NSAIDs
Medicine Bms 6404 with Rowe at University of Florida
About this deck
By: Philip Gilbo
Created: 2012-04-02
Size: 35 flashcards
Views: 4
Created: 2012-04-02
Size: 35 flashcards
Views: 4
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Where is Cox-2 usually expressed?
Blood vessels, kidney, heart and brain. Cox-1 is more universal (GI + kidney + muscle, platelets)
What are the two pathways arachidonic acid is involved in?
COX pathways and Leukotriene pathways (explains why asthma patients doesn't take aspirin)
What do leukotrienes do?
LTB4 - calls neutrophils
LTC4/LTD4 - bronchiolar constriction, increase capillary permeability
What parts of inflammation do NSAIDs help with?
The acute phase (vasodilation, edema and pain). Corticosteroids affect all stages of inflammation.
In order to achieve an anti-inflammatory effect from an NSAID, how much of a greater dose do you need to give compared with just getting its anti-pyretic/analgesic effect?
~2x as much. These drugs are more effective at fever reduction and pain relief.
Under a low pH situation, will an acidic drug be charged or neutral?
It will be neutral -- it gets protonated aka loses its negative charge.
How do NSAIDs act as analgesics?
The inhibition of COX2 prevents the sensitization of nociceptors to pain. Unlike opioids, these do not alter sensory perception and are ineffective against certain types of pain.
How do NSAIDs get their anti-pyretic effect?
IL-1 will stimulate prostaglandin production which will raise temperature in the hypothalamus. NSAIDs inhibit this through COX-2.
What are NSAID's effects on platelets?
If you block COX-1, you block thromboxane which inhibits platelet aggregation.
Why would Cox-2 inhibitors increase aggregation via thromboxane?
COX-2 derived PGI2 inhibits platelet aggregation; if you block this, then you have increased aggregation from the COX-1 pathway.
Why are proteins esepcially sensitive to irreversible inhibition of COX by aspirin?
Platelets don't make new COX enzymes.
What is a biological antagonist to Ang II's vasoconstrictive effects?
Cox-2 derived PGI2; So if you inhibit COX-2, then you lose the vasodilatory effect of PGI2 and you get a slight raise in blood pressure from Ang II acting unopposed.
What are the effects of COX-2 derived PGs on atherosclerotic plaques?
On the 1 hand, inhibition of Cox-2 can slow development of atherosclerosis. On the other hand, COX-2 derived PGE2 can promote stabilization of plauqes; therefore inhibition by NSAIDs will elad to destabilization of plaques.
What are the important effects of COX-1 and 2 derived PGS on the kidneys?
PGE2 will decrease sodium resorption
PGI2 will increase potassium secretion, increase renal blood flow and GFR (elderly and volume depleted). Will lead to kidney ischemia in some cases
So - NSAIDs tend to promote sodium retention, peripheral edema and can therefore increase BP; counteracts the effects of many anti-hypertensives.
PGs have what effect on the GI?
Inhibit acid secretion, enhance mucosal blood floow
promote intesntinal secretion of cytoprotective mucus
All COX-1
What are the effects of NSAIDs w/COX-1 inhibitory activity?
Gastric distress
Gastric bleeding
Sudden acute hemorrhage
Why would you not use PGs in pregnancy?
PGs are involved in the initiation and progression of labor and delivery. Block them = prolong gestation.
What are the effects of NSAIDs on the respiratory system?
at high levels, have effects that are COX independent -- uncoupling of oxidative phosphorylation w/ increased CO2 production ==> hyperventilation. Even higher doses ==> depression of respiration.
What are the salicylates?
Aspirin - irreversible inhibition of COX;
Salicyclic acid - Reversible inhibition of COX
Methyl Salicylate - topical presentations only
Diflunisal - no notes.
What is special about the metabolism of Salicylate?
It is a z-order reaction.
What is salicylism?
mild: headache, dizziness, sweating, nausea. Severe: cns disturbance, skin eruptions, nausea, respiratory alkalosis followed by combined acidosis
Name 2 non-selective/non-salicylate COX-1 and COX-2 inhibitors
Ibuprofen and Naproxen (Aleve)
Name a COX-2 selective inhibitor
Celecoxib (celebrex); Potential cardiovascular risk (^BP, ^ Thrombus, ^ destabilization of atherosclerotic plaques)
What is the use of acetaminophen?
Anti-pyretic and analgesic only. not anti-inflammatory effects! We're not sure what the mechanism is, but we do know it does not cause GI distress or effect platelet function.
Where is tylenol metabolized?
The liver; high doses = hepatotoxicity.
How can you treat an acetaminophen overdose?
With acetylcysteie -- a sulfhydryl agent that replensihes glutathione levels.
What type of pain would prompt you to use a combination NSAID/Opioid?
Acute pain. Don't use this to treat chronic pain
What is the first line treatment for rheumatoid arthritis?
NSAIDs
What is the difference in acute gout therapy vs. chronic gout therapy?
Acute - target pain and inflam
Chronic - target uric acid production/excretion
What drugs would be used in acute therapy for gout?
NSAIDs -- but NOT ASPIRIN! Asp tends to inhibit uric acid secretion.
Colchicine - inhibits microtubule polyumerization, mitosis and cytokinesis (thought to inhibit leukocyte migration)
What drugs would be used in chronic therapy for gout?
Allopurinol/febuxostat - inhibits enzymatic production of uric acid via xanthine oxidase
Probenicid - Inhibits renal tubular reabsorption of uric acid thereby promoting excretion.
What are Triptans?
Serotonin receptor agonists on intracranial BV. Restores normal blood flow dynamics. May cause coronary artery vasospasms, transient MI, arrhythmias - don't give to a heart disease patient.
Use for moderate migraines.
What would you use for severe migraine?
Triptans, ergot alkaloids, antiemetics.
What woudl you use to treat moderate migraines?
Triptan or ergot alkaloids or opioids.
What would you use to treat a mild migraine?
NSAIDs
About this deck
By: Philip Gilbo
Created: 2012-04-02
Size: 35 flashcards
Views: 4
Created: 2012-04-02
Size: 35 flashcards
Views: 4
About StudyBlue
STUDYBLUE makes things that make you better at school.
Things like online flashcards with photos and audio.
Things like personalized quizzes and friendly reminders about when (and what) to study next.
Think of it as a digital backpack™: access to all of your study materials online and on your phone.
STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.
“I have been getting MUCH better grades on all my tests for school. Flash cards, notes, and quizzes are great on here. Thanks!”
Kathy
Kathy