Autacoids

. .

Autacoids
Autos

= self Akos = medicinal agent [are circulating or locally acting hormonelike substances which originate from diffuse tissues]

Two main function

1. Moderate local circulation 2. Influence the process of inflammation

Major classes
1. Endogenous amines :

histamine, serotonin angiotensin, kinins

2. Polypeptides :

3. Lipid-derived autacoids :

prostaglandins, leukotrienes, thromboxane

Lipid-derived autacoid
1. 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 phospholipid Phospholipase Arachidonic acid
Lipoxygenase pathway Cyclooxygenase pathway

Lipoxygenase pathway
Phospholipids
Arachidonic acid
5-lipoxygenase
12-lipoxygenase

5-HETE Leukotrienes (LT)

LTA4, LTB4, LTC4, LTD4

12-HETE Leukostatic agent

HETE = Hydroxyeicosatetraenoic acid

Leukotriene leukocyte conjugate with triene SRS-A is a mixture of peptide 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 endothelium & to extravasate

Cyclooxygenase pathway
Phospholipids Arachidonic acid
Cyclooxygenase (COX-1; COX2) PGH PGG

PGI TXA PGD PGE PGF (Prostacycline)(Thromboxane) (Prostaglandins)

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

semen : vascular smooth muscle contraction Prostaglandin

Bergstorm

& Sjovall : PGE1, PGF1 Karim 1986 : Oxytocic properties PGE2, PGF2

Pharmacological Properties
Organ 1.Smooth muscle Vascular GI long circular Respiratory Uterus non-pregnancy pregnancy PGE2 TXA2 PGF2a

R C R R
R C

C C C C
C C

C C
-

Pharmacological Properties
Organ 2. Platelet aggregation 3. Body temperature 4. GI tract Gastric secretion Mucous Water & electrolytes 5. Afferent nerve & pain
Sen. = sensitization

PGE2 TXA 2 Sen.

PGF2a -

Metabolism
Lung,

kidney, liver

Inactive end product

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 NSAIDs 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