Prostaglandins & Leukotrienes Dr.Sangeetha Purushothaman

Prostaglandins & Leukotrienes

• Local hormones - very active,many functions..• Autacoids from 20 C PUFA Prostaglandins Prostacyclin Thromboxanes Leukotrienes

Functions

• Inflammation• Smooth muscle tone• Blood coagulation• Reproduction • GI secretion

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PHOSPHOLIPIDS

ARACHIDONIC ACID

PG G2

PGH2

PG I2

LT A4

THROMBOXANE

A2

PGE2

PG D2

PG F2

LT C4

LT D4

LT B4

PHOSPHOLIPASE A2

5 LIPOOXYGENASECYCLOOXYGENASE

ISOMERASE

PROSTACYCLINE SYNTHASE

THROMBOXANE SYNTHASE

SYNTHESIS

. PHOSPHOLIPIDS

ARACHIDONIC ACID

PG G2

PGH2

PG I2

LT A4

THROMBOXANE A2

PGE2 ,PG D2 ,PG

F2

LT C4 LT D4LT B4

PHOSPHOLIPASE A2

5 LIPOOXYGENASECYCLOOXYGENASE

STEROIDS

ZILEUTONNSAIDS

BIOSYNTHESIS OF PROSTAGLANDINSEnzyme is Cyclo oxygenase(COX) COX 1-constitutive. COX 2-inducible

NSAIDS- Nonselective COX inhibitors. COXIBS - Selective COX inhibitorsAspirin- Irreversible inhibition of COX Other NSAIDS- Reversible inhibition

Actions Inflammation Most important mediators.. Synthesised as per need. NSAIDS

Actions –Smooth musclesBlood vessels

Pg E2, Prostacycline - vasodilatation

Thromboxane A2 – constriction

Actions :Smooth muscle Bronchus

• BRONCHO DILATIONPgE2

PgI2

• CONSTRICTIONPgF2α

TXA2

LT

Uterus Both uterus &cervix

Cervical ripening•PgE2

Initiation of Labour•PgE1

•PgF2

Actions • GIT

Natural ulcer protectants.. NSAIDS..

MUCUS

HCO3-

ACID

• GIT

Motility SecretionCramps

Diarrhoea

RENALPgE2,Prostacyclin -protective..

PgE2,PgI2

RENAL VASODILATATION

RBF

DIRECT ON TUBULES

DIURESISNATRIURESIS

Coagulation

TXA2PLATELETS AGGREGATION

PgI2ENDOTHELIUM

(-)AGGREGATION

PG I₂

ENDOTHELIUM

PLATELET

.

Penile erection

CNS-NeurotransmitterEYE-↓IOT

Pulmonary vessels-

vasodilatation

Preparations & Uses

Preparations

Prostaglndin Preparation PgE₁ Misoprostol ,

Alprostadil,LatanoprostPgE₂ Rioprostil , Enprostil

Dinoprostone PgF₂α Prostin15Methyl PgF₂α

Carboprost / Prostodin

Pg I ₂ Epoprostenol

Uses 1.Obstetrics Therapeutic abortion

Cervical ripening

Severe Post partum hge

PgE1/MISOPROSTOL

PgE₁/PgE2

15METHYL PgF2

im/PgE1 Rectal

2.Peptic ulcer PgE1/Misoprostol

PgE2/Enprostil,Rioprostil,Arbaprostil

3.Glaucoma : PgE1 / Latanoprost

4.Erectile dysfunction 5. PDA

6. Primary pulmonary hypertention : PgI₂

PgE1/Alprostadil

Summary of usesUse Preparation Abortion PgE1Cervical ripening PgE1 / E2Peptic ulcer PgE1Glaucoma PgE1-LatanoprostPPH PgI2PDA PgE1

ADR• Vomiting,Diarrhoea,Abdominal

cramps• Uterine cramps• Bronchospasm

LEUKOTRIENES

PHOSPHOLIPIDS

CYCLOOXYGENASE

PROSTAGLANDINS

ARACHIDONIC ACID

LEUKOTRIENES

LIPOOXYGENASE

LEUKOTRIENE RECEPTOR

MAST CELL

Zileuton

ChromoglycateNedochromil

MonteleukastZafirleukast