Autoacoids And Autacoid Antagonists Flashcards
Pupillary sphincter is interacted by _______________
M3
Radial muscle of the eye is innervated by
Autonomic system (PNS/CNS)
What compounds are autacoids?
- histamine
- serotonin
- eicosanoids
All histamine receptors are _________ protein linked and have ___________ activity
G protein; constitutive activity (the receptors still have some activity even in the absence of agonists)
Where can Histamine 1 (H1) receptors be found?
What kind of G protein does it have?
- endothelium
- smooth muscle cells
- nerve endings
-Gq protein (PLC)
Where can H2 receptors be found and what type of G protein are the coupled with?
- gastric mucosa
- cardiac muscle cells
- some immune cells
-Gs (adenylyl cyclase)
Which H receptor is found in the gastric mucosa?
H2
MUCOSA not smooth muscle
H2 receptors cause vasodilation by _______________ while H1 receptors cause vasodilation by ______
Acting on vascular smooth muscle and uses cAMP;
Acting on endothelial cells and cause production of NO
What is the effect of H2 receptors on the heart
↑ contractility and ↑ pacemaker rate
Which histamine receptors are found on the heart?
H2
Histamine induced edema results form the action of histamine on ________ receptors in blood vessels
H1
What is the effect on ____ (histamine) receptor on bronchial and GI smooth muscle?
H1; CONTRACTION
What is the effect of the activation of H2 receptors on gastric parietal cells?
Powerful stimulant of gastric acid secretion
What are the three classes of drugs that are histamine antagonists
- physiological antagonists
- release inhibitors
- receptor antagonists
__________ in a physiological antagonist to histamine
Epinephrine
___________ and ________ are release inhibitors which are histamine antagonists
Cromolyn; nedocromil
Is the MOA of cromolyn and nedocromil and what kind of drugs are they?
They are release inhibitors that act as histamine antagonists
Reduce immunologic mast cell degranulation
_______ agonists appear to be bale to ↓ histamine release
β2
What are two types of H1 receptor antagonists and what is a key difference?
1st generation: sedative effects and anti muscarinic effects
2nd generation: less sedating effect because they have P glycoproteins and less liposoluble
________ generation of H1 receptor antagonists have less sedative effects because of: (2)
2nd generation
- less liposoluble
- P glycoproteins
Examples of first generation H1 receptor antagonist (7)
- chlorpheniramine
- cyclizine
- diphenhydramine
- dimenhydrinate
- hydroxyzine
- meclizine
- promethazine
What 3 drugs are 2nd generation H1 receptor antagonists
- fexofenadine
- loratadine
- cetirizine
H1 blockers are now know to be _______________ because the H1 receptors have constitutive activity
Inverse agonists
H1 receptor antagonists are useful for treating __________ but NOT for __________
Allergic conditions;
NOT useful in treating bronchial asthma because histamine is not the only mediator in that condition
Which class of drugs is useful for treating motion sickness and nausea? MOA?
- 1st generation H1 receptor antagonists
- block central H1 and M1 (emesis) receptors
- second generation is not as full because cant enter CNS as well and dont have the ability to block M1 receptor
What kind of drug is diphenhydramine and what can it be used for?
- 1st generation H1 receptor antagonist
- treat insomnia, allergic reactions
What four drugs are H2 receptor antagonists?
- cimetidine
- ranitidine
- famotidine
- nizatidine
-tidine
What is the main clinical use of cimetidine and other similar drugs?
Inhibits gastric acid secretion (competitively blocks H2 receptors on parietal cells)
Clinical uses for H2 receptor antagonists:
- peptic ulcers
- acute stress ulcers
- GERD
H2 receptor antagonists are very safe drugs except for _________ especially in patients with ________
Cimetidine;
Elderly patients or those who have renal or hepatic dysfunction
What are some adverse effects of cimetidine?
- Confusion, hallucinations, and agitation when given IV to elderly patients or those with renal/hepatic dysfunction
- inhibits P450
- had antiadrogenic effects: gynecomastia, ↓ sperm count and galactorrhea in women
All of sertonin receptors are G protein coupled except _________ which is __________
5 HT3; ligand gated ion channel
______ is the only monoamine NT receptor that functions as a ligand gated ion channel
5-HT3 receptor
What are the two serotonin receptor agonists class of drugs?
5HT 1D/1B
5 HT4
What is the suffix for 5HT 1D/1B receptor agonists?
- -triptan
5 HT 1D/1B receptor agonists are contraindicated in ________
Patients with coronary artery disease or angina because they can cause coronary vasospasm
Triptans are the first line therapy for ________________
TREATMENT of acute severe migraine attacks
What drug is useful in the prophylaxis for migraines?
Propranolol (β blocker)
What is the MOA of 5- HT1D/1B receptor agonists in treating migraines?
- Can bind to the 5-HT 1D receptor on the nerve terminal which then inhibits the release of CGRP form the nerve terminal and thus preventing vasodilation
- Can bind to the 5 HT 1B receptor on the blood vessel which causes vasoconstriction
Vasodilation/vasoconstriction is what causes migraines
Vasodilation
Where is 5HT 1D receptor located and what is the effect when triptans bind to it?
On the nerve terminal;
Prevents the release of CGRP and thus prevents vasodilation
___________ and ________ are 5HT4 receptor agonists
Metoclopramide; cisapride
Both are prokinetic agents
Metoclopramide is a _________ agonist and is a prokinetic agent. How? (2 ways)
5 HT4 receptor;
Prokinetic effect: facilitates gut motility
- Facilitates release of Ach from enteric neurons → contractions
- Counteracts the inhibitory effects dopamine has on cholinergic neurons
What are some adverse effects of metoclopramide?
- somnolence (drowsiness), nervousness and dystonic reactions
- extrapyrmaidal effects and tardive dyskinesia (rare) because it blocks the dopamine effects
________ is no longer given as a prokinetic agent due to cardiac adverse effects due to _________
Cisapride; prolonged QT interval
Classes of drugs that are sertonin antagonists
- 5 HT2 receptor antagonists
- 5 HT3 receptor antagonists
- ergot alkaloids
Cyproheptadine is a _________________ that is used for _______________
5 HT2 receptor antagonist;
Allergic rhinitis, vasomotor rhinitis, and management of serotonin syndrome
Which drug also also potent H1 blocking actions?
Cyproheptadine (5 HT2 receptor antagonist)
This is why it can be used to treat allergic rhinitis
__________ is a 5 HT3 receptor antagonist that is used for _________
Ondansetron;
Anti emetic that is used for severe nausea and vomiting that occurs with chemotherapy
Ergot alkaloids are useful for treating migraine pain; specifically _________ and _________
(triptans are preferred)
Ergotamine and dhihydroergotamine
What class and specific drugs would be used to treat hyperprolactinemia caused by a pituitary tumor?
Ergot alkaloids;
Bromocriptine and cabergoline
If oxytocin is ineffective in controlling postpartum hemorrhage, give ______ or ________
Ergonovine or methylergonovine IM
Ergot alkaloids
Ergonovine given via IM can be used to treat ____________ but if given via IV, can be used for __________
Postpartum hemorrhage (if oxytocin is ineffective)
Diagnosis of variant angina because it causes coronary spasm in patients with it
_____________ of variant angina can be done via what ergot alkaloid?
Diagnosis;
Ergonovine given via IV
What are some clinical uses that ergot alkaloids are used for?
- treatment of migraines (ergotamine and dihydroergotamine)
- hyperprolactinemia (bromocriptine and cabergoline)
- post partum hemorrhage ( ergonovine or methylergonovine)
- diagnosis of variant angina (ergonovine)
What are adverse effects of ergot alkaloids and when is it contraindicated?
- vasospasm
Contraindicated in:
- pregnant women
- patients with peripheral vascular disease, coronary artery disease, HTN, and impaired hepatic/renal function
- don’t give with drugs that cause vasoconstriction
What are the main subgroups of eicosanoids and what is the main course of eicosanoids ?
Subgroups:
- prostaglandins
- prostacyclins
- thromboxanes
- leukotrienes
Arachadonic acid is the main source
COX 1 is found in ___________ as a ________ and is involved in _______
Most cells; constitutive enzyme; normal homeostasis
COX 2 is found in __________
Inflammatory cells; induced by inflammatory stimuli
____________ and _______ are leukotrienes that are potent _________ and secreted in asthma and anaphylaxis
LTC4 and LTD4;
Bronchoconstrictors
The contractile effects of eicosanoids on smooth muscle are mediated by ______ while the relaxing effects are mediated by _______
Calcium; cAMP
____________ is an eicasanoid analog (_____ analog) that is used to prevent peptic ulcers in patients taking high doses of NSAIDS
Misoprostol; PGE1 analog
Reasoning: NSAIDs block COX1 and thus prevent the formation of prostaglandins which are protective in the gastric mucosa and prevent erosion.
Which eicasanoid drug is a PGE2 analog?
Dinoprostone
Ripens cervix near term and is an abortifacient
____________ is a ______ analog that is used to maintain patency of the ductus arteriosus and is also used for _______
Alprostadil; PGE1 analog
Also used for impotence
Epoprostenol, a _____ analog is used for (2)
- severe pulmonary hypertension
- prevent platelet aggregation in dialysis machines
Analog of a prostacyclin
What is the use of latanoprost?
It is a PGF2α derivative used for glaucoma
What are the three classes of drugs that are eicosanoid antagonists?
- leukotrienes pathway inhibitors: 5-lypoxygenase inhibitors and LTD4 receptor antagonists
- glucocorticoids
- NSAIDs
Zileuton inhibits ______
5-lypoxygenase (enzyme)
What are the two antagonists against LTD4 RECEPTORS
- zafirlukast and montelukast
Glucocorticoids inhibits __________ and also inhibits the synthesis of _________
- PLA2 → no release of arachadonic acid
- synthesis of COX 2
