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CPR Exam 2 > Intro To ANS Pharmacology > Flashcards

Intro To ANS Pharmacology Flashcards

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
Q

Where are sympathetic mAChR (metabotropic) found?

A

Sweat glands

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26
Q

What is the function of sympathetic mAChR?

A

Sweat secretion

27
Q

What is adrenergic neurotransmission?

A

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
Q

Describe the synthesis of catecholamines

A

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
Q

What transports tyrosine into the nerve terminal during catecholamine synthesis?

A

Na dependent tyrosine transporter

30
Q

Describe the storage of catecholamines

A

VMAT-2 transports DA, NE, epi and serotonin into the vesicle during catecholamine synthesis

31
Q

What drug can inhibit VMAT-2?

A

Reserpine

Leads to the depletion of catecholamine so from sympathetic nerve endings

32
Q

Describe the release of catecholamines from the vesicles

A

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
Q

Describe the binding of catecholamines to adrenergic receptors

A

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
Q

What is the major mechanism that terminates the actions of catecholamines?

A

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
Q

What is the secondary mechanism for termination of catecholamine signaling?

A

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
Q

What is the action of MAO (monoamine oxidase)?

A

Metabolizes catecholamines that have been released and undergone reuptake
Associated with the outer surface of the mitochondria

37
Q

What is the action of COMT (catechol-O-methytransferase)?

A

Metabolism of endogenous circulating and administered catecholamines (particularly in the liver)
Largely cytoplasmic

38
Q

In contrast to cholinergic signaling, termination of catecholamine action by degradative enzyme (e.g. AChE) is what?

A

Nonexistent in adrenergic signaling

39
Q

What is the end result of alpha1 receptor activation?

A

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
Q

What does the activation of alpha2 receptors result in?

A

Vascular smooth muscle contraction, decreased insulin secretion and a decreased release of NE (presynaptic alpha2 receptors)

41
Q

The activation of any beta adrenergic receptor results in what?

A

Activation of adenylyl cyclase and increased concentrations of cAMP through the stimulatory Gs protein

42
Q

Describe beta1 receptors

A

Found in the myocardium

Activation results in an increased force and rate of heart contraction and AV nodal conduction velocity

43
Q

Describe beta2 adrenergic receptors

A

Found on smooth muscle and most other sites

Activation causes vascular, bronchial, genitourinary and GI smooth muscle to relax

44
Q

Describe beta3 adrenergic receptors

A

Found only in adipose tissue

Activation results in lipolysis

45
Q

Epinephrine has equal effects on which receptors?

A 
A1 = a2 
Beta1 = beta2
46
Q

NE has equal effects on which receptors?

A

Alpha1 = alpha 2

47
Q

NE has a stronger effect on which receptors?

A

Beta 1&raquo_space; beta2

48
Q

Muscarinic receptor activation results in what?

A

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
Q

DA can activate D1 receptor in renal smooth muscle and cause what?

A

Increased cAMP and causes dilation

Stimulation of D1 results in vasodilation, natriuresis and diuresis via renal vascular smooth muscle

50
Q

At higher concentrations DA can stimulate alpha1 and beta1 adrenergic receptors causing what?

A

An increase in HR and generally vascular vasoconstriction

51
Q

What is the general effect of alpha1 receptors upon autonomic stimulation?

A

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
Q

What is the general effect of beta2 autonomic activation?

A

Relaxation of all SM
Relaxation of tracheal and bronchial SM
Relaxation of uterine SM
Relaxation of intestinal SM

53
Q

How can blood vessels respond to parasympathetic (ACh and muscarinic) stimulation if the SM of blood vessels is not innervated by parasympathetic neurons?

A

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
Q

Describe how NO can effect vascular SM

A

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
Q

Describe the adrenal medulla

A

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
Q

What happens upon the injection of a drug that increases BP (ex. Phenylephrine)?

A

Baroreceptor firing increases
PNS stimulated
SNS response decreased

57
Q

What happens upon the injection of a drug that will decreases BP (ex. Histamine)?

A

Baroreceptor firing decreases
PNS response decreases
SNS stimulated

58
Q

What are cholinomimetic agents?

A

Drugs that mimic ACh
AChR agonists
AChE inhibitors

59
Q

What are cholinoreceptor-blocking drugs?

A

AChR antagonists

60
Q

What are sympathomimetic agents?

A

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

61
Q

What are adrenoreceptor blocking drugs?

A

Alpha and beta receptor antagonists

62
Q

What is an agonist?

A

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
Q

What is are antagonists?

A

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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