Anti-inflammatory (NSAIDs) Drugs, Pharmacology, Animation

00:05:12
https://www.youtube.com/watch?v=sUt7cnzJv1U

Summary

TLDRNonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their effectiveness against inflammation. They work by inhibiting the production of prostaglandins, which are compounds involved in inflammatory responses and physiological functions. There are two main types of cyclooxygenase (COX) enzymes: COX-1, which is involved in producing protective prostaglandins, and COX-2, which is mainly induced during inflammation. Non-selective NSAIDs inhibit both COX-1 and COX-2, while selective COX-2 inhibitors (coxibs) aim to reduce gastrointestinal irritation but may increase cardiovascular risks. Aspirin, a unique NSAID, irreversibly inhibits COX-1, making it effective at reducing blood clot formation but potentially harmful for patients at risk of bleeding. Overall, the use of NSAIDs can lead to various side effects including gastrointestinal irritation, cardiovascular events, and renal impairment, highlighting the importance of understanding their mechanisms and risks.

Takeaways

  • 💊 NSAIDs are the most widely used anti-inflammatories.
  • 🧪 They inhibit the production of prostaglandins involved in inflammation.
  • ⚖️ COX-1 produces protective prostaglandins, while COX-2 is associated with inflammation.
  • 🩸 Aspirin permanently inhibits COX-1, reducing platelet aggregation.
  • 🚨 Aspirin's anti-thrombotic effect can pose bleeding risks.
  • 🥴 Non-selective NSAIDs may lead to gastric irritation and ulcers.
  • 🤔 Coxibs aim to lessen gastrointestinal side effects but may increase cardiovascular issues.
  • 🩺 Some NSAIDs can affect renal blood flow and cause renal impairment.

Timeline

  • 00:00:00 - 00:05:12

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to inhibit prostaglandin production, reducing inflammation, fever, and pain. Unlike other anti-inflammatories, they do not suppress the immune system. Prostaglandins, derived from arachidonic acid via COX enzymes, play various physiological roles and maintain homeostasis. There are two main COX enzymes: COX-1, which produces physiological prostaglandins, and COX-2, which is induced by inflammation. NSAIDs are classified as non-selective or COX-2 selective, with aspirin noted for its irreversible COX inhibition, particularly affecting platelet aggregation, making it a potent anti-thrombotic agent. However, it poses bleeding risks and is contraindicated in certain patients. Non-selective NSAIDs may cause gastric irritation and ulcers due to COX-1 inhibition. COX-2-specific NSAIDs aim to minimize gastrointestinal toxicity but raise cardiovascular concerns. The balance of prostaglandin inhibition by NSAIDs may lead to increased risks of hypertension, renal issues, and exacerbated heart failure.

Mind Map

Video Q&A

  • What are NSAIDs?

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used anti-inflammatory medications that inhibit the production of prostaglandins.

  • What do prostaglandins do?

    Prostaglandins contribute to the inflammatory response and are responsible for symptoms like fever and pain.

  • What is the difference between COX-1 and COX-2?

    COX-1 is constitutively expressed and primarily responsible for physiological prostaglandins, while COX-2 is induced by inflammation and mainly produces inflammatory prostaglandins.

  • What is the role of aspirin in relation to COX enzymes?

    Aspirin permanently modifies COX enzymes, preventing platelet aggregation, making it a potent anti-thrombotic agent.

  • Why are coxibs controversial?

    Coxibs selectively inhibit COX-2, which may increase cardiovascular risks due to the inhibition of protective vasodilatory prostaglandins.

View more video summaries

Get instant access to free YouTube video summaries powered by AI!
Subtitles
en
Auto Scroll:
  • 00:00:03
    Nonsteroidal anti-inflammatory drugs, NSAIDs, are the most widely used anti-inflammatories.
  • 00:00:10
    NSAIDs inhibit production of prostaglandins, a group of compounds that contribute to inflammatory
  • 00:00:15
    response and are responsible for signs such as fever and pain.
  • 00:00:20
    NSAIDs are very effective, and unlike other anti-inflammatories, they have no immunosuppressive
  • 00:00:26
    effect.
  • 00:00:29
    Prostaglandins are synthesized from arachidonic acid by the action of cyclooxygenase (COX)
  • 00:00:35
    enzymes.
  • 00:00:36
    COX metabolizes arachidonic acid to prostaglandin H2, PGH2, which is then converted to different
  • 00:00:43
    isoforms in different tissues, where they fulfill different functions.
  • 00:00:49
    Physiological prostaglandins act to maintain local homeostasis such as temperature regulation,
  • 00:00:54
    bronchial tone, uterine tone, gastric mucosal barrier, among others.
  • 00:01:00
    Some prostaglandins exert opposing effects to maintain balance.
  • 00:01:05
    For example, platelet’s TXA2 constricts blood vessels and promotes platelet aggregation,
  • 00:01:12
    while endothelial PGI2 dilates blood vessels and inhibits platelet aggregation.
  • 00:01:19
    Together they modulate the interaction between activated platelets and blood vessel wall.
  • 00:01:25
    Physiological levels of prostaglandins are generally very low, but they go up drastically
  • 00:01:30
    immediately upon acute inflammation, with PGE2 involved in most of its cardinal signs.
  • 00:01:37
    There are 2 known COX enzymes: COX-1 and COX-2.
  • 00:01:41
    COX-1 is expressed constitutively in most cells and is the major source of physiological
  • 00:01:46
    prostaglandins.
  • 00:01:48
    COX-2 is selectively induced by inflammatory stimuli and is the predominant source of inflammatory
  • 00:01:55
    prostaglandins.
  • 00:01:56
    But COX-2 also has some physiological functions in some tissues.
  • 00:02:01
    NSAIDs can be classified as non-selective, meaning they inhibit both COX-1 and COX-2,
  • 00:02:07
    albeit with different efficiencies; and COX-2 selective.
  • 00:02:12
    All non-selective NSAIDs, except aspirin, act as reversible COX inhibitors.
  • 00:02:19
    They compete with arachidonic acid for binding to the enzyme.
  • 00:02:23
    Aspirin, on the other hand, covalently modifies and permanently destroys COX enzymes.
  • 00:02:29
    The irreversible action of aspirin is most notable in blood platelets, which cannot synthesize
  • 00:02:35
    new enzymes because they have no nucleus.
  • 00:02:38
    Once the enzyme is inactivated by aspirin, no production of TXA2, and hence no platelet
  • 00:02:45
    aggregation, is possible for the entire lifespan of the platelets.
  • 00:02:50
    This makes aspirin stand out as a potent anti-thrombotic agent.
  • 00:02:54
    In fact, aspirin is commonly prescribed to reduce risk of blood clot formation, as a
  • 00:03:00
    preventive measure for heart attacks and ischemic strokes.
  • 00:03:04
    For maximum effect, aspirin should not be taken together with other nonselective NSAIDs
  • 00:03:09
    as these will compete with aspirin for a common binding site on the platelet’s COX-1.
  • 00:03:15
    Being anti-thrombotic, aspirin prolongs bleeding and is therefore contra-indicated in patients
  • 00:03:20
    with bleeding risks or hemorrhagic disorders.
  • 00:03:24
    Aspirin is also linked to Reye’s syndrome.
  • 00:03:28
    COX-1-dependent prostaglandins suppress gastric acid secretion and help maintain gastric mucosal
  • 00:03:34
    barrier, providing protection to the stomach lining.
  • 00:03:37
    Because non-selective NSAIDs inhibit COX-1, they may cause gastric irritation, peptic
  • 00:03:43
    ulcer disease, and gastrointestinal bleeding.
  • 00:03:47
    The newer COX-2-specific NSAIDs, coxibs, are designed to reduce this gastrointestinal toxicity,
  • 00:03:55
    but their use is controversial, as they appear to increase cardiovascular occlusive events.
  • 00:04:01
    A possible explanation is that coxibs selectively inhibit COX-2-dependent PGI2, which is vasodilatory
  • 00:04:08
    and anti-thrombotic, while having no effect on COX-1-dependent TXA2, which is pro-thrombotic
  • 00:04:16
    and vasoconstrictory, and thus tipping the scales of homeostasis in favor of blood clot
  • 00:04:21
    formation and vasoconstriction.
  • 00:04:25
    Some non-selective NSAIDs also exhibit various levels of cardiovascular toxicity depending
  • 00:04:30
    on their COX-2 versus COX-1 inhibition ratio.
  • 00:04:34
    Suppression of physiological vasodilatory prostaglandins by NSAIDs may increase the
  • 00:04:40
    risk for hypertension, edema, and exacerbate pre-existing heart failures.
  • 00:04:46
    Inhibition of renal vasodilatory prostaglandins, in the context of circulatory stress, may
  • 00:04:52
    reduce renal blood flow and glomerular filtration rate, and ultimately cause renal ischemia
  • 00:04:58
    or failure.
Tags
  • NSAIDs
  • prostaglandins
  • COX enzymes
  • Aspirin
  • Gastrointestinal risks
  • Cardiovascular risks
  • Renal function
  • Inflammation
  • Antithrombotic
  • Coxibs