ANS Flashcards
1
Q
Ganglionic neurons for Parasympathetic (Length)
A
pre: long
post: short
2
Q
Ganglionic neurons for Sympathetic (Length)
A
pre: short
post: long
3
Q
In BOTH parasympathetic and sympathetic neurons - ______ is released to activate _______ receptors on ___ganglionic neurons
A
Ach; nicotinic; post
4
Q
In Parasympathetic neurons - _______ receptors on target organs are activated by
A
muscarinic; Ach;
5
Q
In sympathetic neurons ________ receptors on target organs are activated by
A
adrenergic; norepinephrine
6
Q
3 exceptions to the sympathetic nervous system “rules”
A
sweat glands; kidneys; adrenal gland
7
Q
Sweat Glands:
- If stress-related (sweaty palms) ________ is excreted
- if thermoregulation _______ is released to work on _______ receptors
A
norepinephrine; Ach; muscarinic
8
Q
Kidneys:
________ is released by postganglionic neurons to work on the smooth muscle of the renal vascular bed which cause _________
A
dopamine; vasodilation
9
Q
Adrenal gland:
- Do the preganglionic neurons synapse in paravetebral sympathetic ganglion?
- Preganglionic neurons release _____ to activate _______ receptors ON the adrenal gland
- the adrenal gland will release ________ into systemic circulation
A
Nope;
Ach; nicotinic
epinephrine
10
Q
Types of cholinergic receptors
A
Nicotinic; muscarinic
11
Q
Nicotinic receptors are a ______ type of receptor
and
Muscarinic receptors are a ______ type of receptor
A
ligand gated ion channel;
GPCR
12
Q
2 main types of Muscarinic Receptors and where they are found
A
M3 - glands and smooth muscle
M2 - found in heart
13
Q
Which G protein pathways do M3 and M2 use?
A
M3 - Gq (makes DAG and IP3)
M2 - GI (inhibits adenylycyclase)
14
Q
Main kinds of Adrenergic Receptors
A
alpha 1; alpha 2; beta (1 and 2)
15
Q
where are alpha 1 and alpha 2 receptors found
A
alpha 1 - VASCULAR smooth muscle - BP regulator
alpha 2 -receptors in brain stem/ off switch
16
Q
where are Beta 1 and Beta 2 receptors found
A
Beta 1 - heart and kidneys
beta 2 - lungs/smooth muscle/ bronchioles
17
Q
What kind of G protein does alpha 1 receptors use
A
Gq
18
Q
what kind of G protein does alpha 2 receptors use
A
GaI
19
Q
what kind of G protein does beta receptors use
A
GaS
20
Q
which receptor causes vasodilation of skeletal muscle when activated
A
B2 (adrenergic receptor)
21
Q
which receptor cause constriction of arteries when activated
A
alpha1
22
Q
which receptor cause bronchodilation of the lungs when activated
A
B2
23
Q
which receptor cause bronchoconstriction of the lungs when activated
A
M2/M3
24
Q
which receptor causes the salivary glands to increase secretion when activated
A
BOTH PARA AND SYM!
alpha1; M3
25
which receptor decreases secretion (of acid) from GI tract when activated
alpha2
26
which receptor increases secretion (of acid) from GI tract when activated
M2/M3
27
which receptor is activated to prevent prelabor contractions
beta 2
28
why do anticholinergics cause dry mouth?
anticholinergics work on muscarinic receptors; muscarinic receptors when activated will cause salivary excretion
29
which receptor will cause "goosebumps" when activated
goosebumps = piloerection; contraction
alpha1
30
what does the canal of schlemm do and where is it found
found in eye...
| it acts as the "drain" for aqueous humor
31
what is canal of schlemm opening controlled by
cilliary muscle
32
ciliary muscle controls what things
opening for canal of schlemm
AND
focusing of the lens in the eye
33
what receptor is found on the ciliary muscle
muscarinic
34
what makes aqueous humor in the eye
ciliary epithelium
35
what does the ciliary epithelium do
makes aqueous humor
36
what receptor is in the circular muscle and what does the muscle cause when contracted
muscarinic; miosis
37
what receptor is in the radial muscle and what does the muscle cause when contracted
Alpha; myDriasis
| radial has the letters a and d in it...
38
Miosis vs mydrasis
```
miosis = constrict pupils
mydriasis = dilate pupils
```
39
When a muscarinic (3) receptor is activated in the eye - what happens
contracts ciliary muscle and circular muscle -cause pupil constriction and more drainage of aqueous humor
40
What happens when the alpha 1 receptor is activated in the eye
contract radial muscle - causes mydriasis/pupil dilation;
41
what happens when Beta 2 receptor is activated in the eye
relaxation of ciliary muscle AND increase secretion of aqueous humor (aka hella aqueous humor)
42
where does alpha 1 receptor work/what does it do there
```
vasoconstrictor of arteries and veins;
radial eye constrictor;
goosebumps - piloerection
stress sweat
increase salivation
contracts sphincter
```
43
where does alpha 2 receptor work/what does it do there
vasoconstrict veins; relax GI wall; inhibits acid secretion
44
where does Beta 2 receptor work/what does it do there
lungs - bronchodilator
eye - relaxes ciliary muscle; increases aqueous humor production
relaxes GI wall;
uterus - relaxes it
45
where does M3 receptor work/what does it do there (M3 only)
increases saliva; releases EDRF
46
what does M2 do own its own and where
heart - decrease HR rate contraction
47
where does Beta 1 receptor work/what does it do there
heart and kidney
| increase HR and increase Renin secretion
48
What are ways to enhance/mimic the cholinergic system
nicotinic agonist
muscarinic agonist
AchE inhibitor
49
ways to block or inhibit the cholinergic system
```
nicotinic antagonist
muscarinic antagonist
inhibit choline uptake
inhibit vesicular storage
inhibit release
```
50
In the cholinergic system - what drug is used to prevent uptake of choline
Hemocholinium
51
In the cholinergic system - what drug is used to prevent vesicular storage
vesamicol
52
In the cholinergic system - what drug is used to prevent release (of Ach)
botulism
53
How is Ach made in the cholinergic system
Choline and Acetate are made into Ach via ChAT (choline acetyl transferase)
54
Main groups Direct Acting Cholinergic Agonists
Esters, Alkaloids, Synthetic analogs
55
Examples of Direct Acting Cholinergic Agonists - Esters
Acetylcholine; Carbachol; Methacholine; Bethanechol
56
Examples of Direct Acting Cholinergic Agonists - Alkaloids
Muscarine; Nicotine
57
Examples of Direct Acting Cholinergic Agonists - Synthetic Analogs
Pilocarpine
58
Reactions (amino acid properties) found in the active site of Ach binding to muscarinic receptors
Two aromatic rings - pi cation interaction with the + amine in the Ach
59
Do all the muscarinic receptors have the same amino acids in there active site?
No! - therefore can use this factor to create selectivity
60
Stereochemistry of Ach
| trans and cis points
cis - more stable
| trans - stereochemistry present when Ach is bound to the receptor
61
Why are antimuscarininc drugs contraindicated in glaucoma?
antimuscarinics prevents the canal of schlemm from opening/draining aqueous humor via paralyzing the ciliary muscle
62
Main components of Ach
+ amine; choline chain (alpha and beta carbons); ester
63
what are the two sites in AchE
anionic and esteraic sites
64
What happens when you modify the choline chain - alter number of atoms...
5 is best
| 4 atoms will cause it to lose activity
65
what happens when you substitute a methyl group on the alpha carbon vs the beta carbon in Ach
```
alpha = more nicotinic reactive
beta = more muscarinic selective and more resistant to metabolism bc carbon group is near ester
```
*AN and BM*
66
What happens if you alter the acetyl group in Ach by adding carbons
violating 5 atom rule --> makes it more nicotinic selective (muscarininc doesn't like extra bulk)
67
What happens if you alter the acetyl group in Ach by making the end group a carbamyl group
makes carbachol drug = non selective still but will decrease metabolism
68
What happens if you alter the acetyl group in Ach by making the end group a carbamyl group AND adding a methyl group at the beta carbon
makes it more muscarinic selective AND more resistant to metabolizing
69
What are ways to mimic/activate the adrenergic system
- adrenergic receptor agonists
- increase release (NE transporter working backwards)
- block uptake in two diff places (preventing breakdown or block NE uptake into the post synaptic region)
- decrease metabolism
70
Ways to reduce/block the adrenergic system
- adrenergic receptor antagonist
- decrease release of
- deplete vesicular stores
- decrease synthesis
71
Synthesis steps for making Catcholamines
1- tyrosine - DOPA (via tyrosine hydroxylase)
2 - DOPA - dopamine (decarboxylate)
3 - dopamine - NE (hydroxylase)
4 - NE - Epi (add a methyl)
72
What step in the making of catecholamines is the rate limiting step
first step: tyrosine to DOPA
73
NE is metabolized by what enzymes?
MAO and COMT
74
What is the end product of NE metabolism
VMA = vanilymandelic acid
75
Example drugs of alpha 1 agonists
phenylephrine
methaoxamine
oxymetazoline
(also NE and Epi can activate alpha 1 just not selectively)
76
what pathway is stimulated via alpha1 agonists
Gq pathway
77
Example drugs of alpha 2 agonists
```
clonidine
methyldopa
guanfacine
guanabenz
tizanidine
```
78
what pathway is stimulated by alpha 2 receptors
GI/O (less adenlylcyclase - less cAMP - less PKA)
79
Example drugs of beta non-selective agonists
isoproterenol
80
Example drugs of beta 1 selective agonists
dobutamine
| dopamine
81
Example drugs of beta 2 selective agonists
```
terbutaline
metaproterenol
albuterol
salmeterol
ritodrine
```
82
what adrenergic receptors does NE activate
alpha and beta1
83
what adrenergic receptors does Epi activate
all - it is non selective
84
what adrenergic receptors does dopamine activate
beta receptors
85
NE and Epi are substrates for what enzymes
MAO and COMT
86
a1 receptor agonists - 2 - aralkylimidazoline examples
Naphazoline
tetrahydrozoline
oxymetazoline
87
what are a1 receptor agonists - 2 - aralkylimidazoline use for
nasal or ophthalmic decongestants
88
are a1 receptor agonists (2 - aralkylimidazoline) full or partial agonists?
partial
89
caution/rule for a1 receptor agonists - 2 - aralkylimidazoline
3 day rule - rebound decongestant - alpha receptors get desensitized
90
What compound is used in NE and Epi preparations to prevent oxidation
Sodium Bisulfite
91
Phenylephrine as an ophthalmic produt - what does it do
phenylephrine - is an alpha1 agonist
alpha 1 in eye cause MYDRIASIS but does it without paralyzing the ciliary muscle (cycloplegia)
(muscarinic receptor - is in cilary muscle)
92
a1 receptor agonists - 2 - aralkylimidazoline have ________ ring that is (acidic/basic)
imidazoline; acidic
93
If an alpha 2 receptor works in the brain - it is working at the __________ control center
cardiovascular
94
If an alpha 2 receptor works in the brain - it will cause an overall a DECREASED ____________
sympathetic outflow (or decreased BP)
95
If an alpha 2 receptor works in the brain - it will cause the blood pressure to ____________
decrease
96
If an alpha 2 receptor works in the brain - it will cause the blood pressure to decrease by what mechanisms
less renin secreted; less vasoconstriction; decreased heart rate
97
clonidine is a _______ receptor agonist
alpha2
98
phenylephrine is a _______ receptor agonist
alpha1
99
methoxamine is a _______ receptor agonist
alpha 1
100
oxymetazoline is a _______ receptor agonist
alpha1
101
methyldopa is a _______ receptor agonist
alpha2
102
guanabenz is a _______ receptor agonist
alpha2
103
guanfacine is a _______ receptor agonist
alpha2
104
tizanidine is a _______ receptor agonist
alpha2
105
isoproterenol is a _______ receptor agonist
beta (non-selective between 1 and 2)
106
dobutamine is a _______ receptor agonist
beta 1 selective
107
dopamine is a _______ receptor agonist
beta 1 selective
108
terbutaline is a _______ receptor agonist
beta 2 selective
109
albuterol is a _______ receptor agonist
beta 2 selective
110
salmeterol is a _______ receptor agonist
beta 2 selective
111
metaproterenol is a _______ receptor agonist
beta 2 selective
112
ritodrine is a _______ receptor agonist
beta 2 selective
113
Effects on HR and BP (and why) - Norepinephrine
NE - works at alpha and beta1
- increase in BP (alpha
- DECREASE in HR because baroreceptor reflex from the the increase in BP...
114
Effects on HR and BP (and why) -
| Epinephrine
Epi - works at all adrenergic receptors
- increase HR
- no change in BP (because alpha 1 and beta 2 cause vasoconstriction and vasodilation, respectively which leads to them canceling out)
115
Effects on HR and BP (and why) -
| Isoproterenol
works at Beta receptors (non-selectively)
Beta 2 - vasodilation = decrease in BP (will trigger baroreceptors to increase HR)
Beta 1 - increase HR
116
Effects on HR and BP (and why) -
| Phenylephrine
works at alpha 1 receptor
| will increase BP (will cause baroreceptors to work and decrease HR as compensation)
117
Edrophonium is apart of what drug class
quaternary ammonium alcohol = AchE inhibitor
118
Neostigmine is apart of what drug class
carbamate - AchE inhibitor
119
Pyridostigmine is apart of what drug class
carbamate - AchE inhibitor
120
Physostigmine is apart of what drug class
carbamate - AchE inhibitor
121
Isofluorophate is apart of what drug class
organophosphate - AchE inhibitor
122
Echothiphate is apart of what drug class
organophosphate - AchE inhibitor
123
Sarin is apart of what drug class
organophosphate - AchE inhibitor
124
Soman is apart of what drug class
organophosphate - AchE inhibitor
125
Malthion is apart of what drug class
organophosphate - AchE inhibitor
126
Diazinon is apart of what drug class
organophosphate - AchE inhibitor
127
Important part of Malathion and Diazinon
PRODRUGS - they are insecticides that get metabolized by CYP450 by insects to become an active insecticide
128
Why does malthion and diazinon not harm humans?
mammals (and birds) metabolize the drugs with a carboxyesterase which makes the drug inactive
129
Are organophosphates reversible or irreversible? and why?
irrevesible! it has "aging" where bond gets stronger the longer it is there/once it gets hydrolyzed
130
How do you treat an overdose of an organophosphate drug (nerve gas drug)
use 2-PAM (pralidoxime) - works best if given within the first few hours of exposure
131
Contraindications for parasympathomimetic drug
Asthma
COPD
peptic ulcers
obstructions in urinary or GI tract
132
Tacrine is apart of what drug class
AchE inhibitor - for Alzheimers
133
Donepezil is apart of what drug class
AchE inhibitor - for Alzheimers
134
Rivastigmine is apart of what drug class
AchE inhibitor - for alzheimers
135
Galantamine is apart of what drug class
AchE inhibitor - for alzheimers
136
what is the problem with AchE inhibitors in Alzheimers
they lose their effectiveness as the disease progresses
137
Namenda is apart of what drug class
NMDA receptor antagonist (decreases glutamate in the brain)
138
Which alzheimer drug is an inhibitor of P450 enzymes (and can lead to drug-drug interactions)
galantamine
139
Carbachol is apart of what drug class
cholinergic agoinst - ester
140
Ach is apart of what drug class
cholinergic agonist - ester
141
Methacholine is apart of what drug class
cholinergic agonist - ester
142
Bethanechol is apart of what drug class
cholinergic agonist - ester
143
Varenicline is apart of what drug class
partial nicotinic receptor agonist
144
Pilocarpine is apart of what drug class
cholinergic agonist - synthetic analog
145
Atropine is apart of what drug class
antimuscarinic - long lasting tertiary amine
146
Scopolamine is apart of what drug class
antimuscarinic - long lasting tertiary amine
147
Homatropine is apart of what drug class
antimuscarinic - short acting tertiary amine
148
Tropicamide is apart of what drug class
antimuscarinic - short acting tertiary amine
149
benzotropine is apart of what drug class
antimuscarinic - tertiary amine for parkinsons
150
Atropine - is what kind of amine
tertiary
151
Atropine is short or long lasting
long
152
Scopolamine - is what kind of amine
tertiary
153
Scopolamine is short or long lasting
long
154
Homatropine is what kind of amine
tertiary
155
Tropicamide is what kind of amine
tertiary
156
Homatropine is short or long lasting
short
157
Tropicamide is short or long lasting
short
158
Glycopyrrolate is apart of what drug class
antimuscarinic - quaternary amine for GI disorders
159
Glycopyrrolate is what kind of amine
quaternary
160
Glycopyrrolate is used for what kind of disorder
GI disorders - peptic ulcers/GI spasms
161
Benzotropine is used for what kind of disorder
parkinsons
162
propantheline bromide is apart of what drug class
antimuscarinic - quaternary amine for GI disorders
163
propantheline bromide is used for what disorder
GI disorders - peptic ulcers/GI spasms
164
propantheline bromide is what kind of amine
quaternary
165
Important note about quaternary amines -
| They are ________ and therefore (do or do not) cross the gut well
CHARGED; do NOT
166
Two main types of antimuscarinics
tertiary amines or quaternary amines
167
Clinical uses for Anticholinergics
causes Mydriasis; stops Cycloplegia; causes Bladder Relaxation; Irritable bowel syndrome (relaxes GI tract and reduces acid secretion); Pre-Op Anti secretory; COPD; Motion Sickness; Parkinson's Disease
168
Ipratropium bromide is apart of what drug class
antimuscarinic - quaternary amine for COPD
169
Ipratropium bromide is what kind of amine
quaternary
170
Ipratropium bromide is used for what kind of disorder
COPD
171
What happens if someone overdose on an anticholinergic - how do you treat it?
give an AchE inhibitor
172
Clinical uses for nicotinic receptor antagonists
Muscle relaxation for surgery; tracheal intubation; control of ventilation; treat convulsions
173
Nicotinic receptor antagonists are also known as _________ blockers
neuromuscular
174
What are the 2 modes of action for neuromuscular blockers on the nicotinic receptor
depolarizing competitive and nondepolarizing competitive
175
Short, medium, or long acting neuromuscular blocker:
| Succinylcholine
short (v.short)
176
Short, medium, or long acting neuromuscular blocker: Pancuronium
long acting
177
What are some alpha - non selective antagonist drugs
phenoxybenzamine
| phentolamine
178
What are some alpha antagonist drugs - Alpha 1 selective
the "Quinazolines"
| aka prazosin, doxazosin, terazosin
179
what drugs are used for pheochromocytoma
phentolamine; phenoxybenzamine
180
What drugs (and the drug class) is used for BPH (benign prostatic hypertrophy)
the alpha 1 selective antagonists - prazosin, terazosin, doxazosin
181
What are the side effects of alpha 1 selective antagonists
orthostatic hypotension; nasal stuffiness; tachycardia; inhibition of ejaculation
182
Phentolamine and Phenoxybenzamine are both non-selective alpha antagonists - but which one is irreversible?
phenozybenzamine
183
What drugs are NON-selective Beta antagonists (beta blockers!)
Propranolol, naldolol, timolol, pindolol, carteolol
184
Which non-selective Beta antagonists have "ISA" intrinsic sympathomimetic activity" aka is a partial agonist
pindolol, carteolol
185
Therapeutic uses for beta-adrenergic receptor antagonists
- HTN
- CHF (early stages)
- Arrhythmias
- Migraines
- Stage fright
- Angina
- glaucoma
- thyrotoxicosis
186
How do beta blockers effect pupil size?
they don't! - only M3 and alpha1 affect pupil size
187
Pharmacologic effects of propanolol
- decreased cardiac output and heart rate
- decreases RENIN RELEASE (biggest factor for the anti-HTN effect)
- inhibits compensatory glycogenolysis/glucose release aka symptoms of hypoglycemia are masked
- bronchial airway resistance
188
What 2 patient populations should be under caution when taking propranolol (a beta blocker) and why/whats the mechanism of action?
asthma patients - because beta blockers prevent bronchodilation
diabetic patients - the drug will mask symptoms of hypoglycemia by inhibiting glycogenolysis and glucose release
189
what drugs are "cardioselective" beta blockers
atenolol, metoprolol, bisoprolol
190
what are characteristics you want for a good beta blocker drug
- low lipophilicity
- beta 1 selective
- want longer 1/2 life
191
"cardioselective" beta blocker actually means _____ selective...
cardio & renal selective - renal because B1 - Kidney/renin effect
192
which beta blocker acts VERY SHORT (like 9 minute half life) and why?
Esmolol - because it is rapidly hydrolyzed by esterases
193
What is the special characteristics of Bystolic?
it is beta 1 selective and decrease BP by also causing vasodilation via nitric oxide
194
Which drugs are mixed adrenergic receptor antagonists - and what do they "antagonize"
Carvediolol; Labetolol
non selective beta antagonist and a1 antagonist
195
Side effects of beta-blockers
bradycardia; sedation (if crosses BBB/ are very lipophilic); AV block (can cause arrhythmias) mask symptoms of hypoglycemia; withdrawal syndrome
196
Common uses for Parasympathomimetics (direct and indirect)
glaucoma, alzheimers, myasthenia gravis
197
What is neostigmines clinical use
myasthenia gravis; used to reverse surgical paralysis;
198
What is donepezil used for
alzheimers - it is a AchE inhibitor
199
what is isoflurophate used for
glaucoma (organophosphate AchE inhibitor)
200
what is echothiophate used for
glaucoma (organophosphate AchE inhibitor)
201
what drug is used to treat an overdose of anticholinergic drugs
physostigmine
202
what conditions are contraindicated with parasympathomimetics
Asthma, COPD, Peptic Ulcers, Obstructions in GI/Urinary tracts
(bc lungs constrict, more acid secreted, causes you to go...)
203
Signs and Symptoms of Parasympathomimetic (aka too much cholinergics) toxicity/side effects
SLUD (Salivation, lacrimation, urination, defecation)
| and decreased HR, pupils constricted; CNS effects; increased sweating
204
How to treat cholinergic overdose
atropine (a cholinergic receptor antagonist)
205
Which beta blocker drugs have a characteristic to prevent tachycardia reflex (and what is the characteristic)
Carvedilol; Labetolol
these drugs have beta antagonist and alpha 1 antagonist properties -
alpha antagonist - causes vasodilation - but the body doesn't compensate because the beta receptors are blocked
206
Mechanism that makes phenoxybenzamine irreversible
the drug forms and aziridinium ion (which is very electrophilic) and it makes a covalent bond with the receptor
