Lecture 10 (DSA): Intro to ANS Pharm Flashcards
How do agonists activate a receptor?
Activate the receptor to signal as a direct result of binding to it.
Agonists can activate a receptor to produce effects in what 2 ways?
1) All of the receptors biologic functions
2) Selectively promote one function more than another
Antagonists do what to the signaling of receptor?
Block the generation of a signal by binding to the receptor
What are cholinomimetic agents?
Drugs that mimic ACh:
- AChR agonists
- Acetylcholinesterase inhibitors
What are cholinoceptor-blocking drugs?
AChR antagonists
What are sympathomimetic agents?
Drugs that mimic or enhance α- and β- receptor (agonists)
What are 2 ways sympathomimetic agents act as an agonist?
1) Enhance catecholamine release
2) Block re-uptake of catecholamines
What are adrenoceptor-blocking drugs?
α- and β- receptor antagonists
How does sympathetic innervation of the SA node affect heart rate?
Increases heart rate
What is the receptor on the SA node for sympathetic innervation?
β1 adrenergic receptor
How does parasympathetic innervation of the SA node affect heart rate?
Decrease in heart rate
What is the receptor on the SA node for parasympathetic innervation?
M2 (muscarinic)
What does sympathetic innervation of the atria cause?
Increase in contractility and conduction velocity?
What is the receptor in the atria for sympathetic innervation?
β1 adrenergic receptor
What does parasympathetic innervation of the atria cause?
Decrease in contractility
What is the receptor in the atria for parasympathetic innervation?
M2 (muscarinic)
What does sympathetic innervation of the tracheal and bronchial smooth muscle cause?
Relaxation
What is the primary receptor for sympathetic innervation of the bronchial and tracheal smooth muscle?
β2 adrenergic receptor
What does parasympathetic innervation of the tracheal and bronchial smooth muscle cause?
Contraction
What is the primary receptor for parasympathetic innervation of the bronchial and tracheal smooth muscle?
M2=M3 (muscarinic)
What does sympathetic innervation of the bronchial glands cause?
Decreased secretion or increased secretion
What are the α1 receptors of bronchial glands responsible for?
Decreased secretion
What are the β2 receptors of bronchial glands responsible for?
Increased secretion
What does parasympathetic innervation of the bronchial glands cause?
Contraction
What receptors are found on bronchial glands for parasympathetic innervation?
M2, M3 (muscarinic)
What are the neurotransmitters and receptors for parasympathetic nervous system?
NT: ACh
Receptors: nAChR and mAChR
What are the neurotransmitters and receptors for sympathetic nervous system?
NE > Epi; ACh
Receptors: α, β, nAChR, and mAChR
Sympathetic nervous system uses what NT to activate which receptor in the adrenal medulla to release what NT?
ACh activates nicotinic ACh receptors to release epinephrine
Sweat glands contain what receptor on them and are innervated by what part of the autonomic NS?
Muscarininc choline receptos (mAChR) activated by ACh from the sympathetic nervous system
Synthesis of epinephrine primarily occurs where; from what?
Adrenal medualla from NE—->Epi
Dopamine is the precursor to what?
NE and epinephrine
Which muscarinic receptors are coupled to Gq/11 and their activation results in?
M1, M3, M5
- Activation of PLC; IP3, DAG cascade (smooth muscle contraction)
When IP3 levels go up what occurs?
Contraction of smooth muscle
Which muscarinic receptors are coupled to Gi/o and their activation results in?
M2 and M4
- Inhibition of AC; decreased cAMP production, activation of K+ channels
A decrease in cAMP production controlled by the M2 receptors of cardiac muscle have what affect?
Decrease in strength and force of contraction in cardiac tissue, decreases rate.
Why is having M3 receptors important in the gut?
When stimulated by the parasympathetic nervous system will causes contraction allowing for digestion to resume
Explain the basic mechanism of tyrosine to NE?
Tyrosine enters the nerve and is converted to dopa, then to dopamine (in the cytoplasm). Dopamine is shuttled into vesicle where it is converted to NE.
After the NE or epi has performed its function on the α- or β-receptors what occurs?
Will undergo reuptake by a transporter and be stored until needed again.
What is the vesicular monoamine transporter (VMAT-2)?
- Transports NE, Epi, DA, and serotonin into vesicles for storage
- Inhibited by Reserpine
What does cocaine inhibit?
Blocks the transporter of NE, causes NE accumulation
What are the 2 main enzymes for the metabolism of catecholamines?
1) Monoamine oxidase (MAO)
2) Catechol-O-methyltransferase (COMT)
Are there degradative enzyme for catecholamines during signaling?
No, they differ from cholinergic signaling, and instead undergo reuptake into the nerve.
Where are the Alpha-1 receptors found?
Vascular, GU smooth muscle, intestinal smooth muscle, Heart
What is the Alpha-1 response in the vascular and GU smooth muscle?
Contraction = Vasoconstriction
What is the Alpha-1 response in the heart?
Increased contractile force, arrhythmia’s
Where are the Alpha-2 receptors found?
Vascular smooth muscle, pancreatic islet (B cells), Platelets, and nerve terminals
Function of Alpha-2 receptors in nerve terminals and vascular smooth muscle?
Nerve terminals - Decreased release of NE
Vascular - Contraction
Function of Alpha-2 receptors on platelets?
Aggregation
Where are the Beta-1 receptors found?
Heart and Juxtaglomerular cells
Function of the Beta-1 cells in the heart?
Increased force and rate of contraction and AV nodal conduction velocity
Where are the Beta-2 receptors found?
Smooth muscle (vascular, bronchial, GI, GU), Skeletal muscle
Function of Beta-2 receptors
- Relaxation of smooth muscle
- Glycogenolysis; uptake of K+
Epinephrine has a stronger affect on which adrenergic receptor?
Beta-2
In the heart which receptor produces the greatest sympathetic effects?
Beta-1
In the blood vessels which receptor predominates for the sympathetic nervous system?
Alpha-1
In the heart which receptor predominates for parasympathetic innervation?
Muscarinic (M2)
In the blood vessels which receptor predominates for parasympathetic innervation?
Muscarinic (M3)
ACh & muscarinic agonists given IV cause what, due to?
Vasodilation due to release of nitric oxide (NO)
Smooth muscle of blood vessels are NOT innervated by?
Parasympathetic neurons
Activation of mAChRs on endothelial cells causes production and release of?
Endothelium-derived relaxing factor (EDRF), also known as nitric oxide (NO)
Where are chromaffin cells located and what kind of receptor do they contain?
Found within the Adrenal Medulla and contain NAChR’s
What are the effects of Reserpine?
Blockade of NE storage and depletion by MAO
Botulinum toxin effects?
Anticholinergic; inhibition of NT release
Nicotine and pilocarpine are?
nAChR and mAChR agonists (Cholinomimetic)
Tubocurarine and atropine are?
nAChR and mAChR antagonists (Anticholinergic)
Alpha blockers (phentolamine) and beta blockers (propranolol) are?
Antiadrenergic
Alpha agonists (nepinephrine) and beta agonists (albuterol) are?
Adrenomimetic