Pain Management Pharmacology
Describe the Fentanyl lozenge on a stick (Actiq) dosage and usage
(Actiq): 200, 400, 600, 800, 1200, 1600 mcg lozenge. may be good for breakthrough pain or for patients who have trouble swallowing example hospice pt who cant swallow.
recommended doses of opiods
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Drug Treatment options- 3 groups of analgesics.
3 Groups of analgesics: Non-opioids - acetaminophen & NSAIDs Opioids - μ agonists & mixed agonist-antagonists Adjuvants - multipurpose & specific to type of pain
How long after placing a Fentanyl patch are significant systemic levels reached?
6-12hours until significant systemic levels reached but 14+ hours before plateau.
Once and equivalent dose of a pain med is calculated how much should be started?
80% of the total. This is especially important for converting to methadone since it takes longer to get out of the system.
Define true addiction
AKA psychological dependance compulsive use despite harm. many times triggered by cravings in response to specific cues. Lifestyle is eared to the acquisition of the drugs. See: Borrowing from others, injecting oral formulations, prescription loss, requesting specific drugs Quality of life is not improved by the medication and eventually it becomes compulsive (?wanting without liking") Occurs rarely with chronic pain Relapse is very common even after successful withdrawal.
which of the following medications would be useful for acute pain or breakthrough pain with a pt on hospice who can not swallow?
Actiq (Fentanyl lozenge)
What general pain symptoms are immediate release pain meds best used for?
Acute pain and breakthrough pain.
Define the controlled substance schedules and examples of each.
All have abuse potential but higher schedule less likely. Schedule I: can not be prescribed. Research only- Heroin Schedule II: More likely to be abused.- Morphine, fentanyl, meperidine, hyromorphone, oxycodone, methadone, hydrocodone Schedule III: Safer, less likely to be abused- Combo products with codeine Schedule IV: Proven effective as acetaminophen- Propoxyphene products, benzodiapepines (lorazepam, diazepam, oxazepam) Schedule V: Might help a cough- expectorants with codeine
Describe how to assess if a pt is using methadone for pin relief or opiod addiction
Assessing why pt is using methadone: If pt is using methadone for pain then will likely have a short acting pain med for breakthrough pain and will be taking 2-3x/day and are in fairly high doses. If pt is using methadone for opiod abuse usually taking only 1x/day tend to be under 100mg/d.
Describe the use and elimination of Methadone
Biphasic elimination Alpha (analgesic) phase - t ½ 8-12 hours Beta t ½ 24-36 hours (protects against withdrawal) Indicated for the management of opioid abuse AND in the management of chronic pain (drug rotation based on structure) Serves to decrease withdrawal. But can abuse methadone as well. Risk of accumulation toxicity Equianalgesic dosing = not linear!!! Equianalgesic dose of methadone will decrease progressively as morphine equivalents increase
Which pain medication is a class C 4? C3?
C4- Tramadol C3- Codeine (for pain management)
Describe mixed opiod agonist/antagonist
Can get pain control and inhibition of withdrawl depending on drug. Exhibit partial agonist or antagonist activity at the mu receptors. Show agonist or antagonist activity at the kappa receptors Examples: Pain control: Butorphanol (Stadol)- nasal spray for migraine headaches but it isn't really used. Nalbuphine (Nubain), Pentazocine (Talwin)- both are older drugs for pain control with less addiction problems. TREATMENT of opioid abuse: Buprenorphine (Buprenex)- harder to get high from it compared to methadone. Buprenorphine/Naloxone (Suboxone)- requires registered practitioner to prescribe and can only have a set number or pts under care. expensive compared to methadone and not covered by insurance. Can get in pill or strip form. Adverse effects Less respiratory depression & less abuse potential? Precipitate withdrawal in an opioid-dependent patient
Describe the dosage, use and MOAs of Tapentadol
Class C2 Tapentadol (Nucynta); 50, 75, and 100 mg tablets every 4 to 6 hours Opioid agonist and norepi reuptake inhibitor. Newer drug that has weaker affinity to kappa and delta receptors therefore less side effects. ADRs: sedation, seizures? Use in patients who need a strong analgesic (like oxycodone) but that cannot tolerate the GI side effects like constipation
Describe the dosage, use and MOA of Tramadol
Class C4- can have one refill supply Tramadol (Ultram) 50mg tabs; Tramadol ER 100,200,300mg tabs; 37.5mg Tramadol with 325mg APAP (Ultracet) Directions: Tramadol (50-100mg every 4-6hrs; do not exceed 400mg/day) Tramadol ER 100-300mg once daily (not to exceed 300mg/day) Tramadol +APAP (2 tabs every 4-6 hrs prnp; don not exceed 8 tabs/day MOA: Dual action- mu recetptors and inhibits neuronal uptake of sertonin and norepinephrine. Given orally for moderate pain and has been used for chronic pain. Lowers seizure threshold, increases serotonin and norepinephrine levels (WATCH DRUG INTERACTIONS WITH TRIPTANS, MAOIs, SSRIs)
Describe Codeine dosage and usage
Codeine 15, 30, and 60 mg tablets WEAK analgesic. Now Schedule II. Add acetaminophen/aspirin - Schedule III Tylenol #2 = 325 mg acetaminophen & 15 mg codeine ****Tylenol #3 = 325 mg acetaminophen & 30 mg codeine (most popular) Tylenol #4 = 325 mg acetaminophen & 60 mg codeine 1 - 2 tablets every 4 - 6 hours as needed for pain (not to exceed 4 grams of APAP per day) available as a suspension also Add expectorant - Schedule V
Why is codeine most likely to cause a pt to vomit?
Codeine binds most strongly to CNS chemoreceptor center causing nausea and vomiting. Try taking with some food.
Which of the following meds should not be manipulated or crushed/chewed?
Controlled release/ long acting
What needs to be written or discussed with pt regarding dosage of pain meds that contain APAP (tylenol)?
Do not exceed 4g of APAP daily
How do opiod antagonists work as antidotes?
Ex: Narcan and ReVia Rapidly reverse effects of morphine & other opioid agonists. Used to treat opioid overdose causes "antagonist-precipitated withdrawal" within 3 minutes after injection the s/sx of withdrawal appear; peak in about 10-20 minutes and subside in about 1 hour Adverse effects(> 10%): insomnia, headache, nervousness, low energy
What medication has a black box warning for use in acute pain?
Fentanyl Patch
Long acting pain meds
Fentanyl Patch Morphine- MS Contin, Avinza, Kadian OxyContin (CR)
What opiod is the most potent?
Fentanyl Patch followed by Hydromorphone/Dilaudid
Describe Fentanyl Patch dosages and usage
Fentanyl Patch (Duragesic) 12.5, 25, 50, 75, 100 mcg/hr patches ("apply one patch every 3 days to chest wall"); crappy adhesive so brand name is better. Long acting. Should not be used more frequently than every 2 days. if a patient tells you that they want "brand name only"...believe them!!! 6-12 hours until significant systemic levels, 14 or more hours before plateau "black-boxed" by FDA for acute pain Pts can react to adhesive. Can use tegaderm adhesive over patch with a cut out over patch so its not occlusive.
What medications are NOT appropriate for a pt that is opiod naive? (no pain meds in past few months)
Fentanyl Patch- the MOST potent Opiod!!
Describe hydromorphone (dilaudid) usage
Hydromorphone (Dilaudid) 2 and 4 mg tablets ("take 1 - 2 tablets every 4 to 6 hours as needed for pain")- immediate release. hydromorphone ER (Exalgo) (available as 8, 12, and 16 mg tablets given once daily. very expensive and no reason to use) Used for moderate to severe pain very potent
How is Pain determined?
It is very subjective. Everyone has a different pain threshold. Acute pain can be assessed by vitals, pupils, sweating. Chronic pain cannot be assessed that way since the body 'resets' itself to a level of pain being its baseline.
Which group of pain meds are less likely to result in addiction, long or short acting?
Long acting since it is low dose at a consistent level in the system
What basic group of pain meds are appropriate for chronic pain?
Long acting, SR, CR,
Immediate release pain meds
MSIR Dilaudid Percocet
Describe the basic usage of Opiods (narcotics)
Mainstay of Therapy No maximum daily dose limitation Useful for ACUTE and CHRONIC pain Meperidine and morphone have active toxic metabolites. Choices for morphine and derivative allergic persons may be meperidine, fentanyl or methadone.
What opiods have active metabolites?
Meperidine and morphine
What medication is used for chronic pain management and opiod addiction?
Methadone
What pain medication does not have a linear relationship when calculating an equianalgesic morphine equivalent?
Methadone
Describe mild, moderate and severe pain numerical pain scale and what meds should be given
Mild pain = 1 - 3 (big difference between 1 and 3): could be combo or partial dose Acetaminophen, Ibuprofen, Tramadol Moderate pain = 4 - 6 (huge difference): Tramadol Tylenol with codeine Tylenol with hydrocodone (Vicodin, etc.) Severe pain = 7 - 10 (largest difference between 7 and 10): Tylenol with hydrocodone Tylenol with oxycodone (Percocet, etc.) Morphine, Hydromorphone, Fentanyl Patch, Tapentadol There is crossover between meds in some of the groups. Ex: Tramadol can be used to treat a 3 and at high doses a 4.
Pain drugs for severe pain
Morphine Dilaudid
Examples and usage of Morphine
Morphine (MS Contin, Avinza, Kadian) MSIR (Morphine sulfate immediate release)(IR caps) 15, 30 mg (q 3-4 hours prn)- good for acute or breakthrough pain. MS Contin (Continuous Release tabs) 15, 30, 60, 100, 200 mg (q 8-12 hours)- Avinza (CR caps) 30, 60, 90, 120 mg (q 24 hours) Kadian (CR caps) 20, 30, 50, 60, 100 mg (q 12 - 24 hours) [Controlled Release is basically = Sustained Release=Long Acting. Designed to give basal control of pain. These are not prn and should be taken daily] Kadian and Avinza caps may be opened and the pellets sprinkled on apple sauce...but pellets should not be chewed Altering drug deliver system = daily drug supply released immediately = potential OD and death SR products should not be crushed or chewed Standard for comparison of other agents Used for severe pain Avinza and Kadian provide 24 hour SR of morphine = fewer fluctuations in drug levels and less frequent dosing
Describe the use of adjuvant analgesics with opiods for pain.
NSAIDS- not safe for longterm use Antidepressants- fantastic even for pts without depression. Increases serotonin levels which increase pain threshold Anticonvulsants- good for nerve pain Corticosteroids- good for decreasing inflammatio Benzodiazapines- good for decreasing anxiety and for msucle relaxation Muscle relaxers.
Pt presents to ER with broken bone. No signif PMH. Pt is taking 60mg/d oxycodone for separate pain issue. Pt is to be admitted for ABX and pain management. Pt takes 20mg oxycodone in am and pm. Take 4 tabs x 5mg oxycodone IR per day on average. What dose of hydrocodone or morphine needs to be provided in hospital to match current meds?
Need to cover for pain control. Taking: 60mg oxycodone-40mg long acting total and 20mg immediate release. Conversion: Must remember they were on a long acting dose. Hydrocodone needs 60mg Morphine needs 90mg. Most would start at about 80% of the equivalent dose Admitted patients can be placed on Patient controlled pump or as infusion. Outpatients need short and long acting combos conversions.
Define the two types of Pain
Nociceptive Pain - normal processing of stimuli that damages normal tissues; how pain becomes conscious; responsive to nonopioids and opioids Neuropathic: abnormal processing of sensory input by the peripheral or central nervous system; treatment includes adjuvant analgesics (difficult to treat)
Describe the equianalgesic dose equivalent of hydrocodone and methadone and hydromorpone
Note: last box is hydromorphone (diluadid) which comes in 2,4 or 8mg tabs therefore it is usually estimated about 8mg equivalents.
Describe a few different pain scales.
Numerical scale (most common) 0-10 (10 = worst pain) Faces scale May be better for children and the elderly Colors scale Corresponds to numbers blue/white => red (red = 10) Utilize vitals, appearance to correlate if in doubt.
Pt presents with pain. Allergy to codeine (assuming it is a true allergy and not just an upset stomach). What pain med can be given?
ONLY meperidine, fentanyl and methadone can be given. Having a codeine allergy eliminates the use of ALL other pain drugs.
Define tolerance
Occurs with any drugs that plug into a sympathetic receptor. Escalation of dose to maintain effect (analgesia). If effect is euphoria then usage is being abused.
Describe Hydrocodone +APAP examples and dosage
Only available as a combo product. Can not get hydrocodone alone. Hydrocodone + APA (Norco, Vicodin, Lortab); Hydrocodone (7.5mg) + IBU 200mg (Vicpprofen)- hydrocodone 2.5,5, 7.5, 10mg plus APAP 325, 500, 650mg Vicodin= 5/500, Vicodin ES= 7.5/750, Vicodin HP- 10/660. Generic= 5/300; 7.5/300; 10/300 Lortab= 2.5/500, 5/500, 7.5/500, 10/500 Norco= 5/325. 7.5/325, 10/325 Take 1-2 tabs/cap every 4-6 hrs as needed for pain not to exceed 4 grams of APAP per day All hydrocodone products are Schedule II!!! Can only write one month supply with no refills. Script can not be filled after 6mths but this is pharmacy specific. Best to write script for generic 'hydrocodone Xmg/ APAP X mg"
MOA of Opiods
Opium is derived from poppies; relieves pain and induces euphoria by binding to the opioid receptors (mu, kappa, delta) in the brain. AGONISTS. [Mu receptor is the most important/primary pain receptors but kappa and delta are secondary receptors that cause a lot of the side effects- all pain meds differ simply based on affinity to these receptors] They mimic the actions of endogenous opioid compounds: enkephalins, dynorphins, endorphins
Examples of Oxycodone products
OxyCONtin (CR tab) 10, 15, 20, 30, 40, 60, 80 mg tablets (q 12 hours...once in a while q 8 hours); new formulation is out to help control abuse because it becomes gel and can not be drawn into a syringe. But there are ways around it. OxyIR (IR cap) 5 mg Roxicodone solution 5 mg/5 mL with APAP: Percocet and Endocet (oxycodone/APAP dose) - 2.5/325, 5/325, 7.5/325, 7.5/500, 10/325, 10/500, 10/650 tablets ("Take 1 - 2 tablets by mouth every 4 to 6 hours as needed for pain"; not to exceed 4 grams of APAP per day!!!) Roxicet solution - oxycodone 5 mg + 325 mg APAP/ 5 mL Percodan (oxy + asa) - no one uses this product Beware of combination with acetaminophen (Percocet), various strengths ? More addictive than heroin
What are the typical PCA IV meds in hospital?
Patients may use less total narcotic than traditional PRN dosing Morphine 1 mg/ml Fentanyl 10 mcg/ml Hydromorphone 0.2 mg/ml
What caution should be discussed with a pt who is placed on opiods for the first time
Pt should not drive for 2-3 weeks until become tolerant
When would you need to calculate equianalgesic dosages?
Pt who uses opiods for chronic pain and now needs meds for acute pain. Pts who are on high dose meds and needs to be tapered off. Pts who are on one med but need to switch to another that is available.
which drugs should be used with caution together for potential serotonin syndrome?
SSRIs- (prozac, zoloft, lexapro, celexa); Tramadol; MAOIs; Triptans for migraine
Adverse effects of opiod meds
Some side effects pts will become tolerant to. CONSTIPATION-anticipate it! Pts will not become tolerant and this will not go away but it may improve. Most problematic. All patients should receive a stool softener + stimulant combo (ex. docusate + senna with max dose x2 am and x2 pm) OR 'smooth move ' tea Pruritis is common and pt becomes tolerant to. If can see whelts/rash or respiratory involvement that is concerning. This is more likely to occur with IV meds vs PO. Give benedryl nausea/vomiting- pt becomes tolerant to. hits NV trigger zone. Codeine is worst offender! Sedation- Pt becomes tolerant. respiratory depression - this is what kills a patient!! This does not disappear. CNS mediated. inhibition of cough reflex (do not become tolerant) Confusion (if related to sedation will become tolerant) dysphoria or euphoria hallucinations occurs for some people prolongation of labor urinary retention- become tolerant to. miosis- enhances parasympatheitic stimulation to eye resulting in pinpoint pupils.
Define pseudoaddiction
The end result of under treatment of pain. Appropriate drug seeking behaviors- asking for doses before scheduled time or drug hoarding. May be going to more than one pharmacy and MD. Usually "cured" by increasing the daily dose of opiod and monitoring the pt
What is the goal for managing ACUTE pain?
The goal for managing acute pain is to keep the patient as comfortable as possible while minimizing the ADRs from the pain meds.
What is the goal for managing CHRONIC pain?
The goals for managing chronic pain are to keep the patient as comfortable as possible (this may not mean the patient is pain free), and integrating the patient back into a "normal life" and activities of daily living, while minimizing the ADRs from the pain meds. When appropriately managed a pt does not 'look' like a chronic pain pt and should not be slurring words.
Describe the basics of opiod withdrawl
The shorter the half-life the more intense the withdrawl. The more the pts are on the more intense the withdrawl. number and intensity of signs and symptoms are largely dependent on the degree of physical dependence that has developed Symptoms: first symptoms are typically diarrhea and yawning and anxiety. Rhinorrhea, lacrimation, yawning, chills, gooseflesh (piloerection), hyperventilation, hyperthermia, mydriasis, muscular aches, vomiting, diarrhea, anxiety, hostility. Muscular aches can last longer (3wks-3mths). administration of an opioid (PO) at the time of s/sx of withdrawal = suppression of abstinence signs and symptoms almost immediately (even before liberation takes place).
What opiod pain medication has a maximum daily dose?
Tramadol
What opiod pain medication plugs into mu receptors and inhibit uptake of serotonin and norepinephrine
Tramadol
Which of the following medications would be completely inappropriate for treatment of severe pain? tramadol, oxycodone, hydrocodone, morphine, tapentadol.
Tramadol
Describe the dosage, adverse ractions and usage of Meperidine
Used only in rare situations. Meperidine (Demerol) 50, 100 mg tabs (50 mg every 3 - 4 hours) Euphoric, stimulates drug seeking No longer preferred for acute or chronic pain Active metabolite - normeperidine CNS stimulant, causes seizures, visual disturbances, twitching, anxiety May only be appropriate in morphine allergic pt
What medications can decrease seizure threshold?
Wellbutrin; Tramadol; possibly Tapentadol
Define breakthrough pain
acute pain that occurs on top of chronic pain
define 'oral PCA'
basal rate with breakthrough = CR (or long-acting) product plus something for breakthrough pain
Describe the equianalgesic dosing relationship with methadone and morphine.
equianalgesic dosing of methadone will decrease as morphine equivalent increases
define tolerance
escalation of dose to maintain effect
which of the following is the most potent? Methadone, hydrocodone, morphine, fentanyl, hydromorphone
fentanyl
What is the number one street drug pain med
immediate release Oxycodone. Percocet is a popular street drug
What general pain med group is most appropriate for acute pain management?
immediate release.
define dependance
not always a sign of drug abuse. Occurs in all pts on chronic opiods- occurs after opiod is stopped or quickly decreased. Occurs because the receptors are used to having the drug plugged in.
Important opiod drug interactions
other CNS depressants. Could lead to death but is unpredictable and does not require large doses. Methadone has a CYP4503A4 drug interactions
Describe the use of APAP + opiod analgesics
provide synergistic pain relief decrease the amount of flexibility in dosing may lead to unintended ADRs ex. Vicodin (5mg hydrocodone + 500mg of APAP) 2 tablets q 4 hours = daily dose of 6 g of APAP for a few days this is fine, but daily doses of ≥ 5 g APAP may lead to liver enzyme changes (risk factors: alcoholism, concurrent use of enzyme inducers)
How do you approach long term use of pain meds to help keep the doses low?
rotate through different chemicals to keep tolerance as low as possible.
What directions are written on a script for opiod immediate release pain meds for acute and breakthrough pain?
take 1 - 2 tablets every 4 to 6 hours as needed for pain. Must have PRN pain
