Analgesics

Question 0

Indomethacin (Indocin)

Answer 0

Class: Acetic acid derivative, more potent inhibitor of COX than aspirin
Indication: acute gout, osteoarthritis, IV formulation for closure of persistent patent ductus arteriosus
ADR: high incidence of side effects, requiring short term dosing, e.g. Gastritis, renal dysfunction

Question 1

Aspirin

Answer 1

Class: NSAID
MOA: irreversibly inactivates COX via acetylation, platelets cannot synthesize new COX (no nucleus) unlike other cells
PK: elimination half-life (2.5h for low dose to 19h for high dose), peak blood level 1h after oral dose, effects last life of platelet 10-14 days
Special: consider using in HTN pts, anti-pyretic
Contraindicated: peptic ulcer, gastric irritation!

Question 2

Diclofenac (Cambia, Cataflam, Voltaren, Voltarol, Zipsor)

Answer 2

Class: COX-2 selective NSAID, similar to Celebrex
Indication: significant post-operative pain relief
ADR: hepatotoxicity should be monitored
PK: accumulates in synovial fluid (effect is considerably longer than half life of 1-2h
Special: topical works via peripheral and not central activation, combination with Misoprostol (Arthrotec)

Question 3

Ketorolac (Toradol)

Answer 3

Class: NSAID
MOA: non-selective COX inhibitor
Indication: short-term management of pain, can be administered iv, very strong analgesic, post-surgical pain
ADR: use must be limited to less than 5 days, increased risk of allergic rxn in pts with asthma, can precipitate/exacerbate renal failure
Interaction: adverse GI effects increased by other NSAIDs, use with acetaminophen increases liver toxicity
PK: enteric, opthalamic, paraenteral delivery, 180-800x more potent than aspirin, analgesic effect in 30min, 4-6h duration

Question 4

Naproxen

Answer 4

Class: propionic acid NSAID
Description: possibly less CV risk compared to other NSAIDs, so consider in pts with CV disease, less GI irritation compared to aspirin, twice daily dosing, peak conc 4-6h, half life 14h

Question 5

Ibuprofen (Advil, Motrin)

Answer 5

Class: propionic acid NSAID
Description: doses>1200mg/d have predominantly analgesic effect in arthritis, GI side effect at higher doses -2400mg/d, proven efficacy in h/a, menstrual pain, and acute post-operative pain, multiple OTC combination products for cold medicine

Question 6

Oxaprozin (Daypro)

Answer 6

Class: propionic acid NSAID
Description: in addition to good nonselective COX-1/2 activity, additional mechanisms identified, NF-kb and metalloproteinase inhibition, endogenous cannabinoid modulation, long-acting medication qd dosing, diffuses readily into inflamed synovial tissues

Question 7

Meloxicam (Mobic)

Answer 7

Class: enolic acids (oxicam) NSAID
Description: COX-2 preferential, esp at low doses, not altered by renal or hepatic insufficiency, dose adjustment not needed in elderly, so consider in elderly

Question 8

Celecoxib (Celebrex)

Answer 8

Class: Selective cox-2 NSAID
ADR: GI bleeding but may be less than non-selectives, risk of renal toxicity and MI
Interaction: levels increased by drugs that inhibit cyt p450 2c9, decreases effects of angiotensin-converting enzyme inhibitors and diuretics, increases lithium levels
Special: does not interfere with platelet aggregation, perioperative administration possible without increased bleeding, less CV and GI complications
Contraindicatiin: sulfa allergy

Question 9

Acetaminophen (Tylenol)

Answer 9

Class: analgesic, antipyretic
MOA: not entirely clear, may act centrally to inhibit cyclooxygenase, lacks antiplatelet activity, inhibits central prostaglandin synthesis with minimal effect peripherally
Clinical use: mild to moderate pain, fever
ADR: none usually, od can cause fatal hepatic failure esp in combination with etoh.
Interaction: additive liver toxicity with NSAID
PK: peak .5-3h po, half life 2-3h, duration 4-6h, metabolized in the liver by conjugation and hydroxylation to inactive metabolites
Special: safest and most cost-effective nonopioid analgesic, reduces opioid consumption 35-45% in post-op pain in parenteral form

Question 10

Gabapentin, Pregablin

Answer 10

Class: anticonvulsant
MOA: prevent Ca2+ influx in dorsal horn
Indication: neuropathic pain
ADR: dizziness, fatigue, wt gain, drowsiness, peripheral edema
Special: no drug interaction, complicated dosing regimen

Question 11

Tricyclic Antidepressant, SNRI

Answer 11

MOA: NE and serotonin reuptake inhibitor
Indication: neuropathic pain, appetite stimulant, sleep aid
ADR: innumerable–sedation, increased appetite, dry mouth, sexual dysfunction, orthostatic hypotension
Interaction: use with caution in elderly, chronic pts do no want to gain wt, use with caution with other serotonin reuptake inhibitors

Question 12

For opioids

Answer 12

See ‘Substance Use Disorder’ deck