Week 2- Autonomic Pharmacology

Front 1

Parasympathetic neurons- pre and post ganglionic neuron NT's and receptors

Back 1

pre-ganglionic- Ach, nicotinic
post-gangionic- Ach, muscarinic

Front 2

Adrenal gland- NT and receptor

Back 2

NT- Ach, nicotinic

Front 3

Sympathetic NS- sweat glands- pre and post ganglionic neuron NT's and receptors

Back 3

preganglionic- ACh, nicotinic

postganglionic- ACh, muscarinic

Front 4

Sympathetic NS- Skeletal muscle- NT- and receptor

Back 4

Ach, nicotinic

Front 5

SNS- catecholamine synthesis pathway

(tyrosine -->epinephrine. How?)

Back 5

Tyrosine
Dopa
Dopamine
Norepinephrine
Epinephrine

Front 6

What's the function of the alpha 1 adrenoreceptor?

What system?

Back 6

think CONTRACTION!

smooth muscle contraction
intestinal/bladder sphincter contraction
pupilary dilator muscle contraction

Sympathetic NS

Front 7

What is the function of the alpha 2 adrenoreceptor?

What system?

Back 7

In brain stem. Negative feedback.
Decreased SNS outflow, insulin release

decrease sympathetic nervous system outflow and blood pressure

Sympathetic NS

Front 8

What is the function of the beta 1 adrenoreceptor? What system?

Back 8

increased HR/contractility/renin/lipolysis

Sympathetic NS

Front 9

What is the function of Beta 2 adrenoreceptor?
What system?

Back 9

Dilator!
vasodilation/bronchodilation, decreased uterine tone

BUT increased HR/contractility/renin/lipolysis/insulin release

Sympathetic NS

Front 10

Muscarinic and nicotinic receptors are receptors for what kind of NT?

Back 10

actetylcholine

Front 11

What is the function of M1 receptors? What type of receptor, what system?

Back 11

muscarinic receptors, parasympathetic nervous system

largely for CNS and enteric nervous system!

Front 12

What is the function of M2 receptors? What type of receptor, what system?

Back 12

Muscarinic receptors, parasympathetic NS

this one is for parasympathetic innervation of the heart

Think decreased heart rate and atrial contractility

Front 13

What is the function of M3 receptors? What type of receptor, what system?

Back 13

M3, muscarinic, parasympathetic
increased exocrine gland secretions, like sweat or gastric acid

more peristalsis, more blader contractions

endothelial vasodilation

bronchoconstriction

pupillary sphincter muscle contraction

ciliary muscle accommodation

Front 14

What is the post ganglionic NT for most sympathetic neurons?

Back 14

norepinephrine/noradrenaline

1. sweat is Ach
2. adrenals are Ach because they release epinephrine

Front 15

Pupil constriction is associated with what NS?

Back 15

PNS, muscarinic receptors, M3

Front 16

What are the Nm and Nn nicotinic receptors associated with, respectively ?

Back 16

Nm= neuroMuscular junction

Nn= autoNomic ganglia

Front 17

What's special about nicotinic acetylcholine receptors?

Back 17

They are ion channel receptors! Others are not.

Don't use receptors!

Front 18

How does the second messenger cellular signaling work for all receptors besides nicotinic acetylcholine receptors?

Back 18

G protein coupled receptors, effector, second messenger (cAMP), cellular response

Front 19

What is the function of Gs g-protein coupled receptors?

Back 19

Gs= stimulating receptor, increase cAMP, increase pKA

Front 20

What is the function of Gi g-protein coupled receptors?

Back 20

inhibiting receptor, decreases cAMP, decreases PKA

Front 21

What is the function of Gq g protein coupled receptors?

Back 21

uses different second messenger, uses protein kinase C, more direct effect, separate pathway that directly increases calcium from ER

Front 22

*!This one's a hard one! Give the type of G protein coupled receptor for all the different kinds of receptors!

Back 22

Alpha1= q
Alpha2= i
Beta1=s
Beta2/3=s

M1=q
m2=i
M3=q

D1=s
D2= i
H1=q
H2= s
V1=q
V2=s

Front 23

What's the function of D1 receptors

Back 23

relaxes renal smooth muscles

Front 24

What's the function of D2 receptors

Back 24

modulates NT release, especially in brain

Front 25

What's the function of H1 receptors

Back 25

increased nasal/bronchial mucus, increased pain/itching

Front 26

What's the function of H2 receptors?

Back 26

increased gastric acid secretion

Front 27

What's the function of V1 receptors?

Back 27

increased vascular smooth muscle contraction

Front 28

What's the function of V2 receptors?

Back 28

increased free water absorption in kidney

Front 29

What is the function of Choline Acetyl Transferase?

What is the function of Acetylcholine Esterase?

Where are they?

Back 29

CAT combines Choline and Acetyl CoA to make Acetyl Choline- CHOLINE SYNTHESIS in cholinergic receptro

ACheE breaks down Acetylcholine into Choline and Acetate- ACETYLCHOLINE BREAKDOWN, in synapse!

Front 30

What is myasthenia gravis?

Back 30

antibodies block Ach, receptors, treatment is to try to overcome receptors with more Ach

Front 31

Is acetylcholine an agonist or antagonist of muscarinic receptors?

Back 31

Agonist!

Front 32

What would be a good class of NT agonists/ antagonists to use for
open angle claucoma, urinary retention, gastroparesis, and Sjögren’s*syndrome?

Back 32

Muscarinic agonists!

Front 33

What is pilocarpine? How does it work? What does it do, anyway?

Back 33

M3 receptor agonist,

eye drops for open-angle glaucoma, makes circular muscles contract to get pupils smaller, stimulations ciliary muscles

Front 34

What's going on here?

• Blind*as*a*bat,**
• mad*as*a*ha`er,**
• red*as*a*beet,**
• hot*as*Hades,**
• dry*as*a*bone,**
• the*bowel*and*bladder*lose*
their*tone,**
• and*the*heart*runs*alone*

Back 34

A muscarinic blockade!

Anticholinergic

Front 35

What class of agonists/antagonists would be good to use for

respiratory (decrease bronchial secretion)
asthma
parkinson's disease
motion sickness
diarrhea
pesticide poisoning
mushroom poisonin
sarin gas poisoning?

Back 35

Muscarinic antagonists!

Front 36

What are acetylcholinesterases, and where might you find them?

Contrast this with pseudocholinesterases!

Back 36

"true cholinesterase," found in neurons and RBC's

psuedocholinesterases are in plasma and other tissues

Front 37

How does sarin gas work?

Back 37

War agent that is a cholinesterase inhibitor, increases Ach availability, functions as an Ach "agonist"

Front 38

myasthenia*gravis*
What class of medications might be good for treating the following conditions?

• openeangle*glaucoma*
• overdose*reversal*
• insec;cide*
• poor*GI*mo;lity*
• parasympathe;c*failure*
• Demen;a*e.g.*donepezil*(Aricept)*

Back 38

Cholinesterase inhibitors!

Front 39

What is the mechanism of action of sevin/carbaryl?

Back 39

it's a pesticide, a slowly reverisble cholinesterase inhibitor

Front 40

What would be a good mechanism of emergency treatment of acetylcholinesterase inhibitor poisoning

Back 40

Atropine- blocks muscarinic receptor effects

pralidoxime- separates organophosphate from Acetylcholinesterase inhibitor

Front 41

What does Pralidoxime (2-PAM) do in the case of acetylcholinesterase inhibitor poisoning?

Back 41

separates organophosphate from AChE inhibitor

Front 42

Adrenergic receptors, alpha1 and alpha2. What do they each do?

Back 42

alpha 1- on vascular smooth muscle, for vasoconstriction

alpha 2- presynaptic adrenergic nerve terminals, and vascular smooth muscle, they work for inhibition of norepinephrine release and vasoconstriction

Front 43

What do beta 2 adrenergic receptors on vascular smooth muscle do?

Back 43

vasodilation!

Front 44

What do beta 2 adrenergic receptors on bronchial smooth muscle do?

Back 44

bronchodilation!

Front 45

What do beta 2 adrenergic receptors on liver cells do?

Back 45

stimulate glycogenolysis

Front 46

What receptors do these drugs target/stimulate, on what continuum?

• Norepinephrine*
• Epinephrine*
• Dopamine*
• αeMethyldopa*
• Clonidine*
• Dexmedetomidine*

Back 46

they target alpha adrenergic receptors!

Spectrum
alpha1>>alpha2

• Norepinephrine*
• Epinephrine*
• Dopamine*
• αeMethyldopa*
• Clonidine*
• Dexmedetomidine*
alpha2>>>alpha1

Front 47

Effects of α1 Adrenergic Stimulation

Back 47

Vasoconstriction
Increase blood pressure
pupils dilate (contract iris muscles

Front 48

Effects of α2 Adrenergic Stimulation

Back 48

decreased sympathetic outflow
decreased norepinephrine release
vasoconstriction

Front 49

Effects of β1- Adrenergic stimulation

Back 49

increased heart rate! more AV node contracting!

more renin from kidney, higher BP!

Front 50

Effects of β2- Adrenergic stimulation

Back 50

bronchodilation
uterine relaxation
relaxation of bladder
decreased motility of GI tract
increased glucose metabolism of GI tract
relaxation of smooth muscle

Front 51

Dopamine is a precursor of ????

Back 51

dopamine-->norepinephrine-->epinephrine

Front 52

What is epinephrine's precursor?

Back 52

dopamine-->norepinephrine-->epinephrine

Front 53

What is norepinephrine's precursor?

Back 53

dopamine-->norepinephrine-->epinephrine

Front 54

Epi/epinephrine/ adrenaline

What receptors does it hit?
What does low dose IV target?
What does high dose IV target?

Back 54

Hits ALL (α1,*α2,*ß1,*ß2) receptors!

Low dose IV - more beta effect
High dose IV- more alpha effect, especially alpha 1 (vasoconstriction!)

Front 55

Norepinephrine/NE/noradrenaline

What receptors does it hit?

What's the net effect?

Back 55

Hits all receptors EXCEPT for BETA 2! (α1,*α2,*ß1)

Net effect ↑HR, ↑ BP

Front 56

Isoproterenol

What receptors does it hit?

What's the net effect?

When would you use it in treatment?

Back 56

Synthetic epinephrine analogue
ONLY hits beta receptors! No alpha receptor effects!

Good for patients with low heart rates!
Great for patients with a heart block before pacemaker can be implanted, or systolic dysfunction and low HR, like after cardiac surgery

Front 57

Dopamine!

What receptors does it hit?
What does low dose IV target?
What does medium dose IV target?
What does high dose IV target?

Back 57

Dopamine is a precursor of norepinephrine!

At low doses it hits dopamine receptors, we call it "renal dose dopamine" hits renal vascular beds, diuretic

at medium dose, hits beta 1, norepinephrine release, so then beta 1 and some alpha 1 are activated

at high dose- alpha 1! vasoconstriction! great for hypotension and shock!

Front 58

Dobutamine!

This is a synthetic analogue of what?

What receptors does it hit?
What does low dose IV target?
What does medium dose IV target?
What does high dose IV target?

Back 58

DOPAMINE analog, better for patietns who have heart failure!

stimulates beta1, beta2, and alpha1 (minimally), doesn't affect dopamine receptors

Front 59

Phenylephrine! What does it stimulate? What is it for?

Back 59

Phenylephrine is a selective alpha1 agonist!

paradoxically decreases heart rate because beta 1 is not stimulated

Front 60

Let's talk about the baroreflex!
When/how activated? What does it do?

Back 60

Input- reduced BP from the carotids and aortic arch

Output- increased heart rate, increased vasoconstriction

Front 61

Let's talk about the bezold-jarisch reflex!
When/how activated?

Back 61

Triggered by mechanoreceptors in heart and chemoreceptorsin the inferior wall

it lowers HR and causes vasodilation

Front 62

What is the diving reflex?

Back 62

elicited by coldness on forehead, decreases oxygen/energy demand!