Table of Contents
- 1 Which NSAIDs cross the blood brain barrier?
- 2 What is the mechanism of action of NSAIDs?
- 3 Do pain medications cross the blood-brain barrier?
- 4 How is NSAIDs metabolized?
- 5 How do NSAIDs inhibit prostaglandin synthesis?
- 6 What are the risks of taking NSAIDs?
- 7 How are NSAIDs bound to plasma proteins?
- 8 How important is plasma protein binding in drug development?
Which NSAIDs cross the blood brain barrier?
Conclusions: Free ibuprofen, flurbiprofen, and indomethacin rapidly cross the BBB, with ibuprofen exhibiting a saturable component of transport. Plasma protein binding limits brain NSAID uptake by reducing the free fraction of NSAID in the circulation.
Are NSAIDs highly bound to plasma proteins?
The NSAIDs are highly bound to plasma proteins (mainly albumin), which limits their body distribution to the extracellular spaces. Apparent volumes of distribution of NSAIDs are, therefore, very low and usually less than 0.2 L/kg.
What is the mechanism of action of NSAIDs?
The main mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. [9] The therapeutic effects of NSAIDs are attributed to the lack of these eicosanoids.
What organs are damaged by NSAIDs?
However, data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications.
Do pain medications cross the blood-brain barrier?
Pharmacological treatment of peripheral inflammatory pain requires that therapeutics attain efficacious concentrations in the brain. This objective requires that analgesic drugs (i.e., opioids) are able to successfully cross the BBB.
Does celecoxib cross the blood-brain barrier?
Celecoxib was shown to reduce glioma cell viability by inducing DNA damage, leading to p53-dependent G1 cell-cycle arrest and autophagy (10). However, the use of celecoxib in patients with glioblastoma has seen mixed results, due in part to the low potential of the drug to cross the blood–brain barrier (BBB) (11, 12).
How is NSAIDs metabolized?
Most NSAIDs are absorbed completely, have negligible first-pass hepatic metabolism, are tightly bound to serum proteins, and have small volumes of distribution. NSAIDs undergo hepatic transformations variously by CYP2C8, 2C9, 2C19 and/or glucuronidation.
How are NSAIDs distributed?
NSAIDs are highly bound to plasma proteins, specifically to albumin (>90\%). The volume of distribution of NSAIDs is low, ranging from 0.1 to 0.3 L/kg, suggesting minimal tissue binding. NSAID binding in plasma can be saturated when the concentration of the NSAID exceeds that of albumin.
How do NSAIDs inhibit prostaglandin synthesis?
NSAIDs generally work by blocking the production of prostaglandins (PGs) through the inhibition of two cyclooxygenase enzymes. PGs are key factors in many cellular processes, such as gastrointestinal cytoprotection, hemostasis and thrombosis, inflammation, renal hemodynamics, turnover of cartilage, and angiogenesis.
When are NSAIDs contraindicated?
NSAIDs are contraindicated in patients with renal insufficiency, peptic ulcer disease, gastritis, bleeding diatheses, or aspirin hypersensitivity. These agents must be used on a regular basis (as-needed use is not adequate in most patients) for several days.
What are the risks of taking NSAIDs?
NSAIDs can cause severe or life-threatening gastrointestinal (GI) bleeding and ulcers in some people. NSAIDs have also been linked to a higher risk of strokes, heart attacks, and heart-related deaths, especially when used for a long period of time.
What are the long term effects of taking NSAIDs?
Older adults commonly take nonsteroidal anti-inflammatory drugs (NSAIDs) chronically. Studies of older adults show that chronic NSAID use increases the risk of peptic ulcer disease, acute renal failure, and stroke/myocardial infarction.
How are NSAIDs bound to plasma proteins?
NSAIDs are highly bound to plasma proteins, specifically to albumin (>90\%). The volume of distribution of NSAIDs is low, ranging from 0.1 to 0.3 L/kg, suggesting minimal tissue binding. NSAID binding in plasma can be saturated when the concentration of the NSAID exceeds that of albumin.
How do NSAIDs affect platelets?
Aspirin and nonaspirin nonsteroidal antiinflammatory drugs (NSAIDsJ inhibit platelet cyclooxygenase, thereby blocking the formation of thromboxane A2• These drugs produce a systemic bleeding tendency by impairing thromboxane-dependent platelet aggregation and consequently prolonging the bleeding time.
How important is plasma protein binding in drug development?
High concentration of proteins in plasma and the propensity of numerous drugs to bind to them have led drug development groups to recognize the importance of plasma protein binding (PPB) in modulating the effective drug concentration at pharmacological target sites.
What factors affect the pharmacokinetics of NSAIDs?
Hepatic or renal disease can alter NSAID protein binding and metabolism. Some NSAIDs with elimination predominantly via acylglucuronidation can have significantly altered disposition. Pharmacokinetics are also influenced by chronobiology, and many NSAIDs exhibit stereoselectivity.