COURSE: PHARMACOLOGY
TOPIC: ANALGESICS
Analgesics are drugs that are used to relieve pain without loss of consciousness. They are
commonly referred to as painkillers.
Classification of analgesics
Opioid analgesics
Nonopioid analgesics
- Steroid anti-inflammatory drugs
- Non-steroidal anti-inflammatory drugs
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
Arachidonic acid pathway
When injury occurs, arachidonic acid (AA) is released from the membranes of cells damaged by the
injury. AA is then metabolized in two pathways: prostaglanding (PG) pathway and leukotriene
pathway (LT). Both of these pathways result in inflammation, edema, headache and other
characteristics of pain. In PG pathway, AA is converted to various PGs by cyclooxygenase (COX)
enzyme thereby increasing vasodilation and vasopermeability in the production of edema and pain.
If PGE2 is synthesized in the hypothalamus, fever results. In LT pathway, AA is converted into
various LTs by lipoxygenase (LOX) enzyme also promoting more edema and pain.
Mode of action of NSAIDs
NSAIDs work by inhibiting the PG pathway, LT pathway, or both by blocking the activities of COX
enzyme, LOX enzyme, or both to relieve pain, headache and inflammation.
There are two types of COX: COX-1 and COX-2. COX-1 is beneficial in various body functions such as
maintaining an intact GIT mucosa. COX-2 is the one that promotes the synthesis of PGs involved in
inflammatory processes. Therefore some NSAIDs are currently made to specifically inhibit COX-2
and have no effect on COX-1 in order to reduce the prevalence of GIT ulcer. Other NSAIDs function
nonspecifically by inhibiting both COX-1 and COX-2.
NSAIDs reduce fever by inhibiting PGE 2 in the hypothalamus. NSAIDs, especially Aspirin, have a
blood-thinning effect and can result in increased bleeding because they prevent platelets
aggregation. For this reason, Aspirin is used to prevent blood clot formation in myocardial
infarction.
Indication
NSAIDs are used for their anti-inflammatory, analgesic, antigout, antipyretic effects in conditions
such as osteoarthritis, mild-to-moderate pain, fever, gouty arthritis, rheumatoid arthritis, etc. They
are also used to relieve vascular headache and for platelet inhibition.
Contraindication
1
Hypersensitivity, risk for bleeding, 3rd trimester pregnancy, vitamin K deficiency.
Adverse effects
GIT distress, noncardiogenic pulmonary edema, nausea, vomiting, anorexia, dyspepsia, altered
haemostasis, rash, tinnitus.
Examples of NSAIDs
1. Acetic Acids 4. Fenamic Acids
Diclofenac sodium (Voltaren) Meclofenamate
Diclofenc potassium (Cataflam) Mefenamic acid (Ponstel)
Indomethacin (Indocin) 5. Napthylalkanones (Nonacidic)
2. Carboxylic Acids Nabumetone (Relafen)
Aspirin (many brands) 6. Oxicams
Etodolac (Lodine) Meloxicam (Mobic)
Ketorolac (Toradol) Piroxicam (Feldene)
Magnesium salicylate (Arthropan) 7. Propionic Acids
3. COX-2 Inhibitors Fenoprofen (Nalfon)
Celecoxib (Celebrex) Ibuprofen (Motrin, Advil, others)
Naproxen (Naprosyn, Aleve)
Note: Acetaminophen (Paracetamol) is partially considered as an NSAID because of its weak anti-
inflammatory effect which is only significant in low amount of AA where COX-2 is most dominant,
and this explains why paracetamol is similar to COX-2 inhibitors. Also, it acts around the central
nervous system istead of the peripheral areas of the body. This is why it lacks the side effects of
other NSAIDs.
Dosage examples
- Aspirin. PO/PR 25 – 1000 mg 4 – 6 times a day (max. 4 g/day); or PO/PR 3.2 – 6 g/day divided q4-
6h
- Celecoxib. PO 100mg – 200 mg OD
- Ibuprofen. Adult PO 1200 – 3200 mg/day divided TID – QID; Paed. 20 – 40 mg/kg/day divided TID
– QID
- Diclofenac potassium. Adult PO 100 – 150 mg divided BID – TID; or for milder cases, PO 75 – 100
mg divided BID – TID; or IM 75 mg to be repeated after 6 h prn, not to exceed 150 mg in 24 h. For
potoperative pain, IV infusion 75 mg over 30 – 120 mins, to be repeated after 4 – 6 h prn, not to
exceed 150 mg in 24 h.
