Term
| What is the MOA of NSAIDS? |
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Definition
| *Blocking prostaglandin synthesis through inhibition of cyclooxygenase (COX) |
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Term
| Describe how prostaglandin is formed in cell damage. |
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Definition
| *Damaged cell membranes release eicosanoids, including arachadonic acid, that are broken down by either the cyclooxygenase (primarily effected), lipoxygenase, or cytochrome p450 enzyme systems. |
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Term
| Describe how prostaglandins cause pain. |
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Definition
| *The cyclooxygenase system produces prostaglandins that sensitize nociceptors to respond to normally non-noxious stimuli by altering sodium channel permeability and promoting their response to other inflammatory mediators. |
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Term
| How do NSAIDS interfere with prostaglandins? |
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Definition
| *NSAIDS by inhibiting prostaglandin's effects inhibit peripheral nociceptor stimulation and thus decrease pain perception |
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Term
| Which COX is constituitively expressed (always present) in all tissues? |
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Definition
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Term
| What are the main functions of COX-1? |
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Definition
*Essential for platelet aggregation
*Controls renal hemodynamics and GFR
*Serves as a gastric cytoprotector- defense and repair |
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Term
| Which COX both initiates and resolves pain and inflammation and is inducible? |
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Definition
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Term
| What functions does COX-2 have? |
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Definition
*Primarily responsible for many of the therapeutic benefits of NSAIDS.
*Directly regulated by feedback from prostaglandins through their influence on cellular cAMP levels
*Effects salt and water retention/excretion
*Steroids modulate this enzyme |
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Term
| What does COX break down into? |
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Definition
*Prostaglandins
*Thromboxane
*Prostacyclin |
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Term
| What are prostaglandins and what do they effect? |
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Definition
*Potent hormone-like unsaturated fatty acids that act on target organs
*Effects- changes in vasomotor tone, capillary permeability, smooth muscle tone, platelet aggregation, endocrine and exocrine function
*Modulates vasoconstricting effects of hormones such as AT2, NE, and Vasopressin |
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Term
| What are prostacyclins and what do they do? |
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Definition
*Prostacyclins are synthesized by vascular endothelium
*Powerful vasodilator and inhibitor of platelet aggregation
*Affects renal homeostatic mechanisms- if production is blocked, hyperkalemia and acute renal failure can result |
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Term
| What is thromboxane and what does it do? |
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Definition
*Causes vasoconstriction (Smooth muscle) and platelet aggregation
*TXA(2) inhibitors and synthesis inhibitors have been developed for cardiovascular indications |
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Term
| What is a product of lipoxygenase? |
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Definition
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Term
| What does metabolism of arachadonic acid by lipoxygenases result in the production of? |
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Definition
*Hydroxyl derivatives
*Leukotrienes |
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Term
| What cells are leukotrienes produced from? |
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Definition
| *Inflammatory cells: Basophils, mast cels, eosinophils, macrophages |
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Term
| What are certain leukotrienes associated with? |
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Definition
| *Potent bronchoconstriction |
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Term
| How do NSAIDS and leukotrienes interact? |
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Definition
| *NSAIDS do not inhibit lipoxygenases, thus do not decrease production of leukotrienes. |
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Term
| What are the three contraindications for use of NSAIDS? |
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Definition
*Allergy
*Late pregnancy
*Renal Failure (Can cause CHF like symptoms) |
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Term
| What are the five relative contraindications of NSAID use? |
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Definition
*Peptic ulcer disease
*Hypovolemic states such as
-CHF
-Cirrhosis
-Prolonged NPO status
*Previous thrombosis/any blood dyscriasis
*Aspirin-sensitive asthmatics
*Current steroid use |
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Term
| What are drug interactions that can occur with the use of NSAIDS? |
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Definition
*Indomethacin- can induce digitalis tox
*Hypoglycemia may occur
*Antacids may increase excretion of salicylates
*ASA+Nitroglycerine may cause unexpected hypotension
*Blunting antihypertensive effects of diuretics, B-blockers, or ACE-Inhibitors. (may be r/t increase in Na+ retention and PVR)
*Can displace coumadin or other anti-coagulants increasing blood levels
*Can reduce diuretic response
*Prolonged apnea following NSAIDS and NDMRs reported |
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Term
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Definition
*Irreversibly inhibits COX activity in platelets for 5-7 days
*Results in blockade of prostaglandin |
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Term
| what is a propionic acid derivative? |
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Definition
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Term
| What is a para-aminophenol dervative? |
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Definition
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Term
| What is an acetic acid derivative? |
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Definition
| *Heteroaryl acetic acids: Ketorolac (Toradol) |
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Term
| What properties does torodol possess? |
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Definition
*anti-inflammatory
*Analgesic
*Antipyretic |
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Term
| What is the onset and DOA of toradol? |
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Definition
*Onset: 30 minutes
*DOA: 4-6 hours
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Term
| What is the maximum effect and the half life of toradol? |
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Definition
*1-2 hours after IV or IM is max effect
*Half life: 5.5 hours |
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Term
| What % of toradol is protein bound and how is it metabolized and excreted? |
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Definition
*99% Protein bound
*90% excreted in urine, 6% in feces
*Metabolized in liver |
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Term
| How many mg of Morphine is 30mg of toradol equivalent to? Demerol? Fentanyl? |
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Definition
*6-12mg of Morphine
*50-100mg of Demerol
*100mcg of Fentanyl |
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Term
| What are the advantages of use of toradol? |
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Definition
*Beneficial in pats with respiratory disease, obesity, and those with a history of drug abuse
*MAC, BP and ventilation are NOT affected
*Side effects of opiates are not seen: n/v, resp depression, increase in biliary tract pressure, decreased bowel function
*Less opioid needed if used in combination therapy |
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Term
| What are the general side effects of NSAIDS? |
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Definition
*GI: Increased gastric acid and pepsin secretion with a decreased mucus secretion. Excess H+ penetrates the gastric mucosa and damages blood vessels
*Hematological:Platelet function should be assumed to be decreased for 1 week following ASA therapy and 3 days for all other NSAIDS.
*Renal: vasodilation leads to increased RBF and decreased proximal tubular Na+ reabsorption (Na retention and edema). Decreased renin release. Nephrotoxicity.
*Hypersensitivity: Bronchospasm, laryngeal edema, hypotension- Most susceptible are ASA-sensitive asthmatics. Steven Johnson's Syndrome.
*CNS: stimulation with salicylate overdose. Altered mood and or cognition
*Hepatic: Elevation of LFTs
*CV: BP control can be hindered in pts taking ACEI, diuretics, or BB. Increased risk of CHF.
*Respiratory: ASA-sensitive asthmatics
*Orthopedic: Bone remodeling may be inhibited.
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