Non-Opioid Analgesics Flashcards
NSAIDs MOA
Cyclooxygenase (COX) inhibitors
Prevent arachidonic acid binding to COX enzyme
Inhibit prostaglandin biosynthesis
Analgesic, anti-inflammatory, antipyretic
COX-1
Cyclooxygenase isoenzyme 1
Renal function maintenance
GI tract mucosal protection
Thromboxane A2 (platelet aggregation)
COX-2
Cyclooxygenase isoenzyme 2
Pain mediation
Inflammation
Fever
Non-Selective NSAIDs
COX 1 & COX 2 isoenzymes
Limited use in perioperative setting d/t GI toxicity & platelet dysfunction
Delayed bone healing
Toradol (Ketorolac) most commonly used peri-op
Toradol (Ketorolac)
Non-selective NSAID
15mg IV or IM Q6H
Decrease dose in elderly patients
Known renal impairment do not administer
COX-2 Inhibitor
No platelet aggregation inhibition
Celebrex only available COX 2
Celebrex (Celecoxib)
COX-2 inhibitor
Decreased GI toxicity
Increased cardiovascular risk
Commonly given as ERAS protocol (enhanced recovery after surgery)
Celebrex Dose
400mg PO pre-op
200mg BID x5 days post-op
NSAIDs PK
Weak acids Low Vd 0.1-0.3L/kg Rapid GI absorption Increased protein binding Primarily liver metabolism Eliminated by renal & biliary excretion
NSAIDs SE
Impaired platelet function primarily via COX-1
GI complications: Mild ulcers to perforation & bleeding (elderly, H pylori infection, previous ulcer, concomitant use - ASA, anticoagulants, or corticosteroids)
Cardiovascular: Increased MI risk, heart failure, & hypotension
Renal: Na+ excretion, tubular function, interstitial nephritis, & reversible failure
Liver: Transaminase level elevation & liver failure
Pulmonary: ASA exacerbated disease r/t COX-2
Hypersensitivity rare - allergic rhinitis + nasal polyps + asthma = anaphylaxis
Drug-drug interactions: Increased bleeding w/ antiplatelet agents & decreased digoxin/lithium clearance (secondary to prostaglandin inhibition & altered renal flow)
Aspirin ASA
Salicylic acid derivative
Irreversible platelet inhibitor - primary use
Overdose S/S: Abdominal pain, N/V, hearing impairment, CNS depression
Higher doses can result in metabolic acidosis, renal failure, CNS changes (agitation, confusion, coma), & hyperventilation w/ respiratory alkalosis
Urine alkalinization increases salicylate elimination
ASA Metabolism
Rapidly metabolized - plasma esterases, erythrocytes, & liver
Acetaminophen (Tylenol)
Analgesic & antipyretic properties
Central analgesic effect via serotonergic pathway activation & antagonism NMDA, substance P, and nitric oxide pathways
NO anti-inflammatory actions
Acetaminophen Metabolism
Metabolized in liver
Chronic usage <2g not associated w/ liver damage
Metabolite N-acetyl-p-benzoquinoeimine leads to liver failure by depleting glutathione (natural antioxidant)
Treatment: Charcoal to remove acetaminophen & acetylcysteine to replace glutathione
Acetaminophen Dose
325-650mg Q4-6H
Do not exceed 4,000mg per 24hrs (2,000mg for chronic alcoholics)
Ofirmev IV 1,000mg Q6H
Gabapentin
Structural analogue of gamma-aminobutyric-acid (GABA)
Acts on VG Ca2+ channels inhibiting glutamate
Approved as anticonvulsant
Demonstrated some efficacy in neuropathic pain
ERAS protocols - generally accepted as effective in reducing immediate post-op pain & opioid consumption
Gabapentin PK
Absorption limited to duodenum (small portion)
Antacids impair absorption
Minimal protein binding & excreted w/out significant metabolism
Gabapentin Dose
Pre-op 1,200mg 1-2hr prior to surgery
600mg Q8H x14 days
Gabapentin SE
Sedation Dizziness Headache Visual disturbances Respiratory depression Long lasting effects
Lidocaine
Amide local anesthetic Weak base pKa 7.9 MOA uncertain - VG Na+ channel? Block polymorphonucelar granulocytes priming
Lidocaine PK
Blocks nerve transmission
First-pass extraction in the lungs
Metabolized in liver - prolonged in patients under general anesthesia
Lidocaine Dose
Induction 1.5mg/kg bolus
Infusion 1-2mg/kg/hr
Lidocaine Benefits & Concerns
Benefits - reduces pain, speeds up bowl function return (laparoscopic cases), improves functional outcomes in prostatectomy thoracic & major spine cases
Concerns - accumulation however given at doses per ERAS protocols serum levels are well below toxicity
Infusion at higher toxicity risk
Monitoring at risk patients is advised
Magnesium Sulfate
Analgesic properties r/t regulation Ca2+ influx into cells & NMDA receptors in CNS antagonism
↓ opioid consumption & pain
SE: Bradycardia & hypotension
Multi-modal drug NOT sole analgesic
Magnesium Sulfate Dose
Bolus 30-50mg/kg
Infusion 10mg/kg/hr
Capsaicin
TRPV1 (transient receptor potential vanilloid) channel agonist
Activation releases high-intensity impulses & substance P
Primary pungent ingredient of chili peppers & botanicals
Topical application for neuralgia & neuropathies
Available OTC in 0.025% 0.075% 0.25% creams & transdermal patches
Ketamine
NMDA antagonist modulates central sensitization (induced by incision & tissue damage)
Role in preventing opioid-induced hyperalgesia
SE: Psychomimetic, dizziness, blurred vision, N/A
Ketamine Dose
0.5-1mg/kg prior to surgical incision
Dexmedetomidine (Precedex)
Acts on locus coeruleus (alertness) located in brain
Selective α2 agonist - blunts sympathetic response
SE: Bradycardia & hypotension
Dexmedetomidine Dose
0.5-2mcg/kg
Bolus 4mcg up to 16mcg
Peripheral Opioids
Analgesic effects mediated by peripheral opioid receptors
↓ plasma extravasation, vasodilation, pro-inflammatory neuropeptides, immune mediators, & tissue destruction
Role in arthroplasty & inflammatory bowel disease
NSAID Anaphylaxis Risk Factors
Allergic rhinitis
Nasal polyps
Asthma
True hypersensitivity rarely occurs
