1. Histamine: the king of chemical mediators of acute inflammation
a) What does it do to arterioles? Vasodilates
b) Venules? Increased vessel permeability
a) What amino acid makes serotonin? Tryptophan
b) Is serotonin a neurotransmitter? Yes
c) In a deficiency, you get depression (also decreased NE)
d) a vasodilator and increases vascular permeability
3. Complement system: Anaphylatoxins – C3a, C5a. Function: stimulate mast cells to release
histamine, leading to vasodilation and increased vessel permeablility. They also play a role in
shock, b/c when there is inflammation the compliment system is activated, therefore there will
be mast cells and histamine, therefore C3a, and C5a will both be there.
4. Nitric oxide – made mainly in endothelial cells, and is a potent vasodilator. It is used for
treating pulmonary hypertension. It has a big time role in septic shock.
5. IL-1 associated with a fever, it is a pyrogen, therefore stimulates the hypothalamus to make
PG’s, which stimulate thermoregulatory system to produce fever. Aspirin works by inhibiting
the synthesis of prostaglandins thereby reducing the fever.
6. Arachidonic acid metabolites:
a) Corticosteroids inhibits Phospholipase A ,2therefore do not release arachidonic acid from
phospholipids, therefore not making PG’s or leukotrienes. This is the supreme
antiflammatory agent b/c BOTH PG’s and leukotrienes are blocked by blocking
phospholipase A . 2rachidonic acids make linoleic acid (omega 3), which is found in fish oils
and walnuts. It is very good for you b/c it acts like aspirin, and blocks platelet aggregation,
and that’s how omega 3 protects your heart.
b) Lipoxygenase pathway: Zileutin blocks 5-lipoxgenase, other drugs act by blocking the
receptors, example: zirkufulast, etc. Leukotriene (LT) C4, D4, E4 (the slow reactor
substances of anaphylaxis) seen in bronchial asthma. They are potent bronchoconstrictors;
therefore it can be seen why zileutin works well in asthma b/c it blocks the leukotrienes,
including these (LT-C4, D4, and E4). LT B4 is an adhesion molecule in chemotaxis.
c) Cyclooxygenase pathway: Aspirin blocks cycoloxygenase, irreversibly in platelets. PGH2:
where everything seems to be derived from. PGI2: derives from endothelial cells, it’s also
called prostacyclin synthase; is a vasodilator and inhibits platelet aggregation (exact the
opposite of TxA2). Thrombaxane A2 (the enemy of PGI2) is made in the platelet; it’s a
vasoconstrictor, a bronchoconstrictor, and promotes platelet aggregation. What drug
blocks thrombaxane synthase and is used to stress testing for CAD? Dipyrramidal blocks the
enzyme, TxA2 synthase, therefore does not have to perform a treadmill stress test, all you
have to do is use the drug dipyrramidal. PGE2: vasodilator in kidney; keeps patent ductus patent in baby heart; makes the mucous
barrier in GI (stomach) thereby preventing ulcers; can cause dysmenorrhea woman and
increased uterine contractility, and it an abortifactant, to get rid of fetal material.
d) COX 2-make sure you know how this works!
e) Corticosteroids blocks phospholipase A2, and it also decreases adhesion molecule
synthesis, along with other steroids like epinephrine and NE. Decreased adhesion molecule
synthesis, will lead to increased neutrophils on CBC; in immuno, 50% neutrophils are stuck
to the endothelial vessels, and the other 50% are circulating, therefore, decreasing adhesion
molecule synthesis will lead to doubled WBC (b/c the 50% of neutrophils that were stuck are
now circulating). Corticosteroids destroy B-cells b/c they are lymphocytotoxic. Mechanism:
decrease WBC’s (B and T cells) via apoptosis; therefore, corticosteroids are the signal to
activate the caspasases. Eosinophils, mainly seen in type one HPY rxn, corticosteroids