Autacoidsผศ . พญ . มาลียา

มโนรถ

Autacoids Autos = self Akos = medicinal agent [are circulati

ng or locally acting hormone-like substances which originate from diffuse tissues]

Two main function

1. Moderate local circulation 2. Influence the process of

inflammation

Major classes1. Endogenous amines :

– histamine, serotonin2. Polypeptides :

– angiotensin, kinins3. Lipid-derived autacoids :

– prostaglandins, leukotrienes, thromboxane

Lipid-derived autacoid1. Eicosanoids

Polyunsaturated fatty acid (Arachidonic acid)

– Prostaglandins (PG)– Prostacycline (PGI)– Thromboxane (TXA)– Leukotrienes (LT)

Lipid-derived autacoid

2. Modified phospholipids– Platelet-activating factor (PAF) – Potent vasodilator– Potent stimulator of platelet aggregation

Circulating leukocyte Platelets Endothelial cells

Origin and synthesis PGs

Cell membrane phospholipidPhospholipase

Arachidonic acid

Lipoxygenasepathway

Cyclooxygenase pathway

Lipoxygenase pathway Phospholipids

Arachidonic acid12-lipoxygenase5-lipoxygenase

5-HETELeukotrienes (LT)

LTA4, LTB4, LTC4, LTD4

12-HETELeukostatic agent

HETE = Hydroxyeicosatetraenoic acid

Leukotriene พบท่ี leukocyte conjugate wit

h triene - SRS A is a mixture of pep

tide leukotriene (LTC4 ,LTD4 , LTE4)

Leukotrienes Biosynthesis take place chiefly in leukocytes Pharmacologic effects

– LTC4, LTD4, LTE4 (SRS-A)� Potent vasoconstrictor� Potent bronchoconstrictor permeability of postcapillary venules mucus secretion

Leukotrienes LTB4

– Chemotactic & chemokinetic – Leukocytes adhere the vascular endoth

elium & to extravasate

Cyclooxygenase pathwayPhospholipids

Arachidonic acidCyclooxygenase (COX-1; COX-2)

PGG PGH

PGI(Prostacycline)

TXA(Thromboxane)

PGD PGE PGF(Prostaglandins)

Prostaglandins

Kurzrok & Lieb 1930 semen : uterus Goldblatt 1933 and Von Euler 1934

– semen : vascular smooth muscle contraction Prostaglandin

Bergstorm & Sjovall : PGE1, PGF1

Karim 1986 : Oxytocic properties PGE2, PGF2

Pharmacological Properties

Organ PGE2 PGF2 TXA2

1.Smooth muscle• Vascular R C

C• GI long C C

- circular R C

-• Respiratory R C

C• Uterus non-pregnancy R C

- pregnancy C C

-

Pharmacological Properties

Organ PGE2 PGF2 TXA2

2. Platelet aggregation - 3. Body temperature - -4. GI tract

• Gastric secretion --

• Mucous -

• Water & electrolytes -

5. Afferent nerve & pain Sen. - -

Sen. = sensitization

Inactive end product

Metabolism

Lung, kidney, liver

PGI2 : 6 keto-PGF1

TXA2 : TXB2

PGF : 15- 13,14-dihydro PGF2

Clinical Uses

1. CVS : dilate– PGI : 1o, 2o pulmonary hypertension– PGE1 : maintain patency of ductus arteriosus

2. GI : inhibit– PGE : cytoprotection (prevention of NSAI

Ds induced gastric ulcer)

Clinical Uses 3. Uterus : contract

– PGE, PGF : abortion, postpartum hemorrhage, facilitation of labor

4. Platelets : inhibit– PGI & analog : in place of heparin during dialysis– PGI & PGE : improving storage of blood platelets

for therapeutic transfusion