The word NSAID is expanded as Non Steroidal Anti-inflammatory Drugs. The same group of drugs are also called Non-Narcotic Analgesics or Analgesic-Antipyretic-Anti-inflammatory Drugs.
The word used is – Non-steroidal – because steroids are one of the most potent anti-inflammatory drugs; and we want to emphasize that NSAIDs exert anti-inflammatory effect, but they are not steroidal in nature.
Why the word Non-Narcotic Analgesics –
The most potent analgesic drugs are Narcotics (Narcosis = Central nervous system depression) (Morphine-like drugs).
NSAIDs produce analgesic effect without depressing central nervous system; hence they are termed Non-Narcotic Analgesics.
Its extremely important not to have narcotic / central nervous system depressant effect for for relieving minor pains in day to day life. Thus Non-Narcotics are the most commonly used drugs for relieving pain.
Mention the differences between Narcotic Analgesics and Non-narcotic Analgesics.
|Narcotic Analgesics||Non-Narcotic Analgescis|
|Produce CNS depression||Less CNS depression|
|Analgesic action is mainly central||Analgesic action is mainly peripheral|
|Opioid receptors||Peripheral pain receptors|
|Cardiovascular system depression||Minimal|
|Abuse liability is remarkable (Drug dependence)||No abuse liability|
|Physical dependence||No physical dependence|
|Mostly used for emergencies and severe pains||Mostly used for day to day pain relief and mild to moderate pains|
|e.g. Morphine, Buprenorphine, Pethidine, Pentazocin, Fentanyl||e.g. Aspirin, Paracetamol, Ibuprofen, Diclofenac,Naproxen, Mefenamic acid|
|Type of pain relieved|
|Severe||Mild to moderate|
|Visceral pain||Integumental; sometime also visceral|
|Deeper pain||Superficial pain|
Mention the non-narcotic analgesics without anti-inflammatory action.
Paracetamol (Acetaminophen) and Ketorolac have analgesic action, but they are poor (modest) at anti-inflammatory action.
This is why paracetamol is mostly used for relieving pain (analgesic action) and decreasing body temperature (anti-pyretic action), but not for inflammatory conditions.
Ketorolac is mostly used to relieve the pain.
Mention pharmacological actions of Aspirin / NSAIDs / Non-narcotic analgesics.
- Analgesic action: This is mostly peripheral, by acting on peripheral pain receptors by decreasing their sensitivity. Because NSAIDs inhibit cyclooxygenase-2 (COX-2) and inhibit synthesis of prostaglandins (PGs), Bradykinin (BK) TNF-alpha (Tumor necrosis factor alpha).
- Antipyretic action: By 2 mechanisms. 1- Central, by acting on hypothalamus and re-setting the thermostat. 2-Peripheral, by producing cutaneous vasodilation (dilation of blood vessels in the skin) and sweating –> dissipation of heat
- Anti-inflammatory action: Inhibit the synthesis of chemical mediators of inflammation, stabilize the lysosomal membrane, decrease the mucopolysaccharides, decrease the edema (1.2-1.5 g q 8h)
- Antiplatelet action: (anti-aggregatory action on platelets) (only ASPIRIN IN LOW DOSES)): Inhibits TXA2 synthesis [(Thromboxane A2)– Irreversible COX inhibition – (acetylation) – Long lasting effect – 7-10 days – (lifetime of platelets) (platelets – no nucleus – no de novo protein synthesis)]
- Respiration & Acid base imbalance: Moderate doses: Resp alkalosis. Toxic doses: accumulation of Co2 , respiratory acidosis and metabolic acidosis
- Decrease renal and stomach PGs: This action is minimal with highly selective COX-2 inhibitors, because the enzyme present at these sites is COX-1.
Enumerate the therapeutic uses of Aspirin / Salicylates / NSAIDs.
- Symptomatic relief of fever
- Symptomatic relief of pain: Headache, bodyache, arthralgia, myalgia, injuries, toothache, dysmenorrhea.
- Symptomatic relief of inflammation in various conditions such as: Arthritis/osteoarthritis, ankylosing spondylitis, rheumatoid arthritis, Still’s disease, ligament injury, muscle sprain/strain, osteomyelitis, myositis, fractures.
- Newer uses of LOW-DOSE ASPIRIN due to its Anti-platelet action: (Aspirin is used in the dose of 75 or 81 or 100 or 162 mg every day for this effect)
- Primary prevention of myocardial infarction
- Secondary prevention of myocardial infarction/anginal attacks
- Prevention of strokes
- It is used in ACUTE MYOCARDIAL INFARCTION to halt the progress of ongoing platelet aggregation and eventually to minimize/restrict the size of infarct.
Mention the adverse effects of salicylates/Aspirin/NSAIDs.
Remember the adverse effects based on –
-They inhibit PG synthesis. When this is also inhibited in the stomach or kidnyes – two adverse effects are likely – One, GI toxicity; Second: Renal damage
-When Cyclooxygenase is inhibited, the arachidonic acid moves to the other pathway (Lipoxygenase), and then Leukotrienes are formed which are potent chemical mediators of asthma as well as skin allergies.
Adverse Effects of Aspirin / Salicylates / NSAIDs
1. Gastrointestinal intolerance, hyperacidity, nausea, vomiting, peptic/duodenal ulcers, bleeding from ulcers.
2. Analgesic Nephropathy: Renal damage due to chronic use of analgesics. They inhibit the PG synthesis in Kidneys. So the PG mediated vasodilation is inhibited. So there is decreased renal blood flow. This leads to renal damage.
3. Precipitation of bronchial asthma: Analgesics inhibit PG synthesis, leading to increased Leukotrienes, which are potent chemical mediators of asthma.
4. Skin reactions: Some NSAIDs may lead to skin rash, dermatitis, skin reactions, allergic manifestations – Steven Johnson Syndrome / Fixed drug eruption. These are related to Leukotriene synthesis.
5. Respiratory depression and acidosis in toxic doses.
6. Reye’s syndrome: ONLY KNOWN WITH ASPIRIN. When aspirin is used to decrease fever in children with viral infections, it is known to produce elevated transaminase levels and liver damage. This is called Reye’s syndrome. This is why aspirin is never used to relieve fever in children with viral infection. Drug of choice for this fever is Paracetamol.