2 - Non-Opioid Analgesics Flashcards
What is nociceptive pain?
Pain caused by an injury to body tissues
What is neuropathic pain?
Damage to or dysfunction of the nerves, spinal cord, or brain
Name some non-pharmacologic options for pain management:
Physical therapy Acupuncture Exercise Stretching Weight loss Cognitive therapy Yoga Chiropractic
Therapeutic effects of analgesics:
Antipyretic Anti-inflammatory Ceiling effect to the analgesia Do not cause tolerance Do not cause dependence
What releases arachidonic acid from the cell membrane?
Phospholipase A2
Cox 1, 2, and 3 coverts _____ to _____.
Arachidonic acid to prostaglandins
Cox 1 is found mostly in:
Platelets, endothelium, stomach
Cox 2 is found mostly in:
Inflammatory cells, kidney
Cox 3 is found mostly in:
The CNS
What are the chemical mediators that trigger inflammation?
Histamine, prostaglandins, bradykinin
Acetaminophen (Tylenol) - MOA:
Not fully understood
Inhibits prostaglandins (via unknown binding site)
Does not have significant anti-inflammatory or anti-platelet effects
CENTRALLY ACTING as analgesic and antipyretic
Acetaminophen (Tylenol) - clinical use:
Self-limiting painful condition (e.g. HA, MSK pain), osteoarthritis, lower back pain
Mild to moderate non-inflammatory nociceptive pain
Acetaminophen especially useful in patients with:
Gastric problems, or where bleeding time is a concern
Acetaminophen metabolism (primary):
Primary - glucuronidation and sulfation, then renally excreted
Acetaminophen metabolism (secondary):
CYP3A4, CYP2E1: N-hydroxylation
Toxic metabolite “NAPQI”
If glutathione is depleted, hepatic damage occurs
Acetaminophen (Tylenol) - AE’s?
N/V, HA
OD -> Hepatotoxicity
What level of APAP is hepatotoxic?
10 to 15 grams
What level of APAP is potentially fatal?
20-25 grams
First 24hrs s/p APAP OD - clinical symptoms:
Mild - GI s/s (N/V)
24 - 72 hrs s/p APAP OD - clinical presentation?
ABD pain
Liver tenderness
Elevated transaminase levels
Possible jaundice
4 days to 2 week s/p APAP OD - clinical presentation:
Either resolution or progressive deterioration to death from hepatic failure
Antidote for APAP OD?
N-acetylcysteine [NAC] (Mucomyst, Acetadote)
How does Acetadote work?
Increases supply of glutathione
Combines with NAPQI to produce non-toxic metabolite
What is the Rumack-Matthew nomogram?
Used to determine course of treatment for a patient that has overdosed on Tylenol
Indications for using N-Acetylcysteine:
- Concentration above the treatment line on Rumack-Matthew 4hrs s/p ingestion
- Suspected ingestion > 150mg/kg
- Unknown ingestion time, concentration > 10mcg/mL
- Pt hx APAP ingestion and ANY evidence of liver injury
- Delayed presentation (>24hrs) w/ evidence of liver injury
Max adult daily dose APAP?
4 grams
Children’s dose for Tylenol?
10-15mg/kg/dose q4-6hrs
NSAID’s - MOAS?
Reversibly inhibits COX-1 and 2 enzymes, which results in decreased formation of prostaglandin precursors
Has antipyretic, analgesic, and anti-inflammatory properties
Undesirable NSAID effects from COX-1 inhibition:
Gastrotoxicity —> ulcers
Undesirable NSAID effects from COX-2 inhibition:
Increased BP
Increased salt retention
Clinical uses of NSAIDS (four main categories):
- Antipyretic
- Anti-platelet
- Analgesic
- Anti-inflammatory
What medicine is contraindicated in peds with viral infections (influenza, chicken pox), and why?
ASA, d/t Reye’s Syndrome
What impact does higher COX-2 selectivity have an platelet aggregation?
Higher COX-2 selectivity DECREASES the beneficial effects on platelet aggregation
Which is better at decreasing platelet aggregation - COX-1 or COX-2?
COX-1
NSAID’s that are more ___ selective carry a higher cardiovascular risk:
COX-2
AHA recommendations for patients with CVD who need pain meds:
- APAP
- ASA
- Tramadol
- Opioids (short-term)
- Non-acetylated salicylates
IF ALL THAT FAILS…NSAIDS
Characteristics of “high risk” for NSAID ulcers:
- Hx of previously complicated ulcer
2. Multiple (>2) other risk factors
Criteria of “moderate risk” for NSAID ulcers:
- Age > 65 yrs
- High-dose NSAID therapy
- Previous hx uncomplicated ulcer
- Concurrent use of ASA, corticosteroids, or anticoagulants
How to prevent NSAID dyspepsia?
Combine NSAID with PPI or H2 blocker
How to avoid NSAID cardiovascular complications?
Naproxen preferred NSAID for CV patients
In general, CVD patients should avoid NSAIDS
What NSAID should be used cautiously in asthma patients?
ASA - can exacerbate asthma
How many days before surgery must ASA therapy be stopped?
7 to 10 days
Avoid NSAIDS in pregnancy (especially close to term) due to:
Risk of premature closure of ductus arteriosus
NSAIDS and renal disease:
Avoid in pt’s taking ACEI’s and ARB’s
Signs of salicylate toxicity:
Tachypnea
Tachycardia
Febrile
Metabolic acidosis and respiratory alkalosis
Common NSAID drug interactions:
ACEI/ARB
Antiplatelet
Corticosteroids
ASA can displace:
Highly protein-bound drugs
General dosing principles for NSAIDS:
Use lowest dose possible to get desired effect
Ceiling effect (higher doses do not equal better therapeutic effects)
Lower doses for analgesia
Higher doses for inflammation
What is the most commonly used salicylate?
ASA
Do salicylates cross the BBB and placenta?
Yes
Non-acetylated salicylates may be preferred when ______ is undesirable
COX-1 inhibition
Describe Salsalate (Disalcid):
Non-acetylated salicylate
Indicated for relief of rheumatic disorder
What is Choline Magnesium Trisalicylate indicated for?
OA, acute flare-up of RA, acute shoulder pain
Describe Diflunisal:
Non-acetylated salicylate
For OA/RA (mild-moderate)
Does not cross BBB or placenta
Describe Bismuth Subsalicylate:
Pepto-Bismol
Antisecretory, antimicrobial, anti-inflammatory
Diarrhea, heartburn, upset stomach
ADE: dark/black tongue
ASA MOA?
Irreversibly inhibits COX-1 and COX-2 enzymes
Decreased production of TXA2 form AA
Lasts the life of the platelet (7 to 10 days)
Clinical use for Ketorolac (Toradol)?
Not for peds
Can decrease opioid requirement up to 50%
moderate to severe pain
Ketorolac (Toradol) - black box warning:
Bleeding risk
Use short term (<5 days)
Ketorolac (Toradol) - CI’s
Surgery coming up soon
Don’t use with other NSAIDS
Don’t use in labor and delivery
Don’t use in pt’s with ESRD
Which NSAID has the lowest CV risk?
Naproxen (Aleve)
What specific disease is Naproxen approved for?
Gout attacks
What is an advantage of Naproxen over other NSAIDS in terms of convenience?
Longer half life, BID dosing
Indomethacin - clinical use:
NSAID of choice for gout attacks
Ophth preparation for conjunctival inflammation
Accelerated closure of PDA
What was the first NSAID to show accelerated closure of PDA?
Indomethacin (Indocin)
What is the most commonly used NSAID in the US?
Ibuprofen
Ibuprofen - GI and CVD risks:
Low GI risk
Higher CVD risk
Ibuprofen - AE’s?
GI irritation (less than with ASA)
Tinnitus
Ibuprofen - CI’s?
Agioedema
Bronchospasm (if ASA sensitive)
Nabumetone (Relafen) - clinical use:
OA/RA
Nabumetone (Relafen) - characteristics:
Long half-life = once daily dosing
More expensive
COX-2 selective (less GI SE’s)
Diclofenac (Cataflam) - clinical use:
Chronic MSK pain (mild to moderate)
OA/RA
Ophthalmic - post-cataract surgery
Topical - OA, sprains, strains
Diclofenac - AE’s:
High CVD risk
Celecoxib (Celebrex) - MOA:
Reversibly inhibits COX-2 (with minor COX-1)
Celecoxib (Celebrex) - clinical use:
OA
RA
AS
Primary dysmenorrhea
Minimal GI SE’s
High CVD risk
Celecoxib (Celebrex) - CI’s
Contains a sulfa-group - don’t give to pt with sulfa allergy
Flurbiprofen - use:
Inhibition of intraoperative miosis
