Autonomic Pharmacology Flashcards
what are 2 key roles of the autonomic nervous system
1) modulate contraction of smooth muscle
2) secretion from (endocrine and exocrine) glands
where are the neural connections of the somatic vs the autonomic (PSNS and SNS) nervous systems
Somatic: in the CNS
Autonomic: in the PNS (PSNS - ganglia located close to the organ; SNS - ganglia located close to the spinal cord)
in the autonomic nervous system, ganglia are located in (afferent/efferent) pathways
efferent
the autonomic nervous system has (myelinated/unmyelinated) preganglionic neurons and (myelinated/unmyelinated) postganglionic neurons
myelinated; unmyelinated
what are the 2 arms of the autonomic nervous system
PSNS and SNS
what is the outflow of the sympathetic NS
thoracolumbar
what is the outflow of the parasympathetic NS
craniosacral
what is the ratio of pre to postganglionic neurons for the sympathetic ns? parasympathetic ns?
sympathetic: one pre to many post
parasympathetic: one pre to one post
what is the distribution of RESPONSE and DISCHARGE for the sympathetic ns? parasympathetic ns?
sympathetic: generalized response, diffuse discharge
parasympathetic: limited response; discrete discharge
T/F in general the SNS and PNS are physiological antagonists
T
is the SNS or PNS essential for life
PNS
what are 5 functions of the PNS:
1) pupillary ____________
2) _________ GI motility
3) __________ urination and defecation
4) __________ hr and bp
5) __________ absorption of nutrients
1) constriction
2) increased
3) increased
4) decreased
5) increased
which branch of the autonomic nervous system is not essential for life
sympathetic nervous system
what are the 6 functions of the SNS:
1) ________ heart rate and blood pressure
2) splenic ___________
3) ___________ of vessels in the skin
4) pupillary ____________
5) broncho___________
6) ________ blood glucose
1) increase
2) contraction
3) constriction
4) dilation
5) dilation
6) increase
where are the sites of chemical transmission in the autonomic nervous system
1) between the pre and post-ganglionic neuron
2) between the post-ganglionic neuron and the target organ
what are the 7 sites for pharmacological intervention in the PRESYNAPTIC neuron
1) action potential
2) synthesis of NT
3) storage of NT
4) metabolism of NT
5) release of NT
6) reuptake of NT
7) degradation of NT
what are the 3 sites for pharmacological intervention in the POSTSYNAPTIC neuron
1) receptor binding
2) receptor stimulation (effectors)
3) response (secondary messengers)
most drugs act via modifying actions on the pre or postsynaptic receptor
postsynaptic
cholinergic neurons release
ACh
all motor fibers to skeletal muscle use what NT at the neuromuscular junction
ACh
what is the subdivision of cholinoreceptors
nicotinic (Nn and Nm) and muscarinic (M1-M5)
what is the difference between Nn and Nm cholinoceptors
Nn: nicotinic neuronal (aka postganglionic)
Nm: nicotinic motor end plate (neuromuscular junction)
adrenergic neurons release
catecholamines (dopamine, E, NE)
the adrenal medulla releases primarily _________, and some _________
epinephrine; norepinephrine
α1 and α2 adrenoceptors are involved in
contraction
describe the location of the following adrenoceptors:
β1:
β2:
β3:
β1 - heart
β2 - smooth muscle
β3 - fat
all preganglionic neurons release the NT ______, which binds to ______ receptors on the postganglionic neuron
ACh; nicotinic (N)
what effectors have muscarinic ACh receptors for the PARASYMPATHETIC NS
cardiac and smooth muscle; gland cells; nerve terminals
what effectors have muscarinic ACh receptors for the SYMPATHETIC and PARASYMPATHETIC NS
sweat glands
what effector organs respond to dopamine as a NT from the SYMPATHETIC NS
renal vascular smooth muscle
what effector organs have α and β adrenergic receptors for NE from the SYMPATHETIC NS
gland cells; cardiac and smooth muscle
what type of ACh receptors exist at the gastrointestinal and genitourinary smooth muscle
M3
what type of ACh receptors exist at the bronchiolar SM
M3
what type of ACh receptors exist at the heart
M2
what type of ACh receptors exist at the salivary gland
M3
what type of ACh receptors exist at the eye
M3
what type of ACh receptors exist at the autonomic nerve endings
M2
what type of SNS receptors exist at the heart
β1
what type of SNS receptors exist on smooth muscle of the skin and splanchnic vessels
α1
what type of SNS receptors exist on smooth muscle of the skeletal muscle vessels
β2
what type of SNS receptors exist on splenic smooth muscle
α1
what type of SNS receptors exist at the bronchiolar SM
β2
what type of SNS receptors exist at the GI tract wall? GI tract sphincters
α2, β2; α1
what type of SNS receptors exist at the genitourinary tract SM of the:
1) bladder wall
2) sphincter
3) pregnant uterus
1) β2
2) α1
3) β2, α1
what type of SNS receptor exists at the penis and seminal vesicle smooth muscle
α1
what type of SNS receptor exists on salivary glands
α1
what type of SNS receptor exists on the eye muscles to cause:
1) contraction
2) relaxation
α1; β2
what type of SNS receptor exists at autonomic nerve endings
α2
adrenergic receptors alter
1) rate and force of contraction of the heart
2) tone of the blood vessels
what is the effect of α receptors on vascular smooth muscle
contraction: increased TPR -> increased BP -> reflex decrease in heart rate
what is the effect of β receptors on vascular smooth muscle
relaxation: decreased TPR -> decreased BR -> increased heart rate
Epinephrine:
1) what type of agonist/antagonist
2) what receptors activated
1) mixed α/β agonist
2) activates all α and β subtypes
What are the cardiac effects of epinephrine and why
increases rate (chronotropy) and force (ionotropy) of contraction via β1
What are the vascular smooth muscle effects of epinephrine and why
mainly vasoconstriction -> increased TPR via α1
some vasodilation -> decreased TPR via β2
By activating α1 receptors, what are some other effects of epinephrine
contraction of spleen, contraction of bladder sphincter, contraction of radial muscle of the iris causing mydriasis
By activating β2 receptors, what are some other effects of epinephrine
bronchodilation, decreased GI contractions, decreased uterine motility, relaxed bladder
How do drugs that stimulate α1 receptors cause the eyes to dilate
Contracting the radial muscle of the iris -> mydriasis
Clenbuterol:
1) what type of agonist/antagonist
2) what receptors activated
1) selective β agonist
2) β2
Terbutaline:
1) what type of agonist/antagonist
2) what receptors activated
1) selective β agonist
2) β2
Dobutamine:
1) what type of agonist/antagonist
2) what receptors activated
1) selective β agonist
2) β1
Phenylephrine:
1) what type of agonist/antagonist
2) what receptors activated
1) selective α agonist
2) α1
Isoproterenol:
1) what type of agonist/antagonist
2) what receptors activated
1) non-selective β agonist
2) β1/β2
What are the effects of clenbuterol/terbutaline and uses in the different species
bronchodilator
cats: asthma
dogs: chronic bronchitis
horses: lower airway disease
Ractopamine:
1) what type of agonist/antagonist
2) what receptors activated
1) non-selective β agonist
2) mainly β1, some β2
What is the therapeutic use of ractopamine and in what species
growth promotion in cattle; increases lean muscle deposition
What is the main therapeutic use of dobutamine and why
cardiac support (CHF) -> improves contracility and bp without significant tachycardia
what is a consequence of dobutamine overdose
ventricular tachycardia and hypertension
what is the main use of isoproterenol and what is a benefit with this drug particularly
stimulates heart (heart block or bradycardia); β2 stimulation also results in decreased TPR and decreased BP
what are the main therapeutic uses of phenylephrine
1) vasoconstriction and increased BP (with reflex drop in heart rate possible)
2) BP support
3) pupillary dilation
4) nasal decongestion (because of constriction)
what is unique about dopamine
dose-dependent effects
Dopamine receptor stimulation and effect:
1) low doses
2) moderate doses
3) high doses
1) D1: dilates renal vasculature -> increased GFR
2) β1: increases contractility
3) α1: increases TPR -> increased BP
what are ephedrine, pseudoephedrine, and phenylpropanolamine
direct and indirect acting sympathomimetics -> activation of α and β and release of NE
what are the two main therapeutic uses of ephedrine and pseudoephedrine
1) decongestion
2) urinary tract incontinence
what is the main therapeutic use of phenylpropanolamine
urinary incontinence due to hypotonic urethra
what 2 adrenergic agonists can you give a patient with low BP or reduced blood flow (vascular hypotension) in the short-term
1) epinephrine
2) phenylephrine
what can you give a patient presenting with cardiac insufficiency (bradycardia, cardiogenic shock, CHF)
1) dopamine
2) dobutamine
3) epinephrine
4) isoproterenol
what can you use in combination to produce LOCAL vasoconstriction
epinephrine and lidocaine
what can you use to treat bronchoconstriction
1) clenbuterol (horse)
2) terbutaline (small animal)
3) epinephrine (respiratory issues associated with anaphylaxis)
what can you use to treat nasal congestion
1) phenylephrine
2) pseudoephedrine
3) ephedrine
what is the mainstay treatment of anaphylaxis (which causes both bronchospasm and cardiovascular collapse from vasodilation)
epinephrine
what can you use as a mydriatic to facilitate retinal examination
phenylephrine
phenoxybenzamine:
1) what type of agonist/antagonist
2) what receptors activated
1) non-selective α-antagonist
2) α1, a2
prazosin:
1) what type of agonist/antagonist
2) what receptors activated
1) selective α-antagonist
2) α1
atenolol:
1) what type of agonist/antagonist
2) what receptors activated
1) selective β-antagonist
2) β1
metoprolol:
1) what type of agonist/antagonist
2) what receptors activated
1) selective β antagonist
2) β1
proponalol:
1) what type of agonist/antagonist
2) what receptors activated
1) nonselective β antagonist
2) β1, β2
carvedilol:
1) what type of agonist/antagonist
2) what receptors activated
1) mixed adrenergic antagonist
2) β > α1
what are the therapeutic uses of phenoxybenzamine
1) diagnosis and treatment of pheochromocytoma
2) hypertonic urethra
what is a major adverse effect of phenoxybenzamine and an important therapeutic consideration
can cause severe hypotension (blocking α1) -> do not want to give epinephrine to reverse because the α receptors are blocked, so only the β effects of epinephrine will remain -> can get even further hypotension
what are the therapeutic uses of prazosin
hypertonic urethra due to functional obstruction; can be used to help treat CHF
in regards to β antagonists, drugs with higher affinity for what receptor are more useful clinically
β1
β antagonists are used for what 2 diseases
1) cardiovascular
2) ocular
what is the therapeutic use of propanolol
supraventricular and ventricular tachyarrhythmias, thyrotoxicosis for cats with hyperthyroidism, pheochromocytoma, HCM in cats
what β antagonist has minimal hepatic first pass effects
atenolol
what are the therapeutic uses of atenolol and metoprolol
same as propanolol BUT they have reduced adverse effects like bronchospasm
what are the therapeutic usees of carvedilol
cardiomyopathy in dogs, free-radical scavenger
bethanechol:
1) what type of agonist/antagonist
2) what receptors activated
1) cholinergic agonist
2) muscarinic
what is the therapeutic use of bethanechol
stimulates urinary bladder -> hypocontractile bladder
when is bethanechol contraindicated
GI or urinary obstruction
what is a possible side effect of bethanechol and what is the antidote
salivation, lacrimation, urination, defacation; atropine (muscarinic blocker)
what are the therapeutic uses of pilocarpine
pupillary constriction (miosis) and tear production
what is the mechanism of action of edrophonium and what are 2 key factors about it
prolongs half life of ACh by binding to the active site of acetylcholinesterase; short duration of action and poor penetration into the CNS
what is the mechanism of action of neostigmine/pyridostigmine and what are 2 key factors
carbamylates active site of acetylcholinesterase; longer duration of action than edrophonium and poor penetration into CNS
what are the therapeutic uses of edrophonium/neostigmine/pyridostigmine
intestinal motility disorders (ex. paralytic ileus)
what are the 2 classes of non-selective muscarinic cholinergic antagonists
tertiary amides, quaternary ammonium compounds
what cholinergic antagonists are tertiary amides
atropine, oxybutynin tropicamide
what cholinergic antagonists are quaternary ammonium compounds
propantheline, ipratropium, hyoscine
what are the therapeutic uses of atropine
mydriasis (pupil dilation) and reduced ciliary spasms (uveitis), treating organophosphate poisoning, bradyarrhythmias
what are the therapeutic uses of tropicamide
pupil dilation (mydriasis)
what are some possible adverse effects of oxybutynin
constipation and urine retention
what are the therapeutic uses of oxybutynin and what is a general caution
spastic bladder; do not use if bladder or GI obstruction or if there is an infection
do tertiary amines or quaternary ammoniums have more CNS effects
tertiary amines
what are the therapeutic uses of propantheline
GI motility disorders, spastic bladder
what are the therapeutic uses of ipratropium
bronchospasm associated with respiratory disorders
what are the therapeutic uses of hyoscine and what is a potential adverse effect
GI motility disorders; can cause tachycardia and reduced GI motility
what is a potential use of hyoscine
acute severe exacerbations of airway obstruction in horses -> it causes immediate bronchodilation
