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Therapeutics I - Spring 2017 > ANS > Flashcards

ANS Flashcards

1
Q

Ganglionic neurons for Parasympathetic (Length)

A

pre: long
post: short

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2
Q

Ganglionic neurons for Sympathetic (Length)

A

pre: short
post: long

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3
Q

In BOTH parasympathetic and sympathetic neurons - ______ is released to activate _______ receptors on ___ganglionic neurons

A

Ach; nicotinic; post

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4
Q

In Parasympathetic neurons - _______ receptors on target organs are activated by

A

muscarinic; Ach;

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5
Q

In sympathetic neurons ________ receptors on target organs are activated by

A

adrenergic; norepinephrine

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6
Q

3 exceptions to the sympathetic nervous system “rules”

A

sweat glands; kidneys; adrenal gland

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7
Q

Sweat Glands:

  • If stress-related (sweaty palms) ________ is excreted
  • if thermoregulation _______ is released to work on _______ receptors
A

norepinephrine; Ach; muscarinic

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8
Q

Kidneys:
________ is released by postganglionic neurons to work on the smooth muscle of the renal vascular bed which cause _________

A

dopamine; vasodilation

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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

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10
Q

Types of cholinergic receptors

A

Nicotinic; muscarinic

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11
Q

Nicotinic receptors are a ______ type of receptor
and
Muscarinic receptors are a ______ type of receptor

A

ligand gated ion channel;

GPCR

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12
Q

2 main types of Muscarinic Receptors and where they are found

A

M3 - glands and smooth muscle

M2 - found in heart

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13
Q

Which G protein pathways do M3 and M2 use?

A

M3 - Gq (makes DAG and IP3)

M2 - GI (inhibits adenylycyclase)

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14
Q

Main kinds of Adrenergic Receptors

A

alpha 1; alpha 2; beta (1 and 2)

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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

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16
Q

where are Beta 1 and Beta 2 receptors found

A

Beta 1 - heart and kidneys

beta 2 - lungs/smooth muscle/ bronchioles

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17
Q

What kind of G protein does alpha 1 receptors use

A

Gq

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18
Q

what kind of G protein does alpha 2 receptors use

A

GaI

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19
Q

what kind of G protein does beta receptors use

A

GaS

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20
Q

which receptor causes vasodilation of skeletal muscle when activated

A

B2 (adrenergic receptor)

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21
Q

which receptor cause constriction of arteries when activated

A

alpha1

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22
Q

which receptor cause bronchodilation of the lungs when activated

A

B2

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23
Q

which receptor cause bronchoconstriction of the lungs when activated

A

M2/M3

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24
Q

which receptor causes the salivary glands to increase secretion when activated

A

BOTH PARA AND SYM!

alpha1; M3

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25
Q

which receptor decreases secretion (of acid) from GI tract when activated

A

alpha2

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26
Q

which receptor increases secretion (of acid) from GI tract when activated

A

M2/M3

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27
Q

which receptor is activated to prevent prelabor contractions

A

beta 2

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28
Q

why do anticholinergics cause dry mouth?

A

anticholinergics work on muscarinic receptors; muscarinic receptors when activated will cause salivary excretion

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29
Q

which receptor will cause “goosebumps” when activated

goosebumps = piloerection; contraction

A

alpha1

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30
Q

what does the canal of schlemm do and where is it found

A

found in eye…

it acts as the “drain” for aqueous humor

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31
Q

what is canal of schlemm opening controlled by

A

cilliary muscle

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32
Q

ciliary muscle controls what things

A

opening for canal of schlemm
AND
focusing of the lens in the eye

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33
Q

what receptor is found on the ciliary muscle

A

muscarinic

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34
Q

what makes aqueous humor in the eye

A

ciliary epithelium

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35
Q

what does the ciliary epithelium do

A

makes aqueous humor

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36
Q

what receptor is in the circular muscle and what does the muscle cause when contracted

A

muscarinic; miosis

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37
Q

what receptor is in the radial muscle and what does the muscle cause when contracted

A

Alpha; myDriasis

radial has the letters a and d in it…

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38
Q

Miosis vs mydrasis

A 
miosis = constrict pupils
mydriasis = dilate pupils
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39
Q

When a muscarinic (3) receptor is activated in the eye - what happens

A

contracts ciliary muscle and circular muscle -cause pupil constriction and more drainage of aqueous humor

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40
Q

What happens when the alpha 1 receptor is activated in the eye

A

contract radial muscle - causes mydriasis/pupil dilation;

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41
Q

what happens when Beta 2 receptor is activated in the eye

A

relaxation of ciliary muscle AND increase secretion of aqueous humor (aka hella aqueous humor)

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42
Q

where does alpha 1 receptor work/what does it do there

A 
vasoconstrictor of arteries and veins; 
radial eye constrictor;
goosebumps - piloerection
stress sweat
increase salivation 
contracts sphincter
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43
Q

where does alpha 2 receptor work/what does it do there

A

vasoconstrict veins; relax GI wall; inhibits acid secretion

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44
Q

where does Beta 2 receptor work/what does it do there

A

lungs - bronchodilator
eye - relaxes ciliary muscle; increases aqueous humor production
relaxes GI wall;
uterus - relaxes it

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45
Q

where does M3 receptor work/what does it do there (M3 only)

A

increases saliva; releases EDRF

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46
Q

what does M2 do own its own and where

A

heart - decrease HR rate contraction

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47
Q

where does Beta 1 receptor work/what does it do there

A

heart and kidney

increase HR and increase Renin secretion

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48
Q

What are ways to enhance/mimic the cholinergic system

A

nicotinic agonist
muscarinic agonist
AchE inhibitor

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49
Q

ways to block or inhibit the cholinergic system

A 
nicotinic antagonist
muscarinic antagonist
inhibit choline uptake
inhibit vesicular storage
inhibit release
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50
Q

In the cholinergic system - what drug is used to prevent uptake of choline

A

Hemocholinium

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51
Q

In the cholinergic system - what drug is used to prevent vesicular storage

A

vesamicol

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52
Q

In the cholinergic system - what drug is used to prevent release (of Ach)

A

botulism

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53
Q

How is Ach made in the cholinergic system

A

Choline and Acetate are made into Ach via ChAT (choline acetyl transferase)

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54
Q

Main groups Direct Acting Cholinergic Agonists

A

Esters, Alkaloids, Synthetic analogs

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55
Q

Examples of Direct Acting Cholinergic Agonists - Esters

A

Acetylcholine; Carbachol; Methacholine; Bethanechol

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56
Q

Examples of Direct Acting Cholinergic Agonists - Alkaloids

A

Muscarine; Nicotine

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57
Q

Examples of Direct Acting Cholinergic Agonists - Synthetic Analogs

A

Pilocarpine

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58
Q

Reactions (amino acid properties) found in the active site of Ach binding to muscarinic receptors

A

Two aromatic rings - pi cation interaction with the + amine in the Ach

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59
Q

Do all the muscarinic receptors have the same amino acids in there active site?

A

No! - therefore can use this factor to create selectivity

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60
Q

Stereochemistry of Ach

trans and cis points

A

cis - more stable

trans - stereochemistry present when Ach is bound to the receptor

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61
Q

Why are antimuscarininc drugs contraindicated in glaucoma?

A

antimuscarinics prevents the canal of schlemm from opening/draining aqueous humor via paralyzing the ciliary muscle

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62
Q

Main components of Ach

A

+ amine; choline chain (alpha and beta carbons); ester

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63
Q

what are the two sites in AchE

A

anionic and esteraic sites

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64
Q

What happens when you modify the choline chain - alter number of atoms…

A

5 is best

4 atoms will cause it to lose activity

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65
Q

what happens when you substitute a methyl group on the alpha carbon vs the beta carbon in Ach

A 
alpha = more nicotinic reactive
beta = more muscarinic selective and more resistant to metabolism bc carbon group is near ester

AN and BM

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66
Q

What happens if you alter the acetyl group in Ach by adding carbons

A

violating 5 atom rule –> makes it more nicotinic selective (muscarininc doesn’t like extra bulk)

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67
Q

What happens if you alter the acetyl group in Ach by making the end group a carbamyl group

A

makes carbachol drug = non selective still but will decrease metabolism

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68
Q

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

A

makes it more muscarinic selective AND more resistant to metabolizing

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69
Q

What are ways to mimic/activate the adrenergic system

A
  • 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
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70
Q

Ways to reduce/block the adrenergic system

A
  • adrenergic receptor antagonist
  • decrease release of
  • deplete vesicular stores
  • decrease synthesis
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71
Q

Synthesis steps for making Catcholamines

A

1- tyrosine - DOPA (via tyrosine hydroxylase)
2 - DOPA - dopamine (decarboxylate)
3 - dopamine - NE (hydroxylase)
4 - NE - Epi (add a methyl)

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72
Q

What step in the making of catecholamines is the rate limiting step

A

first step: tyrosine to DOPA

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73
Q

NE is metabolized by what enzymes?

A

MAO and COMT

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74
Q

What is the end product of NE metabolism

A

VMA = vanilymandelic acid

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75
Q

Example drugs of alpha 1 agonists

A

phenylephrine
methaoxamine
oxymetazoline
(also NE and Epi can activate alpha 1 just not selectively)

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76
Q

what pathway is stimulated via alpha1 agonists

A

Gq pathway

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77
Q

Example drugs of alpha 2 agonists

A 
clonidine
methyldopa
guanfacine
guanabenz
tizanidine
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78
Q

what pathway is stimulated by alpha 2 receptors

A

GI/O (less adenlylcyclase - less cAMP - less PKA)

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79
Q

Example drugs of beta non-selective agonists

A

isoproterenol

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80
Q

Example drugs of beta 1 selective agonists

A

dobutamine

dopamine

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81
Q

Example drugs of beta 2 selective agonists

A 
terbutaline
metaproterenol
albuterol
salmeterol
ritodrine
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82
Q

what adrenergic receptors does NE activate

A

alpha and beta1

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83
Q

what adrenergic receptors does Epi activate

A

all - it is non selective

84
Q

what adrenergic receptors does dopamine activate

A

beta receptors

85
Q

NE and Epi are substrates for what enzymes

A

MAO and COMT

86
Q

a1 receptor agonists - 2 - aralkylimidazoline examples

A

Naphazoline
tetrahydrozoline
oxymetazoline

87
Q

what are a1 receptor agonists - 2 - aralkylimidazoline use for

A

nasal or ophthalmic decongestants

88
Q

are a1 receptor agonists (2 - aralkylimidazoline) full or partial agonists?

89
Q

caution/rule for a1 receptor agonists - 2 - aralkylimidazoline

A

3 day rule - rebound decongestant - alpha receptors get desensitized

90
Q

What compound is used in NE and Epi preparations to prevent oxidation

A

Sodium Bisulfite

91
Q

Phenylephrine as an ophthalmic produt - what does it do

A

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
Q

a1 receptor agonists - 2 - aralkylimidazoline have ________ ring that is (acidic/basic)

A

imidazoline; acidic

93
Q

If an alpha 2 receptor works in the brain - it is working at the __________ control center

A

cardiovascular

94
Q

If an alpha 2 receptor works in the brain - it will cause an overall a DECREASED ____________

A

sympathetic outflow (or decreased BP)

95
Q

If an alpha 2 receptor works in the brain - it will cause the blood pressure to ____________

96
Q

If an alpha 2 receptor works in the brain - it will cause the blood pressure to decrease by what mechanisms

A

less renin secreted; less vasoconstriction; decreased heart rate

97
Q

clonidine is a _______ receptor agonist

98
Q

phenylephrine is a _______ receptor agonist

99
Q

methoxamine is a _______ receptor agonist

100
Q

oxymetazoline is a _______ receptor agonist

101
Q

methyldopa is a _______ receptor agonist

102
Q

guanabenz is a _______ receptor agonist

103
Q

guanfacine is a _______ receptor agonist

104
Q

tizanidine is a _______ receptor agonist

105
Q

isoproterenol is a _______ receptor agonist

A

beta (non-selective between 1 and 2)

106
Q

dobutamine is a _______ receptor agonist

A

beta 1 selective

107
Q

dopamine is a _______ receptor agonist

A

beta 1 selective

108
Q

terbutaline is a _______ receptor agonist

A

beta 2 selective

109
Q

albuterol is a _______ receptor agonist

A

beta 2 selective

110
Q

salmeterol is a _______ receptor agonist

A

beta 2 selective

111
Q

metaproterenol is a _______ receptor agonist

A

beta 2 selective

112
Q

ritodrine is a _______ receptor agonist

A

beta 2 selective

113
Q

Effects on HR and BP (and why) - Norepinephrine

A

NE - works at alpha and beta1

  • increase in BP (alpha
  • DECREASE in HR because baroreceptor reflex from the the increase in BP…
114
Q

Effects on HR and BP (and why) -

Epinephrine

A

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
Q

Effects on HR and BP (and why) -

Isoproterenol

A

works at Beta receptors (non-selectively)
Beta 2 - vasodilation = decrease in BP (will trigger baroreceptors to increase HR)
Beta 1 - increase HR

116
Q

Effects on HR and BP (and why) -

Phenylephrine

A

works at alpha 1 receptor

will increase BP (will cause baroreceptors to work and decrease HR as compensation)

117
Q

Edrophonium is apart of what drug class

A

quaternary ammonium alcohol = AchE inhibitor

118
Q

Neostigmine is apart of what drug class

A

carbamate - AchE inhibitor

119
Q

Pyridostigmine is apart of what drug class

A

carbamate - AchE inhibitor

120
Q

Physostigmine is apart of what drug class

A

carbamate - AchE inhibitor

121
Q

Isofluorophate is apart of what drug class

A

organophosphate - AchE inhibitor

122
Q

Echothiphate is apart of what drug class

A

organophosphate - AchE inhibitor

123
Q

Sarin is apart of what drug class

A

organophosphate - AchE inhibitor

124
Q

Soman is apart of what drug class

A

organophosphate - AchE inhibitor

125
Q

Malthion is apart of what drug class

A

organophosphate - AchE inhibitor

126
Q

Diazinon is apart of what drug class

A

organophosphate - AchE inhibitor

127
Q

Important part of Malathion and Diazinon

A

PRODRUGS - they are insecticides that get metabolized by CYP450 by insects to become an active insecticide

128
Q

Why does malthion and diazinon not harm humans?

A

mammals (and birds) metabolize the drugs with a carboxyesterase which makes the drug inactive

129
Q

Are organophosphates reversible or irreversible? and why?

A

irrevesible! it has “aging” where bond gets stronger the longer it is there/once it gets hydrolyzed

130
Q

How do you treat an overdose of an organophosphate drug (nerve gas drug)

A

use 2-PAM (pralidoxime) - works best if given within the first few hours of exposure

131
Q

Contraindications for parasympathomimetic drug

A

Asthma
COPD
peptic ulcers
obstructions in urinary or GI tract

132
Q

Tacrine is apart of what drug class

A

AchE inhibitor - for Alzheimers

133
Q

Donepezil is apart of what drug class

A

AchE inhibitor - for Alzheimers

134
Q

Rivastigmine is apart of what drug class

A

AchE inhibitor - for alzheimers

135
Q

Galantamine is apart of what drug class

A

AchE inhibitor - for alzheimers

136
Q

what is the problem with AchE inhibitors in Alzheimers

A

they lose their effectiveness as the disease progresses

137
Q

Namenda is apart of what drug class

A

NMDA receptor antagonist (decreases glutamate in the brain)

138
Q

Which alzheimer drug is an inhibitor of P450 enzymes (and can lead to drug-drug interactions)

A

galantamine

139
Q

Carbachol is apart of what drug class

A

cholinergic agoinst - ester

140
Q

Ach is apart of what drug class

A

cholinergic agonist - ester

141
Q

Methacholine is apart of what drug class

A

cholinergic agonist - ester

142
Q

Bethanechol is apart of what drug class

A

cholinergic agonist - ester

143
Q

Varenicline is apart of what drug class

A

partial nicotinic receptor agonist

144
Q

Pilocarpine is apart of what drug class

A

cholinergic agonist - synthetic analog

145
Q

Atropine is apart of what drug class

A

antimuscarinic - long lasting tertiary amine

146
Q

Scopolamine is apart of what drug class

A

antimuscarinic - long lasting tertiary amine

147
Q

Homatropine is apart of what drug class

A

antimuscarinic - short acting tertiary amine

148
Q

Tropicamide is apart of what drug class

A

antimuscarinic - short acting tertiary amine

149
Q

benzotropine is apart of what drug class

A

antimuscarinic - tertiary amine for parkinsons

150
Q

Atropine - is what kind of amine

151
Q

Atropine is short or long lasting

152
Q

Scopolamine - is what kind of amine

153
Q

Scopolamine is short or long lasting

154
Q

Homatropine is what kind of amine

155
Q

Tropicamide is what kind of amine

156
Q

Homatropine is short or long lasting

157
Q

Tropicamide is short or long lasting

158
Q

Glycopyrrolate is apart of what drug class

A

antimuscarinic - quaternary amine for GI disorders

159
Q

Glycopyrrolate is what kind of amine

A

quaternary

160
Q

Glycopyrrolate is used for what kind of disorder

A

GI disorders - peptic ulcers/GI spasms

161
Q

Benzotropine is used for what kind of disorder

A

parkinsons

162
Q

propantheline bromide is apart of what drug class

A

antimuscarinic - quaternary amine for GI disorders

163
Q

propantheline bromide is used for what disorder

A

GI disorders - peptic ulcers/GI spasms

164
Q

propantheline bromide is what kind of amine

A

quaternary

165
Q

Important note about quaternary amines -

They are ________ and therefore (do or do not) cross the gut well

A

CHARGED; do NOT

166
Q

Two main types of antimuscarinics

A

tertiary amines or quaternary amines

167
Q

Clinical uses for Anticholinergics

A

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
Q

Ipratropium bromide is apart of what drug class

A

antimuscarinic - quaternary amine for COPD

169
Q

Ipratropium bromide is what kind of amine

A

quaternary

170
Q

Ipratropium bromide is used for what kind of disorder

171
Q

What happens if someone overdose on an anticholinergic - how do you treat it?

A

give an AchE inhibitor

172
Q

Clinical uses for nicotinic receptor antagonists

A

Muscle relaxation for surgery; tracheal intubation; control of ventilation; treat convulsions

173
Q

Nicotinic receptor antagonists are also known as _________ blockers

A

neuromuscular

174
Q

What are the 2 modes of action for neuromuscular blockers on the nicotinic receptor

A

depolarizing competitive and nondepolarizing competitive

175
Q

Short, medium, or long acting neuromuscular blocker:

Succinylcholine

A

short (v.short)

176
Q

Short, medium, or long acting neuromuscular blocker: Pancuronium

A

long acting

177
Q

What are some alpha - non selective antagonist drugs

A

phenoxybenzamine

phentolamine

178
Q

What are some alpha antagonist drugs - Alpha 1 selective

A

the “Quinazolines”

aka prazosin, doxazosin, terazosin

179
Q

what drugs are used for pheochromocytoma

A

phentolamine; phenoxybenzamine

180
Q

What drugs (and the drug class) is used for BPH (benign prostatic hypertrophy)

A

the alpha 1 selective antagonists - prazosin, terazosin, doxazosin

181
Q

What are the side effects of alpha 1 selective antagonists

A

orthostatic hypotension; nasal stuffiness; tachycardia; inhibition of ejaculation

182
Q

Phentolamine and Phenoxybenzamine are both non-selective alpha antagonists - but which one is irreversible?

A

phenozybenzamine

183
Q

What drugs are NON-selective Beta antagonists (beta blockers!)

A

Propranolol, naldolol, timolol, pindolol, carteolol

184
Q

Which non-selective Beta antagonists have “ISA” intrinsic sympathomimetic activity” aka is a partial agonist

A

pindolol, carteolol

185
Q

Therapeutic uses for beta-adrenergic receptor antagonists

A
  • HTN
  • CHF (early stages)
  • Arrhythmias
  • Migraines
  • Stage fright
  • Angina
  • glaucoma
  • thyrotoxicosis
186
Q

How do beta blockers effect pupil size?

A

they don’t! - only M3 and alpha1 affect pupil size

187
Q

Pharmacologic effects of propanolol

A
  • 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
Q

What 2 patient populations should be under caution when taking propranolol (a beta blocker) and why/whats the mechanism of action?

A

asthma patients - because beta blockers prevent bronchodilation

diabetic patients - the drug will mask symptoms of hypoglycemia by inhibiting glycogenolysis and glucose release

189
Q

what drugs are “cardioselective” beta blockers

A

atenolol, metoprolol, bisoprolol

190
Q

what are characteristics you want for a good beta blocker drug

A
  • low lipophilicity
  • beta 1 selective
  • want longer 1/2 life
191
Q

“cardioselective” beta blocker actually means _____ selective…

A

cardio & renal selective - renal because B1 - Kidney/renin effect

192
Q

which beta blocker acts VERY SHORT (like 9 minute half life) and why?

A

Esmolol - because it is rapidly hydrolyzed by esterases

193
Q

What is the special characteristics of Bystolic?

A

it is beta 1 selective and decrease BP by also causing vasodilation via nitric oxide

194
Q

Which drugs are mixed adrenergic receptor antagonists - and what do they “antagonize”

A

Carvediolol; Labetolol

non selective beta antagonist and a1 antagonist

195
Q

Side effects of beta-blockers

A

bradycardia; sedation (if crosses BBB/ are very lipophilic); AV block (can cause arrhythmias) mask symptoms of hypoglycemia; withdrawal syndrome

196
Q

Common uses for Parasympathomimetics (direct and indirect)

A

glaucoma, alzheimers, myasthenia gravis

197
Q

What is neostigmines clinical use

A

myasthenia gravis; used to reverse surgical paralysis;

198
Q

What is donepezil used for

A

alzheimers - it is a AchE inhibitor

199
Q

what is isoflurophate used for

A

glaucoma (organophosphate AchE inhibitor)

200
Q

what is echothiophate used for

A

glaucoma (organophosphate AchE inhibitor)

201
Q

what drug is used to treat an overdose of anticholinergic drugs

A

physostigmine

202
Q

what conditions are contraindicated with parasympathomimetics

A

Asthma, COPD, Peptic Ulcers, Obstructions in GI/Urinary tracts

(bc lungs constrict, more acid secreted, causes you to go…)

203
Q

Signs and Symptoms of Parasympathomimetic (aka too much cholinergics) toxicity/side effects

A

SLUD (Salivation, lacrimation, urination, defecation)

and decreased HR, pupils constricted; CNS effects; increased sweating

204
Q

How to treat cholinergic overdose

A

atropine (a cholinergic receptor antagonist)

205
Q

Which beta blocker drugs have a characteristic to prevent tachycardia reflex (and what is the characteristic)

A

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
Q

Mechanism that makes phenoxybenzamine irreversible

A

the drug forms and aziridinium ion (which is very electrophilic) and it makes a covalent bond with the receptor

Therapeutics I - Spring 2017 (17 decks)

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