Final Non-Opiates Flashcards
What are the categories of non-opioids?
Salicylates (aspirin)
Arylpropionic Acids (ibuprofen, naproxen)
Arylacetic Acids (indomethacin, diclofenac, ketorolac, etodolac)
Enolic Acids (Piroxicam, Meloxicam)
What are the 4 uses of NSAIDs?
Analgesic
Anti-inflammatory
Antipyretic (fever)
Prophylactic (reduce MI risk) -aspirin
What are the 4 components of the inflammatory response?
Rubor, Tumor, Calor, Dolor
(redness, swelling, heat, pain)
What are the 3 stages of the inflammatory response?
Acute
Subacute
Chronic
What happens in the Acute Phase of the inflammatory response?
Vasodilation
(increased permeability of blood vessels)
What happens in the Subacute Phase of the inflammatory response?
Infiltration
(of neutrophils which causes inflammation, pain, and mast cell degranulation)
What happens in the Chronic Phase of the inflammatory response?
Proliferation
Recruitment of which molecule contributes to inflammatory pain?
Eicosanoids
Eicosanoids are metabolites of what?
Arachidonic acid
Why do NSAIDs want to block COX-2?
To reduce prostaglandin formation and reduce inflammation + pain
NSAIDs are COX inhibitors in what pathway?
Arachadonic acid pathway
What is the cascade that occurs after an injury occurs, leading to release of molecules involved in tissue repair?
Tissue injury
Leads to Activation of H Protein Couples Receptors
These couple with Phospholipase A2 (PLA2)
This creates Arachadonic Acid
Arachadonic Acid leads to COX-1 and COX-2
COX-1:
-Thromboxane (TXA2) release in platelets
-PGE2 + PGI2 release in mucosa (protects stomach lining)
COX-2:
-PGE2 in nociceptors and platelets
What substances released into the mucosa by COX-1 after tissue injury protect the stomach lining?
PGE2 (prostaglandin)
PGI2 (prostacyclin)
What substance creates Arachadonic Acid?
Phospholipase A2 (PLA2)
Arachadonic Acid is a substrate for what?
COX-1
COX-2
5-LOX (lipoxygenase)
What is the only NSAID that irreversibly inhibits COX 1/2?
Aspirin
What is the MOA of aspirin?
-Irreversibly inhibits COX 1/2 by acetylation of COX
What affect does aspirin have on COX-2 function?
Modifies COX-2 activity through acetylation
-This turns off the ability of COX-2 to produce prostaglandin but turns on the ability to produce protective lipid mediators
(Less prostaglandin, More protective lipid mediators)
What is the MOA of NSAIDs other than aspirin?
Competitive, reversible inhibitors of COX 1/2
What is the most common use of aspirin?
Prophylactic for anti-coagulation
True or False: Aspirin tolerance is a big problem
FALSE - there is no tolerance development to the analgesic affects of aspirin
Why should children not be treated with aspirin?
Risk of developing Reye’s Syndrome
-if child’s fever is of viral origin
What is the typical half-life of salicylates vs aspirin?
Salicylates: 6-20hr
Aspirin: 15min (but duration longer due to irreversible inhibition)
How fast is aspirin absorbed?
Rapidly
How can we increase the excretion of aspirin from the body?
Excretion increases with increased urinary pH (make more basic)
(ex:bicarb)
What are the symptoms of salicylism/aspirin poisoning?
Mild:
Vertigo, Tinnitus
CNS:
Respiratory Alkalosis (hyperventilation)
Metabolic Acidosis (low blood pH)
What is the treatment for salicylism/aspirin poisoning?
Reduce salicylate load
*Increase urinary excretion by increasing pH with Dextrose or Sodium Bicarbonate
What are the arylpropionic acid NSAIDs?
Ibuprofen (Advil)
Naproxen (Aleve)
What is the MOA of arylpropionic acids?
REVERSIBLE cyclooxygenase inhibitors
What are the half-lives of the two common arylpropionic acids?
Ibuprofen: 2hr
Naproxen: 14hr
What are the Arylacetic Acid Derivatives?
Diclofenac (Voltaren)
Indomethacin (Indocin)
Sulindac (Clinoril)
Which Arylacetic Acid Derivative is available as a gel?
Diclofenac
What is a concerning side effect of diclofenac (Voltaren)?
Peptic Ulcer
What drug can be used to reduce the risk of developing a peptic ulcer while taking Diclofenac?
Misoprostol (PGE1 analog)
Which Arylacetic Acid Derivative is a potent reversible inhibitor of PG biosynthesis?
Indomethacin (Indocin)
What side effects are we worried about with Indomethacin (Indocin)?
*High incidence and severity of side effects
-Acute gouty arthritis
What is the less toxic derivative of indomethacin?
Sulindac (Clinoril)
What are the Enolic Acids?
Meloxicam
Piroxicam
“oxicam” drugs
What are the Enolic Acids used to treat?
Arthritis
*great joint penetration
What is the MOA of meloxicam?
COX-2 selective at low doses
What are the half-lives of the two enolic acids?
Meloxicam= 20 hours
Piroxicam= 57 hours***
What are the side effects of NSAIDs?
Renal Function Issues
(inhibition of renal PGE2 synthesis can cause increased sodium reabsorption and peripheral edema)
Increased bleeding risk
(inhibition of platelet aggregation)
Inhibition of uterine motility
(promethazine)
GI distress and ulcers
Which NSAID can be used to delay preterm labor by inhibiting uterine motility?
Promethazine
What are the uses for acetaminophen?
Analgesic
Antipyretic
**limited anti-inflammatory activity
True or False: Acetaminophen is an NSAID
FALSE
-limited anti-inflammatory activity
What are the advantages of acetaminophen over NSAIDs?
No GI toxicity
Can use in children
What are the disadvantages of acetaminophen compared to NSAIDs?
Overdose may lead to fatal hepatic necrosis
(hepatotoxic)
Causes more vasoconstriction than NSAIDs
The risk of hepatic necrosis with acetaminophen increases with what?
Alcohol
(increases toxic acetaminophen metabolites [NAPQI])
What drug is used to treat the increase in toxic acetaminophen metabolites (NAPQI) associated with hepatic necrosis?
n-acetylcysteine
What are the selective COX-1/2 inhibitors and what side effects are they associated with?
Aspirin/ Acetaminophen/ Non-Salycilate NSAIDs
-Stomach ulcers
-GI bleeds
What is the selective COX-2 inhibitor and what are its side effects?
Rofecoxib (Vioxx)
Reduces ulcers and GI bleeds
*Withdrawn due to chance of blood clots, strokes, and heart attacks
Who should not take NSAIDs?
Patients with:
-Chronic Kidney Disease
-Peptic Ulcer Disease
-History of GI Bleed
All NSAIDs carry what risk?
Cardiovascular risk in patients with coronary heart disease
Highest risk: Diclofenac
Lowest risk: Naproxen
When used at high doses, all NSAIDs can interfere with what?
Bone healing
NSAIDs can cause what?
Asthma exacerbations
Local anesthetics are what kind of drugs?
Sodium Channel Blockers
What are the local anesthetics?
Lidocaine
Bupivacaine
Benzocaine
Which sodium channel blocker local anesthetic has a higher allergy risk?
Benzocaine
(esters)
Which sodium channel is being targeted for analgesia?
NaV1.7
A gain of function / loss of function mutation in the sodium channel NaV1.7 leads to what?
Gain of Function: Severe neuropathic pain
Loss of Function: Congenital insensitivity to pain
What psychiatric drugs are also sodium channel blockers?
Anticonvulsants:
-Lamotrigine
-Carbamazepine
Tricyclic Antidepressants:
-Amitriptyline
SNRIs have what function?
Increase norepinephrine levels
SNRIs act on what receptors in the spinal cord?
Alpha 2A- adrenergic receptors
Which SNRI’s are used for pain and what type of pain are they used for?
Duloxetine: Peripheral neuropathy
Venlafaxine: Diabetic neuropathy
Milnacipran *lacks sodium channel function
What two calcium channel blockers may be possible analgesics?
Gabapentin
Pregabalin
What are the clinical pearls of the two analgesic calcium channel blockers?
a2 delta- Cav1,2 selective
Not metabolized
No drug-drug interactions
Half life= 4-8hr
How do calcium channel blockers work to produce analgesia?
Blocking calcium reduces glutamate release which reduces firing
(calcium channels opening typically triggers the release of glutamate)
What is the recommended dosing for acetaminophen (Tylenol) in adults?
325-1000mg PO q 4-6h prn
What is the MAX dose of acetaminophen in adults?
3-4 g/day
What is the recommended dosing for acetaminophen (Tylenol) in kids?
10-15 mg/kg PO q4h prn
What is the MAX dose of acetaminophen (Tylenol) in kids?
75 mg/kg/day
OR
3-4 g/day
Acetaminophen is the GOLD STANDARD treatment for which disease state?
Osteoarthritis
(less side effects in geriatric patients than NSAIDS)
What do NSAIDs have a black box warning for?
GI bleeding
Who should NSAIDs be used with caution in?
Geriatric patients
(Beers List)
Systemic use of NSAIDS should be avoided in which disease states?
Cardiac history (can use topical)
Liver disease
Chronic kidney disease
What is the recommended dosing of aspirin in adults?
325mg-1000mg po q4-6h PRN
What is the MAX dose of aspirin used in adults?
4g/day
What is the recommended dosing of aspirin in kids?
DO NOT USE IN KIDS Under 18)
-Reyes Syndrome
What patients should avoid taking aspirin?
Patients taking blood thinners or antiplatelets
Children
What is the Adult dosing of Ibuprofen?
200-800 mg po q6-8h prn
What is the MAX dose of ibuprofen in adults?
3200 mg/day
What is the Child dosing of Ibuprofen?*
(>6 months old): 5-10 mg/kg po q4-6h prn
What is the MAX dose of Ibuprofen in children?
40 mg/kg/day or 2400mg
*whichever is less
Besides tablet/capsule, what other form does aspirin come in?
Suppository
Besides tablet/capsule, what other forms does ibuprofen come in?
Suspension
IV solution
Besides tablet/ capsule, what other forms does diclofenac come in?
IV solution
Suppository
Topical gel
Topical solution
Opthalmic solution
Patch
Besides capsules/tablets, what other forms does Naproxen come in?
Suspension
Besides tablets, what other forms of ketorolac are available?
IV/IM solution
Nasal spray
Opthalmic solution
What are the clinical pearls for ketorolac?
Max duration is 5 days
Increased GI bleeding risk when longer!
What differentiates Celecoxib (Celebrex) from other NSAIDs?
COX 2 selective
-less GI toxicity
Which of the following options offer a not po option?
Aspirin
Ibuprofen
Diclofenac
Naproxen
Ketorolac
Celebex
Aspirin (Suppository)
Ibuprofen (IV)
Diclofenac (IV, Suppository, Gel, Topical solution, Ophthalmic solution, Patch)
Ketorolac (IV/IM solution, nasal sprat, ophthalmic solution)
Which of the following have an oral solution/suspension?
Tylenol
Bayer
Motrin
Voltaren
Aleve
Toradol
Celebrex
Tylenol
Motrin
Aleve
What are the gabapentinoids?
Gabapentin (Neurontin)
Pregabalin (Lyrica)
What pain are gabapentinoids useful for?
-Fibromyalgia
-Neuropathy
-Post-op pain
Nerve pain
What is the MAX dose of gabapentin (Neurontin)?
3600 mg/d
What is the MAX dose of pregabalin (Lyrica)?
600 mg/d
What are the side effects of the gabapentinoids?
Sedation
Dizziness
Edema
What are the SNRIs used for pain?
Venlafaxine (Effexor)
Duloxetine (Cymbalta)
What types of pain are SNRI’s used for?
Fibromyalgia
Neuropathy
nerve pain
What is the max dose of Venlafaxine?
225 mg/day
What is the max dose of Duloxetine?
60 mg/day
When do we avoid using Duloxetine?
CrCl < 30 ml/min
What are the TCAs used for pain?
Amitriptyline (Elavil)
Nortriptyline (Pamelor)
When are the TCA’s used for pain?
LAST LINE
-because of SE
What are the muscle relaxants used to treat pain?
Cyclobenzaprine (Amrix, Fexmid)
Baclofen (Lioresal))
Methocarbamol (Robaxin)
Carisoprodol (Soma)
Tizanidine (Zanaflex)
What pain are muscle relaxants used for?
Musculo-skeletal pain/spasms
How long should muscle relaxants be used for?
SHORT TERM
<3 weeks
Which antiepileptic is used in pain treatment?
Carbamazepine (Tegretol)
What type of pain is an antiepileptic used for?
Neuropathic pain
Which drug auto induces CYP metabolism of itself?
Carbamazepine (Tegretol)
When do we use the antiepileptic (Carbamazepine) for pain?
LAST LINE
*many side effects
What topical agents are available for pain management?
Lidocaine
Capsacian
What are the instructions for applying a lidocaine patch?
Apply 1 patch to affected area daily and remove 12 hours later
How does capsacian work?
Counter-irritant
-irritates spot when you put it on which tricks the brain to not focus on other pain
What are the clinical pearls of capsacian?
-Do not get medicine into eyes (burning)
-Wash hands after applying
-Some formulations available OTC
Older adults an increased risk of what with NSAIDs?
GI bleeding
Peptic Ulcer Disease
How should elderly patients take NSAIDs?
Avoid chronic use unless alternative not available
*If taking, take gastroprotective agent too
-Avoid short-term scheduled use
Which NSAID has the highest risk for adverse effects?
Indomethacin
*avoid in elderly
Which are the 3 worst skeletal muscle relaxants to take in older adults?
Carisoprodol
Cyclobenzaprine
Methocarbamol
Which muscle relaxants are the better ones to use in the elderly?
Baclofen
Tizanidine
Why are SNRIs, TCAs, and Carbamazepine in the Beers Criteria?
Exacerbate or cause SIADH (syndrome of inappropriate antidiuretic hormones)
May cause hyponatremia
*monitor sodium
Why are opioids/benzodiazepines in the beers criteria?
Increase risk of overdose and AE
*avoid use
Which pain medications CAN be used in the elderly to minimize side effects?
Topical agents (lidocaine, diclofenac, capsaicin)
Acetaminophen
SNRIs
Gabapentinoids
