Spring 25 - Farm -NSAIDS Flashcards
Properties of NSAIDs
– Analgesic
– Anti-inflammatory
– Anti-pyretic
NSAIDs are mostly used to treat?
- Pain (analgesia)
- Inflammation
+ affect on platelet function
+ Protection of GI mucosa
Origin of NSAIDs
- Derived from the bark of willow tree
- non-specific inhibitor of isoform COX-1 and 2
COX-2 is induced by?
- Induced by cellular cytokines
- In localized areas of injury
- In the spinal cord in response to tissue damage.
Nociception physiology
extremes of temperature, painful
mechanical stimuli, and noxious chemical stimuli are detected by the distal ends of primary afferent neurons. These neurons then terminate in the dorsal horn of the
spinal cord with their cell bodies located within the dorsal root ganglia
Production of prostaglandins physiology
inflammatory process triggers COX to produce prostaglandins which increase
the sensitivity of the nociceptive neurons to bradykinin, histamine, serotonin, and other mechanical, chemical, and thermal stimuli.
What substance is released from membrane phospholipid
Arachidonate
What does COX do to arachinodates
COX oxidizes arachidonate to PGG2, which is
then further oxidized to PGH2.
COX-1 distribution
– GI tract
– Platelet
– Kidney
– Most other tissues
COX-2 distribution
– Female reproductive tract
– Brain
– Kidney
– Cancer cells
Example of Competitive, reversible inhibitors
Ibuprofen
Example of Time-dependent inhibitors
Indomethacin
Example of Mixed kinetic inhibitors (slow weakly binding)
Naproxen
Example of Irreversible inhibitors
Aspirin
Where are NSAID absorpbed and distributed?
– Rapidly absorbed from GI tract
– Highly protein bound
– Found within most tissues, including synovial fluid and CSF
How are NSAID Metabolised and excreted?
– From non-specific esterases to complex hepatic pathways
– Excretion is primarily renal
Example of COX-2 inhibitors
- Celebrex (celecoxib),
- Vioxx (rofecoxib),
- Bextra (valdecoxib)
How do COX-2 inhibitors differ from other NSAIDs
- Highly lipophilic
- Neutral
- Nonacidic molecules
- With limited aqueous solubility
How do NSAIDs increase the risk of bleeding?
- Potentiate anticoagulation
- GI Bleeding
What are the CV effects of NSAIDs?
- Hypertension
- Edema
(Both due to decreased renal function)
What challenges do patients with hepatic and renal disease face in metabolizing NSAIDs?
Patients with hepatic and renal disease may have difficulty in metabolizing and excreting these agents.
What is the most potent NSAID?
Ketorolac (Toradol)
What is a possible complication of preoperative administration of NSAIDs?
It may increase the risk of bleeding
What are advantages of giving NSAIDs over Opioids?
- Less sedation (early emergence)
- Less PONV
- Less respiratory depression
- Less GI and GU retention
Toradol Dosing
– 30 mg IV/IM q6h for patients <65 years
– 15 mg IV/IM q6h for patients >=65 years
What is the maximum length for administering Ketorolac due to its increased risk of GI ulceration and bleeding?
5 days
What is the Max daily oral dose of Ketorolac?
40 mg/day (10 mg po q6h)
Aspirin po analgesic dosing
3 grams daily
Aspirin po cardioprotective dosing
81 - 325 mg daily ( be nice, keep aspirin < 162 mg daily)
Diclofenac po dosing
75 - 150 mg/daily
Ibuprofen po dosing analgesia dose
200 - 400 mg po Q 4 - 6 hours
Ibuprofen po Anti-inflammatory dose
400 - 800 mg po Q 6 hours
Naproxen daily dose ranges
- 250 - 375 mg BID up to 375 - 750 mg BID
Celecoxib po dosing adults/older
- adults 400 mg
- older/sicker 200 mg
Contraindication for NSAIDs
– History of hypersensitivity to NSAIDs
– Bleeding complications
– GI disease
– Elderly patients
– Children
– Congestive heart failure
– Hepatic impairment
– Renal impairment
– Hypertension
– Multiple NSAIDs
Properties of Acetaminophen/max daily dose
- Affective analgesic and antipyretic
- No anti-inflammatory properties
- Synergistic with other opioids
- Max daily dose 4 grams
Acetaminophen IV dose
1000 mg given as a 15-minute infusion
Ibuprofen IV (Caldolor) dose/contraindicaiton
– Dose 400 - 800 mg over 30 min Q 6 hours (max 3200 mg/24 hours)
– DO NOT give during CABG
Diclofenac IV (Dyloject) dose/contraindication
– Dose 37.5 mg over 15 seconds every 6 hours, not to exceed 150 mg/24-hour
– DO NOT give during CABG
Which agents cannot be used during CABG?
- IV Ibuprofen
- IV Diclofenac
What was the first use of Clonidine?
Clinidine was first developed as a nasal decongestant
What is the MOA of Clonidine?
Alpha 2 agonist
What medication would you NOT use to rescue an alpha-two mediated hypotension
- Norepi
- Dopamine
What are the three subtypes of alpha 2
- 2a
- 2b
- 2c
What are the uses for Alpha 2a?
Sedation, hypnosis, analgesia, sympatholysis
What are the uses for Alpha 2b?
Mediates vasoconstriction, anti shivering action, analgesia
What agents will treat post-op shivering?
- Precedex
- Demerol
- Stadol (Butorphanol)
- Meperidine
What are the uses for Alpha 2c?
Learning and startle response
What is the intrathecal/spinal dose of Precedex?
5 - 10 mcg
What is the epidural dose of Precedex?
10 - 20 mcg
What are the primary effects of alpha 2
- Hypotension
- Bradycardia
At what level does Alpha two mediated analgesia occur?
Dorsal horn of the spinal cord
What are the clinical effects of Alpha 2 agonists
- Analgesia at the spinal cord level
- Sedation
- Hypotension
- Peripheral stimulation of Alpha 2b
What is the hemodynamic response to peripheral stimulation of Alpha 2b?
Transient hypertension
What medication would be used to treat hypotension due to Alpha 2 administration?
- Ephedrine
- Phenylephrine
- Dobutamine
Which medication will cause
Methyldopa
What are the main characteristics of Clonidine?
- Moderately lipid-soluble
- Complete oral absorption
How does Clonidine compare to Alpha 2?
200 times more potent at alpha 2
What is the onset of Clonidine IV/Epidural?
- IV 60 - 90 minutes
- Epidural 14 - 20 minutes
What is the Elimination half-life of Clonidine?
12 - 24 hours
What is the protein binding and metabolism of Dexmedetomidine?
- Highly bound to albumin
- Extensive liver metabolism
How does Dexmedetomidine compate to Clonidine?
8 times greater Alpha 2 than clonidine
What is the distribution half-life and elimination half-life of Dexmedetomidine
- Distribution - 6 minutes
- Elimination - 2 hours
Why is Dexmedetomidine short-acting?
It has a rapid distribution out of the brain
What route allows more prominent analgesia of Dex?
Epidural
How is Dexmedetomidine metabolized?
Extensively metabolized in the Liver
What are the clinical effects of Dexmedetomidine?
- Analgesia
- Sedation / Anxiolysis
- Hypotension / Bradycardia
- Anti-shivering
Describe the sedative properties of Dexmedetomidine
- Mimics normal sleep
- Deeply sedated patient can be aroused to full consciousness.
What would you do to your dose of anesthetic and analgesics pre-op if the patient is on Dexmedetomidine?
Decrease doses.
What are some pre-op uses of Dexmedetomidine?
- Decrease doses of other anesthetic/analgesics
- Xerostomia
- Decreased GI transit
- Blunts sympathetic response to intubation
What special populations may show increased benefits from using Dexmedetomidine?
- Drug and ETOH addicts
- Chronic cancer and non-cancer pain
- Hypertension
- Adjuvant to Ketamin
- Ophthalmologic procedure
How does Dexmedetomidine enhance hemodynamic stability?
Blunts the release of catecholamines
How does Dexmedetomidine enhance local anesthetic block?
- Less vasoconstrictive than Epi
- Decrease cardiac output - decrease clearance
- Increased quality and duration of block.
How does the action of Dexmedetomidine in Intrathecal differ from Epidural?
- In epidural block, there is less hypotension
How is Dexmedetomidine used post-op for analgesia?
Usually, as an epidural infusion
What is the dose of Dexmedetomidine for labor?
30 - 150 mcg epidural
What is a side effect of Dexmedetomidine on the Fetus?
- Dexmedetomidine can cross the placenta and cause decreased fetal heart rate.
- Limit dose to 1 mcg/kg
How are Alpha 2 used to treat
- Chronic pain
- Sharp shooting pain
- Chronic pain - Epidural (Lidocaine + clonidine)
- Sharp shooting pain - Transdermal patch
How does a local anesthetic achieve a differential nerve block?
- Na Channel blocks sensory info
- limited blockade at K, Ca channels
List 5 Amides (2i caines) local anesthetics
- Lidocaine
- Prilocaine
- Mepivicaine
- Ropivicaine
- Bupivicaine
List 5 Ester local anesthetics
- Cocaine
- Procaine
- 2-chloroprocaine
- Tetracaine
- Benzocaine
Which Amide has the longest onset and duration
Bupivacaine
Which local anesthetics cause vasoconstriction
- Cocaine
- Ropivucaine
- Levobupivicaine
What are characteristics of Local Anesthetics?
- Weak bases
- Lipid soluble
- Neutral
- Increased protein binding
- Racemic mixture
Which local anesthetics are not a racemic mixture?
- Lidocaine
- Ropivicaine
- Levobupivicaine
Which hand of the local anesthetic has the greater efficacy but more significant systemic toxicity?
R - enantiomers
How can we increase local anesthetic activity?
- Administer epinephrine
- Alkalinization
- Opioids
- Alpha 2 agonists
How does epinephrine impact local anesthetic?
Prolongs local anesthetic block and
decreased systemic absorption (vasoconstriction slows clearance from injection site)
How does Alkalinization affect local anesthetic?
1 ml of sodium bicarbonate per 10 ml of lidocaine will hasten blockade by 3-5 minutes
How do opioids impact local anesthetics?
- Synergistic analgesia (except 2-chlorprocaine)
- Intra-articular and infiltration administration of local anesthetic/opioid combinations
