Intro to ANS pharm Flashcards by Andrea Parsons

what is an agonist?

activate the receptor to signal as a direct result of binding to it

some agonists activate a receptor to produce all of the receptor’s biologic functions

some agonists selectively promote one receptor function more than another

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what is an antagonist?

bind to receptors but do not activate generation of a signal

interfere with the ability of an agonist to activate the receptor

some antagonists suppress the basal signaling of receptors that are constitutively active

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what is the sympathetic response of the ANS

fight or flight

thoracolumbar location

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what is the parasympathetic response

rest and digest

craniosacral

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what is the major NT of parasympathetic NS

ACh

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what are the major receptors in the parasympathetic pathway

nicotinic AChr (found at all postganglionic nerves)

muscarinic AChR (found on all smooth muscle in the parasympathetic NS)

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what are the two exceptions to the normal rules of sympathetic and parasympathetic innervation and NT’s

sweat glands
-main receptor is muscarinic
and the main NT is ACh
this is a sympathetic response

adrenal medulla
-main receptor is nicotinic
and the main NT is ACh
this is a sympathetic response

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what is adrenergic?

Sympathetic nervous system

“adrenaline” fight or flight

usually involves beta and alpha receptors

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what is cholinergic

parasympathetic nervous system

usually involves the nicotinic and muscarinic receptors

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what is the major NT of the parasympathetic NS

Acetylcholine

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where is ACh found

All preganglionic autonomic fibers
All postganglionic parasympathetic fibers
Few postganglionic sympathetic fibers (sweat glands–> ACh activating muscarinic receptors in the sympathetic ns)

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what is the significance of norepinephrine

where is its location

The major neurotransmitter of the sympathetic nervous system
The vast majority of postganglionic sympathetic fibers

it is a catecholamine

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where is epinephrine synthesized

Synthesis only occurs in the adrenal medulla and in a few epinephrine-containing neuronal pathways in the brainstem

epinephrine is a catecholamine

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what is dopamine a precursor for

and what is dopamines function

NE and Epi precursor
Acts on the CNS and renal vascular smooth muscle

dopamine is a catecholamine

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WHAT are the steps in cholinergic neurotransmission?

1 Junctional transmission
 Synthesis of acetylcholine (ACh)
 Storage
 Release
 Destruction (reuptake)

2 ACh signaling

3 End organ effects

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what is the function of nicotinic receptors?

excitatory

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what is the function of muscarinic receptors

excitatory or inhibitory

sweat excretion

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Norepinephrine location

principal NT of most sympathetic postganglionic fibers and of certain tracts in the CNS

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how does tyrosine get into the nerve terminal?

sodium dependent transporter

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why is sodium ECF important?

because of transport of tyrosine (for catecholamine synthesis)
and because of transport of choline into the nerve terminal to make ACh

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what is the order of synthesis of catecholamines

tyrosine
dopa
dopamine
norepinephrine
epinephrine

(tyrosine to dopamine in nerve cytoplasm)
NE to Epi in the adrenal medulla

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why is cocaine a sympathetic stimulant?

because it blocks the reuptake of NE back in to the nerve terminal remaining there longer, leading to increased sympathetic output

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VMAT-2

Transports NE, Epi, DA, and serotonin into vesicles (promiscuous)

Release upon action potential and Ca2+ influx

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what does resperine do?

blocks VMAT-2 (transporter)

decreased amount of NE stored in the vesicle
decreased amount of NE when released activates less alpha and beta receptors
now have decreased sympathetic tone and decreased blood pressure
but not a good drug b/c it was not very selective

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what does NET do? | DAT?

imports NE into the nerve terminal | DAT transports dopamine

metabolism of catecholamines occurs via what 2 enzymes?

MAO | COMT

in contrast to cholinergic signaling, termination of catecholamine action by degradative enzymes (i.e.. AChe) is....

is nonexistent in adrenergic signaling

is there parasympathetic innervation to the smooth muscle that surrounds the vasculature?

NO so no opposite response

what is the role of ACh and muscarinic agonist given IV?

cause vasodilation due to release of NO

what does NO do? what type of patient is this good for?

causes vasodilation for someone having a heart attack this is good because it dilates vessels around the heart, leading to increased perfusion

what are the agonists for alpha 1 what is the result of ligand binding to alpha 1

Epi ≥ NE >> Iso Phenylephrine Formation of IP3 and DAG, increased intracellular Ca2+

what is the end result of alpha 1 activation

``` Contraction vasoconstriction Glycogenolysis; gluconeogenesis Hyperpolarization and relaxation (in the gut) Increased contractile force; arrhythmias ```

what tissue is alpha 1 usually in

``` Vascular, GU smooth muscle Liver Intestinal smooth muscle Heart ```

alpha 1 known for....

smooth muscle contraction

alpha 2 known for its function in...

presynaptic vascular smooth muscle contraction decreased insulin production decreased release of NE

alpha 2 agonists result of ligand binding to alpha 2

Epi ≥ NE >> Iso Clonidine ligand binding causes inhibition of adenyl cyclase and decreased cAMP

tissue location of alpha 2

Pancreatic islets (β cells) Platelets Nerve terminals Vascular smooth muscle

Beta 1 primary location

heart juxtaglomerular cells

beta 1 agonists

Iso > Epi = NE Dobutamine

result of ligand binding to beta 1

stimulation of adenyl cyclase increased cAMP

end result/function of beta 1

Increased renin secretion Increased force and rate of contraction and AV nodal conduction velocity

beta 2 agonists

Iso > Epi >> NE Terbutamine

beta 2 location

``` Smooth muscle (vascular, BRONCHIAL, GI, GU) Skeletal muscle ```

beta 2 function/outcome

Relaxation of smooth muscles- vascular, bronchial, genitourinary, gastrointestinal Vasodilation/bronchiodilation Glycogenolysis; uptake of K+ USED IN ASTHMA

beta 3 agonists

Iso = NE > Epi

location of beta 3 and outcome of beta 3 activation

adipose tissue lipolysis

where is the location of M2 (muscarinic)

primarily found in heart

what is the outcome of activation of M2 receptors

slows down heart rate inhibition of cAMP production activation of K+ channels

where is the primary location of the M3 receptors

Glands, smooth muscle, endothelium | smooth muscle surrounding organs in the parasympathetic NS

what is the function of M3

constriction of lungs does so by.... IP3, DAG cascade -increased Ca to cause muscle contraction

what are alpha 1 blockers used for?

high blood pressure

what percentage of catecholamine release from the adrenal medulla is NE and how much Epi

80 % epi 20 % NE

what causes the release of epi and nE

triggered by the release of ACh from preganglionic fibers Ach binds to Nicotinic ACh receptors and produces a localized depolarization

what type of receptor are the dopamine receptors?

GPCR's

what is the result of Dopamine activating D1 receptors. Where are D1 receptors

D1 receptors are on renal smooth muscle it causes increases cyclic AMP and causes dilation vasodilation, natriuresis, and diuresis via renal vascular smooth muscle

what can dopamine at higher concentrations activate? and what would be the outcome of this

can activate alpha 1 and beta 1 receptors to cause and increase in heart rate and general vasoconstriction

what is necessary to have vascular relaxation in response to ACh?

an intact epithelium (endothelium) b/c when ACh activates mAChR's on endothelial cells NO is subsequently produced by the endothelial cells where it diffused back to the smooth muscle cells surrounding blood vessels and causes relaxation

what is the primary controlled variable in cardiovascular function

MAP

what are cholinomimetic agents

drugs that mimic ACh ``` AChR agonists Acetylcholiesterase inhibitors (keeps ACh in cleft longer) ```

what are cholinoceptor blocking drugs?

AChR antagonists

what are sympathomimetic agents

drugs that mimic or enhance alpha and beta receptor stimulation Agonists--> drugs that enhance catecholamine release, drugs that block reuptake

what are adrenoceptor blocking drugs

alpha and beta receptor antagonists

what are two examples of agents/drugs that interfere with NT synthesis

ChAT inhibitors (so can't make ACh) alpha-methyltyrosine (blocks tyrosine hydroxylase) so can't make tyrosine to Dopa this causes depletion of NE and minimal depletion of ACh

what are two examples of agents that inhibit NT storage?

Vesamicol--> cholinergic -blocks ACh storage Resperpine--> adrenergic -blocks NE storage and depletion by MAO so it slows the parasympathetic output

what does botulinum toxin do

it is an anticholinergic and blocks NT release

what does bretylium and guanadrel do?

antiadrenergic by blocking the release of NT

what does hemicholinium do?

blocks choline uptake and causes subsequent ACh depletion | inhibition of NT reuptake

what does cocaine do?

blocks transport of NE | so there is a buildup of NE and prolongs adrenergic effects

what do AChE inhibitors do?

cause ACh accumulation at the synapse | so that means there is a prolonged symapthetic response

what do MAO inhibitors cause?

catecholamine accumulation in the nerve terminal because normally MAO metabolizes catecholamines that have been released and undergone reuptake within the nerve terminal