Serotonin &
Prostalandins
Dr. Nazla Shamsuddoha
MBBS (MCWH), MD Pharmacology (BSMMU)
Assistant Professor,
Department of Pharmacology & Therapeutics
Medical College For Women & Hospital.
Serotonin/ 5-Hydroxytryptamine (5-HT)
Act as neurotransmitter in CNS and local hormone in gut
Distribution: 90% found in enterochromaffin cell of intestine (GIT)
And 10% in blood platelets and CNS
Enterochromaffin cell secrets serotonin and this serotonin remain store in platelet.
When platelet bind to a clot, it release serotonin.
In high concentration serotonin acts as a vasoconstrictor .It can also act as vasodilator
by releasing nitrous oxide from endothelial cell.
Synthesis of serotonin:
Tryptophan
Tryptophan hydroxylase
5-hydroxytryptophan
5-hydroxytryptophan Decarboxylase
5-hydroxytryptamine (serotonin/5-HT)
Serotonin is metabolized by mono amino oxidase and dehydrogenase
Metabolites of serotonin:
5-hydroxyindol acetic acid
5-hydroxytryptophol & melatonin
Location of serotonin receptors:
Serotonin receptors location Function
5- HT1 Brain- Constriction of cranial
hippocampus,substantial blood
nigra,globus pallidus, vessels
basal ganglia, cortex,
putamen
5- HT2 Platelet, smooth muscle, Smooth muscle
skeletal muscle, fundus contraction platelet
of the stomach, Brain- aggregation, neuronal
cerebral cortex, activation in brain
hippocampus, substantia
nigra
5- HT3 Sensory and enteric Emesis, gut peristalsis,
nervous system bradycardia, pain
5- HT4 Smooth muscle of gut, Increased intestinal
5-Hydroxytryptamine:
Physiological Functions
• Peristalsis
• Vomiting
In • Platelet aggregation & hemostasis
•
periphery Inflammation
• Nociception
• Microvascular control
• Appetite
• Sleep
• Mood
In CNS • Hallucination
• Stereotyped behaviour
• Pain perception
• Vomiting
Serotonin causes triphasic response in blood pressure-
Decrease heart rate, cardiac output and blood pressure caused by
chemoreceptor response .
Blood pressure increase due to vasoconstriction.
Blood pressure decrease due to vasodilatation of skeletal muscle
blood vessels
5-Hydroxytryptamine:
Pathological Conditions
•Migraine
•Mood disorders
•Anxiety
•Vomiting
•Carcinoid syndrome
5-Hydroxytryptamine:
Agonists
Agonists
5-HT1A 5-HT1B,1D 5-HT4
Metocloprami
de
Sumatriptan
Tegaserod
Buspirone Zolmitriptan
Renzapride
Ergotamine
Cisapride
5-Hydroxytryptamine: Antagonists
Antagonists
5-HT2A 5-HT3
5-HT7
Methysergide
Pizotifen
Ondansetron
Cyproheptadin
e Granisetron Clozapine
Risperidone Palanosetron
Trazodone
Indication of serotonin agonist:
Buspiron: used as anxiolytic
Azapiron: used as anxiolytic
Sumatriptan: used in acute migraine attack
Cisapride: used in gastro-oesophageal reflux disease
Indications of serotonin receptor antagonist:
1. Radiotherapy and chemotherapy induced vomiting:
Ondansetron
Granisetron
Dolasetron
2. Septic shock: Ritanserin
There are some other drugs which can also antagonize serotonin receptor-
Ergotamin- used in acute migraine attack, prevention of post partum hemorrhage
Methylsergide- used in migraine
Cyproheptadine-used in allergic reaction
Promethazine-used in allergic reaction
Kitotifen-used in allergic reaction
Clozapine- used as atypical antipsychotic drug
Risperidon-used as typical antipsychotic drug
Chlorpromazine-used as typical antipsychotic drug
Functions of
Prostaglandins
1. Smooth muscle:
i) CVS: Vasodilatation → PGI2, PGE2
Vasoconstriction → TXA2, PGF2
ii) GIT: Mucosal protection → PGE2
iii) Airways:Bronchodilatation→PGI2, PGE2,
Bronchoconstriction → TXA2, PGD2, PGF2
2. Platelets: Platelet aggregation → TXA2
Prevent Platelet aggregation PGI2
3. Reproductive organs:
Female Uterus:
Uterine contraction of both pregnant & non pregnant uterus : PGF2
Contraction of pregnant and relaxation of non pregnant uterus: PG E2
Male: Penile erection: PGE1
4. GIT: Contraction of longitudinal muscle and relaxation of circular muscle:
PG E2
Contraction of both longitudinal and circular muscle: PG F 2
Reduces HCL secretion in stomach: PG E2
Functions of Prostaglandins
5. Kidneys:
↑GFR
↑ Renal blood flow
PGI2,
Na, k & water excretion PGE2
↑Renin release
Intra-renal Vasoconstriction →
TXA2
Functions of Prostaglandins
6. CNS: At hypothalamus PGE2 mediate
bacterial and other pyrogen induced
fever and Malaise
7. Endocrine system:
PGE2 causes release of Anterior pituitary hormone GH, Prolactin, ACTH,
FSH and LH :
Functions of Prostaglandins
6. Inflammation & Immunity:
PGI2, PGE2
7. Bone metabolism: ↑Bone turnover: PGE2
8. Eye: IOP: PGF2
Prostaglandins & Pain
• ↑ the sensitivity of nociceptors and
potentiate pain perception
• ↓ the threshold to stimulation of
nociceptors causing peripheral
sensitization
• ↑ excitability in pain transmission
neuronal pathways in the spinal cord,
causing hyperalgesia
Route of administration- oral, parenteral, topical, vaginal
Misoprostol(oral)
Epoprostenol(I/V)
Latanoprost(topical)
Dinoprostone(per vagina)
Indication of Prostaglandins
1. Termination of 5. Peptic ulcer disease :
pregnancy/therapeutic abortion: PG E1: misoprostol
PG E2-dinoprostone PG E2 :enprostil
PG F2 alfa- dinoprost, carboprost 6. Prevent platelet aggregation
2. Induction of labour PG I2 : epoprostenol
PG E2 dinoprostone 7. To maintain patency of ductus
arteriosus:
3. Post partum haemorrhage
PGE1: Alprostadil
PG F2 alfa-carboprost
8. Erectile dysfunction: (penile injection):
4. Glaucoma
PGE1 : Alprostadil
PG F2 alfa : latanoprost
Prostaglandin analogues: PGE1
Misoprost Alprostadi
ol l Gemeprost
Induction of
labour PDA Termination of
pregnancy
Erectile
Termination of
dysfunctio
Pregnancy
n
PPH
NSAIDs induced
PUD
Prostaglandin analogues: PGE2
Dinoprostone Enprostil
1. PUD
i) Induction & augmentation of
labour
ii) Termination of pregnancy
Prostaglandin analogues: PGF2
Carboprost Latanoprost Dinoprost
Induction &
Open angle Termination of
augmentation of Pregnancy
labour glaucoma
Termination of
Pregnancy
PPH
Prostaglandin analogues: PGI2
Epoprostenol:
Pulmonary hypertension
Prostaglandin analogues: Adverse
effects
1. GIT: Watery diarrhea, abdominal pain, nausea,
vomiting
2. Broncho constriction
3. Local pain
4. Fever, shivering, flushing of face
5. CVS: Hypotension, Bradycardia
6. Eye: Dryness, conjunctivitis
7. Reproductive system: Uterine cramps Penile
Monteluka
st
Leukotrienes:
Leukotrienes are synthesized by lipoxygenase pathway.
Found in lungs, platelet, mast cell, white blood cells.
LTC4, LTD4 and LTE4 are known as slow reacting substance of anaphylaxis.
They also known as inflammatory mediators. They produce that effects through specific receptors.
Leukotrienes causes vasoconstriction, alter vascular permeability leading to oedema. Increased
airway mucus Secretion and causes bronchospasm.
Leukotriens have role in inflammation including Rheumatoid arthritis, psoriasis, ulcerative colitis.
They also to bronchial causes bronchial hyper responsiveness asthma.
Leukotrien receptor antagonist:
Montelukast
Zafirlukast
Leukotrien receptor antagonist:
Zileuton are useful in the treatment of bronchial asthma and allergic rhinits
