L10- Autacoids Overview Flashcards
list and define the Autacoids
-histamine, serotonin, eicosanoids
- diverse physiological and pharmacological activities
- brief lifetime, act near site of synthesis (autocrine, paracrine activity)
Histamine has (1) number of (2) type receptors all (with/without) constitutive activity. (4) are the clinically important receptors.
1- 4: H1/2/3/4
2- G protein
3- with constitutive activity
4- H1, H2
H1 are G(s/q/i) receptors found on the following, (2)
1- Gq (PLC activation)
2- endothelium, smooth muscle cells, nerve endings
H2 are G(s/q/i) receptors found on the following, (2)
1- Gs (adenylyl cyclase activation)
2- gastric mucosa, cardiac muscle cells, some immune cells
His causes vaso-(constriction/dilation) due to H(1/2) receptors found on (3) cells
1- vasodilation
2- both H1, H2
3- H2 vascular smooth muscle, H1 endothelial cells (NO formation)
His causes (increased/decreased) heart contractility and (increases/decreases) heart rate due to H(1/2) receptors
1- inc contractility
2- inc pacemaker rate
3- H2 receptors
His causes (increased/decreased) capillary permeability causing (2) due to H(1/2) receptors on (4).
1- inc permeability (separation of endothelial cells)
2- edema (fluid and molecules in perivascular space)
3- H1
4- BVs - endothelium
=> urticaria (His release in skin)
His will cause (constriction/relaxation) of GI tract smooth muscle via H(1/2)
His will cause (constriction/relaxation) of bronchiolar smooth muscle via H(1/2)
1- contraction (inc motility)
2- H1
3- bronchoconstriction
4- H1
His is responsible for mediating (1) signals at nerve endings in the CNS via H(1/2)
1- pain, itching
2- H1
His promotes secretion of (1) in the (2) via H(1/2)
1- gastric acid
2- parietal cells
3- H2
(1) are histamine releasing inhibitors by reducing (2). (3) are other drugs that can reduce His release.
1- cromolyn, nedocromil
2- mast cell degranulation
3- β2 agonists
compare 1st and 2nd generation H1 receptor antagonists
1st- sedative effects, more likely to block ANS receptors (more liposoluble); also has cholinergic, α-adrenergic, serotonin, Na channel antagonist effects
2nd- less sedating (less liposoluble) b/c less CNS effects + substrates of P-glycoprotein in BBB
H1 blockers MOA
inverse agonists (although still called H1 receptor antagonists)
what are the 3 uses for H1 receptor antagonists
- allergies: allergic rhinitis, urticaria
- motion sickness, nausea (1st gen. block H1, M1 since they have CNS effects)
- somnifacents (1st gen., insomnia Tx due to CNS effects)
list the adverse effects of H1 receptor antagonists
- sedation (more for 1st gen.)
- dry mouth (mostly 1st gen. –> anti-cholinergic effects)
H2 receptor blockers are mainly used to inhibit (1) in the treatment of (2) via (3) mechanism
1- gastric acid secretion
2- peptic ulcer, acute ulcer, GERD
3- competitive antagonism
list the adverse effects of H2 receptor antagonists
(generally extremely safe- <3% have adverse effects)
-HA, dizziness, diarrhea, muscular pain, constipation
-Given IV: confusion, hallucinations, agitation –> ICU patients that are elderly or have renal/hepatic dysfunction
Cimetidine is a (1) type drug used for (2) and has (3) and (4) as the main adverse effects.
1- H2 receptor antagonist
2- GERD (dec gastric acid secretion)
3- inhibits cytochrome P450 –> slows metabolism of other drugs
4- binds androgen receptors (antiandrogenic effects) => gynecomastia, reduced sperm count in men / galactorrhea in women
briefly describe the types of serotonin receptors
- 6 G-coupled protein receptors
- 1 ligand gated ion channel = 5-HT-3*****
what are the two types of serotonin agonists used
- 5-HT-1d/1b receptor agonist
- 5-HT-4 receptor agonist
(1) are the 5-HT-1d/1b receptor agonists used to treat (2). The main adverse effect is (3), therefore it is contraindicated in patients with (4).
1- sumatriptan / triptans
2- migraines (acute, severe)
3- coronary vasospasm
4- CAD, angina
describe the MOA of 5-HT-1d/1b agonists for treating migraines
Migraines: trigeminal nerve releases CGRP (calcitonin G-related peptide) on vasculature (CGRP receptor) causing vasodilation => migraine
-Triptans: i) binds 5-HT-1d on Trigeminal nerve to prevent CGRP release; ii) binds 5-HT-1b on vasculature –> vasoconstriction => migraine relief
describe the adverse effects for each 5-HT-4 receptor agonists
-Metoclopramide: somnolence, nervousness, dystonic rxns + rare extrapyramidal effects and tardive dykinesia
Cisapride: long QT interval => cardiac effects
list the types of serotonin antagonists
- 5-HT-2 antagonists
- 5-HT-3 antagonists
- Ergot Alkaloids
