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CPR Exam 2 > Intro To ANS Pharmacology > Flashcards

Intro To ANS Pharmacology Flashcards

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1
Q

Describe the synthesis of ACh

A

Choline transporter transports choline from the extracellular space into neurons
ChAT catalyzes the synthesis of ACh by combing the acetyl moiety of acetyl coenzyme A with choline

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2
Q

Describe the storage of ACh

A

ATP-ase dependent ACh vesicular transporter transports ACh into vesicles

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3
Q

What is the order of cholinergic neurotransmission?

A

Synthesis of ACh
ACh storage
Release of ACh
ACh destruction

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4
Q

Describe the release of ACh

A

When the AP reaches the axon terminal depolarization causes the opening of voltage gated Ca channels resulting in a Ca influx
Ca influx promotes the fusion of the vesicular membrane with the cell membrane and ACh is released

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5
Q

Which protein is responsible for the fusion of the vesicle membrane and the synaptic membrane?

A

SNARE protein (VAMPs and SNAPs)

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6
Q

What terminates ACh signaling?

A

Cleavage of ACh into acetate and choline by AChE

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7
Q

What are the NTs and receptors for the somatic NS?

A

NT = ACh

nAChR

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8
Q

Describe the somatic NS

A

Consciously controlled actions

Movement, respiration, posture

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9
Q

Describe the ANS

A

Unconscious actions

CO, blood flow to various organs, digestion

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10
Q

What is the NT and receptor for the PNS/

A

ACh

Receptors: nAChR and mAChR

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11
Q

What are the NTs and receptors for the SNS?

A

NE > Epi (DA) and sometimes ACh

Receptors: alpha and beta adrenergic, (D) + nAChR and mAChR

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12
Q

Describe ACh

A

Major NT of the PNS
Found at all preganglionic autonomic fibers, all postganglionic parasympathetic fibers and a few postganglionic sympathetic fibers (e.g. sweat glands)
Activates nicotinic and muscarinic ACh receptors

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13
Q

Describe norepinephrine

A

Major NT of the SNS

Found at the majority of postganglionic sympathetic fibers

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14
Q

Describe epinephrine

A

Synthesized in the adrenal medulla and in a few epinephrine containing neuronal pathways in the brainstem
Upon depolarization of the preganglionic sympathetic neuron ACh is released and grinds to nAChRs (Nn) on the adrenal medulla releasing catecholamines (80% epi, 20% NE)

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15
Q

Describe dopamine

A

Precursor to NE and E
Synthesized in the cytoplasm of neurons
Has actions in the CNS and renal vascular smooth muscle

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16
Q

What are some co-neurotransmitters?

A

ATP, neuropeptide Y, vasoactive intestinal peptide, substance P, others

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17
Q

Where are parasympathetic nAChR (ionotropic) found?

A

CNs and autonomic ganglia (Nn)

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18
Q

What is the function of parasympathetic nAChR?

A

Excitatory

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19
Q

What are the agonists for nAChR?

A

ACh and nicotine

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20
Q

Where are sympathetic nAChR (ionotropic) found?

A

Adrenal medulla (Nn)

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21
Q

What is the function of sympathetic nAChR?

A

Release of catecholamines (mostly E)

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22
Q

Where are parasympathetic mAChR (metabotropic) found?

A

CNS, autonomic ganglia, effector organs (cardiac and smooth muscle, gland cells, nerve terminals)

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23
Q

What is the function of parasympathetic mAChR?

A

Excitatory and inhibitory

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24
Q

What are the agonists for a parasympathetic mAChR?

A

ACh and muscarine

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25
Where are sympathetic mAChR (metabotropic) found?
Sweat glands
26
What is the function of sympathetic mAChR?
Sweat secretion
27
What is adrenergic neurotransmission?
Neurotransmission in which catecholamines are released NE is the principal NT of most sympathetic postganglionic fibers Epi is the major NT released by the adrenal medulla DA is the predominant NT of the mammalian extrapyramidal system
28
Describe the synthesis of catecholamines
Tyrosine is transported into the cytoplasm of the nerve terminal Tyr —> DOPA —> dopamine In the vesicle: dopamine —> NE —> Epi NE to Epi mainly occurs in the adrenal medulla
29
What transports tyrosine into the nerve terminal during catecholamine synthesis?
Na dependent tyrosine transporter
30
Describe the storage of catecholamines
VMAT-2 transports DA, NE, epi and serotonin into the vesicle during catecholamine synthesis
31
What drug can inhibit VMAT-2?
Reserpine | Leads to the depletion of catecholamine so from sympathetic nerve endings
32
Describe the release of catecholamines from the vesicles
Occurs upon AP and influx of Ca Triggering event in the adrenal medulla is the release of ACh by the preganglionic fiber and its interaction with nAChRs on chromaffin cells to produce a localized depolarization
33
Describe the binding of catecholamines to adrenergic receptors
Catecholamines diffuse across the synaptic cleft and bind to adrenergic alpha and beta receptors (GPCRs), activating stimulatory and inhibitory G proteins depending on the receptor type
34
What is the major mechanism that terminates the actions of catecholamines?
Reuptake into the nerve terminals Two neuronal membrane transporters, NET (NE transporter) and DAT (dopamine transporter) are involved After reuptake catecholamines are stored in vesicles by VMAT2
35
What is the secondary mechanism for termination of catecholamine signaling?
Dilution by diffusion out of the junctional cleft and uptake at extraneuronal sites by the transporters ENT, OCT1 and OCT2 (non-neuronal catecholamine transporters found at various sites such as the liver, intestines, kidney, blood vessels) and subsequent metabolic transformation by MAO and COMT
36
What is the action of MAO (monoamine oxidase)?
Metabolizes catecholamines that have been released and undergone reuptake Associated with the outer surface of the mitochondria
37
What is the action of COMT (catechol-O-methytransferase)?
Metabolism of endogenous circulating and administered catecholamines (particularly in the liver) Largely cytoplasmic
38
In contrast to cholinergic signaling, termination of catecholamine action by degradative enzyme (e.g. AChE) is what?
Nonexistent in adrenergic signaling
39
What is the end result of alpha1 receptor activation?
Muscle contraction Smooth muscle contraction results in vasoconstriction Cardiac muscle contraction leads to an increase in contractile force on the heart (an exception is in the gut where activation of a1 receptor and subsequent increase in Ca causes hyperpolarization and muscle relaxation by activation of Ca dependent K channels)
40
What does the activation of alpha2 receptors result in?
Vascular smooth muscle contraction, decreased insulin secretion and a decreased release of NE (presynaptic alpha2 receptors)
41
The activation of any beta adrenergic receptor results in what?
Activation of adenylyl cyclase and increased concentrations of cAMP through the stimulatory Gs protein
42
Describe beta1 receptors
Found in the myocardium | Activation results in an increased force and rate of heart contraction and AV nodal conduction velocity
43
Describe beta2 adrenergic receptors
Found on smooth muscle and most other sites | Activation causes vascular, bronchial, genitourinary and GI smooth muscle to relax
44
Describe beta3 adrenergic receptors
Found only in adipose tissue | Activation results in lipolysis
45
Epinephrine has equal effects on which receptors?
``` A1 = a2 Beta1 = beta2 ```
46
NE has equal effects on which receptors?
Alpha1 = alpha 2
47
NE has a stronger effect on which receptors?
Beta 1 >> beta2
48
Muscarinic receptor activation results in what?
Contraction of smooth muscle (different intracellular signal than alpha 1 receptors) Miosis due to contraction of iris sphincter muscle Contraction of bladder detrusor muscle Contraction of intestinal SM Stimulate decrease in HR in SA node and contractility in cardiac muscle
49
DA can activate D1 receptor in renal smooth muscle and cause what?
Increased cAMP and causes dilation | Stimulation of D1 results in vasodilation, natriuresis and diuresis via renal vascular smooth muscle
50
At higher concentrations DA can stimulate alpha1 and beta1 adrenergic receptors causing what?
An increase in HR and generally vascular vasoconstriction
51
What is the general effect of alpha1 receptors upon autonomic stimulation?
Stimulate contraction of all smooth muscle Vasoconstriction due to contraction of vascular SM Mydriasis (pupil dilation) due to contraction of iris radial muscle Uterine contraction during pregnancy
52
What is the general effect of beta2 autonomic activation?
Relaxation of all SM Relaxation of tracheal and bronchial SM Relaxation of uterine SM Relaxation of intestinal SM
53
How can blood vessels respond to parasympathetic (ACh and muscarinic) stimulation if the SM of blood vessels is not innervated by parasympathetic neurons?
Vascular relaxation occurs in response to ACh and mAChR activation via release of endothelium derived relaxing factor (EDRF; now known as NO) from endothelial cells
54
Describe how NO can effect vascular SM
In response to an AP parasympathetic neurons release ACh which activates mAChR on endothelial cells Causes NO to be produced by the endothelial cells NO diffuses back to the SM cells surrounding the BVs and causes relaxation
55
Describe the adrenal medulla
Has sympathetic innervation Epi and NE release is triggered by the release of ACh from the preganglionic fibers ACh binds to NnAChRs and produces a localized depolarization Release is 80% Epi and 20% NE
56
What happens upon the injection of a drug that increases BP (ex. Phenylephrine)?
Baroreceptor firing increases PNS stimulated SNS response decreased
57
What happens upon the injection of a drug that will decreases BP (ex. Histamine)?
Baroreceptor firing decreases PNS response decreases SNS stimulated
58
What are cholinomimetic agents?
Drugs that mimic ACh AChR agonists AChE inhibitors
59
What are cholinoreceptor-blocking drugs?
AChR antagonists
60
What are sympathomimetic agents?
Drugs that mimic or enhance alpha and beta receptor stimulation Agonists, drugs that enhance catecholamine release, drugs that block reuptake
61
What are adrenoreceptor blocking drugs?
Alpha and beta receptor antagonists
62
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
63
What is are antagonists?
Bind to receptor 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

CPR Exam 2 (18 decks)

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