Management of Ocular Pain

What are the typical causes for acute ocular pain?

• Conjunctival or Corneal FB

• Conjucntival or corneal abrasion

• Traumatic Iritis

• Herpes Zoster

• Post surgical PRK, PTK, superficial keratectomy among others

What are Nociceptors?

Specialized nerve endings in tissue that transmit pain signals to cortex.

What is the role of Substance P in pain signaling?

• Substance P mediates transmission of pain from activated nociceptors

• Enhances signaling at synapses involved in pain pathways

How do prostaglandins influence pain perception?

• Arachidonic acid metabolites (prostaglandins) enhance/stimulate Substance P activity

• Result: amplified pain signaling and increased sensitivity

Where must pain signals be processed for pain to be consciously perceived?

Pain is only felt if the signal is fully received and processed in the cerebral cortex

Where along the pain pathway can pain be pharmacologically interrupted?

• Periphery: ↓ prostaglandins or substance P → ↓ nociceptor sensitization

• Signal transmission: block nerve conduction → prevent signal reaching cortex

• Central perception: alter pain processing in cerebral cortex

How do NSAIDs reduce pain at the peripheral level?

• Inhibit COX → ↓ prostaglandin (PGE₂) synthesis

• ↓ sensitization of nociceptors to Substance P

Which drugs inhibit Substance P directly, and what is their limitation?

• Capsaicin

• Depletes Substance P → ↓ nociceptor activation

• Dermatologic use only (not used intraocularly)

How do anesthetics reduce pain?

• Block pain signal transmission along nerves

• Prevent signal from reaching the cerebral cortex

How does acetaminophen reduce pain?

• Acts centrally in cortex to alter pain perception

• Minimal peripheral anti‑inflammatory effect

How do opioids reduce pain?

Alters central nervous system perception of pain via 3 receptor types:

• Mu (μ): supraspinal analgesia, sedation, respiratory depression

• Kappa (κ): spinal analgesia

• Delta (δ): relatively unclear/less well‑defined effects

What are the advantages of using topical NSAIDs for ocular pain?

• Direct application to site of injury/inflammation

• Acts locally at nociceptor nerve endings

• Limits systemic absorption and side effects

What are topical ocular NSAIDs used to treat?

• Post Refractive Surgery

• Post Catarct Surgery

• Post FB removal

• Pre/Post Betadine Treatment

• Bullous Keratopathy & Acute Corneal Hydrops

How do NSAIDs work?

• Cyclo-oxygenase inhibitor that prevent/decrease the formation of prostaglandins

• Provides anagesia by reducing PGE2 to reduce pain

• Anti-inflam by reducing PGD2 to decrease vasodilation and vascular permeability

• Anti-platelet properties

• Anti-pyretic properties

What are the NSAIDs and their dosages for acute ocular pain?

• Ibuprofen 400-600mg PO QID (max: 2400mg/24hrs)

• Ketoprofen 50mg PO q6-8hr

• Naproxen sodium 250-500mg PO BID

Take with food to decrease GI effects

What are the SE of oral NSAIDs?

• Hemorrhage

• GI distress, heartburn, duodenal ulcer

• Nephrotoxicity

What are the contraindications for oral NSAIDs?

• Hyphema

• Gastric/peptic ulcer

• Renal insufficiency of CHF

• Pregnant/nursing mothers

• No aspirin for children d/t risk of Reye’s syndrome

What is Acetaminophe/tylenol’s therapeutic effect?

• Analgesia

• Antipyretic

• Has no effect on inflammation or platelets

What are the SE of Acetaminophen?

• No GI SE

• No anticlotting/bleeding effects

• No cross reactivity with NSAIDs

• Safe for kids and during pregnancy

• Liver toxicity if exceed recommended dosage or if in alcoholic or known liver disease

What are the contraindications for Acetaminophen?

Chronic alcoholics

What is the typical dosing of Acetaminophen?

• 325-1000mg PO q6 hour

• Tylenol regular strength: 325mg

• Tylenol extra strength: 500mg

• In 2011, reduced maximal daily dosage from 4g/24hrs to 3g/24hr d/t high incidence of inducing liver disease

How is Acetaminophen and NSAIDs dosed?

Alternate drug every 3 hours

What are opiates/opioid analgesics, and what is the prototypical agent?

• All derived from opium or opium‑like compounds

• Prototypical opioid: morphine

What is the primary mechanism of action of opioid analgesics?

• Alter central nervous system perception of pain

• Act via opioid receptors in the brain and spinal cord

What are the three main opioid receptor types and their clinical effects?

• Mu (μ): supraspinal analgesia, sedation, respiratory depression

• Kappa (κ): spinal analgesia

• Delta (δ): relatively unclear/less well‑defined effects

What are the therapeutic effects of opiates?

• analgesia

• Anesthesia

• Cough suppression

• Anti-diarrheal

What are the SE of opiates?

• Constipation

• Dry mouth

• Nausea

• Sedation, dizziness, weakness

• Addition/dependence d/t euphoric effects

• Respiratory depression, can be fatal

What are the contraindications for opiates?

• Asthma, COPD

  • Beware of sleep apnea

• Pregnancy

• An unidentifiable cause of pain

What should be done or not done when taking opiates?

• Take opiates with food to decrease GI effects

• Avoid driving or other activities requiring alertness

• Avoid alcohol, muscle relaxants

What determines a drug’s DEA schedule?

• Abuse potential

• Medical use in the U.S.

• Risk of dependence (physical or psychological)

• Schedule I = highest abuse, no accepted medical use → Schedule V = lowest abuse

What characterizes Schedule I controlled substances?

• Very high abuse potential

• No accepted medical use

• Illegal to prescribe

What are common examples of Schedule I drugs?

• Heroin

• LSD

• MDMA (ecstasy)

• Peyote

• Quaaludes

• Marijuana (federally Schedule I despite state legalization)

What characterizes Schedule II controlled substances?

• High abuse potential

• Accepted medical use

• Severe dependence liability

What are examples of Schedule II drugs?

• Cocaine

• Amphetamines (including ADHD medications)

• Opioids: morphine, oxycodone, hydrocodone

What characterizes Schedule III controlled substances?

• Moderate abuse and dependence potential

• Accepted medical use

• Less restrictive prescribing than Schedule II

What are examples of Schedule III drugs?

• Ketamine

• Anabolic steroids

• Combination opioids (e.g., Tylenol #3 with codeine)

What characterizes Schedule IV controlled substances?

• Lower abuse and dependence potential

• Accepted medical use

• Refills allowed

What are common Schedule IV drugs?

• Analgesics: Tramadol

• Anti-anxiety agents: Xanax, Klonopin, Valium, Ativan

• Sleep aids: Ambien, Lunesta

What characterizes Schedule V controlled substances?

• Lowest abuse potential

• Accepted medical use

• Limited quantities, lowest level of control

What are examples of Schedule V drugs?

• Antitussives/antidiarrheals with codeine

• FDA‑approved CBD‑containing medications

What are the ocular indications for opiates?

• Severe, acute pain from:

  • Severe Corneal abrasion or FB

  • Post PRK or other corneal surface procedures

  • Herpes Zoster and post-herpetic neuralgia

Which opioid analgesics are within the scope of practice for Ohio optometrists?

• Tramadol (recognized therapeutic amount)

• Codeine ≤ 60 mg, only if combined with non‑narcotic ingredients

• Hydrocodone ≤ 7.5 mg, only if combined with non‑narcotic ingredients

What formulation limits apply to codeine and hydrocodone prescribed by Ohio optometrists?

• Must be combination products

• Must contain other active non‑narcotic ingredients

• Dose limits strictly enforced (codeine ≤ 60 mg; hydrocodone ≤ 7.5 mg)

What are the quantity limits on opioid prescriptions by Ohio optometrists?

• Maximum: single 4‑day supply

• Per episode of illness, injury, and/or treatment

• No extended or repeat opioid prescribing

What is tramadol, and why is it relevant to optometric prescribing?

• Synthetic opioid, analog of codeine

• Trade name: ConZip®

• Became a Schedule IV controlled substance in Oct 2014

• Permitted for Ohio ODs, but requires a DEA number

What is the abuse potential and side‑effect profile of tramadol?

• Low addiction potential

• Similar side effects to codeine: nausea, dizziness, sedation

• Still carries risk of dependence and CNS depression

What is the standard adult dosing for tramadol?

• 50-100 mg PO every 4-6 hours as needed for pain

• Use lowest effective dose for shortest duration

What tramadol combination product is commonly used, and how is it dosed?

• Tramadol 37.5 mg / Acetaminophen 325 mg

• 2 tablets PO every 4–6 hours

• Max: 8 tablets in 24 hours

What drugs interact with Tramadol?

Anti-depressants

What is codeine, and how does it produce analgesia?

• Prodrug of morphine

• Central opioid analgesic effect

What is the DEA schedule and typical non‑analgesic use of codeine?

• Schedule III controlled substance

• Standalone codeine commonly used for cough suppression

What analgesic formulations of codeine are commonly used?

Combination products with acetaminophen:

• 15 mg codeine / 300 mg acetaminophen

• 30 mg codeine / 300 mg acetaminophen

• 60 mg codeine / 300 mg acetaminophen

What is the standard adult dosing for codeine used as an analgesic?

• 30-60 mg PO every 4-6 hours

• Dose must be considered within combination product limits

What is hydrocodone and how is it classified by the DEA?

• Semi‑synthetic opioid analgesic

• Reclassified in October 2014 from Schedule III → Schedule II

• Change due to widespread abuse and dependence risk

How does the potency of hydrocodone compare to codeine?

• 6 times more potent than codeine

• Produces stronger analgesia at lower doses

What are the characteristic side‑effect differences of hydrocodone compared to codeine?

• Less constipation

• Less sedation

• More euphoria

What is the typical adult dosing for hydrocodone?

5-7.5 mg PO every 4-6 hours as needed for pain

How is hydrocodone most commonly formulated?

Combination products with non‑narcotic analgesics

What hydrocodone-acetaminophen combination strengths are available?

• 2.5 mg hydrocodone / 325 mg acetaminophen

• 5 mg hydrocodone / 300–325 mg acetaminophen

• 7.5 mg hydrocodone / 300–325 mg acetaminophen

• 10 mg hydrocodone / 300–325 mg acetaminophen

• Generic formulations only

What hydrocodone-ibuprofen combination strengths are available?

• 2.5 mg hydrocodone / 200 mg ibuprofen

• 5 mg hydrocodone / 200 mg ibuprofen

• 7.5 mg hydrocodone / 200 mg ibuprofen

• 10 mg hydrocodone / 200 mg ibuprofen

• Generic formulations only

Why are Ohio optometrists prohibited from prescribing oxycodone?

• Schedule II opioid

• 10-12× more potent than codeine

• Produces significant euphoria

• High risk of dependence and abuse

What are common trade names and formulations of oxycodone?

• Standalone: OxyContin, Roxicodone, RoxyBond, Xtampza ER

• Combination with acetaminophen:

  • Percocet

  • Endocet

  • Roxicet

What is hydromorphone and why is it excluded from OD prescribing?

• Trade name: Dilaudid

• Schedule II opioid

• Very potent µ‑opioid agonist

• High abuse potential and overdose risk

What is required to obtain a DEA number to prescribe controlled substances?

• 731$ nonrefundable fee

• Covers a 3‑year registration period

Does a DEA number transfer between states?

• No. A separate DEA application is required for each state in which you practice

• Having a DEA number in another state does not exempt reapplication

What is the key mechanism of opioid addiction/overdose, and why is opioid use a major U.S. public‑health issue?

• Addiction: driven by opioid‑induced euphoria

• Overdose deaths: due to respiratory depression

• Epidemic fueled by overprescribing and illicit use

• U.S. = disproportionate consumer: ~5% of world population but ~80% of global opioid use

What are the key legal requirements for prescribing controlled substances in Ohio?

• Must be written or e‑prescribed (cannot be called in)

• Recommended to keep a log of controlled‑substance prescriptions with patient signatures

• Patient education is mandatory (Ohio Revised Code):

  • Must inform patients of the addictive nature of opioids

  • Must provide an opioid/narcotics patient handout

What is OARRS and how does it help reduce substance abuse in Ohio?

• Ohio Automated Rx Reporting System (OARRS)

• Secure database that allows authorized providers to review a patient’s controlled‑substance prescription history

• Helps detect doctor shopping, overprescribing, and misuse

• All pharmacies must report Schedule II–V dispensations at least weekly

How is Opioid Overdose treated?

• Naloxone (Zimhi)

• An opioid antagonist used to reverse effects of opioid overdose

• Injectable by paramedics and also as a nasal spray

What medications are used to treat opioid use disorder, and how do they work?

• Methadone: long‑acting full opioid agonist used as morphine alternative

• Buprenorphine: partial agonist with lower overdose risk

• Naltrexone: opioid antagonist for long‑term relapse prevention

What are the key pharmacologic features and risks of methadone?

• Synthetic full opioid agonist

• Very long half‑life (~60 hrs; up to 150 hrs)

• Takes ~10-12 days to reach steady state

• High overdose risk → involved in ~30% of opioid‑related deaths

Why is buprenorphine considered safer than full opioid agonists?

• Partial agonist at µ‑opioid receptors

• Ceiling effect on respiratory depression

• Lower risk of fatal overdose

What is the role of naltrexone in opioid use disorder treatment?

• Opioid antagonist

• Blocks opioid effects

• Used for long‑term maintenance / relapse prevention

What are the main non‑opioid options for managing ocular pain and their indications?

• Cycloplegia: uveitis, keratitis (reduces ciliary spasm)

• Bandage contact lens: large corneal abrasions

• Topical NSAIDs: corneal hydrops, bullous keratopathy

• Oral NSAIDs: drug of choice for ocular and periorbital pain

• Oral acetaminophen: hyphema present or as alternative to NSAIDs