Cardiovascular System • A powerful vasoconstrictor except in skeletal muscle
• Dimetoxyiodophenylaminopropan → 5-HT ↑→
• Sumatriptan → 5-HT1D → vasoconstraction
• Ergot alkaloids → 5-HT1 → vasoconstraction
• Serotonin → Angiotensin II, norepinephrine, PGF2α↑→
1. Bezold-Jarich reflex → blood pressure ↓ 2. Vasoconstraction → blood pressure ↑ 3. Vasodilation in vessels in skeletal muscle, NO ↑→
Airways
bronchial sensory nerve ending → hyperventilation
• Bronchospasm in asthmatic patients Gastrointestinal tract • The stimulatory response → direct effects of 5-HT in smooth muscle cells (5-
in intestine and 5-HT2B in stomach fundus)
→ stimulation of enteric ganglia (5-HT ↑
→ stimulation of nevre endings on longitudinal and
• Relaxation or contraction in esophagus (5-HT ↑
• Enteric 5-HT → intraluminal pressure↑, pH ↓,
intraluminal pressure↑, pH ↓, peristaltic contraction ↑ (5-HT ↑
Nervous System • present in raphe nuclei of the brain stem, brain
in vomiting center and GI tract → vomiting
reflex X Ondansetron, granisetron.
• A potent stimulant pain and itch sensory nerve ending
chemoreceptor reflex (Bezold-Jarich reflex) → bradycardia and hypotention
Pathophysiologic effects Carcinoid tumors
Enterochromaffin cell tumors → secretion of 5-HT↑→ serotonin crysis X octreotide Migrain • Plasma and platelet 5-HT concentrations vary with the
• Urinary concentrasions of 5-HT and its metabolites↑ Dumping sendrome Postgastrectomy sendrome (flushing, dizziness, weakness, vasomotor collapse, pain and headache) Pulmonary embolism Thromboemboli → Serotonin ve TXA ↑→
(5-HT2 X Ketanserin) Anxiety and depression Serotonin→5-HT →
(Buspirone)
Serotonin Agonists
• Acute treatment of migraine attacks with or without
• Cont: Ischemic heart disease, peripheral and cerebral
vascular syndromes, uncontrolled hypertension, use within 24 hours of ergotamine derivatives, another 5-HT1 agonists; use within 72 hrs CYP3A4 inhibitors, hemiplegic or basilar migraine, prophylactic treatment of migraine, severe hepatic impairment, in patients <18 years of age
• Adverse reactions: Chest pain, palpitation, dizziness,
headache, chills, pain, vertigo, nausea, vomiting,
dyspepsia, abdominal pain/discomfort, weakness, paresthesia, back pain, hypertonia, pharyngitis
• Pregnancy Risk Factor C Eletriptan (Relpax) • It is the latest addition to this group
• Ketoconazole, erytromycin, fluconazole & verapamik
Naratriptan (Naramig) • Is the one of the most potent 5-HT agonist
• The active metabolite, N-desmethyl rizatriptan has
Rizatriptan (Maxalt RPD) • Absorption and elimination are rapid
• Metabolise by MAO-A to inactive metabolites
• Competitive inhibitor of CYP2D6 Sumatriptan (Imigran, Sumatran) • 5-HT1B and 5-HT1D ↑→ Acute migraine and Cluster
• Contraindicated in coronary artery disease and angina
• Naratriptan is contraindicated in severe hepatic or
renal impairment, peripheral vascular syndromes
Zolmitriptan (Zomig) • The dose should be reduced in moderate to severe Ergotamine (Avmigran, Cafergot, Ergafein), dihydroergotamine (Neomigran) • Some of their properties are similar to those of
Additional effects: adrenergic receptors block, vasoconstriction directly
Buspirone (Buspon), gepirone, ipsapirone • 5-HT ↑
Methysergide (5-HT1 and 5-HT2 block)
strong competitive serotonin antagonist, partial serotonin agonist (vasoconstrictor)
• used in the prophylaxis of migraine and Horton
• antidiaretic in carcinoid syndrome and Dumping
• contraindicates in peripheral vascular diseases and
Cyproheptadine (5-HT2A ve H1 block)
• Antidiaretic in carcinoid syndrome and Dumping
• side effects: weight gain, drowsiness and increased
Ketanserin (5-HT1C, 5-HT2 and α1 block)
• used in the treatment of hypertension,
vasospastic conditions and Raynaud syndrome
Ritanserin (5-HT2 block)
• platelet agregation ↓, vasoconstriction↓,
Granisetron >Ondansetron (5-HT3 block)
• used in the prevention of nausea and vomiting Tropisetron (5-HT3 block)
• used in the prevention of nausea and vomiting Pizotifen (Antiserotonerjik, antihistaminik) • used in the prophylaxis of migraine
Summary of prescribing guidance for thetreatment and prophylaxis of influenza-likeillness: TREATMENT PHASEThis guidance is intended to enable health protection units (HPUs) to address local queries aboutthe treatment and prophylaxis of influenza A(H1N1). It is not a substitute for the Summary ofProduct Characteristics (SPC) and the Patient Information Leaflet (PIL) which must accompany theFurt