Autonomic Nervous System Pharmacology

Front 1

How is ACh
synthesiezed, conentrated, and released
HOw are these inhibited?

Back 1

Choline acetyl transferase ChAT I--mehtyl mercury
Vesicular ACh transporter
VAT I---vesamical
Ca dependent release through SNAPS/SNAREs I---Botox

Front 2

How is NE synthesized?

Back 2

Tyrosine hydroxylate-> Levodopa => DA => NE =>Epi
AAAD-> DA
DA beta hydroxylase -> NE
phenyl-ethanolamine N methyltransferase -> Epi (medulla)

Front 3

How is NE concentrated and what inhibits it?

Back 3

VMAT using H+ counter transport I---reserpine

Front 4

How is NE biotransformed?
what is the product?
Reuptake by?

Back 4

catecholOmethyltransferase COMT and MAO--> vanilla mandelic acid

NET I--tryamine, amphetamine cocaine

Front 5

what is DA role in ANS?

Back 5

renal vasodilation
enhacning inotropy
used for blood loss and shock

Front 6

What are the receptors for ACh?

Back 6

Nictotinic: neuro and muscular
Muscarinic:
M1,3-5: IP3/DAG
M2: --I adenylate cyclase, opens K channels

Front 7

Receptors for NE?

Back 7

a1-> IP3/DAG, sm contraction
a2-I A.C.; reduce NE release
B1-> A.C., heart, presynaptic
B2-> smooth muscle
B3-> lipocytes

Front 8

3 nonspecific cholinomimetics

Back 8

Bethanechol: M1-M3>N
carbachol M&N
methalcholine M&N

Front 9

Muscarininc cholinomimetics

Back 9

muscarine M only
Pilocarpine M>>>>N

Front 10

nicotinic cholinomimetics

Back 10

nicotine N only
lobeline
varenicline partial Nn
succinylcholine: Nm

Front 11

ACHEIs

Back 11

Edrophonium
neostigmine
physostigmine
echothiphate
prathion
malathion
sarin (irreversible)
soman (irreversiblle)
VX
pralidoxime

Front 12

4 Nootropics

Back 12

tacrine
donepezil
rivastigmine
galantamine

Front 13

Nonspecific cholinomimetics
MOA
Use
Toxicity

Back 13

fulll M1-M3 agonist increased secretions, sm. mm contraction, reduced HR
Use- post op, neurogenic ileus, urinatry retention

Toxicity: bronchospasm

Front 14

what is the difference between muscarine and pilocarpine?

Back 14

muscarine: quaternary amine
pilocarpine: tertiary, crosses membraines readily

Front 15

Pilocarpine:
MOA
Use
Toxicity

Back 15

full agonist at M1-M3

inc. secretions, sm. mm contraction, reduced HR
used for glaucoma
Tox: bronchospasm

Front 16

Nicotine, Lobeline:
MOA
Use
Toxicity

Back 16

full agonists at Nn and Nm
used in smoking cessation
activate both SANS and PANS (at ganglia)

Tox: increased GI activity N/V/D; increased BP, potential for seizures.

Front 17

why does tobacco cause euphoria and dependence?

Back 17

MAOIs increase DA, NE, and 5HT
Nicotine activates a4B2 Nn presynaptically on DA terminals increasing DA

Front 18

Varenicline

Back 18

partial agonist at a4B2 NnR at presyn DA terms
reduces DA release and addictive supporting actinos
mild sensation of continuing nicotine

Front 19

how do ACHEI alcohols act

Back 19

H-bond to AChE competitively
Inhibits hydrolysis of ACh

Front 20

action of ACHEI carbamates

Back 20

processed like ACh, but carbamoylation step is slowly hydrated-> longer occupancy--> blockade

Front 21

action of AChEI organophosphates and nerve gases (sarn/soman)

Back 21

phophorylates esteric site which eventually irreversibly ages. (pralidoxime can beind to esteric site and regenerate before it ages)

Front 22

Specific AChEIs (Nootropics)

Back 22

Selective for G1, G4 found in cNS

Front 23

Tacrine

Back 23

reversible inhibitor at choline site
LOW bioavailabilityy
Tox: reversible livertoxicity

Front 24

Donepezil

Back 24

non-competitive, reversible AChEI

eliminated renally
sleep disturbances

Front 25

Rivastigmine

Back 25

pseudo-irreversible competitive AChEI

Front 26

Galantamine

Back 26

reversible AChEI,
low potency
also noncompetitive Nn agonist: activates post synaptic receptors in brain-> AD

Front 27

what are the toxic, organ system effects of muscarinic agonists?

Back 27

SLUDGEM
Salivation, lacrimation, urination, defecation, GI upset, emesis, miosis

Front 28

muscarinic effects on Salivation

Back 28

M3> M1 causes contractino of smooth muscle of gland and watery saliva
VIP(PANS) increases blood flow, enhances ACh on acinar

Front 29

muscarinic effects on lacrimation

Back 29

PANS-> M3 -> lacrimal glands

Front 30

Muscarinic effects GI upset

Back 30

PANS activation--> increased peristalsis, increased secretions

Front 31

Emesis effects of muscarinic agonists

Back 31

CTZ has muscarinic recptors (but pre dominated by DA and 5HT.
CTZ and VC project to medullary vomiting center and is rich in cholinergic fibers.

Front 32

Eye effects of muscarinic agonists
MAG

Back 32

Contraction of ciliary muscle
pull trabecular meshwork=> reduce intraocular pressure
M3 and M2
Pilocarpine->glaucoma

Front 33

Cardiac effects of muscarinic agonists

Back 33

M3 ACh=> NO=> vasodilation
neg chronotropic, inotropic, dromotropic , hypotension
masked by baroreceptor responses

Front 34

Affects of ACh on the heart

Back 34

M2=> increase K current in SA/AV, ventricular mm
ACh=> reduces slow inward Ca current and hyperpolarization activated current

Front 35

Effects of muscarinc agonists on Respiratory System

Back 35

M3=> smooth muscle contraction, secretion of mucosal cells in bronchial tree

Front 36

Effects of muscarinc agonists on Sweat Glands

Back 36

Eccrine Glands stimulated to secrete

Front 37

AChEIs effects on NMJ

Back 37

for MG patients, ACh stays around longer at the Nm receptors.

Front 38

Effects of too little or too much AChEI (edrophonium)

Back 38

Too much=> depolarization blockade
Too little also produces MG like symptoms

Front 39

What is the Tensilon test?

Back 39

Edrophonium is short acting AChEI. If mm weakness improves, Edrophonium dose is too low. Vice versa.

Front 40

CV effects of AChEIs

Back 40

Vasocontriction, increased BP

SANS is dominant tone, no PANS innervation of vascular beds

Front 41

Muscarinic antagonists

Back 41

atropine M1-M5
scopolamine M1-5>>Nn
Ipratropium M1-M5>>Nn

Front 42

NMJ Blockers

Back 42

D tubocurarine
atracurium
pancuronium
rocuronium
succinylcholine (depolarization blocker)

Front 43

NMJ Toxins

Back 43

a bungarotoxin
a latrotoxin
tick venoms
botox

Front 44

Specific muscarinic antagonists

Back 44

oxybutinin M3 preferring
tolterodine M3 preferring
Glycopyrrolate peripheral acting

Front 45

what are muscarinic antagonists used for

Back 45

GI disorders, COPD, opthalmic uses, bladder control

Front 46

MOA of Atropine
Scopolamine
ipratropium

Back 46

traps ACh M receptor in inactive state
-Surmountable

Front 47

4 M3 preferring antagonists used in bladder control

Back 47

oxybutynin
tolterodine
darifeacin
solifenacin

Front 48

muscarininc antagonists that don't cross the BBB

Back 48

ipratropium
glycopyrrolate (quaternary compounds)

Front 49

muscarininc antagonists

Effects, uses

Back 49

reduce PANS; sweat and salivary glands most effected, GI peristalsis will return.

Used: bladder control, asthma COPD, GI diarrhea, motion sickness, dilation of eyes

Front 50

contraindications of muscarininc antagonists

Back 50

glaucoma, obstructive GI/GU and intestinal atony

Front 51

Side effects of antimuscarinics

Back 51

-hot as a hare- can't sweat/motor excitement (CNS)
-blind as a stone- cant accomodate
-mad hatter-
-dry to the bone- no secretions bowel, spit, tears, sweat

Front 52

Surgical uses of atropine and scopolamine

Back 52

reduce airway secretions

Front 53

Ipratropium

Back 53

asthma and COPD
--I M3 => mucus secretions, airway
-Few systemic effects

Front 54

uses for antimuscarinics

Back 54

-Incontinence M3=>contractio
-mushroom poisoning
-GI stasis

Front 55

MOA depolarization blockers

Back 55

Hyperstimulate NMJ=>blockade

Front 56

4 Non-depolarizing blockers

Back 56

D-tubocurarine
atracurium
pancuronium\rocuronium (steroidal)

Front 57

non-depolarizing blockers
MOA
Use
Tox

Back 57

-M- surmountable Nm ants =>NMJ blockade
-U- surgery and intubations
-T- respiratory compromise
HA release=> hypotension

Front 58

Depolarization blockers

Back 58

all AChEIs, ACh, succinylcholine

Front 59

2 phases of depolarization blockade

Back 59

I- continual agonizing of receptor prevents repolarization
II- desensitization (even high levels of ACh cannot activate)

Front 60

depolarization blockers
M
U

Back 60

-M- agonist at Nm=> muscle fascilulations-> flcd paralysis
-U- muscle relaxant 4 surgery

Front 61

4 Toxic effects of depolarization blockers

Back 61

-T- HA=> hypotension
respiratory compromise
HyperKalemia
increased intraocular pressure

Front 62

MOA of
a-bungarotoxin
a-laprotoxin
tickvenom

Back 62

1) --I NMJ (=curare)
2)--> presyn. release of NT and depolarization blockade
3) fuses vesicles to membrane preventing release

Front 63

3 ganglionic blockers

Back 63

mecamylamine
hexamethonium
trimethaphan

Front 64

MOA of ganglionic blockers

Back 64

competitive Nn antagonists
Hex- steric hindrance

Mecamylamin/trimethaphan- block actual receptor

Front 65

Effects of ganglionic blockers

Back 65

REDUCE ANS outlfow
Effects based on tone: vasodilation, inc. HR, reduced GI, urinary hesitancy, reduced sweating, impaired sexual function.

Front 66

clinical uses of ganglionic blockers

Back 66

Hypertensive emergencies and neurosurgical procedure to reduce CNS bleeding through peripheral pooling

Front 67

Pharmacokinetics Mecamylamine, trimethaphan, and hemamethonium

Back 67

Hex and Tri- dont cros BBB
Tri- short acting, water soluble