Wk 12 - Analgesic Intro / NSAIDs Flashcards
Local anesthetic agents
- Proparacaine
- Lidocaine
- Benoxinate
- Lidocaine/Prilocaine (EMLA)
EMLA cream / patch
Lidocraine / prilocaine mixture
Uses:
-Pre-‐op for removing skin lesions
-Post-‐herpetic neuralgia
Local anesthetic MOA
Sodium channel blockers
-Block Na channels on nociceptor axons to block the transmission of the pain signal
Local anesthetic Adverse Effects
Long term use slows wound healing and can degrade the cornea, so we never Rx these
-Use in-office only
Peripherally Acting Analgesics
- NSAIDs
- Aspirin
NSAID & Aspirin MOA
COX inhibitors
-Inhibit the enzyme cyclooxygenase to prevent the production of prostaglandins from arachidonic acid
Prostaglandins sensitize nociceptors, so preventing their production helps to prevent pain signal
-NO EFFECT on leukotriene production
-DO NOT prevent the formation of subepithelial infiltrates in the cornea since white blood cell migration is controlled by leukotrienes
- comparison: Remember that steroids inhibit phospholipase to prevent the production of arachidonic acid, prostaglandins, and leukotrienes
Centrally Acting Analgesics
- Opiods
- Acetaminophen
Opiod & Acetaminophen MOA
Block pain signal to the brain (opioid mu agonists, SNRIs, etc.)
Clinical uses of Topical NSAIDs
- Anterior segment
GOOD:
o Pain control
• Abrasions, peri-operative (esp cataract surgery), betadine treatment for EKC
• Topicals are better than oral NSAIDs for A-Seg pain
POOR:
o Anti-inflammatory effects are poorer than oral NSAIDs or topical steroids
o Limited value in treatment of allergy
-Posterior segment
o Treatment of cystoid macular edema
• Caused by inflammation in the retina
• Topical NSAIDs penetrate to the retina well to inhibit prostaglandin synthesis
Adverse effects of Topical NSAIDs
1) May allow formation of subepithelial infiltrates after corneal surgery
2) May delay wound healing
o Not as much as steroids
o Reported more with long term use
3) Corneal melt syndrome
o May cause extreme corneal damage
o More likely in unhealthy eyes and with overdosing
o Generic diclofenac is most likely drug to cause CMS
o Watch patients carefully and stick to FDA recommended dosing
4) Burning, stinging, SPK, and conjunctival hyperemia
o More common with the classic/older NSAIDs
5) Contraindicated in soft CL wearers
o Corneal toxicity and decreased immunity can leave patient more susceptible to bacterial infections
Diclofenac 0.1% (Voltaren)
Topical NSAID
•Older formulation, rarely used today
Indications:
- Post-op inflammation after cataract extraction
- Pain and photophobia in patients undergoing corneal refractive surgery
Dosing: 1 gt qid
Ketorolac 0.5% (Acular)
Topical NSAID
-Ketorolac is an older NSAID, used occasionally today.
Indications:
• Ocular itching due to SAC
• Post-op inflammation after cataract extraction
Dosing: 1 gt qid
Ketorolac 0.4% (Acular LS)
Topical NSAID
Slightly lower concentration reduces stinging
Indication: reduction of pain following refractive surgery
Dosing: 1 gt qid
Ketorolac 0.45% (Acuvail)
Topical NSAID
Preservative free
Indication: treatment of pain and inflammation after cataract extraction
Dosing: 1 gt bid
Bromfenac 0.7% (Prolensa)
Topical NSAID
Newer formulation used commonly.
Comfortable and well tolerated.
Earlier 0.9% formulations (Xibrom and Bromday) have been discontinued.
Indication: Treatment of post-op inflammation and reduction of ocular pain in patients who have undergone cataract surgery
Dosage: 1 gt qday
= 1 gt the day before surgery, 1 gt the day of survery, and 1 gt qday for 14 days after surgery
Nepafenac 0.1% suspension (Nevanac)
Nepafenac is a newer formulation used commonly.
- Comfortable and well tolerated.
- Minimized potential for toxicity
- Pentrates vitreous much better than older NSAIDs like ketorolac
Indication: treatment of pain and inflammation after cataract surgery
Major Off-label use:
Prevention of cystoid macular edema
Dosing: 1 gt tid
Nepafenac 0.4% suspension (Ilevro)
Nepafenac is a newer formulation used commonly.
- Comfortable and well tolerated.
- Minimized potential for toxicity
- Pentrates vitreous much better than older NSAIDs like ketorolac
•Similar performance compared to Nevanac
Indication: post-op cataract surgery
Major Off-label use:
prophylactic for CME
Dosing: 1 gt qday
General info on Topical NSAIDs
-Diclofenac is FDA Category D ; All the rest are Category C
Dosing:
Diclo and Ketoro (older) = QID
Brom and Ilevro (newer) = Qday
Nevanac (low concentration) = TID
Minimum Age:
Ketoro = 3
Nepa = 10
Brom = 18
Oral NSAIDs MOA
Inhibit COX-1 and -2 enzymes to prevent the production of prostaglandins, which sensitize nociceptors
Notes:
1) Ceiling effect
o Beyond a certain dose there is no further analgesic effect
o No ceiling effect in opioids
2) No risk of tolerance or addiction with repeated or chronic use.
o Not the case with opioids
3) Patients vary in response to different NSAIDs.
o If max dose is not effective, switch to an alternate
Oral NSAID Side Effects and Possible Complications
1) Renal and liver excretion
o Use caution in patients with history of renal or liver problems, diabetes, or significant use of diuretics
2) Highly protein bound
o Can cause interactions by displacing other drugs from plasma proteins
3) GI upset, ulcers, etc.
o COX-2 is involved in production of prostaglandins that cause pain
o COX-1 produces prostaglandins that have a protective function in the stomach
o Most NSAIDs are COX nonspecific, so they inhibit the production of good prostaglandins in the stomach
4) Bleeding disorders
o Effects on platelets causes blood thinning
o Can worsen bleeding/clotting disorders
o Increased risk of re-bleed in problems like hyphema and vitreous heme
5) CAUTION IN:
o Asthma, aspirin hypersensitivity, after invasive surgery, 3rd trimester pregnancy
Aspirin
Oral NSAID
Prototype NSAID
o Analgesic, anti-inflammatory, anti-pyretic, and anti-platelet effects
Clinical uses
o Corneal abrasion
o Conjunctival discomfort from viral infection
o Can be combined with Tylenol, codeine, or other narcotics for an additive pain relieving effect
Toxic reaction
o Tinnitus – ringing in the ears
Formulations
o Buffered aspirin has increased dissolution rate
o Enteric coating can reduce GI problems
o **Avoid either of these in acute pain
Contraindication:
children under 18
o Can cause Reyes syndrome
Dosing for Aspirin
Anti-inflammatory dosing
o 3-4 grams/day or 8-16 OTC tabs/day
Adult dose for ocular pain
o Two 325 mg or one 650 mg tab q4h
o Do not exceed 4 gm/day
Ibuprofen (Motrin, Advil, Nuprin, Medipren)
Oral NSAID
non-selective COX inhibitor
More effective analgesic than aspirin. Half-life is 2 hours. Peak levels reached in 1-2 hours. Formulations o 200 mg tabs OTC o 300-800 mg tabs Rx
Dosing
Adult analgesic dose = 400 mg q4h
2400 mg is anti-inflammatory level
3200 mg is max daily dose
Naproxen (Anaprox, Naprosyn, Aleve)
Oral NSAID
non-selective COX inhibitor
May be the safest NSAID
For relief of mild to moderate pain
Adult Rx dose
- 550 mg initially followed by 275 mg q6-8h
OTC dose
- 220 mg q8-12h
Ketoprofen (Orudis, Oruvail)
Oral NSAID
• 2 hour half life
• 50 mg q4h may be as effective as Tylenol+Codeine for analgesia
Adult dose
o Orudis: 50 or 75 mg q6-8h
o Oruvail: 200 mg q?h (Sustained release, Rx only)
Ketorolac
Oral NSAID
Very potent with a much higher risk of side effects.
Used short term only – 5 day max
Dosing: 10 mg q4-6h, max 40 mg/day
Indomethacin
Oral NSAID
Very cheap
Dosing: 25-50 mg bid-tid
Meloxicam (Mobic)
Oral NSAID
• We don’t Rx this much, but common to see patients taking it in clinic
• Easier on stomach
Dosing: 7.5-15 mg qd
Celecoxib (Celebrex)
Oral NSAID
MOA: COX-2 selective inhibitor
o Fewer gastric side effects
Adverse effects:
Increased risk of heart attack and stroke
Dosing: 100 or 200 mg qday-bid
Acetaminophen (Tylenol)
MOA: Centrally acting COX inhibitor
o Exact MOA not fully understood
o Analgesic and antipyretic
o NOT anti-inflammatory or anti-platelet
Use:
For mild-moderate pain
o Often combined with narcotic analgesics
Adverse Effects:
o Risk of liver, renal tubule, and myocardium toxicity
• Contraindicated with liver impairment
• Acetaminophen OD is #1 cause of liver failure
o Limit of 325 mg added to narcotic agents or other meds to prevent overdose
o Known for its safety, except in the case of overdose
Comparison to aspirin:
o Less GI upset
o Greater safety during breastfeeding
o Does not affect platelet clotting factors (No bleeding risk)
Dosing for Acetaminophen (Tylenol)
Adult dose: 325-1000 mg q4h
Max = 4000 mg/day
Synergistic Analgesic Combinations and Adjuvants
Alternate central acting acetaminophen + peripheral acting ibuprofen
o Analgesic effect approximates Tylenol #3 (Tylenol+Codeine) in dental and post-op pain studies
o 650-1000 mg acetaminophen q4h and 400 mg ibuprofen q4h
• Ex. acetaminophen at noon, ibuprofen at 2 pm, acetaminophen at 4 pm, ibupofen at 6 pm
Adujvants
o Added substances like caffeine can enhance the effect of NSAIDs or narcotic agents
NSAID Safety Overview
-Aspirin, Ibuprofen, Meloxicam are all FDA Category D ; Celebrex is C early / D late ; All the rest are Category C.
Minimum Age: Ibuprofen = 2 mos Naprox, Melox, Indometh, Aceta = 2 yr Ketoro = 17 yr Aspirin, Ketopro = 18 yr
Max Dose Per Day Meloxicam has lowest at 15 mg. Ketorolac is just behind at 40 mg. Indomethacin next at 150-200 mg. Ketoprofen at 300 mg. Celebrex at 400 mg. Naproxen at 1000 mg. Ibuprofen at 3200 mg. Aspirin and Acetaminophen are highest at 4000 mg.
Points To Remember
Ocular pain is usually acute and short lived, best treated with an opioid + NSAID, aspirin, or acetaminophen
Schedule III is usually a safe bet and can be Rx’d by ODs in most states
Avoid combining aspirin and codeine with barbiturates
o Watch out for polypharmacy!
Children o Note dosage recommendations, stick to FDA guidelines, and consult with patient’s pediatrician o Avoid aspirin combinations – Reye’s syndrome o Good choices • Acetaminophen 10-15 mg/kg q4h • Ibuprofen 4-10 mg/kg q6h • Naproxen 5-7 mg/kg q8h • Codeine 0.5-1 mg/kg q4-6h
Elderly patients
o Usually have poorer renal/liver clearance
o Increased risk of side effects
• Sedation, constipation, CNS effects
o More likely to be on multiple drugs
• Interactions, polypharmacy
• Opioid allergies are rare
o If present, use tramadol or an NSAID as an alternative
• Use precautions when writing an Rx to avoid tampering
Remember that just because a pain med contains an opioid, it isn’t necessarily the best pain killer
• Ibuprofen 400 mg was shown in this study to give better ocular pain relief than Tylenol #4
