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114 Cards in this Set
- Front
- Back
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With ASA, what does it inhibit more, cox 1 or 2?
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Small doses only inhibits 1, in large doses inhibits 1 and 2 (81 heart vs 650 for pain)
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what types of pain meds does ceiling affect apply to?
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It happens to all non-opoid and opioid pain meds
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Why, chonically, can we get by with only 81 mg of ASA for heart?
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Because at 81 mg, it has efficacy irreversibly affecting the platlet
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What good will happen if you block prostaglandin?
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Lower inflamation, lower sensitivity to spinal neurons
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What is Arachidonic acid?
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A fatty acid that is involved in cellular signaling, as a second messanger
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What does ASA do in the body?
(mention signal molecules.) |
Inhibits cox to prevent the conversion of arachidonic acid to other signal molecules (prosterglandins, thromboxines)
So it goes: Cox, arichdonic acid, ptg/thrmbn's |
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What do prostaglandins do?
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Constrict or dialate vascular smooth musc, regulate inflamation, sensitize spinal nerves to pain
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What do thromboxines do?
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Vaso constrict, is a potent hypertensive agent, facilitates platlet agarigation
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What do prostaglandins and thromboxanes do in the body?
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Protect gastric mucosa, prevent clotting, maintain renal blood flow
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If you block both cox 1 and cox 2, what do you get (good vs. bad)
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Good: less pain and inflamation; Bad: renal vaso cnstriction, lest production of GI mucosa protectant, anti-platlet activity (bleeding risk), higher BP
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ASA to plt reversible?
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No. Must wait for new platlets to be made. That platlet no longer forms thromboxane
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What about NSAIDS and thomboxane inhibition?
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They inhibit it only while in contact. Reversible
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What about NSAIDS, ASA given in adition to other anti-coagulants?
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Enhances the effect.
?potentiate? |
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Does ASA touch every plt?
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No, but touches a good amount
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What is the life span of a platlet?
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5-7 days
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What is the life span of NSAID action of platlet? Or, when do we D/G pre-op
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24 hours
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What are the 4 non-opioid Analgesic catagories?
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ASA, salicylate salts, NSAIDS, APAP
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Which of the non-opoid analgesics are anti-inflamatory?
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All but tylenol. Tylenol is unique pharmacodynamically in that it does not decrease inflamation
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What is a common reaction to ASA?
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Hypersensitivity
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What do ASA and salicylate salts have in common?
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Almost idential structurally
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Which NSAIDS do we need to know?
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Celecoxib (celebrex) Ibupropen (motrin),
Naproxen, Rofecoxib (vioxx) |
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What is cytotec? What does it do?
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It is a prostaglandin analogue.
It works to protect the GI tract from NSAIDS and ASA |
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What are the doses for ASA?
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650 pain, 1300 inflamation (RA), 81-325 MI
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What are the adverse effects of ASA?
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GI dist, bleeding most common. Renal insuf, fluid ret, hypersensitivity (esp. with Asthma), tinnitus, Reyes in kids <12 y.o.
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What about salicylate salts? What do they do? How are they unique?
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Analgesic, anti-fever. Not as much anti-inflamation. Less plt. interaction
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Salicylate salts vs NSAIDS?
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NSAIDS are much easier to use, more effective
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What are the SE's with S.S.?
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GI, tinnitus, Renal insuf, hypergens, ?reys. Pretty much, same as ASA, less bleeding
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What is the method of action of NSAIDS?
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Inhibition of cyclooxygenase
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Do NSAIDS inhibit cox 1 or 2?
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They inhibit both.
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What do you get when you lose GI mucosa and plt. Thromboxane?
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Higher risk for GIB
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Can asthma pts be allergic to NSAIDS?
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Yes, just not as much
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On pH scale, where do NSAIDS fall?
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They are a weak acid
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Can you do away with the GI risk giving an NSAID parenteral?
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A little, because it is a weak acid. However, it still inhibits GI prostaglandins
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Does taking NSAID with food help ulcer risk?
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No. It is sm. intestine you are worried about. Weak acid = irritation of s.i.
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What is risk and limitations with toradol?
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It is very potent. Can only use it for 5 days. Otherwise, the risk of platlet, GI and renal is much higher than any other NSAID
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What is a pro-drug?
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A drug that is metabolized to something else that is active. The active form (metabolize) produces the pharmacodynamic effect
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How does Relatin work as a pro-drug?
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It is an NSAID that is a pro-drug. There is no activity until it is absorbed, metabolized and converted to a weak acid later.
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What is the appeal of Relafen?
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Less GI distress
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Does Relafen lower GIB risk? Explain
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No. It still inhibits prostaglandins. This prostaglandin inhibition process is a systemic property
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If you are a pro-drug metabolized by the CYP system, and a CYP inducer is added, what will happen to S.C.? Explain
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It will increase. Why? Because the active form is brought out by metabolism
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What will a CYP inhibitor do to the S.C. of a pro-drug?
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Lower the S.C.
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Why don't we give misoprostol (cytotec) to everyone?
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It is poorly tolerated. Common GI dist. Plus, is preg. Category X
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What else is cytotec used for besides increasing GI mucosa?
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Uterine contractions during labor (vaginally)
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Chemically, what is misoprostol called?
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A prostaglandin EI Analogue. It is just like prostaglandin. It raises GI mucosa.
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If you are worried about BP with an NSAID, should you be giving a cox 2?
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No. Still has effect on BP (renal bld. flow)
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Will a cox 2 ever inhibit 1?
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In high doses, yes. Whenever you go up on doses (or stay on for a while) you lose specificity
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If you could have the perfect NSAID, what would you have, chemically? (effects)
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The desensitizaiton of pain and decreased inflamation with inhib of prostaglandin, without the high BP, Renal constriction, or lower in GI mucosa
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Cox 2 inhibitors are selective only for the ® side of the diagram. What does this mean for chemical response?
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Inhibits prostaglandin only
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What does thromboxane do to BP, vasculative function?
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It is a potent vaso-constrictor. It also facilitates platlet aggregation
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So what happens, over time, when you are on a cox 2 inhibitor?
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Prostaglandins only are inhibited and thromboxanes are not. Thye body is in a pro-thromboxane state.
If yo take away prostaglandin but leave thromboxane, you get the effects of thromboxanes still. To some extent, there is increased vasoconstrict, increase plt activation potential. |
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What does prostaglandin do to vaso and plat, as opposed to thromboxane?
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It can both dialate and constrict, and can both clamp and un-clamp. So it helps regulate clotting and BP
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Could there be an opportunity for use of an IV cox 2? Explain
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Yes, there would. And the reason why, is, it would only be used in an acute setting (like toradol). It would be safe
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What confounded the initial cox 2 studies, making the celebrex group have more CV side effects over 12 months?
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They were allowed to take ASA and the vioxx group (RA pts) were not allowed to
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When the data regarding vioxx was later examined retrospectively, what was found?
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OA group had modest raise in heart SE's and RA group (devoid of ASA) had sig. higher in SE's (heart)
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Theory of inbalance with cox 2:
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Homeostasis was disrupted
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What does cox 2 inhibition have to do with thromboxane?
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By inhibiting only prostaglandins, it promotes a pro-thromboxane effect (vasoconstriction, higher coag)
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When you give someone a cox 2 inhibitor, what gets taken away? What shift occurs?
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Prostacyclin gets taken away. This shifts the tabels toward thromboxane
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What about other NSAIDS? Is there MI/stroke risk with those too?
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There is some risk for MI/CVA/BP disorders with all NSAIDS, but more so with cox 2 inhibitors
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What was the approve study?
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A study concerning vioxx and colon polyp-profylaxis patients. These patients don't take ASA. Risk for MI or stroke was higher (still not huge). This happened with continued use
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How did the risk of the non-ASA pts in the approve study compare with the ASA study (OA pts)?
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Almost twice the risk for MI or CVA if used long term
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What happened after approve study?
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Merk removes vioxx. Big fall out. FDA, industry investigated by congress
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What did the FDA vote on cox 2's?
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To keep celebrex and vioxx. Celebrex is still on the market
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What about the higher GIB risk study in Canada?
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This may have been skewed because they could have been choosing to use cox 2's with higher risk GIB pts
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What else can you do to protect GI tract from non-narcotic pain meds?
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PPI
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What is the mechanism of action of APAP?
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Poorly understood
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What is max APAP?
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4g/daily
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APAP and cumodin?
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? Interaction - not clear
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What does N-acetylcysteine do?
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Binds with tylenol metabolite and neutralizes toxic effect
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What is blood test to plot APAP/mucemystresp
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Rumak/matthew
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What are the differences between opioid and non-opioid analgesics?
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No CNS involvement. With opioids there is a ceiling effect, tolerance and dependence
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With opioids, tolerance develops to almost all SE's except 1:
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Lower in GI motility
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What receptor do the majority of narcotics bind to?
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The mu (µ) receptor
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How does mu receptor binding work?
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Narc binds to 1 or more of these receptors, just like natural endorphins do. (With tolerance, receptor lowers into cell, to come back later)
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What kinds of addiction are seen with opioids?
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psychological and physical
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Pharmacodynamic effects of opioids:
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Analgesia, euphoria, miosis, seizures with high doses
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What is stimulated when opioids cause N and V?
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CTZ
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What is the GI effect with opioids?
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Delayed gastric emptying, constipation. This is a peripheral effect
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Discuss vasodialation, MS vs fentanyl
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Mediated partly by a histamine response. Fentanyl less
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what is happening with opioids and higher bilary tract pressure?
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Constriction of sphincter of oddi
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List more potent morphine/codine derivitives
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morphine, hydromorphone, oxycodone
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List less poten morphine/codine derivitives
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Codine, vicodin
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Almost all M/C derivitives are met by which pathway?
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1st pass metabolism
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Which systems (enzyme) metobolizes m/c derivatives?
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CYP 450
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Can you give one m/c derivitive (of the 5) to a pt who has an allergy to another m/c derivitive?
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No. They are too similar in structure - do not give one of the others to a patient with true allergy to m/c derivitive.
There are opioids you could give, but not ones structured like these. |
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What is duration of ms?
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4-6 hrs
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Describe codine's analgesic activity (str vs w.)
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Weak
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Describe codine's metabolism:
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Hepatic, via conjugation and CYP 450 system. Metabolites include morphine. Genetic polymorphisms result in variable interpatient response (someone with active metabolite can OD)
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Duration of action for codine:
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Same as morphine
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In the case of the old man who OD's from only 25 TID of codine, explain what happened:
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He had a genetic overexpression of CYP450 2D6. Had some CRI, plus was on Emycin (a CYP 450 3A4 inhibitor) (codine is party metabolized by 3A4)
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In which type of pts is codine not effective?
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Pts who do not have the enzyme CYP 2D6. Over-producers are sensitive
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How much codine is usually metabolized to morphine?
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10 percent
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When is hydromorphone indicated?
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As an alternative to morphine in the elderly, and those with renal impairment
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How strong is hydromorphone comp. to morphine?
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5x
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How is hydromorphone cleared?
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Primarily conjugated in the liver
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what is the Duration of action of hydromorphone?
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Same as MS
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Why do we need only small doses of fentanyl?
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It is lipophillic. It travels easily through c.m. Extremely potent
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When do you consider alternatives to morphine and related agents?
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Lack of efficacy, MS change, different D.O.A.
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What is DOA of methadone?
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Long. 1/2 life 15-40 hours
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How is methadone distributed/metabolized?
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CYP 450 system. High protein binding and tissue distribution. Long acting, even when crushed
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When is methadone indicated? Who do you use it with?
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Opioid w/d, chronic pain
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Can you give methadone with opioid allergy?
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Yes
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What is propoxyphene a derivative of?
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Methadone, but less potent and shorter acting
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Propoxyphene compared to codine?
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1/2 as potent
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What are the risks with propoxyphene?
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Hepatic/renal elimination - metabolite can accumulate and cause cardiotoxicity
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Name 2 synthetic opioids:
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Meperidine, fentanyl
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How is po demerol metabolized?
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1st pass
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What can happen with long term use of Demerol?
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Accumulation of active metabolite nor-meperidine. Can cause tremors and seizure
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Why is Atropine added to meperidine to make diphenoxylate (lomotil)?
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To discourage abuse
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Does immodium penetrate into CNS?
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No
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ASA, @ lower dose, is selective for:
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Cox 1
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What happens when you go higher on ASA with MI? Why not give more?
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Risk vs. benefit. When you lose selectivity risk goes up. You disrupt the balance between prostaglandin and thromboxane
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How much more potent is fentanyl to morphine?
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80-100x
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What are some good things about fentanyl vs other opioids:
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Less histamine release, better BP control
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When do you look to fentanyl first as an analgesic?
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NEVER outside the ICU. Opioid naïve patients will die from it.
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