes.
NSAIDs: When you shut down this pathway, it shift towards leukotriene pathway = potent bronchoconstrictors, and can cause drug-induced asthma.
What NSAID is given rectally?
Aspirin
How long is NSAID response?
Give drug 2-3 weeks to assess patient’s response before trying a new drug.
NSAID Side Effects (5 listed)
Gastric or intestinal ulceration from inhibiting COX1 (gastric barrier), which decreases production of mucus barrier.
Decrease PLT aggregation; bleeding risk.
Hypersensitivity, Asthma (bronchospasm)
Pregnancy - can delay spontaneous labor in third trimester. Can have adverse fetal effects.
Possible increase in liver enzymes and decrease in renal function (it inhibits PG from keeping afferent arteriole open which leads to decrease in renal function).
How do NSAIDs impact the fetus during pregnancy?
Ductus arteriosus between two atria in the heart are open in fetus and allows for blood flow to mix between two.
PGs keep DA open, but when you give an NSAID, you inhibit PG and the DA can close early. If it closes early, blood may not circulate as well.
If a baby is born with patent DA, what can you use to treat them?
If you had a baby when the DA didn’t close, you can give NSAIDs (IV ibuprofen and IV indomethicin) to close it.
Acetylsalicylic acid (Aspirin)
Irreversible inhibitor; lasts for lifetime of PLT. Bleeding risk.
Nonselective for COX1 and COX2
If a baby has a congenital malformation and you want DA open for longer, what can you give?
IV prostaglandin
Alprostadyl drip to keep it open, while they dx the heart.
Aspirin Dosage
Used for heart protection, fever, etc. Can come in powders - pts don’t view this as a drug so its easy for them to overdo it.
Salicysm
Significant metabolic acidosis from OD of aspirin; death may occur.
When do you avoid aspirin and salicylates?
- Bleeding disorders
- Pregnancy
- Children with viral disease, ex: chicken pox or flu (will increase chances of Reye’s syndrome)
Is it ok to give aspirin to pregnant women?
VERY low doses can help with hypertensive disorders like pre-ecclampsia and growth retardation.
Diflunisal (Dolobid)
Salicylate product; used as an anti-inflammatory.
Good for osteoarthritis and rheumatoid arthritis; has good analgesic properties with similar effects you see to aspirin.
Diflunisal (Dolobid) ADR
Steven Johnson Syndrome - AI reaction of rash, that causes skin to slough off.
Proprionic Acid Derivatives
Ibuprofen Naproxen Ketoprofen Fenoprofen Flurbiprofen Oxaprozin
- Well orally absorbed
- Hepatic conjugation, renal excretion
- Treats arthritis, muscle pain, dysmenorrhea
What proprionic acid derivative has the longest half life?
Oxaprozin
40-60 hours
Indomethacin (Indocin)
- Can be used to close a patent DA.
- Large incidence of SE: ulcers, diarrhea, headaches, dizziness
Why does Indomethacin (Indocin) decrease effects of diuretics?
- constricts afferent arteriole
- less glomerular blood filtration occuring; less fluid for diuretics to work on which affects all diuretics since less fluid is being filtered in teh kidney.
Ketorolac (Toradol)
-Given IM/IV
-Analgesic activity similar to opioid
-Good for acute pain
“Opioid sparing”
- Not good anti inflammatory
- BLACK BOX: GI effects (ulcers)
-IM (good if you don’t have IV access).
Why is Ketorolac (Toradol) limited to 5 day use?
Can cause ulceration if given too long.
Probably not used for Crohn’s, good for acute pain not associated with GI tract obviously.
Tolmetin (Tolectin)
Rarely used, because side effects
GI problems
Anticoag effects
Piroxicam (Feldene)
Good for acute lingering pain, like kidney stones
Used in outpatient settings
Meloxicam (Mobic)
10-fold selectivity for COX2
Less GI toxicity than non-selective agents
Nabumetone (Relafen)
- Prodrug, active form when metabolized by liver
- COX-2 selectivity
- Treats rheumatoid and osteoarthritis.
- Can cause stomach cramps or diarrhea.
Diclofenac (Voltaren)
Has a topical formulation gel to use for local pain issues, ex: sprain ankle
Limits systemic side effects, because it only works locally.
Advantages of COX-2 Inhibitors
Similar efficacy to NSAIDs.
Less GI ulcerations.
Disadvantages of COX-2 Inhibitors
Increased CV incidence of heart attack and stroke.
Rofecoxib
Made it through clincal trial, but was pulled from market for the CV incidence of death.
Pulled off market!
COX-2 inhibitor (disadvantage)
Celecoxib (Celebrex)
COX-2 selective
Good for patients with previous GI problems, esp. if they have NO CV risks
Why do COX-2 selective agents increase the risk of CV events?
Imbalance in epithelial cells of blood vessels; can’t produce new blood vessels, so leads to high BP => MI and strokes.
Issue with angiogenesis.
Types of opioids?
Mu, kappa, delta
OP1,2,3 - based on receptor they bind to
Used for moderate to severe pain.
Opioids
Work on opioid receptors primarily in spinal cord, nerves in dorsal tract that lead to brain, or centrally in CNS to block perceptions of pain.
Mu
primary receptor for analgesia, euphoria, and addictive properties of opioids.
Work in spinal cord and brain.
Can be lethal and cause respiratory depression.
What type of opioid is most commonly used for pain?
Agonist
Physical Dependence
Your body maintains homeostasis, when it changes, it tries to achieve a new normal.
Opioids PO QD, the receptors downregulate to reach a new normal set point. Physical dependence happens, because hwne you take away opioid receptor, they can’t be stimulated as easy and it causes withdrawal.
Withdrawal
N/V
Sweating, dysphoria
NOT fatal
Addiction
Psychological dependence
- Impaired control of drug use
- Compulsive use
- Use despite harm
- Cravings
GABA
- Inhibitory NT
- Shuts down dopamine path
Opioid binds to GABA, less GABA comes out, so dopamine fires more frequently causing addiction.
“Dopamine reward pathway”
Tolerance
State of adaption in which effects of the drug diminish over time.
Need to increase dose to maintain that analgesic effect.
No tolerance to side effects; constipation will worsen as dose increases! Worse and worse and worse.
Pseudotolerance
Change in disease state where disease progression pain has gotten worse, but dose of drug hasn’t changed to catch up with it.
Might think they’re tolerant, but its really just increase in pain.
Pseudoaddiction
Often associated with patient drug-seeking behavior (due to under treatment).
Cancer with new metastases => worse pain => ER for exacerbation, seeking meds for it => Drug hasn’t changed, so they think you’re drug seeking, but really you’re just not properly managed on the current meds…..
Addiction or apropriate use?
Addicts will lose function over time; always trying to get more drug.
Non-addicted individuals regain function once pain is controlled.
Physical dependence should be expected for those on long-term therapy.
E-FORCSE
Pharmacies will report opioids that’ve been dispensed for each patient to track them.
Controlled Substances
Defined as a drug with abuse potential.
C5
Low chance for abuse.
C2
Highest abuse potential; has accepted medical purposes.
Cocaine
C1
Highly abusive, but have no accepted medical uses.
Heroine
Marijuana
Codeine (Tylenol #3)
- Broken down into morphine via CYP2D6
- Some patients have rapid CYP2D6, metabolize a ton into morphine, so can lead to toxicity.
- Occurs in children with sleep apnea going in for tonsillectomy.
- Swollen Airway
- Converting codeine to morphine, can lead to respiratory depression. Can lead to death.
Why isn’t codeine used in children anymore? Specifically those with obstructive sleep apnea going in for tonsillectomy and adenoidectomy?
Codeine
- Broken down into morphine via CYP2D6
- Some patients have rapid CYP2D6, metabolize a ton into morphine, so can lead to toxicity.
- Occurs in children with sleep apnea going in for tonsillectomy.
- Swollen Airway
- Converting codeine to morphine, can lead to respiratory depression.
- Can lead to death.
What ethnicities have hyperactive CYP2D6?
Middle Eastern
North African
Important to expect, because you want to avoid toxicity
Morphine
- Formulations: IV, PO, IR, XR
- Metabolized in liver
Pruritis occurs from significant histamine release, not an allergic reaction though.
Good for acute pain management.
Why is morphine bad for old folks?
Morphine-6-glucuronide has greater analgesia properties, which can accumulate and cause toxicity in elderly from this metabolite.
Not recommended for old people with bad kidneys.
Hydrocodone (Norco, Lortab)
- # 1 prescribed in US
- Usually formulated with tylenol (Zohydro is the only “alone” one).
- Metabolized into hydromorphone (Dilaudid) via CYP2D6.
- Less genetic issues than codeine CYP2D6.
Recently made a C2 (from C3) bc of overuse and abuse.
Oxycodone (Roxicodone, Oxycontin)
Oxycontin = XR Roxicodone = IR
- Twice as potent as morphine
- Converted to oxymorphone metabolite (patients might not respond well to that for some reason).
-When converting drugs, keep in mind the potency in relation to each drug. Important to consider, bc otherwise you could under dose or over dose.
- Under dose = pain/withdrawal
- Overdose = CNS and resp. depression
Hydromorphone (Dilaudid)
- IV/PO, PCP pumps
- Good drug used for acute pain issues and patients unable to take morphine due to allergy.
- Doesn’t have the same histamine release as morphine.
Fentanyl (Sublimaze)
-Fully synthetic
-100x more potent than morphine (CHECK YOUR DOSES)
2mg morphine is good
2mg fentanyl = DEATH
- Short-acting; an hour until effects of drugs are out of system
- NOT given orally
- can cross mucus membranes in skin
- IV for sedation
- intranasal for quick pain control
- transdermal for controlled release of drug over long period of time.
Why can’t you use transdermal Fentanyl for acute pain?
Patch needs high concentration in patch of drug to draw it across the skin to the blood, so it takes a day or two to get affect of the drug. Then its continuous afterwards.
Intranasal option is preferred for acute, quick to give, bypasses first pass effect, good analgesia control.
Actee?
Oral Transmucosal Fentanyl Citrate
lollipop; patients self dose with a lollipop
Alfentanil
Sufentil
Remifentanil
- Used in surgical setting
- Similar to Fentanyl.
- Benefit: short acting
- Can wake up patients quick after surgery
- Long acting meds will keep them asleep and have a longer recovery.
What’s an amazing benefit to fentanyl?
Pt allergic to morphine can have cross reactivity with hydrocodone.
Fentanyl could help control their pain without that risk since its fully synthetic.
Methadone
- Works on mu receptors
- Inhibits glutamate
- Blocks reuptake of NE and 5HT
- Half life: 50 hours!!!
- Used for chronic pain
- As you dose, patient will accumulate blood levels.
Neonatal absent syndrome
Mother refuses opioids throughout pregnancy; they have NAS which makes them have withdrawal when born.
Can’t regulate HR, temp, etc.
Long acting doses of methadone help taper withdrawal for weeks to months to get them off of the drug.
Methadone CI
Check Mg, Ca, and EKG before administering; can cause prolongation of QTc interval.
Good drug to get them off of drug addictions.
Meperidine (Demerol)
Never use, unless one specific case.
Older patients with renal function accumulate metabolite, which can cause siezures.
Only used in surgical setting for rigors (post op shaking).
Propoxyphene (Darvon)
Off of the market
produces a metabolite, which can cause seizures if you have renal dysfunction and QRS prolongation.
Buprenorphine (Suboxone, Subutex)
- Good drug to use for opioid addiction.
- Long half life and tight binding affinity for receptors.
- Partial agonist; only activates receptors 50%.
- If patient abuses heroine or other opioids, they won’t get the same kind of high, because that drug can’t bind as well.
Transdermal - low continuous infusion
Implants can be used as well
Suboxone
Coformulated with meloxone (Narcan), reversal for opioids.
- Not absorbed orally
- Inject drug, meloxone blocks buprenorphine/suboxone and you won’t get high
- Meloxone will deter IVDU
- Prevents withdrawal and taper down dose.
Acute pain, no IV access, use?
Intranasal fentanyl
Patient Controlled Analgesia (PCA)
- IV pump
- Reduction in total amount of opioids someone is getting
-Patient controls their medication, decide when they need pain meds
Basal rate
Continuous hourly infusion on PCA pump
“On Demand” Dose
- When patient pushes button, they get a bolus dose set by provider.
- Can get it at certain time intervals. If you push too much, it will “lock out”
Ex: Morphine IV PCA 1mg/hr basal rate w/ 0.5mg Q15min on demand
Benefit of PCA pump?
- Can see how frequently patient is hitting button to adjust dose.
- May need to increase basal rate for inadequately controlled pain.
-If patient is too well controlled and not hitting button, decrease their basal rate to titrate them off and promote recovery.
Who cannot use PCA pump?
- Unconscious patient
- Addicts need locking feature
- Family/staff cannot push button
- Young children and elderly can’t use
Requirements for a PCA Order
- Basal rate of drug per hour
- Demand Dose
- Lockout interval, expressed in minutes
- Total amount allowed during a time period, usually 4hrs
Ex: Morphine IV PCA, basal rate: 1mg/hr, demand dose: 0.5mg, lockout interval: 15mins, maximum of 4 doses per hour, total amount per 4 hrs = 12mg
What drugs cause histamine release and pruritis?
Morphine and its derivatives: codeine
Risk of respiratory depression?
Relatively low with normal doses, unless abuse or self medicating.
Diversion
Medical providers diverting drugs away from their patients.
How do you minimize adverse effects of opioids?
- Start low, go slow.
- Titrate gradually.
- Change drug regimen if they’re not responding well.
- Treat constipation with chronic use of opioids by using prophylactic laxatives.
“Mush and then push”
When a patient is using opioids for chronic pain, what do you dose with?
Stimulant laxatives
- Senna plus docusate
- Bisacodyl
- Mineral oil
May also need to add laxatives with different mechanisms, ex: osmotic laxatives, polyethylene glycol (Miralax), etc.
Opioid Antagonists
Competitively bind to mu receptors to reverse opioids when a patient has overdosed.
Naloxone (Narcan)
Opioid antagonist
- No oral bioavailability
- Given IV, IM, IN
- Fast onset (within seconds if given IV).
- Can induce withdrawal; do not give too much!
Evzio
- Opioid abusers can be prescribe intranasal naloxone as a risk or harm reduction measure.
- Educate family/friends how to use it.
Auto-injector for overdose patients; instructs how to administer.
Peripherally acting agents
Alvimopan (Entereg)
Methylnatrexone (Relistor)
Naloxegol (Movantik)
- Don’t cross BBB.
- Work in GI tract on constipation - “wake up the gut”
- Used post-op to help relieve constipation caused by opioids.
- Doesn’t reverse analgesic affects, bc no CNS effects
- Wakes up the bowel!
Botulinum toxin
Used for severe muscle spasms.
Antiepileptics
- Carbamazepine
- Gabapentin
- Iamtrogene
- Pregabalin
- Start low and go slow
- May have CNS depression: nystagmus and ataxia
- Don’t drive after taking right away.
Tricyclic antidepressants
Older class of antidepressants; block reuptake of NE within CNS synapse.
Increase concentration of NE in synapse to manage pain associated with neuropathies.
Good to treat fibromyalgia and post-herpetic neuralgia.
Tricyclic antidepressants Side Effects
- Anticholinergic
- Cardiac abnormalities
- Sexual dysfunction
- Weight gain, sedation
Local anesthetics
- Ropivacaine
- Bupivacaine
- Lidocaine
Work by blocking Na channels in painful nerves.
Ex: finger laceration - those nerves have pain and send through SC to brain for pain response. BY blocking AP, you prevent the pain signal from reaching the brain.
Used for local anesthesia.
Examples of Local Anesthetics
EMLA cream - numb site around port to avoid pain with needle sticks.
Lidoderm patch - slow release of lidocaine.
Epidural - local or regional blocks; limits amount of opioids patients need.
- Ropivicaine
- Bupivicaine
What is administered for delivery or birth?
Epidural with fentanyl, plus ropivicaine (synergistic effects).
Epidural can only reach a certain level of spinal column to numb a certain area of body. This is why new moms have to sit up when delivering a child.
Also good for ortho surgeries.
Significance of nerve blocks?
Surgery to knee, can have nerve block above knee to block knee sensation and down. Use less opioids.
Epivicaine
Digital block that lasts for 2 days; good for finger laclerations in the ER.
Digital block will cover pain for 2 days and limit use of opioids.
Why do they mix lidocaine with epinephrine?
If local anesthetics are given systemically, they can cause cardiac arrest, bc it blocks sodium channels and prevents hyperexcitable action potentials.
Epivicaine, systemic = cardiac arrest.
With epinephrine, it helps to constrict local blood vessels to reduce amount of bleeding. Also, limits systemic absorption of drug itself.
Lidocaine plain = 5mg/kg
Lidocaine with epi = 7mg/kg
Where do you not want to use lidocaine with epi?
Anywhere with terminal blood flow; ex: tips of fingers, toes, nose, penis.
Don’t want to limit blood circulation there.
How do you tell if an anesthetic is an amide or ester?
Allergies to anesthetics: amides and esters - based on type you’re dealing with, you administer the other type of anesthetic.
Amide - “I” before -CAINE
Ex: Lidocaine (amide) prob has cross reactivity with ropivicaine; can give benzocaine to patient (ester).
Clonidine
spinally administered for pregnancy/delivery; has opioid sparing effects.
Muscle relaxants
Used for spasm from pain conditions.
- Baclofen (Lioresal)
- Cyclobenzapine (Flexeril)
- Metaxolone (Skelaxin)
- Methocarbamol (Robaxin)
- Tizanidine (Zanaflex)
Enhance GABA-B receptors to allow more chloride to flow to neurons to hyperpolarize them and make them less likely to fire off; this provides pain relief by having less muscle spasms occur.
Side effects - drowsiness, dizziness, fatigue, sedations
Capsaicin
- Treats localized neuropathic pain
- Stimulates release of substance P, which is kept in nerves for pain transmission in those fibers. Stimulates nerves to release substance P to initiate pain. Over time, nerves are desensitized and it gets rid of substance P.
- Depletes nerve ability to feel pain, very effective when used correctly.
Use as directed, otherwise, nerves generate substance P and they will feel pain again.
Why do you have to wash your hands after capsaicin?
- May experience burning or stinging. If gets in eye, flush with water.
- Skin, use something with fat in it —- use oil or milk to help displace capsaicin from skin to the fat layer to decrease pain.
Kid playing with pepper spray sprayed family - bathe in olive oil. Fats work better than soaps in this case.
Tramadol (Ultram)
If compounded with acetaminophen, its called Ultracet.
- Moderate agonist
- Blocks reuptake of serotonin and NE to help with neuropathic pain.
- Now a schedule C4 due to abuse (mu binding)
Same toxicity with opioids - sedation, respiratory depression, and QT PROLONGATION. Also — Seizures can occur!
What reverses the effects of Tramadol?
Naloxone
What is medical marijuana used for?
Cancer, epilepsy, glaucoma, PTSD, MS, Parkinson’s disease
Other debilitating conditions of same class or comparable, where benefit would outweight risks, should be used.
What medicinal compound is in marijuana?
- Delta-9-tetrahydrocannabinol
- Cannabidiol
What is Cannabidiol used for?
- In Charlotte’s web, which was legal before
- High dose, useful for epilepsy
THC
- Provides euphoria, munchies, pain benefits, and other effects of marijuana.
- Works on CB1 receptors in the brain and CB2.
- CB1 = psychoactive effects
What are the acute effects of marijuana?
Impaired short term memory, motor coordination, and judgement - NO driving!
Can cause paranoid ideations and can exacerbate anxiety, depression, and psychotic illnesses.
What are some risks with smoking marijuana?
Patient is at increased risk for pulmonary symptoms - bronchitis, pneumonias, and possible association with MI, stroke, and PVD.
What are the recommendations for prescribing medical marijuana?
- A debilitating medical condition that data from randomized control trials, suggests marijuana has a positive effect.
- Multiple failed trials of 1st and 2nd line agents.
- Failed use of an FDA approved canabinoid, such as dronabinol and nabilone.
- No active substance abuse, psych disorder or unstable mood/anxiety disorder prior to therapy.
Administration of Marijuana
Smoking - inhaled, absorbed in lungs, goes through left heart and up to brain. ~instant.
Edibles - ingested, absorbed through GI tract, through liver, bloodstream, heart, and up to brain. ~30 mins.
Case reports - Edibles have a longer onset until action reached, people end up taking too many.
What route of administration is safer for marijuana?
Oral route
Vaping is more pure, but still has pulmonary risks
How long does marijuana remain in urine?
- Depends on chronicity of use and fat stores.
- People with higher fat stores can have it for up to 3 months after use.
Who is at risk for venous thromboembolism?
Hospitalized patient, orthopedic surgery of lower extremities, immobile state, hypercoaguable states (oral contraceptives)
How do you monitor heparin?
- Monitor: aPTT
- Give for VT
How do you monitor warfarin?
What will reverse it?
- PT/INR
- Vitamin K will reverse effects
How do you monitor Lovenox?
- Anti-factor 10 A
- Enoxaparin and fondaparin target factor 10A.
Review anticoag notes for exam!!!!
How do you prevent VTE? What’s preferred?
Low risk individuals:
- Physical activity
- Compression, SCDs
High risk individuals:
- Unfractionated heparin SQ TID
- Enoxparin 1-2x/day (prefered bc of dosing); don’t need to monitor anticoag effect bc its preventative.
- Fondaparinux
Post-op management:
-Require 10-14 days of therapy.
IVC filter
Sits in IVC to catch any clots going to heart; used when anticoagulants are CI.
What clot busters are used for massive PE?
- Alteplase (most common)
- Catheter administered tPA
Catheter administered tPA (new)
- Limits dosing needed
- Sends concentrated dose directly to site
- Limits systemic effects as well
How do you treat PE?
- Continuous infusion of unfractionated heparin
- Or doses of LMWH or Fondaparinux
If pt has a clot, if they don’t have an irreversible cause for clots, what bridge therapy do you put them on?
- (From Heparin) - Bridge to warfarin or Rivaroxaban for 3 mos.
- Can’t keep them on heparin that long.
Same tx for estrogen induced clots.
How do you treat a blood clot from an oral contraceptive?
Same as you would treat a clot from an orthopedic procedure.
