Analgesics Flashcards
n unpleasant sensory and emotional experience
associated with, or resembling that associated with, actual
or potential tissue damage
Pain
What is difference between acute and chronic pain?
Chronic lasts for more than 3 months
_____ 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
Somatic
_____ pain
(from internal organs)
◦Example: appendicitis
◦Often diffuse and poorly localized
Visceral
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)
Neuropathic pain
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
Chronic or persistent pain
Are there any lab tests to objectify pain?
No; only diagnose cause potentially
___-____% of reduction of pain shows clinical improvement
30-50%
*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
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 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)
Acetaminophen
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
Acetaminophen
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
NSAIDs
*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
Non selective NSAIDs
*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
Selective NSAIDs
What is the only COX-2 inhibitor?
Celecoxib/Celebrex
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
COX2 inhibitor
Greater than ____mg of Celebrex is associated with increased incidence of CV thrombotic events
400 mg
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
Nonselective NSAIDs and COX-2 inhibitors
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
Adjuvants/Co-analgesics
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
Gabapentinoids
-Gabapentin and Pregabalin
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
Trigeminal neuralgia
What 2 drugs are used to treat trigeminal neuralgia?
Carbamazepine and Oxcarbazepine
Any substance whether endogenous or synthetic,
that produces morphine-like effects that are
blocked by antagonists such as naloxone
Opioid
Compounds that are found in opium poppy such
as morphine and codeine
Opiate
