Preface
There are many antipyretic and analgesic drugs clinically, commonly used to treat arthritis (anti-inflammatory), dysmenorrhea (pain relief), fever reduction, etc.
These drugs confuse me a lot
- Diverse treatment purposes
- Numerous drug types
- The specific medication often can be one thing or another
- Each drug also has brand names, chemical names, and common names used simultaneously
Therefore, this is a review, with notes including
- Drug names (brand name, chemical name, common name)
- Drug effects and side effects
- English vocabulary
Welcome to supplement or correct; I hope this can help everyone
Supplement on 2025-01-21
This video is concise and clear, explaining several core concepts and key differences very well
Concepts
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Nonsteroidal is a concept relative to steroids (a four-ring nucleus + some side chains). Steroids generally refer to glucocorticoids like cortisone, hydrocortisone, betamethasone, dexamethasone, and budesonide.
Common Characteristics (can be skipped)
NSAIDs often have the following characteristics
- Readily absorbed in the stomach
- Distributed throughout the body
- Removed in the urine
- Accumulate at the site of inflammation where pH is lower
Basic Mechanism
By inhibiting cyclooxygenase (COX), NSAIDs inhibit prostaglandins (PG), which have extensive and complex physiological activities such as inflammation, fever, pain, gastric acid secretion, and contraction of blood vessels, bronchi, and uterine smooth muscle.
PG is an inflammatory mediator that can cause pain and fever and further enhance inflammatory responses (specific mechanisms are not elaborated here).
Thus, NSAIDs inhibiting PG production generally have the following effects
- Antipyretic (fever reduction)
- Analgesic (pain relief)
- Anti-inflammatory
graph TD
A[Phospholipids] -->|Phospholipase A2 (Steroidal anti-inflammatory drugs)| B[Arachidonic acid (AA)]
B --> |Lipoxygenase (LOX)| C[Leukotrienes (LTs)]
B --> |Cyclooxygenase (COX) (Nonsteroidal anti-inflammatory drugs)| D[Prostaglandin PGG2]
D --> E[Prostaglandin PGH2]
E --> G[Prostacyclin PGI2]
G --> F[Prostaglandins (PGs)]
E --> |TXA synthase| I[Thromboxane TXA2]
I --> J[Thromboxane TXs]
Classification and Historical Evolution
The Ancestor Aspirin
As early as the Hippocratic era in Greece, people used willow leaves and others to treat inflammation. Later, salicin was extracted from these plants. Salicin is a precursor of salicylic acid, which was often used to treat arthritis but was hard to take and had strong gastric side effects. In 1899, Bayer’s chemist Felix Hoffman acetylated salicylic acid to synthesize acetylsalicylic acid, i.e., aspirin.
Aspirin, as the ancestral drug, has the above-mentioned common effects and common side effects, the main side effect being bleeding. Later, it was also used for anticoagulation.
More about aspirin see here
Successors Replacing Aspirin
To reduce aspirin’s side effects, many new drugs with different mechanisms have been developed, each with advantages and disadvantages, suitable for different scenarios.
Classified based on COX specificity (COX side effects are detailed below)
- COX-1 specific: only inhibits COX-1, no obvious effect on COX-2. Currently, only low-dose aspirin falls into this category.
- Non-specific COX: inhibit both COX-1 and COX-2, such as ibuprofen, diclofenac sodium, high-dose aspirin, indomethacin, etc.
- COX-2 selective: inhibit COX-2 while not significantly inhibiting COX-1, but at higher doses also inhibit COX-1. Examples are meloxicam, lonoxicam, nimesulide, etc.
- COX-2 specific: almost only inhibit COX-2 and have no activity on COX-1. Examples include rofecoxib and celecoxib.
- Unknown specific mechanism: acetaminophen (paracetamol).
Classified by chemical structure
- Salicylates: aspirin, sodium salicylate, diflunisal, salicylate esters, etc.
- Anilines: phenacetin, aminopyrine, antipyrine, nimesulide, etc.
- Acetic acids: indomethacin, sulindac, acemetacin, etodolac, etc.
- Phenylacetic acids: diclofenac, fenclofenac, etc.
- Propionic acids: ibuprofen, ketoprofen, fenbufen, zaltoprofen, fenoprofen, etc.
- Fenamates: mefenamic acid, meclofenamic acid, etc.
- Pyrazolones: antipyrine, aminopyrine, antipyrine, bentazone, hydroxybentazone, etc.
- Oxicams: piroxicam, tenoxicam, meloxicam, lonoxicam, etc.
- Coxibs: rofecoxib, celecoxib;
- Others: cidofovir, etc.
Side Effects
COX has two isoenzymes: COX-1 and COX-2. The main enzyme causing the inflammatory response is COX-2. COX-1 exists in human tissues (such as gastrointestinal tract, kidney, platelets) and maintains the function of these organs with physiological roles. Inhibiting COX-1 can cause abnormal physiological functions. Most NSAIDs do not distinguish between COX-1 and COX-2 but indiscriminately inhibit both, and inhibition of COX-1 enzyme activity in normal tissues impairs the physiological function of tissue prostaglandins, such as causing reduced gastric mucosal protection and renal blood perfusion, which is the mechanism for serious adverse effects like gastric and renal injury caused by these drugs.
NSAIDs often have the following side effects (specific mechanisms not elaborated here), but many new NSAIDs have been invented to try to reduce side effects. This video briefly introduces the history of NSAIDs invention:
- Gastrointestinal reactions: related to inhibition of COX-1, which protects the gastric mucosa. For patients with significant gastrointestinal reactions or a history of peptic ulcers, using selective COX-2 inhibitors can partially reduce the incidence of gastrointestinal adverse reactions.
- Liver damage: almost all NSAIDs can cause liver damage, ranging from mild liver enzyme elevation to severe hepatocellular necrosis. In addition, there may be cardiovascular risks, including myocardial infarction and stroke. Therefore, in elderly patients or those with cardiovascular risk factors, NSAID use should be carefully risk-assessed and monitored.
- Kidney damage: NSAID-induced kidney damage manifests as acute renal failure, interstitial nephritis, analgesic nephropathy, renal papillary necrosis, sodium and water retention, and hyperkalemia.
- Cardiovascular system: sodium and water retention leading to hypertension and edema, occasionally congestive heart failure. Long-term clinical use of selective COX-2 inhibitors increases the risk of myocardial infarction, stroke, and thrombosis.
- Central nervous system: headache, tinnitus, dizziness, etc.
- Hematologic system: occasional thrombocytopenic purpura, neutropenia, aplastic anemia.
- Others: asthma, various rashes, itching.
Clinical Experience
NSAIDs are commonly used for fever reduction. With so many products, there is not that much fuss; avoid contraindications, and in most cases, drugs can be mixed. For example, acetaminophen (paracetamol) can reduce fever, and so can ibuprofen and loxoprofen sodium.