analgesics Flashcards
Definitions of Pain
Definitions vary – no one universally accepted definition for pain terms
Subjective experience
“An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”
dental pain nociception diagrammed
Ad and C fibers involved to CN V ganglion then to caudal spinal tract then to thalamus and somatosensory
Dental Pain
* Affect what tissues?
* Due to?
* Dental pain is transmitted from the mouth through the:
* Nociceptive pain?
* Acute vs. chronic pain?
- Affect the hard and soft tissues of the oral cavity
- Due to underlying conditions or dental procedures or both
- Dental pain is transmitted from the mouth through the:
◦ Trigeminal nerve
◦ Trigeminal ganglia
◦ Thalamus
◦ Somatosensory cortex and limbic system - Nociceptive pain – stimulation of nociceptors (pain nerves) from external stimuli
- Acute vs. chronic pain (>3 months)
Chemical Mediators in Pain:
excitatory (cause pain perception?)
inhibitory?
peripheral mediators?
targets of drug therapy
somatic examples of nociceptive pain
most dental pain is?
Somatic (from teeth, skin, bone, joints, muscle, connective tissue) – Examples:
◦ Inflammatory (Rheumatoid arthritis)
◦ Mechanical/compression (spine/bone)
◦ Muscle dysfunction (Myofascial pain)
◦ Combinations common
◦ Most dental pain – inflammatory and/or mechanical
Result of traumatic injury or bacterial infection originating from pulpal and periapical tissues
visceral examples of nociceptive pain
Visceral (from internal organs)
◦ Example: appendicitis
◦ Often diffuse and poorly localized
Neuropathic Pain
Pain that originates from direct dysfunction or damage to the peripheral or central nervous system.
◦ trauma or disease of neurons
◦ loss of nerve fiber function
neuropathic pain peripheral/central fiber dysfunctions
Dysfunction of peripheral nerves
◦ focal area
◦ Widespread
Dysfunction of central nervous system
◦ reorganization of central somatosensory processing
neuropathic pain and tissue damage? pain described as?
Independent of any ongoing tissue injury
Typically described as tingling, stinging, burning, and/or numb
is neuropathic pain MC in the orofacial region
Less common type of dental pain compared to somatic pain
◦ Sometimes referred to as neuropathic orofacial pain (NOP)
Chronic or Persistent Pain
Not well understood
May be associated with a chronic pathologic process
mechanisms of chronic pain
◦ Peripheral – persistent stimulation of nociceptors
◦ Peripheral-central – abnormal function of peripheral and central somatosensory system
Partial or complete loss of descending inhibitory pathways
Spontaneous firing of regenerated nerve fibers
◦ Central – disease or injury to CNS
is chronic pain common among various conditions?
what may pts be taking for this?
Many conditions result in chronic pain
◦ Patients may be taking chronic non-opioid and/or opioid pain medications daily
Pain Classification
Multiple ways to classify pain:
◦ Nociceptive vs. Neuropathic
◦ Acute vs. Chronic
◦ Mixed
can we have objective findings for pain?
NO OBJECTIVE ASSESSMENT TO MEASURE PAIN (INTENSITY)
◦ No Laboratory values
◦ No Diagnostic tests
◦ No Radiographic evidence
May use labs, physical exam, diagnostic tests, radiographic evidence to identify or
diagnose a condition that causes pain
Identify risk factors/contributing factors
potential pain assessment scales
Common Non-Pharmacotherapy options for pain management
dental pain
◦ Definitive Dental Treatments: Extractions/Other dental procedures/treatments
◦ Thermal modalities (ice/heat)
Ice/cold is often an important for treatment of dental pain
◦ Mouth Guards
◦ Occupational and Physical Therapy
◦ Acupuncture/Accupressure
◦ Others for medical conditions (cognitive-behavioral, splints therapy, massage, chiropractic etc.)
Pharmacotherapy options for dental pain management
◦ In dentistry **used as an adjunct to dental treatments **(management of post-procedural pain or when there is not immediate access to definitive dental treatments)
Analgesics: Non-opioids (Acetaminophen/NSAIDs)
Adjuvant / Co-analgesics (pain modulators): Anticonvulsants, Antidepressants
Opioids/opioid-like (e.g. morphine, hydrocodone, oxycodone/tramadol)
Mechanisms of action relate to pathophysiology (chemical modulators)
Pharmacologic Treatment
* Targeted at ?
* Realistic pain goal?
* Still pursuing?
- Targeted at symptom relief
- Realistic pain goal: reduce pain and improve function
◦ Target: 30%-50% reduction - clinical improvement
◦ May not be able to eliminate until underlying cause treated/healed - Still pursuing better treatments to address underlying mechanisms of pain
NONOPIOID ANALGESIC CLASSIFICATIONS
Salicylates
Acetaminophen (APAP)
NSAIDS
Salicylates
ASA
NSAIDS
IBU, naproxen, celecoxib
Acetaminophen
(APAP) moa
- Exact MOA unclear
- May inhibit Cyclooxygenase (COX) pathway (possibly COX III) and nitric oxide pathway, mediating neurotransmitters in Central Nervous System (CNS) – inhibiting prostaglandins in the CNS
- May activate the cannabinoid system
- Weak COX-I and COX-II inhibitor in peripheral tissues – not primary mechanism of action
Acetaminophen effect on blood and inflammation
- Possesses NO significant anti-inflammatory activity
- NO anti-platelet activity – No increased bleeding risk
Clinical Uses of acteaminophen
*pain?
* fever?
* In combination with?
* APAP’s analgesic effects comapred to nsaids
- Mild to moderate pain of varied origin (including dental pain)
- Antipyretic activity
- In combination with opioids (synergy)
- APAP’s analgesic effects considered less than or similar to NSAIDs
Acetaminophen Adverse effects
- **HEPATOTOXICITY **(rare but can be severe) - at high doses liver metabolizes to toxic metabolic metabolite (N-acetyl-p-benzoquinoneimine)
- Associated with nephrotoxicity with long-term consumption
- Rare skin reactions
- Some complaints of **GI adverse effects **but less than other analgesic
acetaminophen dosing
Over-the-counter (OTC) recommendations for adults?
* Target per dose?
* Up to gm/day under direction of healthcare provider?
* mg/day recommended for older adult patients?
* children?
Over-the-counter (OTC) recommendations ≤ 3,000mg (3 gm)/day for adults
* Target 325-650 mg/dose (max 1000 mg/dose)
* Up to 4 gm/day under direction of healthcare provider
* 2,000-3,000mg (2-3 gm)/day recommended for older adult patients
* See dosing/package information for children’s weight-based dosing
Avoid APAP use in patients with?
Avoid APAP use in patients with active/severe hepatic disease and alcohol
abuse/dependence → ↑ risk of hepatotoxicity
APAP effect in GI PG’s/plattlets?
Has no effect on GI prostaglandins, CV/platelet effects (vs. NSAIDss)
APAP OD tx
N-acetylcysteine
APAP Drug Interactions:
* compared to other pain medications?
* Caution in combination with other drugs that cause?
◦ examples?
* blood med?
* More than ? alcoholic drinks a day increases liver toxicity risk
- Few, compared to other pain medications
- Caution in combination with other drugs that cause liver toxicity
◦ Leflunomide (Rheumatoid arthritis medication)
◦ Methotrexate (Rheumatoid arthritis medication)
◦ Carbamazepine (Anti-convulsant)
◦ (Others) - Warfarin (but considered safer than NSAIDs)
- More than >3 alcoholic drinks a day increases liver toxicity risk
APAP Patient Education:
* Found in?
* Do not take?
* Watch for acetaminophen in?
* Never take more than the recommended dose of acetaminophen or take it for longer than?
* Caution with?
* Pediatrics?
- Found in more than 600 different medicines (RX and OTC)
- Do not take more than one medicine at a time that contains acetaminophen.
- Watch for acetaminophen in OTC cough/cold, allergy, sleep, pain medications
- Never take more than the recommended dose of acetaminophen or take it for longer than directed on the label, unless directed by a healthcare professional to do so.
- Caution with alcohol (limit to 1-2 drinks/day)
- Pediatrics – follow weight-based guidelines
APAP Prescribing Checklist:
q tolerated?
q Often used in combination with what for dental pain?
q Precautions/Contraindications:
APAP Prescribing Checklist:
q Overall, well tolerated
q Often used in combination with NSAIDs for dental pain
q Precautions/Contraindications
* Allergy to APAP (rare)
* Active liver disease/dysfunction (e.g. active hepatitis)
* Inactive hepatitis or treated hepatitis may not not be a contraindications (check with the patient’s physician for questions about the safety of APAP use)
* > 3 alcoholic drinks/day
* Do not exceed > 4 gm/day in adults (see pediatric weight-based dosing guidelines)
* Only use one APAP containing product at a time
* Caution use with other drugs that cause liver toxicity
NSAID FAMILY
- Non-steroidal Anti-inflammatory Drugs (NSAIDs)
- Traditional/Non-Selective/Non-Aspirin NSAIDs
- Cox-selective NSAIDs
- Related:
Aspirin (acetylsalicylic acid - ASA)
Non-Acetylated Salicylate
How NSAIDs work in Dental Pain
- Tissue injury activates cyclooxygenase II (COX 2)
- COX II converts arachidonic acid to prostaglandin E2 (PGE2)
◦ resulting in pain and inflammation
◦ alters vascular tone and permeability, causing edema - PGE2 sensitizes and lowers threshold to stimulate nociceptors which initiates
transmission of pain to CNS**
NSAIDs block COX II
Blockage of COX Enzymes diagrammed
COX I block causes ADEs
NONSELECTIVE NSAIDS MOA (NSAIDS & ASA
Nonselective inhibition of COX-1 and COX-2 → inhibition of biosynthesis of prostaglandins→ ↓ number of pain impulses received by the CNS, decreases fever
NONSELECTIVE NSAIDS MOA (NSAIDS & ASA) act where for pain?
periphery
NONSELECTIVE NSAIDS (NSAIDS & ASA) effects?
- Anti-inflammatory
- Analgesic
- Antipyretic
- Antiplatelet (low dose ASA)
NONSELECTIVE NSAIDS:
* Anti-inflammatory effects + inhibits pain stimuli
* Anti-inflammatory effects associated with?
* Mediated by?
* ASA- Irreversibly inhibits ?
* Main role ASA?
* ASA use in pain management limited due to?
- Anti-inflammatory effects + inhibits pain stimuli
- Anti-inflammatory effects associated with higher doses
- Mediated by both COX inhibition + inhibition of interleukin-1
- ASA- Irreversibly inhibits platelet COX (lasts 8-10 days). (NSAIDs – reversible platelet effects)
- Main role – low dose in CV event prevention
- ASA use in pain management limited due to adverse effec
COX2 INHIBITORS
(SELECTIVE NSAIDS)
MOA:
Selectively inhibits COX-2 isoenzyme at the site of inflammation → inhibit prostaglandin synthesis → ↓ number of pain impulses received by the CNS, decreases fever
COX2 INHIBITORS effects
- Anti-inflammatory
- Analgesic
- Antipyretic
COX2 INHIBITORS act where for pain
periphery
COX2 INHIBITORS effects on plattlets
non-significant
COX-2 Inhibitors
◦ name (approved one)
Drug class associated with?
◦ increased risk with what doses?
cost?
◦ reserve for patients with?
Only one COX2 inhibitor in the US
◦ celecoxib/Celebrex
Drug class associated with ↑ incidence of CV thrombotic events (rofecoxib, valdecoxib – removed from US market)
◦ Celecoxib – associated with higher CV risk >400 mg/day
More expensive than most nonselective NSAIDs (even with generic)
◦ reserve for patients with increased GI risk
Celecoxib/Celebrex (Selective NSAID) adult dose
100- 200 mg BID
ibuprofen/Motrin* usual adult dose:
* ? mg 3 to 4 times daily;
* Usual dose:
* Usual total daily dose:
* Maximum dose (debated)
- 200 to 800 mg 3 to 4 times daily;
- Usual dose: 400 mg;
- Usual total daily dose: 1,200 to 2,400 mg/day;
- Maximum dose (debated) 2,400 - 3200 mg/day
Naproxen Sodium or Naproxen /Naprosyn,
Aleve* (Nonselective NSAID) usual adult dose
- 440 mg every 12 hours; maximum daily dose: 1,100 mg
- 500 mg every 12 hours or 250 mg every 6 to 8 hours; maximum daily dose: 1,250 mg
Clinical uses of Nonselective NSAIDs and COX-2 inhibitors
Dental pain often includes an? preffered? preop? used in combo with for dental pain?
◦ moderate pain?
◦ Preoperative use 24 hours before the appointment decreases?
◦ Often used in combination with what for dental pain?
* Mild-moderate pain and inflammation of?
* Used in combination with what for treatment of of more severe pain?
◦ NSAID/COX-2 inhibitor + opioid = ?
Used for treatment of joints?
fever?
ASA (low dose) primarily use for?
- Dental pain often includes an inflammatory component
◦ Often considered first line in dental pain for moderate
◦ Preoperative use 24 hours before the appointment decreases postoperative edema and hastens healing time
◦ Often used in combination with acetaminophen for dental pain - Mild-moderate pain and inflammation of varied origin
- Used in combination with opioid analgesics for treatment of of more severe pain
◦ NSAID/COX-2 inhibitor + opioid = synergistic analgesic effect - Used for treatment of rheumatoid arthritis and other acute/chronic inflammatory joint conditions
- Treatment of fever
- ASA (low dose) primarily use for cardiovascular event prevention
Non-Aspirin NSAID Blackbox Warnings
GI Risk - “NSAIDs cause an increased risk of serious gastrointestinal
adverse events including** bleeding, ulceration, and perforation of the
stomach or intestines,** which can be fatal.These events can occur at any
time during use and without warning symptoms. Elderly patients are at
greater risk for serious gastrointestinal events.”
* CV Risk - “NSAIDs may cause an increased risk of serious**
* cardiovascular thrombotic events, myocardial infarction and stroke, which**
can be fatal.This risk may increase with duration of use. Patients with
cardiovascular disease or risk factors for cardiovascular disease may be
at greater risk.”
Coronary Artery Bypass Graft (CABG) Surgery - NSAID use
is contraindicated in the setting of CABG surgery - (short-term) before
and after CABG surgery (aspirin is commonly indicated after CABG
surgery
Key NSAID Adverse Effects:
NSAIDS at renal
- Kidney injury/acute renal failure (prostaglandin mediated kidney flow)
- Decreases renal blood flow. Increased risk in dehydration and other renal toxic medications
- Less with celecoxib and low dose ASA. Avoid NSAIDs with GFR < 30 mL/min
- Can occur after 1 dose
NSAIDS at GI
-
Dyspepsia/Nausea – NSAIDs, ASA and celecoxib – can occur after 1 dose. Take with food.
GI ulcers/bleeding - usually long-term complication with NSAIDs and low dose ASA (less with celecoxib). Do not use if patient has active ulcer
NSAIDS and plattlets
Increased bruising and bleeding – NSAIDs and ASA (less with
celecoxib
NSAIDS and CV
NSAIDs, celecoxib (possibly less with naproxen, more with higher doses of celecoxib >400 mg/day)
**Low dose ASA has CV protective **effects due to irreversibility binding platelets
**All other NSAIDs carry BLACK BOX WARNING **for increased risk of CV events. Avoid in patients with recent coronary artery bypass graft or recent MI without consulting physician
NSAIDS with HTN/HF
Fluid retention/edema = worsen hypertension (HTN) and heart failure (HF)
NSAIDs and celecoxib (less with low dose ASA) – Avoid in uncontrolled HTN
May or may not be clinically significant
When Prescribing OTC or RX NSAIDs
doses? length of tx? ADRs onset? pregnancy?
Key Drug Interactions of NSAIDS and ASA
- ASA/NSAIDs + warfarin
- ASA/NSAIDs + Blood Pressure Medications
- NSAIDs + High Dose Methotrexate
- NSAIDs + Lithium
ASA/NSAIDs + warfarin
◦ Increased bleeding and INR (consider benefit vs. risk- short-term use may outweigh risks)
ASA/NSAIDs + Blood Pressure Medications
+ ACE Inhibitors and Angiotensin Receptor Blockers (ARBs)
+ Diuretics
◦ May diminished BP effects but may not be clinically significant (particularly if the patient’s BP is well controlled)
NSAIDs + High Dose Methotrexate
◦ Decreased Methotrexate renal clearance/increased toxicity
◦ This interaction is CLINICALLY SIGNFICIANT if methotrexate used in high dose
NSAIDs + Lithium
◦ Increase serum concentrations of lithium (decrease clearance)
◦ Monitory lithium concentrations and symptoms of toxicity /consider decreasing dose of lithium if NSAID initiated
Patient Education for NSAIDs
* doses
* mixes
* risks
* take with?
Topical NSAID Treatment
Diclofenac (Voltaren® gel, generics)
Diclofenac (Voltaren® gel, generics)
Use:
* Possible option if patient has?
<% of the amount absorbed after oral administration, but still carries?
Use: FDA approved for treatment of osteoarthritis (OA)
* Possible option if patient has contraindications to PO NSAIDs
<5% of the amount absorbed after oral administration, but still carries Black Box warning for systemic ADRs (see below
diclofenac doses
◦ Lower extremity dose :
◦ Upper extremity dose:
◦ Total body maximum:
◦ Lower extremity dose : 4 gm up to QID, Max dose/joint: 16 g/day
◦ Upper extremity dose: 2 gm up to QID, Max dose/joint 8 g/day
◦ Total body maximum 32 g/day
how could we use diclofenac in dentistry
TMD
diclofenac black box/contraindications
Black Box Warning: GI bleed/ulceration and CV thrombotic events
* Avoid in advanced renal disease - no dosing adjustments provided by manufacturer
* Contraindicated in perioperative pain in the setting of coronary artery bypass graft surgery
diclofenac adrs
Adverse Effects: pruritus, burning, rash
* Still a risk for systemic adverse effects
can we use PO NSAIDS with diclofenac?
Avoid oral NSAIDS in combination - no additional efficacy
NSAID Prescribing Checklist:
q Often considered first line for dental pain (and in combination with APAP)
qOTC doses – more analgesic effects
qRX doses – analgesic + anti-inflammatory
Precautions/Contraindications to Rx NSAIDS
q Allergy?
qGI?
qConcurrent use of ?
qBP?
q CV?
q renal?
q Drug interactions with ?
q Avoid when in pregnacy?
q Allergy to NSAIDs/ASA
qPatients with active GI ulcer or multiple GI risk factors:
qAge > 65, history of GI ulcers/bleed
qConcurrent use of chronic antiplatelets, anticoagulants, corticosteroids, high dose NSAIDs
qUncontrolled BP
q Severe/advanced HF or exacerbations
q Patients with CV disease or multiple CV risk factors
q Patients with renal insufficiency/chronic kidney disease
q Drug interactions with NSAIDs (warfarin, high dose methotrexate)
q Avoid in third trimester pregnancy
Adjuvants / Co-analgesics
Diverse group of drugs with individual characteristics that are useful in the management of pain but aren’t typically considered analgesics
examples of Adjuvants / Co-analgesics
how they works?
◦ Anticonvulsants – may decrease neuronal excitability (blocking sodium channels, modulating calcium channels?)
◦ Antidepressants – block reuptake of serotonin or norepinephrine, enhancing pain inhibition
◦ Local anesthetics (example - topical) – block sodium channels
◦ Corticosteroids – strong anti-inflammatory affects
◦ Others
Most anticonvulsants and antidepressants commonly used in?
Most anticonvulsants and antidepressants commonly used in chronic, neuropathic pain
Full affects of anticonvulsants and antidepressants for pain management usually take?
Full affects of anticonvulsants and antidepressants for pain management usually take 4-6 weeks
Common Adjuvants / Co-analgesics classes
MC ones used>?
pregabalin and gabapentin MC
TCAs used as common adjuvants
amitriptyline
nortriptyline
desimpramine
SNRIs used for common adjuvants
desvenlafaxine
duloxetine
levomilnacipran
milnacipran
venlafaxine / venlafaxine XR
Anticonvulsants used as co-analgesics
carbamazepine
gabapentin
lamotrogine
pregabalin
topiramate
valproic acid
LA used as co-analgesics
lidocaine
roids used as coanalgesics
prednisone
dexamethasone
TCAs common adrs
Anticholinergic side effects (constipation, dry mouth, blurry
vision, trouble urinating), orthostasis, nightmares, weight
gain, confusion
TCA monitoring
- Weight
- Serotonin syndrome
- BP/HR
SNRI adrs
Nausea, vomiting, upset stomach, increased blood pressure
SNRI monitoring
- BP
- Mental status
- Serotonin syndrome
Gabapentin adrs
Dizziness, drowsiness, leg swelling, weight gain, ataxia
Pregabalin (Schedule V) adrs
Dizziness, drowsiness, leg swelling, weight gain, ataxia
gabapentin and pregabalin monitoring
- Periodic renal function
- Weight
- Edema
lidocaine adrs
Itching, rash, changes in skin color
lidocaine monitoring
Skin changes
Perioperative Use of Gabapentinoids
Limited evidence in dental procedures but may decrease pain and amount of opioid medications
No anti-inflammatory property benefits vs. using NSAIDs pre procedure/post procedure
Single dose or 2-3 dose peri operatively
gabapentin and pregabalin perioperative dosing
gabapentionoid abuse?
Growing concerns about gabapentionoid abuse, particularly in combination with opioids/other CNS depressants
◦ Limit use to short-term/small quantities
Trigeminal Neuralgia
Often felt in the jaw, teeth or gums
◦ May result in misdiagnosis and unnecessary dental procedures
what can be used in trigeminal neuraligia
carbazepine and oxcarbazipine
carbazepine use in trigem neuralgia:
level?
◦ doses?
◦ titrate?
◦ ADRs:
◦ Drug interactions:
Carbamazepine (most evidence – Level A=preffered agent)
◦ 200-1200 mg/d in 2-3 doses/day
◦ titrate by 100 mg every other day until sufficient pain relief is attained or until intolerable side effects prevent further upward titration.
◦ ADRs: sedation, dizziness, nausea, vomiting, diplopia, memory problems, ataxia, elevation of hepatic enzymes, and hyponatremia, leucopenia, aplastic anemia, allergic rash, systemic lupus erythematosus, hepatotoxicity, and Stevens-Johnson syndrome (SJS)
◦ Drug interactions: CYP450 (macrolide antibiotics, tramadol, tapentadol, calcium channel blockers
Oxcarbazepine use as trigem neuralgia tx
level?
◦ doses?
◦ titrating?
◦ side effects?
◦ 300-1800 mg/d in 2 doses/day
◦ increased as tolerated in 300 mg increments every third day until pain relief occurs
◦ improved side effect profile and fewer drug interactions than with carbamazepine
level B
Opioid defined
Any substance whether endogenous or synthetic, that produces morphine-like effects that are blocked by antagonists such as naloxone
Opiate defined
Compounds that are found in opium poppy such as morphine and codeine
Narcotic analgesic
- Old term for opioids
- Narcotic refers to their ability to induce sleep
- “negative connotations” – used as a term for drugs of abuse
long or short acting opioids in dentistry
- Very limited role for long-acting opioids in dentistry
- FOCUS: SHORT-ACTING OPIOIDS
Potency of Common Opioids/Opioid-Like Agents
gold standard opioid
- Morphine – “standard” opioid to which others are compared
- Opioids discussed in terms of morphine milligram (mg) equivalents = MMEs
Partial agonist opioid
Buprenorphin
Pure agonist opioids
Hydrocodone
Morphine
Oxycodone
Methadone
Hydromorphone
Oxymorphone
Fentany
Agonist / Antagonist opioids
Pentazocin
Antagonists of opioids
Naloxone
Naltrexone
Opioids
MOA
- Bind to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain
- Produces generalized CNS depression
- Affects opioid receptors in other areas of the body (GI)
Pharmacologic Actions of opioids
Effects on the CNS
Effects on the GI Tract
Effects on the CNS
◦ Analgesia
◦ Euphoria
◦ Respiratory depression
◦ Depression of cough reflex
◦ Nausea and vomiting
◦ Pupillary constriction
Effects on the GI Tract
◦ Constipation
opioids and histamine
Histamine Release
◦ Urticaria and itching at inject site or after IV
◦ Bronchoconstriction
◦ Hypotension
Overview of Effects of Opioid Receptors Sub-types
all produce analgesia
Opioid Black Box Warnings
Addiction, misuse and abuse can lead to?
Alcohol use?
Crushing, dissolving or chewing of long-acting products can cause?
Risk of medication errors with the oral solution ?
Opioid analgesic Risk Evaluation and Mitigation Strategy (REMS)?
respiratory?
neonatal?
Accidental ingestion of even one dose?
Risks from concomitant use with benzodiazepines or other CNS depressants, including alcohol,
may result in? Reserve concomitant prescribing of morphine and benzodiazepines or other CNS depressants for use in patients for whom?
Addiction, misuse and abuse can lead to overdose and death
Alcohol use with extended-release formulations (Kadian, Oxymorphone ER, Zohydro) result in
increased plasma levels and potentially fatal overdoses
Crushing, dissolving or chewing of long-acting products can cause the delivery of a potentially fatal
dose
Risk of medication errors with the oral solution - dosing errors due to confusion between mg and
mL, and other opioid solutions of different concentrations, can result in accidental overdose and
death
Opioid analgesic Risk Evaluation and Mitigation Strategy (REMS) for all opioids which includes an
education program for health care providers, Medication Guides provided to patients and emphasis
on education and safe use
Life threatening respiratory depression
Life threatening neonatal opioid withdrawal syndrome with prolonged use during pregnancy
Accidental ingestion of even one dose, especially by children, can result in a fatal overdose
Risks from concomitant use with benzodiazepines or other CNS depressants, including alcohol,
may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant
prescribing of morphine and benzodiazepines or other CNS depressants for use in patients for
whom alternative treatment options are inadequate. Limit dosages and durations to the minimum
required. Follow patients for signs and symptoms of respiratory depression and sedation
Opioid Adverse Events (ADE)
possible tx of opioid induced sedation
due to stim of?
- Mild sedation with oral common, more severe sedation a risk with injectables (tolerance develops over time)
- Consider holding or decreasing dose if impairs function
- If severe – naloxone (antagonist)
mu receptor stimulated
aacute overdose opioid tx
due to stim of?
naloxone
stimulation of Mu receptor – decreases sensitivity to CO2 in brain stem
opioid nausea and vomitting tx
due to stim of?
- If oral form (take with food to prevent)
- Anti-nausea medication (examples: promethazine, prochlorperazine,
ondansetron)
(stimulation of chemoreceptor trigger zone)
opioid induced constipation tx
Constipation ( stimulation of Mu receptor)
* only ADE for which tolerance does not develop
**Laxative **(examples: polyethylene glycol/Miralax, senna)
o Fiber, water and stool softeners often ineffective in opioid induced constipation
opioid induced itching tx
more common with injectable forms, use of antihistamines (diphenydramine)
Centrally Acting Opioid-Like Agents
Tramadol
Tapentadol
Tramadol moa
μ-opioid activity (30%)
inhibition of NE and 5HT reuptake (70%)
tramadol abuse
Considered less abuse potential (C-IV)
tramadol interactions
CYP2D6 and CYP3A4 interactions
tramadol side effects
◦ dizziness, nausea, constipation, headache, sedation
** Increased seizure risk**
Increased risk of** serotonin syndrome** with other serotonergic drugs
when to use tramadol
Most effective for mild-moderate (not severe) pain
Do not use in pediatric patients (variable metabolism)
◦ < 12 years of age or < 18 years following tonsillectomy/adenoidectomy surgery
tapentadol moa
μ-opioid activity
inhibition of NE
tapentadol abuse potential
CL II controlled
tapentadol interactions
less than tramadol
Do NOT consume alcohol with Nucynta ER
tapentadol side effects
◦ nausea, dizziness, vomiting, constipation and somnolence
Increased seizure risk
tapentadol indicated for?
Indicated for moderate to severe pain
Expensive!
Safety and efficacy in pediatric patients less < 18 years have not been established
Short-acting Oral Opioids (Commonly used in Dentistry)
dosing oxycodone
oxycodones with NSAIDS or APAP
able to dose with separate NSAID and/or
acetaminophen
Oxycodone/APAP dosing
Oxycodone/APAP dose can be limited by?
Dose may be limited by acetaminophen
content
Hydrocodone/APAP dosing
Hydrocodone/APAP dosing can be limited by?
APAP content
Tramadol dosing
Tramadol not given to?
Opioid-like ADEs. Decreases seizure threshold.
Not recommended in pts <12 yrs old
Tramadol/APAP dosing
Tramadol/APAP
Dose may be limited by?
Decreases ?
Tramadol not recommended in ?
Dose may be limited by acetaminophen content.
Decreases seizure threshold.
Tramadol not recommended in pts <12 yrs old
APAP/Codeine dosing
APAP/Codeine:
high rate of?
limited effects of?
Codeine contraindicated in?
high rate of GI ADEs (especially constipation)/
limited analgesic effects.
Codeine contraindicated in pts < 12 yrs ol
Opioid Conversion Charts
morphine mg equivalents
Opioid Partial Agonists/Antagonists
do not use with?
nalbuphine and pentazocine
◦ Don’t use with other opioids because it can precipitate withdrawal
pure opioid antagonists
naloxone/naltrexone
naloxone:
Blocks?
Produces?
Increases?
Treatment of ?
Precipitates?
Blocks all opioid receptors
Produces rapid reversal of opioid effects
Increases patient’s pain
Treatment of respiratory depression cause by opioid overdose
Precipitates opioid withdrawal symptoms but saves live
naloxone dosing
Dose: IV, IM, SubQ: Initial: 0.4 to 2 mg; may need to repeat doses every 2 to 3 minutes
Nasal spray also available (see subsequent slides
Naltrexone
Similar to? dif how?
Treatment option for ?
Similar actions to naloxone but longer duration of action
Treatment option for alcoholics and opioid dependence
naltrexone dosing
Dose: Initial: oral 25 mg; if no withdrawal signs occur, administer 50 mg/day thereafter
Alternative regimens may include higher doses on the weekends or 150 mg 3 times a day
IM: 380 mg once every 4 week
Uses of Opioids in Dentistry
Pain from:
◦ Abscesses/Infection/Inflammation
◦ Trauma
◦ Surgery/Procedures:
Post Procedural Management
Other potential dental conditions causing pain including temporomandibular disorders (TMDs) and masticatory muscle disorder
**Should be considered “last line” for all indications
**
Managing Acute Dental Pain – Putting It All Together
* best regimen?
growing concerns of?
No research on effectiveness of?
Many patients’ first experience with an opioid coincides with?
◦ Among prescribers of opioids for adolescents, who is most common?
misuse often occurs from?
use of prescribed opioid pain medication before high school graduation is associated with a?
misuse of opioids in adolescence - strong predictor of?
Limited evidence of best regimen - best practice is based on anecdotal reports, case studies, systematic reviews, a few randomized controlled clinical trial, and the opinions of experts.
Current practice often includes multimodal analgesic combinations
◦ Most effective combinations and doses not well studied
Growing concerns over opioid abuse
The US consumes 99% of the world’s hydrocodone/acetaminophen combinations
No research on effectiveness of hydrocodone in dental pain
Many patients’ first experience with an opioid coincides with a dental procedure, such as the extraction of wisdom teeth
◦ Among prescribers of opioids for adolescents, dentists are proportionately the most prevalent prescribers (~31%)
◦ In children/ adolescents < 18 yrs old
misuse often occurs from misuse of own previous prescriptions
use of prescribed opioid pain medication before high school graduation is associated with a 33% increase in risk of later opioid misuse
misuse of opioids in adolescence - strong predictor of later onset of heroin use
Comparing NSAID, Opioids, Combination pain relief graph
IBU alone comprable to oxy/IBU
buprofen + APAP vs. Opioid + APAP
ibuprofen + APAP may be more effective than Opioid + APAP
Post-Op Pain After Surgical and Simple Tooth Extractions in Children (12 and under) flow chart
never opioids
oothache Pain with No Immediate Access to Definitive Dental Treatment in Children (12 and under) flow chart
exact same as with extractions, same options and progression
never opioids
Tooth Removed — Simple and Surgical
Children: 0–less than 12 years old medication chart
ibuprofen children dosing guidelines
naproxen children dosing guidelines
APAP children dosing guidelines
Post-Op Pain After Surgical and Simple Tooth Extractions in Adolescents, Adults and Older Adults analgesic flow chart
Toothache Pain with No Immediate Access to Definitive Dental Treatment in Adolescents, Adults and Older Adults analgesic flow chart
tooth ext rx regimens:
first line?
extended management?
if nsaids contra?
if nsaids contra for surgical?
Comparison of Hydrocodone and Oxycodone
Both are?
Both are Schedule?
which is more potent (takes less mg for similar effects)?
differences in efficacy or tolerability at equianalgesic doses?
Noted interpatient ?
◦ Discussing previous patient experiences?
ADEs?
◦ Some studies show hydrocodone is more likely to cause?
◦ Some studies show oxycodone is more likely to cause?
Both have what formulations?
◦ long-acting formations use?
Both are available as combination products with?
◦ using separate tablets rather than combination tablet may be less confusing to patients and minimize risk of exceeding maximum acetaminophen dosing if planning to continue acetaminophen use with NSAID
Both semi-synthetic opioids
Both are Schedule II controlled substances
Oxycodone is more potent (takes less mg for similar effects)
No significant evidence on a populations level of major differences in efficacy or tolerability at equianalgesic doses
Noted interpatient variability with efficacy and tolerability
◦ Discussing previous patient experiences with using hydrocodone or oxycodone may contribute to decision-making
Mostly similar adverse events
◦ Some studies show hydrocodone is more likely to cause GI ADRs, especially constipation
◦ Some studies show oxycodone is more likely to cause sedation, grogginess, fatigue, etc.
Both have short-acting and long-acting formations
◦ long-acting formations should NOT typically be used for dental pain
Both are available as combination products with acetaminophen
◦ using separate tablets rather than combination tablet may be less confusing to patients and minimize risk of exceeding maximum acetaminophen dosing if planning to continue acetaminophen use with NSAID
Opioids and specific formulations that should NOT be used in acute pain
why are these not used?
any long acting opioid is never used
pre-procedure nsaids?
START pre-procedure NSAID 24 hrs prior - unless contraindication
◦ Decreases postoperative edema and hastens healing time
◦ Example ibuprofen 400-600 mg qid X4
NSAIDS/APAP in first 24-74 hrs
Consider scheduled doses of NSAID +/- acetaminophen the first 24-72
hours (depending on procedure) then prn
ADA and corticosteroids use?
The ADA panel suggests against adding oral, submucosal, or intramuscular corticosteroids to standard analgesic therapy for management of post-op dental pain
◦ Recommendations did not address IV administration or post-op complications such as trismus, facial swelling or infection)
◦ Perioperative IV steroids (e.g., dexamethasone) may decrease swelling and discomfort after third molar extractions
If opioid prescribed, the ADA panel recommends to use?
If opioid prescribed, the ADA panel recommends to use at lowest effective
dose, fewest tablets, and the shortest duration, which rarely exceeds 3 days
Counsel patients on expectations
◦ some pain, analgesics should make their pain manageable
◦ discuss with patient their past experiences, preferences and values regarding pain management (shared decision making)
- Avoid routine use of?
- If opioids are used, counsel patients regarding?
- Review the state’s?
- Avoid routine use of “just-in-case” opioid prescriptions for breakthrough pain
- If opioids are used, counsel patients regarding appropriate storage and disposal
- Review the state’s prescription drug monitoring program to determine the co-prescribing of other controlled substances
or all patients who are prescribed opioid pain relievers,
health care professionals should discuss the availability
of ?
or all patients who are prescribed opioid pain relievers,
health care professionals should discuss the availability
of naloxone, and consider prescribing it
Patients who are at increased risk of opioid overdose:
using benzodiazepines or other medicines that depress the central nervous system
history of opioid use disorder (OUD)
who have experienced a previous opioid overdose
Consider prescribing naloxone if:
Patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.
Key Drug Interactions with Opioids
Avoid Combination CNS depressants:
◦ Alcohol
◦ Benzodiazepines/ Anxiolytics (examples: alprazolam, diazepam, lorazepam)
◦ Sedative-hypnotics (examples: eszopiclone, zaleplon, zolpidem)
◦ Anticonvulsants (including gabapentinoids)
◦ Muscle relaxants
Caution in offering opioids to patients taking gabapentinoids and central nervous system active medications or additional opioids to patients already taking opioids for other medical reasons
Consider length of therapy and individual risk to patient (co- morbidities)
Sources of Prescription Opioids for Nonmedical Use
Prescription Drug Collection Boxes
Proper Disposal of Opioids
done?
Remove ?
FDA recommends mixing with?
Some long-acting opioid/others recommended to be?
When preferred options are not available/create barriers
Remove or scratch out personal information from bottles
FDA recommends mixing with unpalatable substances and placing in a non-descript container in the trash:
◦ Coffee grounds
◦ Kitty litter
◦ Dirt
◦ Packets from pharmacy (biodegradable gel)
Some long-acting opioid/others recommended to be flushed due to dangers
◦ Morphine ER, Oxycontin, Fentanyl patches, etc.
◦ See “FDA flush list
Consideration for Prescribing Opioids – Controlled Substances
Most opioids:
◦ Follow?
Tramadol:
Tylenol w/ Codeine tablets:
Opioid containing cough suppressants: C-
Pregabalin:
Caution: do not provide larger quantities than needed due to?
If patient calls requesting additional pain medications after initial quantity,
have patient?
what is required for controlled substances in Missouri and Kansas?
◦ Missouri - annual waiver and exceptions/Kansas biannual waiver and exceptions
Practitioners issuing electronic prescriptions for controlled substances must use a software application that?
Consideration for Prescribing Opioids – Controlled
Substances
Most opioids: C-11
◦ Follow Federal and State Laws
Tramadol: C-IV
Tylenol w/ Codeine tablets: C-111
Opioid containing cough suppressants: C-V
Pregabalin: CV
Caution: do not provide larger quantities than needed due to abuse, misuse,
and/or sharing (most states have quantity limits for opioids for acute pain)
If patient calls requesting additional pain medications after initial quantity,
have patient return for assessment and look for other causes of pain
E-prescribing required for controlled substances in Missouri and Kansas
◦ Missouri - annual waiver and exceptions/Kansas biannual waiver and exceptions
Practitioners issuing electronic prescriptions for controlled
substances must use a software application that meets all Drug
Enforcement Administration (DEA) requirements
State Prescription Drug Monitoring Programs (PDMPs)
Purpose:
Purpose: reduce prescription drug misuse, abuse and diversion while ensuring patients have access to safe, effective treatment
Missouri law PDMPs
and KS
Missouri law does not mandate checking PDMP before prescribing a controlled substance to a patient except for MO HealthNet participants. Kansas law also required checking for KS Medicaid participants
In states not requiring checking the PDMP it is recommended to?
In states not requiring checking the PDMP it is recommended to monitor state’s PDMP to identify concerns BEFORE writing a prescription
Using PDMPs
Centers for Disease Control Opioid Guidelines - ?
Activity report
Dentists - sign up?
Centers for Disease Control Opioid Guidelines - Do not dismiss patients from care
Activity report
◦ Not punitive for prescriber
◦ Reports the prescriber’s controlled-prescription prescribing
◦ Impacts on patients’ overall morphine mg equivalents (MMEs)
Dentists - sign up to access PDMP in MO or their state
◦ May appoint a staff member to be a delegate
Writing an Opioid Prescription format
NO REFILLS FOR CL-2 Rx
Opioid Overdoses: in practice or in the
community
Naloxone Education Basics:
CALL?
Ø If must leave temporarily put in?
Ø Indication for naloxone rescue:
CALL 911- first step
Ø If must leave temporarily put in recovery position (on side)
Ø Indication for naloxone rescue: signs of overdose
Administer naloxone as ?
Administer naloxone as directed/ how to administer, depending on formulation – most common
nasal spray
recovery position for OD pts
Position patients on their side after naloxone administration (recovery position), if breathing
§ they may vomit
if od pt not breathing?
perform rescue breathing or if no pulse, CPR as indicated (may vomit)
how often is naloxone administered
Administer naloxone every 2-3 minutes:
Ø If a patient’s symptoms return or if the patient doesn’t respond or achieve the desired response (i.e., adequate spontaneous breathing), and emergency medical help has not yet arrived
Ø When giving additional doses of Narcan nasal spray, alternate nostrils
Ø Long-acting/potent opioids may require more than 2 doses and repeated doses (EMS should have additional supply – important to transport to Emergency Department ASAP)
Most OD patients respond to?
Most patients respond to naloxone with a return to spontaneous
breathing
If naloxone is given to a patient who is not opioid-dependent or is not
opioid-intoxicated?
If naloxone is given to a patient who is not opioid-dependent or is not
opioid-intoxicated, it has no clinical effects
Dealing with Opioid Allergies: what most pts describe?
What most patient describe as opioid allergies are really ADRs/intolerances
* Examples: nausea, constipation, sedation
* Even histamine related flushing from IV opioids or itching is considered an ADR
If a patient reports an opioid ADR/intolerance options include
- Find an alternative non-opioid, if appropriate
- Change to another opioid either within or in a different class
- Lower the dose of the current drug (if still provides pain relief)
true opioid allergies occurence?
infrequent
When a patient describes or there is documentation of a true opioid allergy:
* cross reactions possible within?
* cross reaction less likely with?
* opioid-like agents?
* Therefore, ?
- cross reactions possible within same structural class
- cross reaction less likely with opioid in a different classes
- opioid-like agents are also contraindicated
- Therefore, reconsider if opioid is needed, pick an opioid in a different drug class if possible or consult with patient’s medical provider or pharmacist for recommendations
Patient Education with opioids?
goals?
safe?
Realistic Goals
Opioids are usually safe to use when prescribed for short periods of time under care of medical professional when other treatments aren’t options (contraindications) or aren’t controlling the pain
pt education: monitoring
Monitoring
◦ Pain improvement?
◦ Side Effects?
Education on using?
◦ Pain improvement (if not improved or worsening have patient return for
follow up appointment)
◦ Side Effects
Education on using laxative for constipation (stool softener and fiber may
not be effective)
Cannabinoids
- 100 cannabinoids in cannabis - two of the main active cannabinoids of cannabis
are delta-9-tetraydrocannabinol (THC) and cannabidiol (CBD) - Hemp-derived - CBD (< 0.3% tetrahydrocannabinol [THC] dry weight) vs. Marijuana – derived products
Quality and variability of canniboid products?
Quality and variability of products complicate and contribute to concern
◦ 2021 CDC Health Advisory: CBD product labeling may underestimate the concentration of THC by not reporting delta-8 THC concentrations, which may result in psychoactive and other adverse effects
◦ May not contain claimed ingredients or may be contaminated with other ingredients, including small amounts of THC or toxins
Complicated by federal and state laws
Cannabinoids in Dental Pain
literature?
Any role in therapeutic use is?
evidence?
◦ further research?
A PAUCITY OF LITERATURE AVAILABLE related to clinical benefits
Any role in therapeutic use is in its infancy
Insufficient evidence exists to support a tangible clinical benefit of cannabinoids in managing orofacial pain
◦ further research is recommended to investigate the benefits of cannabinoids’ use.
CAUTION: Use of cannabis and THC can?
CAUTION: Use of cannabis and THC can enhance sedative, psychomotor, respiratory and other effects of CNS depressants such as opioids, benzodiazepines and alcohol
cannaboids DDI
Potential for CYP450 (liver enzyme) drug interactions with other medications
Marijuana smokers
oral health?
Higher rate/increased risk of:
“cannabis stomatitis” –
Immuno?
Associated with poor quality of oral health
Higher rate/increased risk:
◦ Tooth decay
◦ Missing teeth
◦ Plaque and greater severity of gingivitis than non-users
◦ Xerostomia – higher rate than tobacco smokers
◦ Leukoplakia
◦ Mouth and neck cancers
“cannabis stomatitis” – risk to develop into malignant neoplasia
Immunosuppressant properties - higher prevalence of oral candidiasis compared to non-users
Recommended Pharmacologic Options for Dental Pain Management:
NSAIDs
Consider startin?
Other options?
◦ Ibuprofen* (400 mg q 6 hrs) or Naproxen* (440 mg q 12 hrs)
Consider starting pre-op for extractions/procedures
Other NSAIDs possible options (similar efficacy/safety)
Recommended Pharmacologic Options for Dental Pain Management: APAP
◦ In combination with?
Acetaminophen* (650-1000 mg q 6 hrs)
◦ In combination with NSAID or when NSAID contraindicated
Recommended Pharmacologic Options for Dental Pain Management: opioids
* when to use?
* hydro/oxy doses?
Opioids (for inadequate post-op pain control with non-opioids in adolescents and adults)
◦ Hydrocodone 5-7.5 mg q 6 hrs
◦ Oxycodone 5 mg q 6 hrs
Recommended Pharmacologic Options for Dental Pain Management: Supplemental local anesthetics
◦ Bupivacaine + Epinephrine by block or infiltration injection
◦ Articaine + Epinephrine by infiltration injection
foundation of pain managment?
* avoid products with?
* scheduled then prn?
Use non-opioid analgesics (NSAID +/- Acetaminophen) as foundation of pain
management unless contraindicated
qAvoid multiple APAP//NSAID containing products
qConsider scheduled doses the first 24-72 hours then prn
If prescribing opioid:
qCheck?
qUse ?
qAvoid in patients?
qMay be one of limited options in patients with contraindications to?
qCheck Prescription Drug Monitoring Program (PDMP)
qUse lowest dose/shortest duration Use in combinations with non-opioids (NSAID/APAP)
qAvoid in patients in recovery for substance abuse (work with substance abuse provider)
qMay be one of limited options in patients with contraindications to NSAIDs and APAP
Opioid Precautions/Contraindications
qCodeine and tramadol are contraindicated inwhat ages/why?
qAvoid prescribing opioids in combination with?
q Caution with elderly why?
q Screen for?
qCodeine and tramadol are contraindicated in children younger than 12 and should be avoided/used with extreme caution in ages 12-17, due to variability in metabolism
qAvoid prescribing opioids in combination with benzodiazepines, sedative-hypnotics, or anxiolytics.
q Caution in elderly and patients with renal and hepatic insufficiency
q Screen for drug interactions (cumulative CNS depression)
Educate patients about use, adverse effects
qOpioids:
qMaximum dose of APAP
Educate patients about use, adverse effects
qOpioids: abuse risks and appropriate disposal
qMaximum dose of APAP (4,000 mg)
analgesics site of action?
