Review of Pharmacology - 9E (2015)

Review of Pharmacology
Use of misoprostol in pregnancy
is associated with Moebius
syndrome
Leukotrienes
These are synthesized from arachidonic acid with the help of the enzyme, 5-lipoxygenase.
This enzyme must associate with 5-lipoxygenase activating protein (FLAP) for leukotriene
synthesis. First step is the production of LTA 4
that is converted either to LTB 4
or to
cysteinyl leukotrienes (LTC 4
, D 4
and E 4
). LTC 4
and LTD 4
are also known as slow reacting
substance of anaphylaxis (SRS-A) due to their powerful bronchoconstricting action. LTB 4
is a powerful chemotactic agent and is an important mediator of all types of inflammation.
Action of LTs can be inhibited by:
• Corticosteroids (decrease the production of LTs by inhibiting phospholipase A 2
)
• Lipoxygenase inhibitors (zileuton)
• LT receptor antagonists (zafirlukast, montelukast, iralukast)
Platelet activating factor (paf)
Most potent agent known to
cause increase in the capillary
permeability is platelet activating
facor.
Lyso-PAF is produced by the action of phospholipase A 2
on cell membranes (phospholipase
A 2
is also involved in the production of arachidonic acid). This substance is converted to
PAF by acetylation. PAF is an important mediator of inflammation and allergy. It is the most
potent agent known to cause increase in the capillary permeability.
Drugs affecting PAF are:
• Glucocorticoids decrease the production of PAF by inhibiting phospholipase A 2
• Apafant and lexipafant are PAF antagonists that are being investigated for the
treatment of acute pancreatitis.
Thromboxane A 2
Autacoids
PGF 2α
decreases intraocular
pressure by increasing the
uveoscleral outflow.
Drugs affecting TXA 2
are:
• COX inhibitors like aspirin decrease the synthesis of TXA 2
• Daltroban and sultroban are TXA 2
receptor antagonists.
• Dazoxiben inhibits the enzyme thromboxane synthetase.
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Licofelone is combined COX-
LOX inhibitor that is being investigated
as a disease modifying
anti-osteoarthritis drug
(DMAOAD).
Non Steroidal Anti Inflammatory Drugs (Nsaids)
NSAIDs act by inhibiting COX enzyme and thus prostaglandin synthesis. These drugs act
as antipyretic, analgesic and anti-inflammatory agents. Prostaglandins play a protective role
in the stomach and non-selective COX inhibitors can cause GI toxicity (peptic ulcer) on long
term use.
Classification
• Non selective COX inhibitors (inhibit both COX 1 and COX 2)
• Preferential COX 2 inhibitors (inhibitory activity on COX 2 is greater than COX 1)
• Selective COX 2 inhibitors
Non Selective Cox Inhibitors
(a) Paracetamol (Acetaminophen)
It does not possess anti-inflammatory activity because it is ineffective in the presence of
peroxides generated at the site of inflammation. Other explanation offered is selective COX 3
inhibition in the brain. It produces very little GI toxicity and can be administered in patients
intolerant to other NSAIDs. It is metabolized to N-acetyl paraaminobenzo quinoneimine
(NAPQ) by microsomal enzymes. This metabolite has high affinity for sulfhydryl groups and
can combine with the enzymes and other biomolecules resulting in hepatotoxicity.
Normally acetaminophen is a safe drug because glutathione (contain sulfhydryl group due
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