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69 Cards in this Set
- Front
- Back
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What type of activities do NSAIDS have?
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antipyretic
analgesic anti-inflammatory |
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What do NSAIDs do?
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inhibition of Cyclooxygenase (COX)
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How do NSAIDs work?
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They inhibit COX which leads to inhibition of synthesis of prostaglandins and thromboxanes
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What are the types of COX?
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COX-1: involved in homeostasis
COX-2: generates prostanoids for "housekeeping" |
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What induces COX-2?
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Induced by growth factors, tumor promoters, cytokines
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Where is COX-2 constitutive?
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Kidney and Brain
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What is the primary source of vascular prostacyclin?
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Endothelial COX-2
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What does Kidney COX-2 generate?
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prostanoids important for normal renal development and function
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What is the action of vascular prostacyclin?
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Vasodilation and inhibits platelet aggregation
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Which COX enzyme is responsible for the inflammatory actions that NSAIDs treat?
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COX-2
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Which COX enzyme has a gastric protective function?
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COX-1
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What is Celecoxib?
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COX-2 inhibitor
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How does Aspirin work?
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Irreversibly acetylates cyclooxygenase
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Describe the Mechanism of Action of Aspirin on fever and inflammation.
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Antipyretic and anti-inflammatory effects due to blockade of prostaglandin synthesis at the thermoregulatory center of the hypothalamus and at peripheral sites
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what is TXA2?
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it is generated by platelets and induces platelet aggregation.
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What does Aspirin do?
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Inhibits TXA2 synthesis in platelets and PGI2 synthesis in endothelial cells.
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How does Aspirin inhibit platelet aggregation?
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Inhibits TXA2 synthesis in platelets. Platelets lack nuclei so therefore cannot synthesize new TXA2. The effects last the duration of platelet.
Also inhibits PGI2 in endothelial cells. Enodthelial cells have nuclei and can regenerate lost enzymes. |
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What is the role of PGI2 in clot formation?
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Synthesized by endothelial cells and inhibits platelet aggregation.
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What general actions on the kidneys do NSAIDs have?
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Decrease in renal blood flow
acute interstitial nephritis analgesis nephropathy |
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When do NSAIDs play a role in decreased renal perfusion?
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In persons with already compromised renal hemodynamics
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How do NSAIDs lead to decreased renal blood flow?
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In patients w/ compromised renal hemodynamics the kidney synthesizes PGE2 and PGI2 - both vasodilators.
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What does inhibition of PGE2 in the kidney lead to?
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increased Na and water retention.
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What does inhibition of PGI2 in the kidney lead to?
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hyperkalemia and acute renal failure
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What is Acute Interstitial Nephritis in relation to NSAID use?
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Type 1 hypersensitivity reaction leading to acute renal failure.
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What is Analgesic Nephropathy?
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chronic interstitial nephritis caused by prolonged and excessive analgesic use.
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What are some features of Analgesis Nephropathy?
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Renal Papillary necrosis
chronic interstitial nephritis --> progressive chronic renal failure |
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When are low doses of Aspirin used?
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to prevent ischemic attacks
unstable angina coronary artery thrombosis |
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When do NSAIDs do a better job of pain management than opioids?
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When the pain is due to inflammation.
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What are some conditions that NSAIDs are used for?
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Arthalgia, myalgia, gout, rheumatic fever, rheumatoid arthritis
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Do NSAIDs facilitate closure of a patent ductus arteriosus?
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Yes. PGE2 keeps the ductus arteriosus open.
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When are salicytates analgesic and when are they anti-inflammatory?
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Analgesic at low doeses
anti-inflammatory at high doses |
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What is recommended does of asprin for analgesia?
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Two 325-mg aspirin 4x day
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What is recommended dose of aspirin for anti-inflammatory use?
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45mg/kg/day divided in doses
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How is aspirin metabolized at low doses?
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hydrolyzed to salicylate and acectic acid by esterases in tissues and blood
Salicylate converted by liver into hydrosoluble conjugates (Phase II) that are excreted by kidney |
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What is the elimination kinetics of aspirin at low doses?
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First order w/ half-life of about 3.5 hours
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Aspirin may help reduce which type of cancer?
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Colon
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What happens when large doses of Aspirin are taken?
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conjugation enzymes become saturated and zero-order kinetics are observed
half life increase w/ dose increase |
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What transport system does salicytate use?
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the same one as uric acid
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what do low concentrations of salicytate have on uric acid secretion?
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they compete for the same transporter and uric acid secretion is reduced
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what do high concentrations salicytate have on uric acid secretion?
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high levels of salicytate compete with uric acid for reabsorption and increase uric acid excretion in the urine
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What are some adverse effects of Aspirin?
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GI - epigastric distress
Blood - prolonged bleeding time Hypersensitivity Reye's syndrome |
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How does Aspirin interact with the respiratory center?
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salicylates stimulate the respiratory center leading to hyperventilation and respiratory alkalosis
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What metabolic effects does Aspirin cause? (1/2)
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causes metabolic acidosis* by accumulation of acids as a result of:
1. salicylates are weak acids 2. salicylates impair renal function leading to accumulation of sulfuric and phosphoric acid *on high to toxic doses |
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What metabolic effect does Aspirin cause? (2/2)
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3. salicylates uncouple oxidative phosphorylation --> increased CO production --> increased glycolysis --> lipolysis and fatty acid oxidation --> KETONE BODIES
4. salicylates inhibit dehydrogenase in Krebs cycle --> increased levels of pyruvate and lactate |
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What is a consequence of acute salicylate overdose?
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mixed respiratory alkalosis and metabolic acidosis
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What is a consequence of prolonged high doses of salicylate?
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depresses the medulla
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What can toxic doses of salicylate lead to?
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central respiratory paralysis and circulatory collapse
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How are uric acid levels affected at doses of 2g of Aspirin or less per day?
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serum uric acid levels are increased
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How are uric acid levels affected at doses of greater than 4g of Aspirin per day?
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urate levels are decreased
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What are some other general adverse effects of NSAIDs?
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elevation of liver enzymes
hepatitis (rare) decreased renal function bleeding rashes asthma |
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What are Coxibs?
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selective COX-2 inhibitors
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what are the effects of Coxibs?
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analgesic, antipyretic, antiinflammatory
few gastrointestinal side effects |
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What is one thing that the Coxibs cannot be used for?
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they have no cardioprotective effect
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How is platelet aggregation mediated?
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COX-1
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What adverse effects can Coxibs cause?
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COX-2 is constitutively active in kidney - can lead to renal toxicities same as NSAIDs
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How do Coxibs contribute to a pro-thrombotic state?
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Endothelial cells have both COX-1 and COX-2 which produce PGI2 --> anti-platelet aggegation
Platelets only have COX-1 --> platelet aggegation there is less PGI2 and same TXA2 --> platelet aggregation |
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What is the Coxib not available in the US but used world wide?
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Etoricoxib
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What is Meloxicam
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COX-2 inhibitor but not as selective
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When are COX-2 inhibitors used?
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primarily in inflammatory disorders
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Which NSAIDs have the lowest risk of adverse GI effects?
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Celecoxib
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Which NSAIDs have a low risk of adverse GI effects?
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Ibuprofen
Aspirin Diclofenac |
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Which NSAIDs have a medium risk of adverse GI effects?
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Naproxen
Indomethacin |
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Which NSAIDs have a high risk of adverse GI effects?
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Piroxicam
Azaprpazone |
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Which NSAIDs have associations with serious hematologic reactions?
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Ibuprofen
Indotheacin |
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What type of drug is Celecoxib? And what adverse effect is a result of this?
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It is a sulfonamide and may cause hypersenitivity reactions - rash
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Which NSAID has been known to cause aplastic anemia
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Phenylbutazone
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What properties does Acetaminophen have?
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Analgesis and antipyretic
NO anti-inflammatory or anti-platelet |
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Does acetaminophen affect uric acid levels?
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No
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What is given to treat an Acetaminophen overdose?
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acetylcysteine - a sulfhydryl donor
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