dr.Putrya Hawa, M.

Biomed
Department of Pharmacology
University of Islam Indonesia
26 September 2013

Blok Imunopatologi 2.1 (KBK 2011), 25 September 2013 [07]

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 biological factors
 act like “local hormones”
 have a brief duration
 act near the site of synthesis (paracrine)
 not blood borne

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Decarboxylated Polypeptide Eicosanoid
Amino Acid

Histamine Kinin Prostaglandine

Serotonin (Angiotensin) Tromboxane
Leukotriene

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 VASCULATURE
PGEs  vasodilators.
Prostacyclin (PGI2)  vasodilator hypotension
Thromboxane A2 vasoconstrictor.
Leukotrienes LTC4 and LTD4 capillary leakiness.

**Alprostadil (PGE1) dilates the ductus arteriosus

 PLATELETS
PGI2  inhibits platelet aggregation,
TXA2  platelet activator
LTB4  chemotaxis of eosinophils, monocytes,
neutrophils
prostaglandins inhibit cellular and humoral
immunity
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 LUNG
prostaglandins bronkodilator
TXA2  bronchoconstriction
LTC4 and LTD4  bronchoconstrictors, mucus secretion,
increase microvascular permeability

 UTERUS
Prostaglandins cause uterine contraction in pregnancy,
clinically used as abortifacients or to induce labor
Dinaprostone (PGE2)
Carboprost (15-methyl-PGF2a)

 GIT
PGEs and PGI2  inhibits gastric acid secretion

 RENAL
PGE2 and PGI2  increase renal blood flow,

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 Respiratory volume and rate
 Bronchoconstriction
 motility of small intestine >>
 Vasoconstriction
 Vasodilatation of skeletal muscle beds
 The positive inotropic and chronotropic
 Stimulation of sensory nerves, can contribute to
pain responses
 Stimulation of autonomic ganglia
 Stimulation of catecholamine release from the
Adrenal gland
 5-HT is a neurotransmitter in the CNS and is
responsible for diverse psychoneurologic effects

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Serotonin antagonist: ondansetron (antiemetic)

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Effects on Smooth muscle
contract (gut intestinal muscle, bronchi), or relax (blood capillaries)
vasodilatation (combined H1 and H2 response)
effects on vasculature produce a flushing, decreased peripheral resistance
can produce shock through hypotension reduced blood volume  by increased
vascular permeability, and decreased venous return

Bronchi
H1 contracts bronchi, predominant response; H2 relaxes bronchi
Histamine  bronchospasm in asthmatics

Heart
H2 : increases inotropic (by promoting Ca++ flux) and chronotropic response (increase
diastolic depolarization of the SA node)
H1 : slows AV conduction, increases automaticity

Stomach
Histamine targeting parietal cells is a potent gastric secretagogue,

Stimulation of sensory nerves

Cause pruritis in the epidermis; can produce pain coupled with pruritis in the dermis.

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Bosentan, a non-selective ET-1 receptor antagonist (blocks
ETA and ETB receptors)  Pulmonary hipertension
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Aprotinin Kinin receptor antagonist :decreases activation of
plasminogen and the activity of plasmin

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ISDN  converted by mitochondrial aldehyde
dehydrogenase  NO  vasodilator

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 Direct vasodilation (flow dependent and
receptor mediated)
 Indirect vasodilation by inhibiting
vasoconstrictor influences (e.g., inhibits
angiotensin II and sympathetic
vasoconstriction)
 Anti-thrombotic effect  inhibits platelet
adhesion to the vascular endothelium
 Anti-inflammatory effect  inhibits
leukocyte adhesion to vascular
endothelium; scavenges superoxide anion
 Anti-proliferative effect  nhibits smooth
muscle hyperplasia

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