2 - Non-Opioid Analgesics Flashcards by mike smith

What is nociceptive pain?

Pain caused by an injury to body tissues

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What is neuropathic pain?

Damage to or dysfunction of the nerves, spinal cord, or brain

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Name some non-pharmacologic options for pain management:

Physical therapy
Acupuncture
Exercise
Stretching
Weight loss
Cognitive therapy 
Yoga
Chiropractic

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Therapeutic effects of analgesics:

Antipyretic 
Anti-inflammatory
Ceiling effect to the analgesia 
Do not cause tolerance
Do not cause dependence

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What releases arachidonic acid from the cell membrane?

Phospholipase A2

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Cox 1, 2, and 3 coverts _____ to _____.

Arachidonic acid to prostaglandins

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Cox 1 is found mostly in:

Platelets, endothelium, stomach

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Cox 2 is found mostly in:

Inflammatory cells, kidney

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Cox 3 is found mostly in:

The CNS

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What are the chemical mediators that trigger inflammation?

Histamine, prostaglandins, bradykinin

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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

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Acetaminophen (Tylenol) - clinical use:

Self-limiting painful condition (e.g. HA, MSK pain), osteoarthritis, lower back pain

Mild to moderate non-inflammatory nociceptive pain

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Acetaminophen especially useful in patients with:

Gastric problems, or where bleeding time is a concern

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Acetaminophen metabolism (primary):

Primary - glucuronidation and sulfation, then renally excreted

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Acetaminophen metabolism (secondary):

CYP3A4, CYP2E1: N-hydroxylation

Toxic metabolite “NAPQI”

If glutathione is depleted, hepatic damage occurs

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Acetaminophen (Tylenol) - AE’s?

N/V, HA

OD -> Hepatotoxicity

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What level of APAP is hepatotoxic?

10 to 15 grams

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What level of APAP is potentially fatal?

20-25 grams

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First 24hrs s/p APAP OD - clinical symptoms:

Mild - GI s/s (N/V)

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24 - 72 hrs s/p APAP OD - clinical presentation?

ABD pain
Liver tenderness
Elevated transaminase levels
Possible jaundice

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4 days to 2 week s/p APAP OD - clinical presentation:

Either resolution or progressive deterioration to death from hepatic failure

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Antidote for APAP OD?

N-acetylcysteine [NAC] (Mucomyst, Acetadote)

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How does Acetadote work?

Increases supply of glutathione

Combines with NAPQI to produce non-toxic metabolite

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What is the Rumack-Matthew nomogram?

Used to determine course of treatment for a patient that has overdosed on Tylenol

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Indications for using N-Acetylcysteine:

1. Concentration above the treatment line on Rumack-Matthew 4hrs s/p ingestion 2. Suspected ingestion > 150mg/kg 3. Unknown ingestion time, concentration > 10mcg/mL 4. Pt hx APAP ingestion and ANY evidence of liver injury 5. 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):

1. Antipyretic 2. Anti-platelet 3. Analgesic 4. 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:

1. APAP 2. ASA 3. Tramadol 4. Opioids (short-term) 5. Non-acetylated salicylates IF ALL THAT FAILS...NSAIDS

Characteristics of “high risk” for NSAID ulcers:

1. Hx of previously complicated ulcer | 2. Multiple (>2) other risk factors

Criteria of “moderate risk” for NSAID ulcers:

1. Age > 65 yrs 2. High-dose NSAID therapy 3. Previous hx uncomplicated ulcer 4. 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