Non-Opioid Analgesics Flashcards
1
Q
Advantages of Non-Opioids
A
- wide availability
- familiarity
- effectiveness for mild pain
- ease of admin
- additive analgesia
- low cost
2
Q
Disadvantages
A
- Ceiling effect
- Side effects : renal, GI, thrombotic/CV
- Side effects: hepatotoxicity for acetaminophen
3
Q
Prostaglandins
A
- lipid soluble molecules
- produced by breakdown of arachidonic acid
- can be physiologic mediators or part of inflammatory cascade
4
Q
COX1 and COX2
A
- COX 1
- constitutive enzyme (exists in many tissues)
- produces PGs in gastric tissue (prostcyclin PGI2)
- kidneys PGE2
- platelets TXA2, PGI2
- Endothelium PGI2
- promotes gastric protection, normal kidney function, and promotes platelet aggregation
- COX 2
- induced enzyme
- inflammatory cascade (macrophages, cytokines, etc)
5
Q
How do NSAIDS work?
A
- inhibit COX1 and COX2 PG synthesis
- block cyclooxygenase enzyme = PG synthesis
- reduces inflammation
- reduces pain
- Cytokines etc induce PG synthesis in peripheral tissue and CNS
6
Q
Pharmacology
A
- Absorption
- upper GI tract
- rapid
- Distribution
- rapid
- limited by high protein binding (more stays in plasma)
- Metabolism
- ++ protein bound (99%)
- metabolized in liver CYP450
- Excretion
- urine
7
Q
GI side effects of NSAIDS
A
- nausea, pain, erosion, PUD, bleeding, perforation
- lower GI bleed less risk
- highest risk with non selective COX1/COX2 NSAIDS
- Ibuprofen maybe less risk
- Lower GI risk with COX2 selectives ones
- Risk factors:
- > 65
- PUD in last year
- H pylori
- Steroids, ASA, anticoag use
- advanced disease
- CV disease
- smoking
- ETOH
- Gastroprotection:
- limited evidence, but useful in practice
- PPIs
- Misoprostol (synthetic PG)
8
Q
Renal Side Effects of NSAIDS
A
- water and sodium retention
- edema
- Hyperkalemia
- Decreased effectiveness of antihypertensives and diuretics
- renal papillary necrosis
- RF
Pathophysiology
- PG mediate vascular tone, renin release and salt / water balance
- sodium resorption in distal tubule
- PG increase K secretion
- salt retention –> HTN
- RF –> disruption of PGs
NO difference between COX2 or COX1/2 NSAIDS
- PGE2 and PGI2 depends on COX 2, so both are harmful to kidneys
9
Q
CNS side effects of NSAIDS
A
- Dizziness
- Headache
- Confusion
- Vertigo
- Depression
10
Q
Platelet side effects of NSAIDS
A
- Inhibition of activation of platelets
- increased risk of hemorrhage
- NSAIDS decrease thromboxane A2
- TXA2 potent vasocontrictor
- promotes platelet aggregation
- COX1
- decreased prostacyclin PGI2
- vasodilation
- inhibits platelet aggregation
-
COX2 inhibitors increases relative activity of TXA2
- thrombosis
- COX1 inhibitors higher risk of bleedingf
11
Q
Cardiac side effects and NSAIDS (COX2)
A
- CHF
- MI and Stroke
- COX2 inhibition because COX 2 increases TXA (platelet aggregation)
- Celecoxib high risk
- All NSAIDS have risk as they all inhibit COX2
12
Q
Special areas of hypersensitvity of ALL NSAIDS/ASA
A
- Rhinitis
- Bronchial asthma
- 1/5 people
- PG inhibition causes bronchospasm
- Urticaria
- Flushing
- Hypotension
- Shock
- Samter’s triad
- asthma
- sinusitis /nasal polyps
- sensitivity to ASA and NSAIDS
13
Q
Contraindications to NSAIDS
A
- high risk for GIB
- recent GIB, hx NSAIDS PUD, gastropathy, advanced age, frailty, steroid, anticoag)
- renal insufficiency
- liver disease
- significant cardiac RF
- NSAID asthma
14
Q
Drug-drug interactions with NSAIDS
A
- lithium
- methotrexate
- aminoglycoside (Gentamycin, tobraymycin, amikacin)
- high plasma proteing binding can compete with phenytoin
- toxicity of free phenytoin
- anticoagulation
15
Q
Topical NSAIDS
A
- mininmize systemic absorption
- OA
- maximal plasma concentration 15% of oral dose
- poor pall care evidenc
