Unit 04: treatment of Inflammation Flashcards
what are typical pharmacological interventaions for treatment of inflammation
non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids
what is aspirin
- inhibition of prostaglandin synthesis
- oldest NSAID drug and frequently used to treat various conditions
what are NSAIDs
family of chemically dissimilar drugs iwth antipyretic, analgesic and anti-inflammatory properties
-mechansims of actions invovled inhibition of COX-1 and COX-2 enzymes
*COX-1 is constitutive (it is present and needed in many tissues)
- COX-2 i inducible in inflammatory cells but constitutive in kidney and astrointestinal mucosa
what do most NSAIDs inhibit
both COX-1 nd COX-2
*COX enzymes are responsible for catalyzing the formation of prostaglandins from arachidonic acid, therefore NSAIDs inhibit COX-1 and -2 at this stage.
what are the adverse effects of NSAIDs? why are they expected
- prostaglandins are cytoprotective (so effects are due to inhibition the protection)
- effect sotmach (gastric ulcers) and decrease blood flor to kidney causing impaired renal function adn hypertension
describe effect of NSAIDs on the stomach
- prostaglandins (PGE2 and PG12) reduce acid secretion by hastric parietal cells, dilate blood vessels in gastric mucosa and increase mucus and bicarbonate secretion by gastric epithelium
- NSAIDs causing a decrease in prostaglandins by COX-1 inhibition in gastrointestinal tract will decrease blood flow and increase acid production (PGI2) and decrase gastric mucus (PGE2)
- result = gastric ulcers
describe adverse effect of NSAIDs is the kidney
- in the kidney prostaglandins dilate blood vessels which increase perfusion of renal tissue
- NSAIDs causing a decase in PDE2 in kidneys decreases blood flow leading to ipmaired renal function and hypertension
influence of NSAIDs on clotting
- platelets contain only COX-1 and convert arachidonic acid to TXa2 which stimualtes aggregation or clotting
- Blocking COX-1 with aspirin helps reduce clotting and can prevent some myocardial infaractions
- in these patients excessive reduction of TXA2 can result in bleeding
what drugs preferentially inhibit cox-2? why is this desirable?
- Capfrogen, etodolac and meloxicam
- preferentially inhibit cox2 meaning less gastric ulceration/bleeding
what new drugs are more selective for COX-2
- Rofecoxib (Vioxx) and celecoxib (celebrex)
- now apparent that COX-2 is also important in the gastrointestinal mucosa
- inhibition of COX-2 in he presence of gastric infection or Inflammatory bowel disease may be exacerbated by any mucosal damage
- Continued use in these situations may also lead to bowel perforation and even death
*NSAIDs that selectively target COX-2 produce fewer adverse gastrointestinal effects but only in patients that do not initially present with gastrointestinal disease.
NSAIDs and gastrointestinal disease
NSAIDs that selectively target COX-2 produce fewer adverse gastrointestinal effects but only in patients that do not initially present with gastrointestinal disease.
- bc inhibition of COX-2 in presence of gastric infection or inflammatory bowel disease may exacerbate mucosal damage - can cause bowel perforation and even death
ADME of NSAIDs
- usually administered and absorbed though oral or injectible routes
- majority (99%) is bound to protein
- metabolism invovles depativ conjugation and they are eliminated by the kidneys durign renal filtration and secretion
Describe aspirin
- aka acetylsalicyclic acid
- present in dark of certain willow trees
- irreversibly inhibits COX-1 and -2
- provides anti-inflammatory, antipyretic and analgesic effects
- effective for musculoskeletal and cutaneous pain but poor for visceral or internal organ pain
what is the most common adverse effect of aspirin
- bleeding due to role of aspirin in platelet inhibtion
- even with ordinaty doses, individuals can lose 3-8 mL of blood/day after taking aspirin
- in veyr rare cases Reye’s Syndrome might result: severe condition most often seen in children recovering frmo a viral infection and fever- can result in fatal hepatic necrosis
aspirin and children
- more risky bc in very rare cases can cause Reye’s Syndrome (seen in children recovering from a viral infection and fever, and can result in fatal hepatic necrosis)
- children with chicken pox or toher virus-like illnesses are cautions against administering aspirin or other salicylates
- most cases of eyes syndrome associated with children who took aspirin following a fever in the preceding week
- currently aspirin is not recommended for children and teenagers with a fever - this has sig dec instance of reyes cases
what is ibuprofen
advil
- commonly utilized NSAID with anti-inflammatory, analgesic and antipyretic properties
- inhibits both cox-1 and cox-2
what are adverse effects of NSAIDs
- main adverse effect is gastric ulceration but less intense compared to aspirin
- patients that require NSAIDs for chronic conditions like osteoarthritis are advised to take ibuprofen over aspirin
- following chronic high doses, myocardial infarction risk may be elevated but it appears to be less of a risk than selective COX- inhibitors
what is celecoxib?
- selective COX-2 inhibitor
- approed for osteoarthritis in order to reduce the inflammatory action in the joints
- compared to other NSAIDs, celecoxib has poor to negligible analgesic effects and no effect on platelets or bleeding becuase COX-2 is not invovled in clotting
describe concerns of Celecoxib
- reduced blood flow to the kidneys that can reduce renal function and eventually cause hypertension and intravascular blood clotting
- these events put a patient at an increased risk of stroke and myocardial infraction or heart attack
*patients on celecoxib should be monitored duriing regualt use and should not be used if patients have kidney or cardiovascular disease
describe acetaminophen
- drug used due to antipyretic and analgesic properies that inhibits prostaglandin synthesis in the central nervous system
- no longer considered an NSAID because it has little peripheral activity and therefore poor antiinflammatory effect and no effect on blood clotting
