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Flashcards in Pain Deck (40)
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general notes

All patients on opioid should have constipation prophylaxis and should be monitored for sedation as this is the most important predictor of respiratory depression

1

Stepwise approach to pain management

1. Mild pain can be self treated at the pharmacy and usually responds to acetaminophen or an NSAID
2. Moderate pain is often treated with a combination products such as hydrocodone oxycodone which acetaminophen
3. Severe pain may require opioids although neuropathic pain may respond adequately to non-opioids such as duloxetine or pregabalin
4. Neuropathic pain may respond to an antidepressant such as amitriptyline duloxetine and/or an anticonvulsant such as pregabalin

2

Acetaminophen

MOA: inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain generation

Products:
1. acetaminophen (Tylenol) plus hydrocodone is (Vicodin, Norco, Lortab)
2. Plus codeine (Tylenol number 2, 3 and 4
3. Plus oxycodone (Percocet, Endocet)
4. Plus tramadol (Ultracet)
5. IV Tylenol (ofirmev)-used inpatient to offset higher opioid doses

Dosing:
1. Children: 10 to 15 mg per kilogram every 4 to 6 hours for a max of five doses per day

Blackbox warning: severe hepatotoxicity, potentially requiring liver transplant or resulting in death; hepatotoxicity is usually associated with excessive acetaminophen intake greater than 4 g per day

Side effects: hepatotoxicity (avoid concomitant use with isoniazid, barbiturates, alcohol, zidovudine)

Notes: drug of choice for pain ainpregnancy; antidote is in N-acetylcysteine (restores intracellular glutathione) does that 140 mg per kilogram loading followed by 70 mg per kilogram of 17 doses

3

Aspirin/NSAID

MOA: block the activity of thromboxane and prostaglandins

COX-1 inhibition increases bleeding risk
COX-2 inhibition increases cardiovascular risk

Blackbox warning:
1. Cardiovascular: NSAIDs may cause increased risk of serious CV events (may increase with duration)
2. GI: increased risk of serious G.I. events including bleeding, ulceration, and perforation of the stomach or intestines (elderly, those with a history of G.I. bleed, patients taking corticosteroids, and those taking concurrent SSRIs or SNRIs are at greater risk
3. CABG: contra indicated in CABG surgery

4

Aspirin-acetylsalicylic acid

Bayer, Bayer advanced aspirin, Ascriptin, Bufferin, Ectorin, Excedrin

Avoid in: elderly, children, previous bleed, chronic or high-dose use, commitment anticoagulants, smoking, Renal issues

Side effects: dyspepsia, heartburn, nausea take with food to decrease irritation and nausea, blood-pressure may increase from G.I. irritation and bleeding, renal dysfunction, CNS effects, severe skin rash (stop drug if this occurs)

Notes: stop all NSAIDs at least a week prior to elective surgery, overdose can manifest with tinnitus

5

Salsalate

Similar to aspirin, lower G.I. risk, can cause tinnitus with overdose

6

Ibuprofen (Motrin, Advil)

Max dose of 1.2 g per day (OTC)
Max dose of 3.2 g per day (Rx)

Considerations are similar to aspirin

7

Naproxen Na+

Vimovo (Naproxen-esomeprazole): combo used to protect the gut

Dosing: all given twice a day

Relatively lower cardiac risk than some of the other NSAIDs

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Diclofenac (cataflam, Voltaren XR, Arthrotec (misoprostol component for GI protection), Voltaren gel, Flector patch)

Nonselective and NSAID

DOSING: B.I.D.

BLACKBOX WARNING: SAME AS OTHER NSAIDS PLUS ARTHROTEC NOT TO BE USED IN WOMEN OF CHILDBEARING POTENTIAL (due to misoprostol component which can increase uterine contractions)




9

Indomethacin (Indocin IR, CR)

Approved for gout

High risk for CNS side effects (avoid psych conditions) and G.I. toxicity

10

Piroxicam (feldene)

High risk for G.I. toxicity and severe skin reactions including Steven Johnson syndrome and TEN

use if other NSAIDs fail and may need agent to protect gut such as a PPI or misoprostol

11

Ketorolac (Toradol)

Nonselective NSAID

Can cause severe adverse events including G.I. bleeding and perforation, post op bleeding, acute renal failure, liver failure and anaphylactic shock

For short term moderate to severe acute pain only use a max of five days supply in adults (almost always postop and never pre-op)

12

COX-2 selective drugs

Celecoxib (Celebrex): Cox-2 selectivity
Meloxicam (Mobic): some cox-2 selectivity
Etodolac (Lodine): some Cox-2 selectivity
Nabumetone (Relafen): some Cox-2 selectivity

13

Celecoxib or Celebrex

Indications: OA, RA, juvenile RA, acute pain, primary dysmenorrhea, alkalizing spondylitis

Notes: highest COX-2 selectivity, pregnancy category C prior to 30 weeks gestation (category D beyond 30 weeks gestation)

Contraindications: sulfonamide allergy

Considerations are similar to all other NSAIDs

14

NSAID drug interactions

1. Additive bleeding risk: aspirin, clopidogrel or Plavix, prasugrel or Effient, ticagrelor or brilinta, dipyridamole or Persantine, warfarin, dabigatran, Rivaroxaban, ginkgo biloba and others
2. SSRIS: fluoxetine, paroxetine, sertraline, citalopram, Escitalopram, venlafaxine

15

Opioids

Codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone

Pure opioid receptor agonist at the mu receptor

No ceiling affect therefore they have no limitation to how much pain relief they can offer, however opioids at high doses should be rotated with other opioids to reduce the risk tolerance

16

Opioid auxiliary labels

1. Controlled substance: do not share with others
2. May cause dizziness or drowsiness
3. Do not operate machinery
4. Keep away from children and animals
5. If long-acting: do not crush or chew/swallow whole
6. Do not drink alcoholic beverages
7. Take with food or milk

17

Morphine. CII

Long acting brands: MS Contin, Avinza (daily), Kadian (b.i.d. or daily), Oramorph SR and Roxanol

Avinza and Kadian can be opened and sprinkled on applesauce or soft food

Blackbox warning: fatal respiratory depression, proper dosing in titration should be done by a healthcare professional, counsel on long-acting products, (crushing, dissolving or chewing of a long acting the products can result in the delivery of a potentially fatal dose)

Side effects: G.I. effects (constipation, nausea, vomiting), CNS effects (sedation, dizziness, changes in mood, confusion, delirium), skin reactions

Respiratory depression: associated with overdose or combination with other sedatives and CNS depressants

Notes: constipation often requires stimulant laxatives such as senna or bisacodyl or osmotic laxatives. If a patient fails this therapy consider methylnaltrexone (Relistor) SC injection

18

Cross-reactivity of agents: if allergy to one of the following do not use another in the same group

Morphine, oxymorphone, codeine, hydrocodone, hydromorphone, oxycodone, buprenorphine, butorphanol, or levorphanol

19

Morphine allergy

Can use Sentinelle, meperidine, methadone, tramadol

20

Fentanyl (Duragesic) CII

Other names: Abstral, Fentora SL pills

Dosage forms: injection, lozenge, pills, patches, sub lingual film, nasal spray

patch: available in 12.5, 25, 50, 75, 100 µg/hour; change every 48 hours and do not increase the dose if pain is controlled but doesn't last long enough, in this case you shorten the interval. Should not be used in opioid naïve patients. DO NOT APPLY MORE THAN ONE PATCH AT A TIME AND DO NOT HEAT UP PATCH OR SKIN AREA

BLACKBOX WARNING RESPIRATORY DEPRESSION AND/OR DEATH AND USE WITH STRONG OR MODERATE CYP3A4 INHIBITORS MAY RESULT IN INCREASED EFFECTS AND POTENTIALLY FATAL RESPIRATORY DEPRESSION

DISPOSE PATCH IN TOILET OR CUT IT UP AND PUT IT IN COFFEE GROUNDS, ABSOLUTELY KEEP AWAY FROM CHILDREN AND ANIMALS INCLUDING USED PATCHES

21

Hydromorphone (Dilaudid) CII

Exalgo (hydromorphone extended release)

Doses: two, four, eight mg

Contraindications: Exalgo contraindicated in opioid naïve patients and a two-week washout is required between Exalgo and MAOIs

VERY POTENT AND THERE IS A HIGH-RISK FOR OVERDOSE

Blackbox warning: respiratory depression, and the use of ethanol other opioids and other sinister press it may increase the risk including death

Notes: opioid naïve patient should start with no more than 2 to 4 mg by mouth or 1 to 2 mg by injection every 4 to 6 hours

22

Oxycodone

IR: oxycodone, oxenta
CR: OxyContin, oxyContin OP

With acetaminophen: Endocet, Percocet, Roxicet

Dosing: avoid high-fat meals with higher doses

Blackbox warning: report abuse misuse and diversion, avoid use with three A4 inhibitors as it will increase levels

Notes: OxyContin OP contains polyethylene oxide to deter abuse as it forms a gel when mixed with water; oxenta contains a nasal irritant to deter abuse

23

Oxymorphone (Opana and Opana ER)

CII

Dosing: take on the empty stomach with absolutely no alcohol

Blackbox warning: Opana ER should not be used for as needed analgesic and should not be chewed, dissolved, or crashed; Opana ER is only to be used in long-term, continuous management of moderate to severe chronic pain; ingestion of ethanol with Opana ER may result in accelerated release of the drug and may be fatal

Notes: do not use with moderate to severe liver impairment and use low-dose is elderly, Renal or mild liver impairment

24

Methadone (Dolophine)

Liquid: methadose

CII

Dosing: start at 2.5 to 10 mg every 8 to 12 hours; 40 mg is indicated for detox and maintenance treatment of opioid addicted patients

Blackbox warning: QTC prolongation especially with large or multiple daily doses; fatal respiratory depression, should be prescribed by professionals who know requirements for safe use

Notes: due to variable half-life methadone is hard to go safely and has a risk of QT prolongation, can decrease testosterone and contribute to sexual dysfunction, and in combo with other drugs it is serotonergic and can increase risk of serotonin syndrome

25

Meperidine (demerol)

CII

Avoid as agent for chronic pain management and do not use at all chronically, even short-term and elderly

Warning: renal impairment/elderly at risk for CNS toxicity

Notes: Normeperidine, the metabolite, is renally cleared and can accumulate and cause CNS toxicity including seizures; also has serotonergic effects and can raise the risk of serotonin syndrome especially when combined with other drugs

26

Tramadol (ultram, ultram ER, conzip IR/ER)

+acetaminophen (ultracet)

Dosing: reduce if renal impairment, tramadol ER contraindicated if CrCL less than 30

Warning: increased seizure risk avoid in patients with a history of seizure or head trauma

Side effects: dizziness, nausea, constipation, loss of appetite, flushing, insomnia, headache, ataxia

Notes: respiratory depression can still occur but is rare, serotonin syndrome risk if used in combination with others such as SSRIs and is dose-dependent

27

Tapentadol (nucynta, nucynta ER) CII

Blackbox warning: respiratory depression, extended release tablets must be swallowed whole and should not be split crushed broken chewed or dissolved; no alcohol with ER formulation

Side effects: dizziness, drowsiness, nausea but lower severity of G.I. side effects then stronger opioids

Notes: can call psychological dependence and risk of serotonin added and toxicity; no alcohol at ER formulation as it may increase systemic exposure Ismaili to possible fatal overdose

28

Opioid drug interactions

1. Concurrent CNS depressants such as alcohol, hypnotics, benzodiazepines, muscle relaxants
2. Increased risk of hypoxemia with underlying respiratory disease
3. Avoid agents that affect cardiac function or increase arrhythmia risk with methadone
4. Tramadol and Nucynta: avoid agents that lower the seizure threshold
5. Avoid alcohol with all opioids especially extended release formulation
6. Meperidine should be used with caution in patients with renal function drugs that worsening renal function, elderly and those with a seizure history
7. Excessive sedation may also be seen with alcohol, sleeping pills, antihistamines, sedatives, and tranquilizers

29

Muscle relaxants/spasticity agents

Examples: baclofen (lioresal), cyclobenzaprine (flexmid), tizanidine (Zanaflex)

Aux labels: May cause drowsiness, do not operate machinery

Side effects: excessive sedation, dizziness, confusion

30

Baclofen (Liorseal)

Blackbox warning: avoid abrupt withdrawal as it has resulted in severe hyperpyrexia, rebound or exaggerated spasticity, muscle rigidity and rhabdomyolysis) leading to organ failure

Notes: do not overdose in elderly start low titrate carefully

31

Cyclobenzaprine (flexeril)

Xerostomia

Serotonergic effects and should not be combined with other serotonergic agents

May precipitate or exacerbate cardiac arrhythmias; caution and elderly or those with heart disease

32

Tizanidine (Zanaflex)

Can act as a central alpha-1 agonist causing hypotension, dizziness, xerostomia and weakness

33

Other muscle relaxants and spasticity agents that exert their efforts by sedation

Carisoprodol (soma): drowsiness

Metaxalone (skelaxin): decreased cognitive/sedative effects; hepatotoxic

Methocarbamol: hypertension; Monitor BP

34

Common neuropathic pain agents

Pregabalin (Lyrica), duloxetine (Cymbalta), Gabapentin (Neurontin), amitriptyline (Elavil), milnacipran (savella)

35

Pregabalin (Lyrica)

Schedule: CV

Indications: diabetic neuropathic pain, postherpetic neuralgia, fibromyalgia, spinal cord damage, adjunct to therapy adult patient partial onset seizures

Dose: decrease dose and and increase interval if CrCl less than 60

Side effects: dizziness, somnolence, peripheral edema, weight gain, ataxia, diplopia, blurred vision, xerostomia, mild euphoria

36

Duloxetine (Cymbalta)

Indications: peripheral neuropathic pain, fibromyalgia, musculoskeletal pain, depression, generalized anxiety disorder

Side effects: common to all SNRIs increase blood pressure, increased heart rate, sexual side effects, increase sweating, restless leg, made changes

Duloxetine specific side effects: nausea, dry mouth, somnolence, fatigue, decreased appetite

37

Gabapentin (Neurontin)

Dose: decreased dose or increase interval if CrCl less than 60

Side effects: dizziness, somnolence, ataxia, peripheral edema, weight gain, diplopia, blurred vision, xerostomia

Most uses her off label such as fibromyalgia, pain, headache, peripheral neuropathy, drug abuse, alcohol withdrawal

38

Amitriptyline (Elavil)

Main issue cardiotoxicity: QT prolongation, orthostatic hypotension, tachycardia, anti-cholinergic/dry mouth/Worldvision/urinary retention/constipation/delirium

39

Topical pain agents

Lidocaine 5% patches (Lidoderm)

Approved for postherpetic neuralgia (shingles)

Side effects: minor topical burning, itching, rash

Notes: can cut into smaller pieces before removing backing, do not apply more than three patches at one time, can harm children and pets therefore follow patch and half and discard safely, do not cover with heating pads or electric blankets, do not use on broken or braised skin