Autonomic Nervous System, Adrenergic Agonists Flashcards
What are sympathomimetic drugs? How are their effects mediated?
drugs that mimic pharmacological and physiological actions of the endogenous catecholamines
activation of adrenergic receptors located on their effector cells and tissues
Sympathetic nerve activity mediates ____ release from nerve terminals. What does this neurotransmitter do next?
NE
binds to and activates adrenergic receptors located on postsynaptic effector tissues and presynaptic sites
What are the 3 types of adrenergic agonists?
- direct-acting: neurotransmitter and drug bind directly to and activate adrenergic receptors
- indirect-acting: mediate physiological response that involves increasing the synaptic levels of endogenous catecholamines
- mixed-acting: directly activate adrenergic receptors and increase the release of NE from adrenergic nerve terminals
What affects the capacity of sympathomimetic drugs to produce physiological responses consistent with functional patterns produced by SNS activation?
their similarity in chemical structures in comparison to that of NE and EPI
Why isn’t receptor selectivity for a given agonist absolute?
at higher concentrations, a given drug or catecholamine may interact with and activate other subtypes of classes of receptors
What 6 characteristics influence the pharmacological interactions between specific agonists and adrenergic receptors?
- tissue distribution of adrenergic receptors
- number of adrenergic receptors expressed at specific sites
- interactions between the sympathetic and parasympathetic nervous systems at target sites
- pathophysiological and disease states
- background level of sympathetic nerve activity
- levels of endogenous catecholamines and/or sympathomimetic drugs
What is the phenomenon of adrenergic receptor desensitization? What 3 mechanisms have been suggested to explain this?
prolonged exposure of adrenergic receptors to specific agonists reduces the responsiveness of these receptors, producing a progressive attenuation in the tissue’s capacity to facilitate physiological responses
- sequestration of receptors so that they are unavailable for interaction with ligands
- downregulation - disappearance of receptors by destruction or decreased synthesis
- inability to couple to G-protein due to receptor dephosphorylation on the cytoplasmic end
How do the α-agonists’ receptor selectivity compare?
Phenylephrine - α1>α2»_space;»> β
Dexmedetomidine, Medetomidine, Xylazine - α2>α1»_space;»> β
How do the mixed α- and β-agonists’ receptor selectivity compare?
norepinephrine - α1=α2; β1»β2
epinephrine - α1=α2; β1=β2
How do the β-agonists’ receptor selectivity compare?
Dobutamine - β1>β2»_space;» α
Isoproterenol - β1=β2»_space;» α
Albuterol, Terbutaline - β2»β1»» α
How do the dopamine agonists’ receptor selectivity compare?
Dopamine - D1=D2»_space; β»_space; α
Fenoldopam - D1»>D2
What are the 4 major tissue actions of α1 receptor activation?
- most vascular smooth muscle contraction
- pupillary dilator muscle contraction (dilates pupil)
- urethral smooth muscle contraction
- splenic capsule contraction
What are the 3 major tissue actions of α2 receptor activation?
- platelet aggregation
- adrenergic and cholinergic nerve terminal inhibition of transmitter release
- selected vascular smooth muscle contration
What are the 2 β1 and 3 β2 tissue actions in response to activation?
β1
- increase in rate and force of heart contraction
- increase in renin release from juxtaglomerular cells
β2
- respiratory, uterine, and vascular smooth muscle relaxation
- gluconeogenesis in the liver
- increase in insulin secretion in the pancreas
What is the main tissue action of β3 receptor activation?
activation of lipolysis of fat cells
What are the major tissue actions of D1 and D2 receptor activation?
D1 = vascular smooth muscle dilation of select blood vessels
D2 = modulation of neurotransmitter release from autonomic nerve terminals
How does the action of α, β1, and β2 receptor activity compare in the heart? How does agonist selectivity compare?
α - blood vessel vasoconstriction
- PE; EPI > NE»_space;> ISO
β1 - augmented ionotropic and chronotropic effects
- ISO > EPI >/= NE
β2 - blood vessel vasodilation
- ISO > EPI»_space;> NE