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
A 15-years old Quarter Horse mare presented with cough and increased abdominal effort during the expiratory phase of respiration. It was found that the patient is suffering from recurrent airway obstruction, an allergic form of airway disease (molds in forage). What adrenergic agonist could help control breathing effort in the mare? Why?
β2-adrenergic agonists - these receptors are present in bronchial smooth muscle, and activation results in the relaxation of the muscle and bronchodilation
Albuterol, Terbutaline, Isoproterenol
- Dobutamine β1>β12
What part of the autonomic nervous system is responsible for maintaining baseline airway tone?
PSNS - activation of bronchial muscarinic receptors contracts bronchial smooth muscles
What 3 selective β2-adrenergic receptor agonists are commonly used for respiratory problems?
- Terbutaline
- Albuterol
- Clenbuterol
How is Terbutaline typically used? What 2 activities does it lack?
(selective β2-adrenergic receptor agonist)
small animal patients - parenterally, orally
- at usual doses, it has little effect on cardiac (β1) receptors
- virtually no α-adrenergic activity?
How is Albuterol typically used? How can its aerosol form be used?
(selective β2-adrenergic receptor agonist)
cats and horses - alleviates bronchospasm or cough
improves hypoxemia in anesthetized horses
How is Clenbuterol typically used? What is another possible action? When is use contraindicated?
(selective β2-adrenergic receptor agonist)
horses - bronchodilator
parenterally and orally as a uterine relaxant for dystocia
food-producing animals - toxicity in humans
How can Isoflurane affect blood pressure? How does dose affect this?
potent vasodilator (even at subanesthetic doses), which causes a reduction in peripheral vascular resistance (low BP)
LOW = cardiac output preserved
HIGH = reduced cardiac output with depressant effects on myocardial contractility, which lowers BP
What 6 drugs are typically used for hypotension treatment while a patient is under isoflurane anesthesia?
- dopamine
- ephedrine
- dobutamine
- epinephrine
- norepinephrine
- phenyleprhine
Where does dopamine act? How do low-dose, moderate infusion, and higher rates of infusion affect adrenergic receptor activity?
IV LOW-DOSE = vasodilation of numerous vascular beds (lower BP)
MOD INFUSION RATES = activates cardiac β1-receptors, leading to increased cardiac contractility, heart rate, and cardiac output
HIGH DOSE INFUSION = activates vascular α1 receptors, leading to vasoconstriction and increased peripheral vascular resistance and remains a cardiac β1-receptor agonist
What is ephedrine? How does low and high dose administration compare?
noncatecholamine drug that is an α1, β1, and β2 agonist and induces the release of NE from postganglionic sympathetic nerve terminals
LOW-DOSE = primarily activates cardiac β1 and vascular β2 receptors
HIGH-DOSE = more marked and sustained increases in mean arterial pressure by activating vascular α1 receptors
What does Dobutamine typically act on? What else can it act as an agonist to?
β1 adrenergic receptors —> myocardial contractility > cardiac rate
β2 and α1 adrenergic receptors
What 3 actions does Dobutamine have? What is it particularly used for? Why is it not typically used for isoflurane induce hypotension?
- increases myocardial contractility
- increases cardiac index
- increases stroke volume
- low cardiac output flow states, like CHF
- only a modest agonist at α1 adrenergic receptors that would contract vessels and increase BP
How does epinephrine affect blood pressure? What happens at high doses?
potent cardiac stimulant and vasoconstrictive agent that can reverse marked hypotension and cardiac irregularities associated with anaphylactic shock
potent renal vasoconstrictor - decreases renal blood flow, possibly leading to damage
How does norepinephrine and phenylephrine affect blood pressure?
NE = treats hypotension by causing marked constriction of arteries and veins (can also constrict renal vascular beds
PE = selective α1 agonist that produces peripheral vasoconstriction —> typically used when cardiac output is adequate
What sympathomimetic drugs work best for vasoconstriction?
drugs selective for α-adrenergic agonists or have potent α-adrenergic activity with minimal β2-adrenergic effects
Why is epinephrine added to local anesthetics?
resulting vasoconstriction leads to a delay in the removal of the anesthetics from the site of injection
What adrenergic receptors are expressed on the smooth muscle of the splenic capsule? What does its activation cause? What drug is commonly used to induce this action?
α1-adrenergic receptors - SNS activation produces smooth muscle contraction
phenylephrine (selective α1) is used to induce splenic contraction to discharge RBCs into circulation and reduce the size of the spleen
What is nephrosplenic entrapment? What is typically used as a treatment?
condition common in horses when the left ventral and dorsal colon migrate between the spleen and the body wall and become entrapped over the nephrosplenic ligament, resulting in obstruction of the large colon
phenylephrine (selective α1) - reduces splenic area and thickness, making room for the colon to dislodge from the nephrosplenic space
How is phenylephrine used in opthalmology? How does it work?
selective α1 receptor agonist induces pupillary dilation (mydriases) prior to cataract surgery
α1 receptors are expressed on the radial dilatory muscle of the iris and on conjunctival blood vessels, and upon topical administration, it will cause contraction of the smooth muscle
- blanching and pupillary dilation
What is Horner’s syndrome? How is it treated?
oculosympathetic palsy that causes miosis (constriction), drooping of upper eyelid (ptosis), inward sinking of the eyeball (enophthalmos), and partial protrusion of the nictitating membrane
dilute solution of phenylephrine to both eyes = dilation of affect eye
What 2 selective α2 agonists are typically used in ophthalmology? What are 2 uses? Why are they not typically recommended?
Apraclonidine, Brimonidine
- decreases aqueous humor production
- reduces intraocular pressure (IOP) in humans
systemic side effects and lack of significant IOP lowering effects
What adrenergic receptors are present in the ureters, detrusor muscle, bladder base, and internal urethral sphincter? What happens upon sympathetic activation?
- URETERS = β2 receptors
- DETRUSOR = β2 and β3 receptors —> smooth muscle relaxation of bladder body
- BLADDER BASE = α1 receptors —> smooth muscle contraction of bladder base
- URETHRAL SPHINCTER = α1 receptors —> contraction
What is the most common cause of acquired urinary incontinence in female dogs and cats? How is it treated?
urethral sphincter incompetence
phenylpropanolamine —> increases urethral pressure values and improved urinary continence
How are β-adrenergic agonists in food production? Which one is most common?
growth promotion agents for livestock
Ractopamine - β1 agonist with some β2 activity
- cattle, swine, and turkey food additive to improve rate of weight gain, feed efficiency, and increase carcass leanness
True or false: Terbutaline, a β2-agonist, is considered a safe drug for use in animals with cardiac disease.
TRUE
α1-receptors are associated with which one of the following effects?
a. cardioacceleration
b. vasodilation
c. bronchodilation
d. pupillary dilation
e. pupillary constriction
D
