16 - management of ocular pain

What are common causes of acute ocular pain?

1. conj or corneal foreign body

2. conj or corneal abrasion

3. iritis

4. HZO

5. post-surgical → PRK, PTK, superficial keratectomy

image - corneal abrasion

what are nociceptors?

specialized nerve endings in the tissue that transmit pain signals

where does nociceptor activation transmit signals to?

cerebral cortex

What activates nociceptors?

substance P

What enhances/stimulates substance P activity?

arachidonic acid metabolites → prostaglandins

When is a pain signal felt?

only if it is fully received and processed in the cerebral cortex

What are the 3 categories of drugs for pain management?

1. peripheral acting agents

2. signal inhibiting agents

3. central acting agents

What do peripheral acting agents for pain do?

1. inhibit substance P directly → ↓ nociceptor activation

2. inhibits prostaglandin synthesis to prevent sensitization to substance P

substance P is enhanced by arachidonic acid metabolites

What are examples of peripheral acting agents for pain?

1. capzasin

2. NSAIDs

How does capzasin block pain?

inhibits substance P directly to decrease nociceptor activation

typically only used for joint pain or HZO

How do NSAIDs block pain?

reduce arachidonic metabolites (prostaglandins) which prevent the sensitization of receptors to substance P

What do signal inhibiting agents for pain do?

prevent pain signal (action potentials) from traveling to cortex

What is an example of a signal inhibiting agent for pain?

anesthetics

not therapeutic agents

What do central acting agents for pain do?

act on pain perception centers in the cortex

What are examples of central acting agents for pain?

1. acetaminophen

2. opioids

What are the advantages of using topical NSAIDs for pain?

direct application to site of injury/inflammation:

1. limits side effects

2. MOA takes place in PNS → acts directly at nociceptor

What are the uses of topical NSAIDs for pain?

1. post refractive/cataract surgery

2. post FB removal

3. pre/post betadine tx - typically surgical disinfectant

4. bullous keratopathy

5. corneal hydrops

What is the MOA of oral NSAIDs? What are their effects?

cyclo-oxygenase inhibitors that prevent/decrease the formation of prostaglandins (PGE₂ for pain) to carry out:

1. analgesic

2. anti-inflammatory

3. anti-pyretic

4. anti-platelet effects

What oral NSAIDs are used for acute ocular pain?

1. Ibuprofen 400-600mg PO QID

2. Ketoprofen 50 mg PO q6-8hr

3. Naproxen sodium 250-500mg PO BID

what is the maximum amount of ibuprofen that can be ingested?

2400 mg/24 hrs

what is the DOC for acute ocular pain?

Ibuprofen 400-600mg PO QID → fastest onset of action

what is the second DOC for acute ocular pain?

Ketoprofen 50 mg PO q6-8hr

what is the third DOC for acute ocular pain?

Naproxen sodium 250-500mg PO BID

how to reduce GI effects of oral NSAIDs?

take oral NSAIDs with food

why? - NSAIDs can decrease healthy prostaglandins of the stomach

Which COX pathway creates the protective prostaglandins (starting fatty acid & enzyme)?

omega 3 fatty acid (from phospholipids) & COX-1

Which COX pathway creates the endoperoxides (painful) prostaglandins (starting fatty acid & enzyme)?

omega 6 fatty acid (from phospholipids) & COX-2

What is the ceiling effect and what drug does it occur with?

beyond a certain dosage → no further therapeutic effect is realized

seen with oral NSAIDs

What are the side effects of oral NSAIDs?

1. hemorrhage

2. gastric distress, heartburn, duodenal ulcer

3. nephrotoxicity

what are the contraindications for oral NSAIDs?

1. hyphema - rebleed

2. gastic/peptic ulcer

3. renal insufficiency of CHF

4. pregnant/nursing mothers

5. no aspirin for children d/t risk of Reye's Syndrome

what is the MOA of acetaminophen?

unknown CNS effect → some impact on cortex

What is the therapeutic effect of acetaminophen?

1. analgesia (anti-pain)

2. anti-pyretic (anti-fever)

no effect on inflammation or platelets

when do you prescribe acetaminophen?

if pt is contraindicated for NSAIDs

What are the side effects of acetaminophen?

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

What is a contraindication of acetaminophen?

chronic alcoholics

What are advantages of acetaminophen?

1. no GI SE

2. no anticlotting/bleeding effects

3. safe for kids and pregnancy

4. no cross reactivity with NSAIDs

What are disadvantages of acetaminophen?

1. liver toxicity

2. no effect on inflammation

What must you make sure to tell your patient when prescribing acetaminophen?

do NOT follow package instructions → may take med every 6 hours but do NOT exceed 2000mg in 24 hours

package says 3000mg

what is a typical dose of acetaminophen?

325-1000 mg PO q6h

How should oral NSAIDs and Tylenol be prescribed before using opiates?

exhaust pain management by switching between NSAIDs and acetaminophen (switch every ~4 hrs)

AM - NSAID

Noon - Tylenol

early PM - NSAID

late PM - Tylenol

What is the MOA of opioids?

alters CNS perception of pain via 3 receptor types → mu, kappa and delta

What are the opiates/opioid analgesics derivatives of (aka pharmacology)?

all derivatives of opium flower

what is the prototypical agent of opiates/opioid analgesics?

morphine

What does receptor Mu do?

1. supraspinal analgesia

2. sedation

3. respiratory depression

what does receptor kappa do?

spinal analgesia

what does receptor delta do?

relatively unknown effects

What are the ocular indications of opioid use?

SEVERE, acute pain from:

1. severe corneal abrasion or FB

2. post-PRK or other corneal surgery

3. HZO + post-herpetic neuralgia

if non-opioid analgesics have failed to work

What are the side effects of opioids?

1. constipation → OIC (opioid induced constipation)

2. dry mouth

3. nausea

4. sedation, dizziness, weakness

5. respiratory depression → can be fatal

6. addiction/dependence → d/t euphoric effects (not for every patient)

top 5 are parasympathetic inhibiting

What are the contraindications of opioids?

1. asthma, COPD → beware of sleep apnea

2. pregnancy

3. an unidentifiable cause of pain → could be drug seeker

What should you tell your patient when prescribing opioids?

1. take with food to decrease GI effects

2. avoid driving or other activities requiring alertness

3. avoid alcohol + muscle relaxants

How are DEA controlled substances ranked?

based on abuse/dependency - schedule 1 worse than 5

schedule 1 - very high abuse potential

schedule 5 - limited abuse potential

What opioid controlled substances can be prescribed by Ohio ODs?

1. tramadol

2. ≤60mg of codeine

3. ≤7.5mg of hydrocodone

total quantity prescribed must not exceed a 4 day supply per episode of illness, injury and/or tx

What is the total quantity limit of opioid controlled substance for ODs in Ohio?

shall not exceed a single 4 day supply of opioid substance per episode of illness, injury and/or treatment → no considered primary care anymore!

What is the trade name of tramadol?

ConZip

how does tramadol compare to codeine?

1. synthetic analog of codeine

2. low addiction potential but same SE of codeine

What must you be aware of when prescribing tramadol?

make sure patient is not on antidepressant → DDI

if they are, make sure they do not take it for the few days they are taking tramadol

What is the dosing for tramadol?

50-100mg PO q4-6h

What is a tramadol combination drug?

37.5mg tramadol + 325mg acetaminophen

What is dosing for 37.5mg tramadol + 325mg acetaminophen?

2 tabs PO q4-6h

What is the max dose for 37.5mg tramadol + 325mg acetaminophen combo drug?

8 tabs in 24hours

What schedule drug is tramadol?

Schedule IV

Which opioid should you prescribe first (if all other treatment has failed)?

Tramadol - higher schedule (4), less dependency/abuse potential

what is codeine?

prodrug of morphine

What schedule drug is codeine combo drugs?

Schedule III

What are the formulations of codeine?

15 mg of codeine + 300 mg acetaminophen

30 mg of codeine + 300 mg acetaminophen

60 mg of codeine + 300 mg acetaminophen

only available in generic forms!

what is the dosage for codeine?

30-60 mg PO q4-6 hrs

What schedule drug is hydrocodone?

Schedule II

What is a benefit to hydrocodone?

1. less constipation

2. less side effects

3. more euphoria (possibly) → 6x more potent than codeine

much lower dosage could be the reasons

what is the dosage of hydrocodone?

5-7.5 mg PO q4-6hrs

What other drugs is hydrocodone commonly combined with?

1. Acetaminophen (325mg)

2. Ibuprofen (200mg)

what are the formulations for the hydrocodone combos with acetaminophen?

2.5 mg hydrocodone + 325 mg acetaminophen

5 mg hydrocodone + 325 mg acetaminophen

7.5 mg hydrocodone + 325 mg acetaminophen

what are the formulations for hydrocodone combos with ibuprofen?

2.5 mg hydrocodone + 200 mg ibuprofen

5 mg hydrocodone + 200 mg ibuprofen

7.5 mg hydrocodone + 200 mg ibuprofen

what opioid agents can ohio ODs cannot prescribe?

1. oxycodone

2. hydromorphone

both are schedule II

what are the trade names of oxycodone?

1. oxycontin

2. oxaydo

3. roxicodone

4. roxybond

5. xtampza ER

what are the effects of oxycodone?

10-12x more potent than codeine

significant euphoric effects with high potential for dependence

what are the trade names for oxycodone & acetaminophen combos?

1. percocet

2. endocet

3. roxicet

4. primlev

what is the trade name for hydromorphone?

dilaudid

what are the causes of opioid addiction?

linked to euphoric effect of drugs

what are the adverse effects of opioids?

respiratory depression → fatalities

What is a MED unit and how it used?

MED = morphine equivalent dose

used to measure cautionary doses of opioids that may cause overdose

what is the dose-related risk of overdose?

caution at doses > 50 MED/day

avoid doses > 90 MED/day

avg dose in overdose = 98 MED/day

MED = morphine equivalent dose

what antidepressant should you avoid prescribing opioids with?

benzodiazepines - CNS depressant

What are the rules when prescribing an opioid in Ohio?

1. rx must be written or e-prescribed, cannot be called in

2. keep log of controlled substance rxs with pt signature (recommendation), should check OARRS to make sure they didn't get a script elsewhere (rule)

What are two drugs used to treat an opioid overdose?

1. Naloxone (narcan)

2. Naltrexone

what is naloxone?

opioid antagonist used to reverse the effects of opioid overdose

available as injectable or nasal spray

What is naltrexone?

opioid antagonist used to manage long term treatment of opioid dependence

what is methadone?

synthetic opioid developed as an alternative to morphine, involved in 31% of opioid-related death

why would you use an opioid like methadone/buprenorphine to tx drug addicts?

both have a longer (60-hr) half-life → slowly feeds dependence and helps avoid withdrawal symptoms (takes up to 12 days to reach a steady-state conc)

stops peaks and troughs

what is buprenorphine?

partial agonist tx opioid use

has a lower risk d/t respiratory depression plateaus

what are the risks when initiating tx (for each drug) for opioid use disorder?

methadone: risk of OD during initiation

buprenorphine: risk of precipitated withdrawal → must be in opioid withdrawal before initiation

naltrexone: need to be fully abstinent from opioids prior to initiation

what are the pros and cons of buprenorphine?

pros: quick stabilization of withdrawal, may tx pain

cons: possible overdose risk with alcohol use

what are the pros and cons of methadone?

pros: quick stabilization of withdrawal, may be more effective in tx pain

cons: possible overdose risk with alcohol use

what are the pros and cons of naltrexone?

pros: will tx alcohol use disorder, no risk of withdrawal if pt incarcerated

cons: more severe withdrawal, delay in initiation of tx

What are the options we have to treat ocular pain?

1. cycloplegia

2. bandage CL

3. topical NSAID

4. oral NSAID

5. oral acetaminophen

6. oral opioid

what should you do if pt continues to get worse or do not improve within 2-3 days?

re-evaluate cause of pain and manage or refer as necessary

What must you do for any patient with ocular pain?

make a follow up appointment

Ocular pain is almost always due to what?

inflammation