Analgesics

Question 1

n unpleasant sensory and emotional experience
associated with, or resembling that associated with, actual
or potential tissue damage

Answer 1

Pain

Question 2

What is difference between acute and chronic pain?

Answer 2

Chronic lasts for more than 3 months

Question 3

_____ pain:
(from teeth, skin, bone, joints, muscle, connective tissue) – Examples:
◦Inflammatory (Rheumatoid arthritis)
◦Mechanical/compression (spine/bone)
◦Muscle dysfunction (Myofascial pain)
◦Combinations common
◦Results in most dental pain – inflammatory and/or mechanical
–result of traumatic injury or bacterial infection originating from pulpal and periapical tissues

Answer 3

Somatic

Question 4

_____ pain
(from internal organs)
◦Example: appendicitis
◦Often diffuse and poorly localized

Answer 4

Visceral

Question 5

—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
—Dysfunction of peripheral nerves
◦focal area
◦Widespread
—Dysfunction of central nervous system
◦reorganization of central somatosensory processing
—Independent of any ongoing
tissue injury
—Typically described as tingling, stinging, burning, and/or numb
—Less common type of dental pain compared to somatic pain
◦Referred to as neuropathic orofacial pain
(NOP)

Answer 5

Neuropathic pain

Question 6

—Not well understood
—May be associated with a chronic pathologic process
—Mechanisms
◦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

Answer 6

Chronic or persistent pain

Question 7

Are there any lab tests to objectify pain?

Answer 7

No; only diagnose cause potentially

Question 8

___-____% of reduction of pain shows clinical improvement

Answer 8

30-50%

Question 9

*Exact MOA unclear
*May inhibit nitric oxide pathway, mediating neurotransmitters
*Inhibitor of Cyclooxygenase III (COX III) in the CNS
*Weak COX-I and COX-II inhibitor in peripheral tissues
*Possesses NO significant anti-inflammatory activity
*NO anti-platelet activity – No increased bleeding risk
Clinical Uses
*Mild to moderate pain of varied origin (including dental
pain)
*Antipyretic activity
*In combination with opioids (synergy)
*APAP’s analgesic effects considered less than to similar to NSAIDs

Answer 9

Acetaminophen

Question 10

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 analgesics
Dosing Recommendations/
Comments
*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 and be sure it
is appropriate for age and formulation
*Use the calibrated syringe/measuring cup that comes with the product
*Significant risk of hepatotoxicity with doses ≥ 4,000mg (4gm)/day or overdose
*Common strengths: 80 mg , 160 mg, 160mg/5ml, 325 mg
*Available in tablet, chewable, infant and children’s’ suspensions
*Avoid APAP use in patients with active/severe hepatic disease and alcohol
abuse/dependence →↑risk of hepatotoxicity
*Has no effect on GI prostaglandins, CV/platelet effects (vs. NSAIDs)

Answer 10

Acetaminophen

Question 11

Drug Interactions—
Few, compared to other pain medications
—Caution in combination with other drugs that cause liver
toxicity
◦Leflunomide
◦Methotrexate
◦Carbamazepine
◦(Others)
—Warfarin (but considered safer than NSAIDs)
—More than >3 alcoholic drinks a day increases liver toxicity
risk

Answer 11

Acetaminophen

Question 12

MOA of _____
—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

Answer 12

NSAIDs

Question 13

*Nonselective inhibition of COX-1 and COX-2 → inhibition of
biosynthesis of prostaglandins→ ↓ number of pain impulses received
by the CNS, decreases fever.
*Act peripherally for pain
*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 effect

Answer 13

Non selective NSAIDs

Question 14

*Selectively inhibits COX-2 isoenzyme at the site of
inflammation → inhibit prostaglandin synthesis → ↓ number of
pain impulses received by the CNS, decreases fever.
*Act peripherally for pain
*No significant platelet effects
MOA: Anti-inflammatory, analgesic, antipyretic

Answer 14

Selective NSAIDs

Question 15

What is the only COX-2 inhibitor?

Answer 15

Celecoxib/Celebrex

Question 16

—Only one _______ 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

Answer 16

COX2 inhibitor

Question 17

Greater than ____mg of Celebrex is associated with increased incidence of CV thrombotic events

Answer 17

400 mg

Question 18

Clinical uses of ______
—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

Answer 18

Nonselective NSAIDs and COX-2 inhibitors

Question 19

—Diverse group of drugs with individual characteristics that are useful in the management of pain but aren’t typically considered analgesics
—Examples
◦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 commonly used in chronic, neuropathic pain
—Full affects of anticonvulsants and antidepressants for pain management usually take 4-6 weeks
—Dentists can prescribe adjuvant pain medications, as appropriate
—May wish to consult with patient’s other health care provider(s), if not familiar with selection/dosing

Answer 19

Adjuvants/Co-analgesics

Question 20

—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
No anti-inflammatory effects

Answer 20

Gabapentinoids
-Gabapentin and Pregabalin

Question 21

—Often felt in the jaw, teeth or gums
◦May result in misdiagnosis and unnecessary dental procedures
—Carbamazepine (most evidence – Level A)
◦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 (Level B)
◦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

Answer 21

Trigeminal neuralgia

Question 22

What 2 drugs are used to treat trigeminal neuralgia?

Answer 22

Carbamazepine and Oxcarbazepine

Question 23

Any substance whether endogenous or synthetic,
that produces morphine-like effects that are
blocked by antagonists such as naloxone

Answer 23

Opioid

Question 24

Compounds that are found in opium poppy such
as morphine and codeine

Answer 24

Opiate

Question 25

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 —
Effects on the CNS
◦Analgesia
◦Euphoria
◦Respiratory depression
◦Depression of cough reflex
◦Nausea and vomiting
◦Pupillary constriction
—Effects on the GI Tract
◦Constipation
Other Actions —
Histamine Release
◦Urticaria and itching at inject site or after IV
◦Bronchoconstriction
◦Hypotension

Answer 25

Opioids

Question 26

Which opioid rc is the most important for analgesia?

Answer 26

Mu

Question 27

What is the anatagonist for opioids that can be given to reverse an overdose?

Answer 27

Naloxone

Question 28

WHich adverse effect of opioid does tolerance not develop over time?

Answer 28

Constipation

Question 29

◦MOA
–μ-opioid activity (30%)
–inhibition of NE and 5HT reuptake (70%)
—Considered less abuse potential (C-IV)
—CYP2D6 and CYP3A4 interactions
—Common side effects
◦dizziness, nausea, constipation, headache, sedation
—Increased seizure risk
—Increased risk of serotonin syndrome with
other serotonergic drugs
—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

Answer 29

Tramadol (Ultram)

Question 30

◦MOA
–μ-opioid activity
–inhibition of NE
—C-II controlled substance
—Fewer drug interactions compared to tramadol
—Common side effects
◦nausea, dizziness, vomiting, constipation and
somnolence
—Increased seizure risk
—Indicated for moderate to severe pain
—Expensive!
—Do NOT consume alcohol with Nucynta ER

Answer 30

Tapentadol (Nucynta)

Question 31

–Blocks all opioid receptors
–Produces rapid reversal of opioid effects
–Increases patients pain
–Treatment of respiratory depression cause by opioid overdose
–Precipitates opioid withdrawal symptoms
–Dose: IV, IM, SubQ: Initial: 0.4 to 2 mg; may need to repeat doses every 2 to 3 minutes–A lower initial dose (0.1 to 0.2 mg) should be considered for patients with opioid dependence to avoid acute withdrawal
–Nasal spray also available (see subsequent slides)

Answer 31

Naloxone

Question 32

–Similar actions to naloxone but longer duration of action
–Treatment option for alcoholics and opioid dependence
–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 weeks

Answer 32

Naltrexone

Question 33

Uses of _____ 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

Answer 33

Opioids

Question 34

How many days of opioids are considered sufficient for pain?

Answer 34

4-7 ( prob more like 2-5)

Question 35

Pts are considered opioid tolerant when they are on 60 mg of Morphine for more than ___ weeks

Answer 35

1 week