Autocoids and Autocoid Antagonist Flashcards
What are the 3 different autacoids?
- Histamine
- Serotonin
- Eicosanoids
Name the histamine receptors their MOA and location?
- H1: (Gq) endothelium, smooth muscle cells, and nerve endings
- H2: (Gs) gastric mucosa, cardiac muscle cells, some immune cells
- H3: reduces transmitter relase from histaminergic and other neurons
- H4: mainly on leukocytes in bone marrow/circulating blood
What are the effects of histamine receptors on the cardiovascular system, extravascular smooth muscle, nervous system, and secretory tissue?
CVS:
- vasodilation by H1 (endothelial cells stimulate formation of NO) and H2 receptors (vascular smooth muscle increas cAMP)
- increase contractility and pacemaker rate (mainly H2)
- Increase capillary permeability by H1
Extravascular SM:
- GI tract smooth muscle contraction by H1
- Bronchoconstriction H1
Nervous System:
- powerful stimulant of sensory nerve endings (pain, ithching) by H1
Secretory Tissue:
- powerful stimulant of gastric acid secretion by H2 in gastric parietal cells
What is a use of histamine?
- Pulmonary Function Testing using Histamine aerosol to test for nonspecific bronchial hyperactivity
What is a physiological histamine antagonist?
- Epinephrine has smooth muscule actions opposite to those of histamine
What are the histamine release inhibitors and their mechanism?
Cromolyn and Nedocromil
M: reduce immunologic mast cell degranulation
What is the difference between the first and second generation H1 receptors antagonists?
- First gen: sedative effects and are more likely to block autonomic receptors
- Second gen: less sedating bc are less liposoluble
Both are substrates of the P-glycoprotein transporter
What are examples of first generation H1 receptor antagonists?
Chlorpheniramine, Cyclizine, Diphenhydramine, Dimenhydrinate, Hydroxyzine, Meclizine, Promethazine
What are examples of second genereation H1 receptor antagonists?
- Fexofenadine (Allergra)
- Loratadine (Claritin)
- Cetirizine (Zyrtec)
What are the uses and adverse effects of H1 receptor antagonists?
Uses:
- DOC for allergic rhinitis and urticaria
- First gen prevent motion sickness
- First gen strong somnifacients to Tx insomnia
AE:
- Sedations (less common with 2nd gen)
- Dry mouth (anticholinergic effects)
- Frist gen have additional effects due to blocking of cholinergic, alpha-andrenergic, serotoninc receptors, and Na+ channels
What are the H2 receptors antagonists, mechanism, uses, and adverse effects:
Cimetidine (tagamet), Ranitidine (Zantac), Famotidine (Pepcid), Nizatidine (Axid)
M: inhibition of gastric acid secretion (competitive blocker)
Uses: Peptic ulcers, acute stress ulcers, GERD
AE: headache, dizziness, diarrhea, muscular pain, constipation; when given by IV confusion, hallucinations, agitation; more common with Cimetidine because it inhibits cytochrome P450 and binds androgen receptors (men gynecomastia/reduced sperm and women galactorrhea)
What is the MOA of serotonin
MOA: there are seven families of 5-HT receptors 6 of them are G protein-coupled receptors while 5-HT3 receptor is a ligand-gated ion channel
What is the 5-HT1D/B receptor agonist, MOA, uses?
Sumatriptan (triptans)
MOA: vasoconstriction by 5-HT1B, inhibition of CGRP/vasodilating mediators by 5-HT1d, and inhibition of pain transmission by trigeminal nerve
CA: DOC for acute severe migraine headaches
TCo: pts with coronary artery disease or angina
What are the 5-HT4 receptor agonists?
Metoclopramide and Cisapride
Metoclopramide
M: 5-HT4 receptor agonist
CA: prokinetic agent facilitating ACh relase from enteric neurons, coordinated contractions that enhance transit; antinauseant and antiemetic
AE: somnolence, nervousness, and dystonic reactions; rarely extrapyramidal effects and tardive dyskinesia
Cisapride
M: 5-HT4 receptor agonists
CA: used as a prokinetic
AE: QT interval prolongation (no longer used in US)
What are the types of serotonin antagonists?
- 5-HT2 receptor antagonists
- 5-HT3 receptor antagonists
- Ergot Alkaloids
Cyproheptadine
M: 5-HT2 receptor antagonists (also potent H1 blocking)
CA: allergic rhinitis, vasomotor rhinitis, management of serotonin syndrome
Ondansetron
M: 5-HT3 receptor antagonists
CA: anti-emetic particulary for chemotherapy
What are the Ergot Alkaloids, MOA, CA, AE, TCo?
Egrotamine, Dihydroergotamine, Bromocriptine, Cabergoline, Ergonovine, Methylergonovine
M: agonist/partial agonist/antagonist actions at alpha-andrenoceptors and 5-HT receptors; agonist/partial agonist actions at CNS dopamine receptors
CA: Migraine (ergotamine, dihydroergotamine), Hyperprolactinemia (bromocriptine, cabergoline), Postpartum Hemorrhage (ergonovine, methylergonovine), Dx of variant angina (ergonovine)
AE: vasospasm
TCo: pregnant women, PVD, CAD, HTN, impaired renal/hepatic function, and pts on other vasoconstrictors
Ecosanoids MOA?
M: contracile effects on smooth muscle mediated by Ca2+, relaxing effects mediated by cAMP
Misoprostol
M: PGE1 analog
CA: prevention of peptic ulcers in pts taking high doses of NSAIDS, ripen cervix at/near term, management of postpartum hemorrhage, abortifacient in combination with antiprogestin mifepristone/methotrexate
Dinoprostone
M: PGE2
CA: to ripen cervix at/near term, abortifacient
Alprostadil
M: PGE1
CA: maintain patency of ductus arteriosus, impotence
Epoprostenol
M: PGI2
CA: severe pulmonary HTN, prevent platelet aggregation in dialysis machine
Latanoprost
M: PGF2alpha derivative
CA: glaucoma
What are the two classes of leukotriene pathway inhibitors?
- Inhibitors of 5-lypoxygenase: Zileuton
- Antagonists of LTD4 receptors: Zafirlukast, Montelukast
What is the MOA of glucocorticoids?
- Inhibit PLA2 blocking the release of arachidonic acid
- inhibit synthesis of COX-2
What is the MOA of NSAIDs?
- primarily inhibits cyclooxygenase
- have antipyretic, analgesix, and anti-inflammatory activities
