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.