Pain I Exam Therapeutics

acetaminophen MOA

Inhibition of prostaglandin synthesis in the central nervous system

what medication is first line for mild-moderate pain/antipyretic?

acetaminophen

Antispasmodics with analgesic effects should be used with caution with other _______________________ due to additive risk

CNS depressants

All muscle relaxants cause excessive...

sedation, dizziness, confusion, asthenia (muscle weakness)

T or F: baclofen can cause withdrawal syndrome with cessation

true

what dosage forms does baclofen (Lioresal®) come in?

Tablet, solution, injection, oral suspension, granules

what are side effects with baclofen?

nausea, headache, constipation, hypotension

does baclofen require renal adjustments?

yes

Cyclobenzaprine (Amris®, Fexmid®, Flexeril®) dosage forms

Tablet, capsule

Cyclobenzaprine side effects

dry mouth

cyclobenzaprine is _________, should not be combined with other ____________ drugs

serotonergic

Tizanidine (Zanaflex®) MOA

centrally acting alpha-2 agonist

Tizanidine dosage forms

tablet, capsule

Tizanidine side effects

hypotension, dry mouth, increase in LFTs

Tizanidine contraindications

Use with strong CYP1A2 inhibitors (i.e., fluvoxamine, Cipro)

Antispasmodics that exert their effects by __________

sedation

can withdrawal occur with rapid cessation of carisoprodol (Soma®)?

yes

what is the active metabolite of carisoprodol?

meprobamate

Methocarbamol (Robaxin®) side effects:

- Can discolor urine

- Sedation

what are the 3 primary receptors that opioids interact with?

μ (mu), k (kappa), and delta

Opioids are __ receptor agonists in the CNS, which primarily produce pain relief, but also cause euphoria and respiratory depression

mu

T or F? A REMS exists for all opioid medications.

true

Physical Dependence

Patients using chronic opioids (including those abusing opioids) become physiologically adapted to the opioid and experience physical withdrawal symptoms when the opioid is stopped or a dose is late or missed

Addiction

A strong desire or compulsion to take the drug despite harm. Involves drug-seeking behavior, including exaggerating the pain or physical problems, receiving prescriptions from multiple prescribers, etc.

Opioid Use Disorder (OUD)

A problematic pattern of opioid use that causes significant impairment or distress

Tolerance

A higher opioid dose is needed to produce the same level of analgesia that a lower dose previously provided

Opioid Hyperalgesia

When the opioid dose is increased to treat the pain, but the pain becomes worse rather than better. If suspected, a different class of analgesic or a switch to another opioid should be tried.

Break-Through Pain [(BTP), end of dose pain]

Sharp spikes of severe pain that occur despite the use of an ER opioid. Scheduled opioids are dispensed with a BTP medication until the dose of the scheduled opioid is adequate

Opioid-Indiced Respiratory Depression (OIRD)

The usual cause of fatality in opioid overdose

Centrally-Acting Opioid Antagonists

Block opioids from binding to the mu receptor

what is the definition of Opioid Tolerance?

Receipt of at least 60 mg MME per day for 1 week

Presence of tolerance __________ (does / does not) indicate addiction

does NOT

Opioid Dependence Definition:

Abstinence/withdrawal syndrome following either:

- abrupt dose reduction or discontinuation of opioid

OR

- administration of an opioid antagonist

- N/V, chills, hot flashes, abdominal cramps, diarrhea, insomnia, salivation, lacrimation, diaphoresis

Opioid Induced Hyperalgesia Definition:

enhanced pain sensitization in patients on chronic opioid therapy, symptoms will appear as drug seeking behavior

how to treat opioid induced hyperalgesia

- Wean/taper opioid medications

- Switch to a different class of opioid:

1st line = methadone, other opioids can be used

- Non-opioid and/or adjuvant therapies

APAP, NSAID, anticonvulsant, antidepressant

opioid boxed warning

- Addiction, abuse, and misuse can lead to overdose and death

- Respiratory depression, which can be fatal

OIRD risk factors include:

▪ History of previous overdose

▪ Substance use disorder

▪ Using large doses (≥50 mg morphine or equivalent)

▪ Use with benzodiazepines, gabapentin or pregabalin

▪ Comorbid illnesses, such as respiratory or psychiatric disease

_____________ should be readily available to patients with elevated risk OIR

Naloxone

General Class Opioid Adverse Effects

- mood changes

- somnolence

- N/V

- respiratory depression

- constipation

- urinary retention

- histamine release

- dependence, addiction

- miosis

what adverse effects of opioids do patients never develop tolerance to?

- miosis

- constipation

When opioids are dosed around the clock, such as with an ER opioid, what is required?

constipation prophylaxis

how is opioid-induced constipation treated?

• Stimulant (i.e., senna, bisacodyl)

or

• Osmotic (i.e., polyethylene glycol) laxatives

Bisacodyl dosage forms

- tablet (for prophylaxis)

- suppository (for treatment)

are opioids first line for chronic pain tx?

no

what should be avoided with opioids?

benzos

The common drugs in the same chemical class that cross-react with each other have _______ or ______ in the name

cod or morph

T or F: nausea and itching are true opioid allergies

false

if patient has a true opioid allergy to cod or morph drugs, what should you use?

choose a drug in a different chemical class such as methadone or fentanyl.

what are the naturally occurring opioids?

- Morphine (MS Contin®)

- Codeine

what opioid is considered first line for moderate to severe pain?

morphine

IR dosing for morphine

Every 4-6 hours (can be reduced to every 2 hours if needed)

ER dosing for morphine

Every 8-12 hours

what is the active metabolite of morphine?

morphine-6-glucuronide (M6G)

what is the inactive metabolite of morphine that accumulation can cause unwanted CNS effects (seizures->death)?

Morphine-3-glucuronide (M3G)

who should avoid morphine use?

- CrCl<30 mL/min avoid use

- Do not recommend use for ESRD or dialysis

codeine is a

prodrug, metabolized into morphine via CYP2D6

codeine boxed warning

Respiratory depression and death have occurred in children who were found to be ultra rapid metabolizers (due to a CYP2D6 polymorphism) after tonsillectomy and/or adenoidectomy

codeine contraindications

• Do not use in children <12 years

• Do not use in <18 years (following tonsillectomy/adenoidectomy surgery)

what are the semisynthetic opioids?

• hydrocodone

• hydromorphone (Diluadid®)

• oxycodone (Roxicodone®, OxyContin®)

IR formulation if hydrocodone

combined with acetaminophen 325 mg

(Norco®, Lorcet®, Lortab®, Vicodin®)

IR and ER dosing of hydrocodone

IR dosing is every 4-6 hours

ER dosing is every 12-24 hours

dosage formulations of hydromorphone

tablet, injection, solution, suppository

why should hydromorphone only be used in opioid-tolerant patients?

Risk of medication error with high potency injection

Hydromorphone is a ______ opioid

potent, high risk for overdose

hydromorphone dosing

Oral: 2-4 mg Q4-6H PRN

IV: 0.2-1 mg Q2-3H PRN

when is oxycodone (Roxicodone®, OxyContin®) typically used first line?

if morphine not able to be utilized due to renal function

does oxycodone come IV?

no

oxycodone combo products with acetaminophen

Endocet®, Percocet®

what are the synthetic opioids?

- Meperidine (Damerol®)

- Fentanyl (Duragesic®, Sublimaze®)

Meperidine (Damerol®)

- No longer recommended as an analgesic; limited use in clinical practice

- Short duration of action (pain controlled for max 3 hours)

- Normeperidine (metabolite) is renally cleared and can accumulate causing CNS toxicity, including seizures

- Serotonergic and can increase risk of serotonin syndrome

what opioid is the safest for hepatic or renal impairement?

Fentanyl

in patient and outpatient use of Fentanyl

- IV products indicated for acute pain in hospitalized patients

- Outpatient use of fentanyl is for chronic pain management only

Fentanyl can be used in a

PCA pump

T or F, fentanyl cannot be used in opioid naive patients

true

who can be converted to a fentanyl patch?

patient who has been using equivalent to morphine 60 mg/day or more for at least 7 days

fentanyl products

Injection, patch, transmucosal lozenge on a stick ("lollipop"), buccal tabs, sublingual spray

fentanyl boxed warnings

▪ Potential for medication errors when converting between dosage forms

▪ Use with strong or moderate CYP3A4 inhibitors can result in additive effects and potentially fatal respiratory depression

fentanyl side effects

Hyperhidrosis, dry mouth, asthenia, loss of appetite, application site redness/erythema (patch)

Fentanyl Patch

▪ Apply 1 patch Q72H (can be Q48H)

▪ Apply to hairless skin

▪ Dispose of patch by flushing down the toilet; keep away from pets and children

who is the fentanyl patch indicated for?

opioid tolerant patients., defined as: ≥ 60 mg MME per day for one week

how often should the fentanyl patch be applied?

every 72 hours (some pts require patch change every 48 hours)

who should NOT use fentanyl patches?

cachectic patients

where can the fentanyl patch be applied?

chest, back or upper arm

what dosage forms of fentanyl are used for breakthrough cancer pain?

Transmucosal lozenge, buccal tablet, intranasal, sublingual tablet, sublingual spray

Should not be used in acuteor postoperative pain

fentanyl breakthrough cancer pain therapy + REMS requirements

Only available through restricted program.

Must be enrolled in (TIRF) REMS Access Program

Opioid Drug Interactions

1. Additive CNS effects

- Alcohol, hypnotics, benzodiazepines, muscle relaxants

2. Hypoxemia

- Increased risk with COPD & sleep apnea

3. Methadone

- Caution with agents that cause QT prolongation or other serotonergic agents

4. CYP3A4 inhibitors

- Hydrocodone, fentanyl, methadone & oxycodone are CYP3A4 substrates, avoid use with inhibitors

Centrally acting opioids

- Tramadol (Ultram®)

- Tapentadol (Nucyntar®, Nucynta ER®)

Tramadol

▪ Primarily indicated for moderate pain

▪ BW: respiratory depression and death have occurred in children following tonsillectomy and/or adenoidectomy

▪ CI: do not use with MAO inhibitors or within 14 days of use

▪ Warnings: seizure risk, serotonin syndrome

Tapentadol

▪ Indicated for moderate-severe pain and neuropathic pain (not first-line)

▪ Warnings: seizure risk, serotonin syndrome

which is stronger, Tapentadol (C-II) or Tramadol (C-IV)?

Tapentadol

Centrally Acting Analgesic Drug Interactions

- Seizures

- CYP2D6 inhibitors

- Serotonin syndrome

Continuous intravenous infusion reserved for _____________________ patients

opioid tolerant

what is patient controlled analgesia (PCA)?

- alternative to continuous infusion

Two components

• Continuous infusion, if desired

• PRN medication- Small dose of opioid medication delivered by push of a button, frequency depends on medication administered (q10-20 min)... can be beneficial in post-operative period (24-48 hours)

what medications are frequently used in PCA pumps?

Fentanyl, morphine, hydromorphone

World Health Organization (WHO) Pain Ladder

Step 1: Non-opioids +/- adjuvant

If pain persists or increases-

Step 2: mild-moderate pain opioids +/- nonopioid & adjuvant

If pain persists or increases-

Step 3: moderate-strong opioids +/- nonopioid & adjuvant

Top of ladder: free from cancer pain

Adjuvant medications may be added at any step in the ladder

patient should be _______________ if initiated on ER preparation

opioid tolerant

Adjuvants

- Antidepressants, antiepileptics, muscle relaxants

- Considered for all severities of pain, especially for neuropathic pain

first and second line therapy for acute & subacute low back pain

1st line: Non-pharmacologic therapy

• Superficial heat, massage, acupuncture or spinal manipulation

2nd line: Pharmacologic therapy

• NSAIDs or skeletal muscle relaxants

general acute pain management for mild-moderate pain

• Non-opioid and/or adjuvant first line in combination with non-pharm therapy

• Low dose opioid or centrally acting opioids are second line

general acute pain management for moderate-severe pain

Non-opioid and/or adjuvant first line, opioids may be considered based on the acuity of the situation, with non-pharmacologic therapy