Chapter 29: Non-Narcotic Analgesics Flashcards
In general what is the mechanism in which NSAIDS act?
By inhibiting the COX enzymes in Prostanoid (Prostoglandin) biosynthesis.
What are the different COX pathways?
What are the roles of Prostaglandins in Pain, Fever and Inflammation?
- Sensitize Nociceptors to
- Chemical Mediators of Pain (Bradykinin, Cytokines, Substance P)
- Thermal Stimuli
- Physical Stimuli
- PGs and Prostacyclin (PGI2) increase blood flow to injured tissues which increases leukocyte infiltration and results in edema and inflammation
- Peripheral Inflammation -> Increase Cox 2 expression in the dorsal horn of the spinal cord.
What Cox enzyme to NSAIDS have a higher affinity for?
COX-1
What are the 2 Non-Selective Cox Inhibitor NSAIDs and what are their half lifes?
Aspirin - 0.5 Hours - Binds COX irreversibly
Ibuprofen - 2 hours
What mechanism do Non Selective Cox inhibitor NSAIDS follow?
INhibit COX 1 and 2 reducing formation of Prostaglandins and Thromboxanes.
Inhibit pain sensory transmission in peripheral and CNS.
Reduce elevated body temperature but do not alter normal body temperature appreciably.
May reset the thermoregulatory mechanism in the hypothalamus
- Viruses and bacterial endotoxins(LPS in Gram Negative) COX II in the hypothalamus.
Seldom Necessary to lower mild to moderate fever.
Aspirin irreversibly binds causing a longer lasting affect even though a shorter half life.
What Non selective COX NSAIDS has less GI effects?
Ibuprofen
What are the adverse effects of NSAIDS?
GI Effects
- Normally PGI2 decreases acid and PGE2 increases stomach protective mucus.
- NSAIDS decrease therese leading to GI ulceration and Irritation.
Decrease Blood Coagulation
Kidney Effects: Effect Elderly More
- Decrease Renal Blood Flow
- Interstitial Nephritis
Side effect 1 + 2 Can cause GI perforation and severe bleeding in old.
Explain how ASA overdoses work?
The analgesic activity occurs at lower doses
The anti inflammatory dose is higher
At anti-inflammatory doses, hepatic enzymes(responsible for drug metabolism) are saturated producing a zero order kinetic pattern.
Increasing doses can change half life. Saturated Enzymes
What is a Selective COX 2 NSAID and what is its half life?
Celecoxib - 11 Hrs
What are the possible cautions with selective COX 2 NSAIDs?
Take a look at this.
Look at First 4 + Naproxen
What is the mechanism of Acetaminophen and does it have more of an effect on pain or inflammation?
Weak inhibition of prostaglandin formation in peripheral tissues, lacks anti-inflammatory and antiplatelet actions.
First metabolite, AM404, recently shown to **act on TRPV1 receptors on terminals of C fibers **in the spinal dorsal horn and to some extent on endocannabinoid receptors in the brain to **exert analgesic effects. **
How does the adverse effects of Acetaminophen compare to NSAIDS?
Less GI distress.
Overdose can be fatal due to highly hepatotoxic metabolites however need around 10-15 grams.
What is the antidote to Acetaminophen overdose?
N-Acetylcysteine
What is Neuropathic Pain and its characteristics?
What is the Pathophysiology of Neuropathic Pain and possible treatments?
The primary afferent neurons are hyperactive discharging spontaneously.
Overtime the neurons in the dorsal root ganglia and dorsal spinal horn change. -> Na and Ca Channels Increase.
Treatments
Na Blockers - Carbamazepine/Lamotrigine
Ca2 Blockers - Pregabalin/Gabapentin
Serotonin and NE Reuptake Inhibitors - Tricylcic Antidepressants (Nortriptyline/Amitriptlyine)
And
Duloxetine/Venlafaxine
What is Trigeminal Neuralgia and what are some possible treatments?
What is Fibromyalgia and are some possible treatments?
What is Gout?
What is the Acute Treatment of gout?
Goal - Reduce Inflammation
NSAIDS and Corticosteroids - Predisone
Cholchicine - Reduce inflammation and phagocytosis by leukocyte migration via disaggregation of microtubules.
What is the long term treatment of Gout?
Goal - Decrease Uric Acid
Allopurinol - Blocks Hypoxanthine Oxidase
Probenecid - Increase Urate excretion by kidneys by competing with uric acid for absorption via renal tubular acid transporter which decreases urate reabsorption.
Could also use medication to increase kidney excretion.
Normally 90% urate reabosrbed.
