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CV 2 > ANS Pharmacology > Flashcards

ANS Pharmacology Flashcards

1
Q

Examples of drug targets

A 
DNA
Proteins:
Hormone receptors
Growth factor receptors
Transcription factor receptors
Neurotransmitter receptors
Ion channels
Enzymes 
Transport proteins
Glycoproteins
Structural proteins
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2
Q

Full agonist

A

mimics the full response of an endogenous ligand

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3
Q

antagonist

A

blocks the response of an endogenous ligand

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4
Q

inverse agonist

A

has the opposite effect of the endogenous ligand

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5
Q

Actions of sympathetic division of ANS

A

dilate pupil (via smooth muscle contraction)
tear glands maintain eye moisture
inhibit excess salivary secretion
accelerate heart rate, constrict arterioles
dilate bronchi
inhibit stomach motility and secretion, inhibit pancreas
inhibit intestinal motility
relax bladder
stimulate ejaculation

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6
Q

actions of parasympathetic division of ANS

A 
constrict pupil (via smooth muscle contraction)
stimulate tear gland
strong stimulation of salivary flow
slow heart rate
constrict bronchi
stimulate digestive juice secretion
stimulate intestinal motility
contract bladder
stimulate erection
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7
Q

Adrenergic receptors

A

alpha 1, alpha 2

beta 1, beta 2

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8
Q

ACh receptors

A

M3, M2

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9
Q

Eye muscles, actions and receptors

A

Radial muscle, iris (contraction: alpha 1)
Sphincter muscle, iris (contraction: M3, M2)
Ciliary muscle (relaxation for far vision: beta 2, contracction for near vision: M3, M2)

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10
Q

Heart receptors, actions

A 
SA node (increase heart rate: B1> beta 2; decrease heart rate: M2>> M3)
Atria (increase contractility and conduction velocity: B1> beta 2; decrease in contractility: M2>>M3)
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11
Q

Lung receptors and actions

A 
Tracheal and bronchial smooth muscle (relaxation: beta 2; contraction: M2=M3)
Bronchial glands (decrease secretion: alpha 1, increase secretion: beta 2; stimulation: M3, M2)
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12
Q

Stomach receptors and actions

A

motility and tone (decrease: alpha 1&2, beta 1&2), increase: M2=M3)
sphincters (contraction: alpha1, relaxation: M3, M2)
secretion (inhibition (alpha2, stimulation: M3, M2)

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13
Q

Intestine receptors and actions

A

Motility and tone (decrease: alpha 1&2, beta 1&2; increase: M3, M2)
sphincters (contraction: alpha1, relaxation: M3, M2)
secretion (inhibition: alpha2, stimulation: M3, M2)

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14
Q

Pre-ganglionic neurons in ANS

A

use ACh

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15
Q

parasympathetic transmitters and receptors

A

Neurotransmitter: ACh
Receptors: nAChR, mAChR

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16
Q

sympathetic transmitters and receptors

A

Neurotransmitters: NE > Epi (DA); ACh
Receptors: α, β, (D), nAChR, mAChR

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17
Q

What does “-ergic” mean?

A

Tells you the neurotransmitter that a nerve sythesizes and releases.

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18
Q

Acetylcholine

A

(cholinergic)
The major neurotransmitter of the parasympathetic nervous system
All preganglionic autonomic fibers (sympathetic and parasympathetic)
All postganglionic parasympathetic fibers
Few postganglionic sympathetic fibers (sweat glands)

19
Q

Norepinephrine

A

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

20
Q

Epinephrine

A

(adrenergic)

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

21
Q

Dopamine

A

NE and Epi precursor

Acts on the CNS and renal vascular smooth muscle

22
Q

co-neurotransmitters

A

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

23
Q

Cholinergic neurotransmission

A

Axonal conduction

Junctional transmission (cholinergic)
Synthesis of acetylcholine (ACh)
Storage of ACh
Release of ACh
Destruction of ACh

ACh signaling

End organ effects

24
Q

4 steps of cholinergic transmission

A

ACh synthesis

ACh storage

ACh release

ACh destruction

25
Subtypes of muscarinic receptors
in the periphery: M2- heart, nerves, smooth muscle (GPCR), inhibits cAMP production, aactivates K+ channels M3- glands, smooth muscle, endothelium. (GPCR), Mechanism: IP3, DAG cascade
26
PNS sybtype of nicotinic receptor
N(N). Located in postganglionic cell body, dendrites, CNS. | alpha and beta types only. Mechanism: sodium, K+ depolarizing ion channel
27
Voltage-gated sodium channels
Example: Na+ channels (Nav1.1 – Nav1.9) Structure: 4 x 6 TM domains Activated in response to membrane depolarization Function: propagate action potentials
28
Ligand-gated sodium channels
Example: nicotinic AChRs (nAChRs, neuronal and muscle subtypes) Structure: pentamer of 5 subunits, each containing 4 TM domains Activated in response to ligand binding Function: excitatory neurotransmission, muscle contraction, etc.
29
steps in adrenergic neurotransmission
1. Axonal conduction ``` 2. Junctional transmission (adrenergic) Synthesis of catecholamines Storage Release Destruction (reuptake) ``` 3. Adrenergic signaling 4. End organ effects
30
all adrenergic receptors are?
metabotropic. Work on GPCR receptors.
31
catecholamines
dopamine, norepinephrine, epinephrine (all come from tyrosine)
32
Steps of catecholamine synthesis
Tyrosine--> dopa--> dopamine (in the nerve cytoplasm) | dopamine--> norepinephrine--> epinephrine (occurs in the vesicle, last step mainly in the adrenal medulla)
33
details of adrenergic transmission: types of transporters
Na+-dependent tyrosine transporter Transports tyrosine into the nerve terminal Vesicular monoamine transporter (VMAT-2) Transports NE, Epi, DA, and serotonin into vesicles (non-selective) Release upon action potential and Ca2+ influx ``` NE transporter (NET) Imports NE into the nerve terminal Dopamine uptake occurs via a separate transporter (DAT) ```
34
Catecholamine signal termination
Reuptake into nerve terminals Major mechanism that terminates the actions of catecholamines NET (norepinephrine transporter) and DAT (dopamine transporter) After reuptake, catecholamines are stored in vesicles by the VMAT-2 Metabolism of catecholamines (2 main enzymes) Monoamine oxidase (MAO) Catechol-O-methyltransferase (COMT) Play secondary role in catecholamine metabolism after reuptake *In contrast to cholinergic signaling, termination of catecholamine action by degradative enzymes (i.e., AChE) is nonexistent in adrenergic signaling
35
adrenergic receptor signaling pathways
G alpha i - inhibits cAMP | G alpha s- stimulates cAMP
36
Rules of thumb for smooth muscle and autonomic receptors
Alpha1 (α1) receptors: Stimulate contraction of all smooth muscle Vascular smooth muscle – vasoconstriction Beta2 (β2) receptors: Relax smooth muscle – vasodilation Muscarinic receptors: Contract smooth muscle (different intracellular signal than α1 receptors) Apparent discrepancy – ACh & muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)
37
Response of Blood Vessels to Autonomic Nerve Impulses
Adrenergic receptors in blood vessels receive sympathetic innervation, which cause vessel constriction (alpha1 receptors) or dilation (beta2 receptors) when activated Smooth muscle of blood vessels is NOT innervated by parasympathetic neurons AChRs (muscarinic and nicotonic) are not readily found on smooth muscle of blood vessels; but endothelial cells express mAChRs Blood vessels relax in response to exogenously applied ACh as long as the endothelium is intact
38
mAChRs, EDRF (NO), and Vasodilation
Activation of mAChRs on endothelial cells causes production and release of endothelium-derived relaxing factor (EDRF), aka nitric oxide (NO)
39
adrenal medulla
Sympathetic innervation Epi and NE release is triggered by the release of ACh from the preganglionic fibers ACh binds to NNAChRs and produce a localized depolarization Release is approximately: 80% Epi 20% NE
40
baroreceptor relex- example of what?
is an example of compensatory changes in the ANS
41
Cholinomimetic agents
drugs that mimic ACh AChR agonists Acetylcholinesterase inhibitors
42
Cholinoceptor-blocking drugs
AChR antagonists
43
Sympathomimetic agents
drugs that mimic or enhance α- and/or β-receptor stimulation Agonists Drugs that enhance catecholamine release Drugs that block reuptake
44
Adrenoceptor-blocking drugs
α- and β-receptor antagonists

CV 2 (3 decks)

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