Autacoids (Histamine, Serotonin, Ergot) Flashcards
histamine is synthesized form what AA?
Histidine
what enzyme converts Histidine to Histamine
Histidine Decarboxylase
Histamine in mast cell is inactive in a complex with?
proteases
heparan sulfate
chondroitin sulfate
most histamine are contained in what type of cells? (2)
Mast cell
Basophil
histamine not in cell is found in what tissues and functions as what
Brain, Stimach
Neurotransmitter, neuromodulator, neuroendocrine control, cardiovascular regulation.thermal & body weight regulator, sleep & arousal
2nd most important site of histamine storage
Enterochromaffin like-cells(ECL cells)
functions of histamine released by Enterochromaffin like-cells(ECL cells)
activate parietal cells to produce HCl
immunologic release of histamine is mediated by
IgE
what mode of release: displaces histamine from the heparin-protien complex within cells
Chemical & Mechanical release (drugs and alcohol)
the type of histamine receptor subtypes
G-protein coupled receptors
distribution of H1 receptors
Endothelium Brain Smooth muscle
what is the triple response?
mediated through H1 receptor:
Red spot (vessel dilation)
Edematous
Wheal and flare
distribution of H2 receptors
Gastric mucosa
Cardiac muscle
Mast cell
effects of H2 stimulation
Gastric acid sceretion
Increase SA nodal rate
(+) Inotropism
Presynaptic AUTORECEPTORS & heteroceptors in the brain, myenteric plexus
H3 receptors
functions of H3 receptor stimulation
Feedback inhibitions
Neurotransmitters
distribution of H4 receptors
Eosinophils, neutrophils, CD4 and T cells
function of H4 stimulation
Chemotactic response
General Histamine Antagonists (and action)
Epi: physiologic antagonist
Cromolyn & Nedocromil: release inhibitors
Buramide: receptor antagonist (H2)
types of H1 antagonists
1st generation (sedating) 2nd generation (less sedating)
converts the 2nd generation H1 antagonists to active form
CYP3a4 isozyme
H1 antagonists: Allergic reaction
Diphenhydramine (atopic dermatitis)
H1 antagonists: Motion sickness & Vestibular DO
Scopalamine
Dimenhydrinate
H1 antagonists: Nausea and Vomiting in Pregnancy
Bedectin
Doxylamine
H1 antagonists: Anti parkinsonism
Diphenhydramine
H1 antagonists: Anti cholinoceptor
Ethanolamine
Ethylenediamine
H1 antagonists: Adrenoceptor-Blocking
Promethazine (orthostatic Hypotension)
Cyproheptadine (anti serotonin agent)
H1 antagonists: Local Anesthesia
Procaine
Lidocaine
Diphenhydramine
Promethazine
Toxicity: Fatal Arrhythmia in 2nd gen drugs is produced when?
Terfenadine/Astemizole + Ketoconazole/Itroconazole/Erytromycin
other toxicity of H1 antagonist drugs
Sedation, CNS depression Anti muscarinic Excitation Tolerance Seizure Fatal Arrhythmia
H2 receptor blocker
Ranitidine ( - acid secretion)
H3 receptor antagonists
Tiprolisant
Action of Tiprolisant
for sleep DO, Obesity, Narcolepsy, Cognitive and psychiatric DO
other name of serotonin
5’-Hydroxytryptamine
a mediator of the S/Sx of Carcinoid Syndrome
Serotonin
AA precursor of Serotonin
Tryptophan
what is the Rate Limiting step in the synthesis of Serotonin
Hydroxylation at C5
Blocker of Rate Limiting Step in Serotonin Synthesis
p-chlorophenylalanine
p-chloramphetamine
Stored serotonin can be depleted by
Reserpine
distribution of serotonin
ECL cells
Platelets
Brainstem (raphi cells)
Describe the serotonin receptors
7 receptors
6-G Protein mediated
1-Ligand gated ion channel
a simple methoxylated and N-acetylated product of Serotonin in the Pineal Gland
Melatonin
agonist at 5HT1a receptors ( a non Benzodiazepine anxiolytic)
Buspirone
Agonists at 5HT1d receptors in cerebral vessels that decreases migraine pain
Sumatriptan (all -“triptans”)
Action of 5HT1 and 5HT2 on CNS
5HT1: Inhibitory
5HT2: Excitatory
Antagonist at 5HT2a receptors in the CNS that deceases Sx of Psychosis
Olanzapine
MOA of Ketanserine
Blocks vascular alpha1 receptor
antagonizes platelet aggregation by serotonin
5HT2 antagonist used in carcinoid and other GIT tumors
Cyproheptadine
5HT2 antagonist that alter bleeding time and thromboxane formation
Ritanserine
Distribution of 5HT3 receptors
CNS Chemoreceptive area Vomiting center Peripheral sensory Enteric nerves
5HT3 antagonist that decreases emesis in chemotherapy and Post-Op’s
Ondansetron (“-setrons”)
distribution of 5HT4 receptors
GI smooth muscles
Enteric nerves
MOA of Cisapride
Activator of 5HT4 receptor
prokinetic in GERD
cardiac K channel blocker
partial 5HT4 agonist that is used for irritable bowel syndrome and constipation
Tegaserod
Serotonin reuptake inhibitor
Its is combine with what other drug to produce “Fen-Phen”
Dexfenfluramine added with Phentermine
derived from fungus that grow on grain
Ergot Alkaloids
common actions of ergot alkaloids
agonists, partial agonists, antagaonists (Alpha Adrenoceptors and Serotonin receptors and dopamine receptors)
What are the effects of Ergot alkaloids in the following organs:
Vessels
Uterus
Brain
Vessels: VC
Uterus: Contraction
Brain: Hallucination
drug used for hyperprolactinemia
Bromocriptine
Carbegoline
Pergolide
for the Dx of Angina
Ergonovine
for senile cerebral efficiency
Dihydroergonotoxine
used for Obstetric bleeding; however, What is the preferred agent?
Ergonovine and Ergotamine
the preferred agent is still Oxytocin
(ergot alkaloid) used for Migraines
Ergotamine
Sever prolonged vasospasm in the GIT as a toxicity of Ergot alkaloids can be antagonized by
Nitroprusside
Chronic usage of Methysergide has what side effects?
hyperplasia of connective tissue
To what receptors do the following drugs have high affinities: Bromocriptine Ergonovine Ergotamine Lysergic Acid Diethylamine Methysergide
Bromocriptine: Dopamine receptors Ergonovine: Alpha adreno & 5HT2 Ergotamine: Uterine Muscle Lysergic Acid Diethylamine: Dopamine receptors Methysergide: none
