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N929 Pharmacology > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

Key Characteristics of Autonomic Nervous System

A

regulates involuntary response (smooth muscle, muscle, glands and heart)
2-neuron pathways
diffuse vs. discrete responses
dual innervation- opposing antagonistic effects
reflex responses
predominant, basal activity/control

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2
Q

Exceptions to Dual Innervation

A 
adrenal medulla (sympathetic)
most sweat glands (sympathetic only)
blood vessels (sympathetic only)
-basal tone 
-receptor distribution determines response
pilorector muscle
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3
Q

Parasympathetic Tone is dominant in what systems?

A

cardiac, bronchial smooth muscle, GI tract, urinary tract, salivary glands

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4
Q

Sympathetic tone is dominant in what systems?

A

sweat glands and arterioles/veins

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5
Q

Adrenal Medulla

A 
sympathetically innervated
only one neuron
postsynaptic neuroendocrine cells
secrete epi/norepi into blood
mimics sympathetic stimulation
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6
Q

sweat glands

A

sympathetic innervation
post ganglionic neuron is cholinergic (not adrenergic)
Ach is NT
receptor at effector tissue is muscarinic

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7
Q

Enteric Nervous system innervates the

A

GI tract

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8
Q

Steps of Neurotransmission

A

synthesis
storage
release (vesicles fuse w/ nerve terminal)
action
termination (reuptake, enzyme degradtion, and diffusion)

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9
Q

Cholinergic Transmission

A 
synthesis from choline, acetyl-CoA
storage in vesicles
action potential triggers Ca2+ entry, then interacts with SNARE protein on vesicle leading to fusion of vesicle and opening/release of Ach
binding to receptor
termination of action
recycle choline
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10
Q

what blocks cholinergic transmission?

A

botulinum toxin blocks

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11
Q

AchE

A

acetylcholinesterease

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12
Q

Major Types of Receptors

A

Ligand Gated Ion Channel
GPCR
Transmembrane w/ linked enzymatic domain
Intracellular receptor

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13
Q

Muscarinic Cholinergic Receptor

A

GCPR
5 subtypes, 2 subgroups
autonomic effector tissues (heart, endothelium, smooth muscle, glands) CNS
endogenous ligand: Ach
Activation mimics post ganglionic parasympathetic neuron stimulation
diverse cellular responses to M agonist
current drugs aren’t very selective

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14
Q

Nicotinic Cholinergic Receptor

A

ligand gated Na K depolarizing channel
major subtypes: NicM NicN
located: autonomic ganglia, skeletal muscle innervated by somatic nerves and CNS
Ach binds causing conformational changes, channel opens and + charged ions pulled through channel
depolarization of post synaptic cell

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15
Q

Where are cholinergic receptors?

A 
M1 CNS
M2 heart
M3 Smooth muscle, glands, endothelium, eye (circular, ciliary m)
M4 CNS
M5 CNS
NicN ANS ganglia, adrenal medulla, CNS
Nicm: Skeletal muscle NMJ
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16
Q

Key Points of Acetylcholine

A

roles in peripheral and central NS

many NT sites (NMJ, ANS ganglia, effector jux of postganglionic parasympathetic neurons and CNS)

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17
Q

Acetylcholine Termination of Action

A

Termination action: AchE
Receptors: Muscarinic, NicotinicN and NicotinicM
Drug Targets:

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18
Q

Receptors of Acetylcholine

A

Muscarinic, NicotinicN and M

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19
Q

Drug Targets of Acetylcholine

A

Ach Synethesis, storage, release AchE

Muscarinic and nicotinic receptors

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20
Q

Drug uSes of Ach

A

heart, eye, lung, GI GU NMJ and CNS

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21
Q

Adrenergic Neurotransmission

A

synthesis of NE (catecholamine)
uptake/storage vesicles
release w/ action potential (indirect adrenergic drugs)
rec binding
termination of action: reuptake via NET (NE transporter)

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22
Q

Catecholamine from

A

AA tyrosine

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23
Q

Alpha Adrenergic Receptors

A

GPCR
ligands: NE, Epi and Dopamine
3 subtypes alpha1 and alpha2

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24
Q

Alpha 1 found in

A

smooth mucle

eye

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25
Q

Alpha 2 is

A

mainly presynaptic

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26
Q

Activation of Alpha 1

A

excitatory

increases Ca2+, calmodulin activity, increase actin-myosin interaction, smooth muscle contraction

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27
Q

Activation of Alpha 2

A

inhibitory

decreases cAMP, decrease NE release

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28
Q

Beta Adrenergic Receptor

A

B1 B2 B3
GCPRs Gs
activation of adenyl cyclase to increase cAMP increase kinase activation and phosphorylation

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29
Q

Beta Adrenergic Effector tissue

A

autonomic

heart kidney liver smooth muscle skeletal muscle and fat cells

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30
Q

Where are Alpha 1 adrenergic receptors located?

A 
smooth muscle
GU sphincters
most vascular (skin, splanchnic)
eye (radial msucle)
heart liver
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31
Q

Where are alpha 2 adrenergic receptors located?

A

presynaptic nerve terminal
platelets
pancreatic beta cell

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32
Q

Where are beta2 adrenergic receptors located?

A 
smooth muscle (bronchiolar, uterine, etc.)
vascular smooth muscle
skeletal muscle beds
liver
skeletal muscle 
heart
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33
Q

Where are beta 1 adrenergic receptors located?

A

heart

kidney JG cells

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34
Q

Where are beta 3 cells located?

A

adipose tissue

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35
Q

Key Points of NE in the peripheral nervous system

A

roles in peripheral and CNS (excitatory)
catecholamine NT
termination of action: reuptake back into presynaptic neuron, diffusion, metabolism- minor role (MAO/COMT)
Noradrenergic receptors (GCPR, negative feedback limits response)/alpha1/alpha2/beta1-3
Drug Targets: NE synethesis, storage, reuptake, metabolism, receptor
Drug uses: cardiovascular, respiratory

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36
Q

Dopamine has roles in

A

peripheral and CNS

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37
Q

Dopamine is a catecholamine NT

A

precursor of NE and E

at effector JXNm sympathetic renal vascular smooth muscle

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38
Q

TOA of Dopamine

A

neuronal reuptake by DA transporter

MAO breakdown

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39
Q

MAO A

A

periphery

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40
Q

MAO B

A

CNS

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41
Q

COMT

A

minor role

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42
Q

Dopamine Receptors

A 
GCPR, cAMP 2nd messanger
D1 class: increases cAMP
D2 class  (d2-d4): decreases cAMP
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43
Q

Dopamine in the periphery (d1)

A

vasodilation in renal mesenteric, coronary vasculature

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44
Q

Dopamine in the periphery (d2)

A

presynaptic, modulates NT release

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45
Q

Dopamine as a drug (low dose)

A

vasodilation

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46
Q

Dopamine as a drug (intermediate)

A

+ inotrope (B1)

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47
Q

Dopamine as a drug (high)

A

vasoconstriction (alpha1)

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48
Q

Other NT utilized by PNS

A 
NO
vasoactive intestingal peptide
calcitonin gene related peptide
neuropeptide Y
substance P
serotonin 
others
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49
Q

PDE5

A

phosphodiesterase 5; the enzyme that breaks down the 2nd messengar

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50
Q

eNOS

A

endothelial nitric oxide synthase; enzyme that makes nitric oxide from L-arginine

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51
Q

Iris

A 
pupillary control
iris radial (mydrasis) Sympathetic NS
Iris circular (miosis) Parasympathetic NS
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52
Q

Ciliary

A

focus lens
Parasympathetic- accomodate near vision
increase outflow aqueous humor

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53
Q

Ciliary Body

A

aqueous humor production

increase secretion of aqueous humor via epithelium (sympathetic)

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54
Q

Aqueous Humor

A

intraocular pressure

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55
Q

adrenergic

A

describes neurons or receptors that use NE, or drugs that mimic sympathetic nerve stimulation

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56
Q

Alpha adrenergic

A

adrenergic receptor activated by NT NE

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57
Q

beta adrenergic

A

adrenergic receptor activated by NT NE

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58
Q

Catecholamine

A

molecule class that contains a caetchol and amine gorup, includes Epi, NE and dopamine

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59
Q

Cholinergic

A

describes neurons or receptors that use Ach or drugs that mimic parasympathetic nerve stimulation

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60
Q

Epipherine

A

adrenalin, produced in adrenal medulla, also NT in CNS

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61
Q

ganglion

A

a cluster of nerve cell bodies

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62
Q

muscarinic receptor

A

cholinergic receptor of PSNS

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63
Q

Nicotinic receptor

A

cholinergic receptor

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64
Q

NE

A

noradrenalin, NT at sympathetic effector tissues in periphery, some produced in adrenal medulla also in CNS

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65
Q

Preganglionic

A

situated before the ganglion

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66
Q

Postganglionic

A

situated after the ganglion

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67
Q

Characteristics of SNS

A 
originated in the thoracolumbar
2 neurons
peripheral ganglia
preganglia -short
post ganglia- long
divergence- diffuse
receptor on post gang- adrenegic/ muscarinic
receptor on target tissue: sweat glands/ adrenal`
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68
Q

Characteristics of PSNS

A 
Central Nervous and below and above scaral region
2 neurons
ganglia locations: SC and CNS
Pre- long, post short
discrete divergence
receptors: muscarinic, nicotinic,
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69
Q

Sympathomimetics

A

drugs with an effect that mimic stimulation of SNS or adrenal medullary discharge

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70
Q

Symopatholytics

A

drugs that antagonize the sympathetic nervous system

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71
Q

three ways sympathomimetics stimulate SNS

A

directly on adrenoreceptors
indirectly by stimulating release of noradrenaline from nerve endings
combination of both mechanisms

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72
Q

Direct acting Cholinergic Drugs

receptor agonist

A

acetylcholine
muscarine
pilocarpine
bethanechol

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73
Q

Direct Acting Cholinergic Direct (Nicotinic Agonist)

A

Acetylcholine
nicotine
succinylcholine
varenicline

74
Q

Indirect Acting (AchE inhibitors)

A

Edrophonium
neostigmine
pyridostigmine, physostigmine
donepezil

75
Q

Indirect Acting AchEi (irreversible)

A

echothiopate

76
Q

Other Cholinergic Agonist Drugs

A

increased muscarinic activity
lack acetate ester function
AChE does not hydrolyze

77
Q

MOA of AChE Inhibitor Drugs

A

Goal: to increase Ach in cleft and increase half life
bind to active site and inhibit AChE
Indirect Muscarinic and nicotinic effects

78
Q

Indirect Reversible AchE inhibitor Drugs

A

alcohol (edrophonium)

Carbamate (neostigmine)

79
Q

Indirect Irreversible AchE inhibitor Drugs

A

echothiophate

80
Q

AchE inihbitors are reversible if

A

the drug covalently bonds

81
Q

Short Duration Reversible AchE inhibitors

A

edrophonium

82
Q

Medium Duration Reversible AchE inhibitors

A

neostigimine, pyridostigmine, physostigmine

83
Q

AchE Effects

A

increases Ach
amplifies effects at cholinergic synapses
indirect stimulant of nicotinic receptors by increasing Ach

84
Q

Clinical Uses of AchE

A 
reversal of NM blockade by ND drug
MG diagnosis and treatment
glaucoma
GI- ileus
Postop Urinary Retention
Alzheimer's Disease
Non-therapeutic insecticide
85
Q

AchE Inhibitor drug effect on ANS

A

bradycardia, bronchoconstriction, increase secretions, increase GI motility, hypotension, miosis (accomdation for near vision)

86
Q

AchE Inhibitor drug effect on NMJ

A

reverses NM block by ND NMR blocker
improves transmission MG
large doses can depolarize block

87
Q

AchE Inhibitor drug effect on CNS

A

therapeutic- dementia tx
toxicity- excitation
Depression follows

88
Q

Edrophonium DOA, Main Site of Action, Onset, Notes

A 
alcohol, quaternary amine, very polar
Reversible blockade
Injectable IV IM
use for reversal
Onset 30-60seconds, duration 10 mins
NMJ, used for MG diagnosis
89
Q

Neostigmine DOA, Main Site of Action, Onset, Notes

A 
medium
NMJ
used IV to reverse
used as oral treatment in MG
visceral side effects
carbamate, quaternary amine, moderately polar
hydrolyzed by AchE, labile covalent bond
IV, orally active
Onset: 10-30 mins
DOA 2-4 hours
90
Q

Physostigmine

A

carbamate, tertiary amine, non-polar CROSSES BBB
hydrolyzed by AchE labile covalent bond
oral, IV/IM, useful for anticholinergic toxicity
onset 3-8 mins, duration 1 hour
medium, Peripheral, used as eye drops for glaucoma treatment

91
Q

Pyridostigime

A

Medium
NMJ
used orally in treatment of myasthenia gravis
better absorbed than neostigmine and has longer DOA

92
Q

Cholinergic Crisis

A 
DUMB BELLS
diarrhea, diaphoresis
urination
miosis
Bradycardia
Bronchoconstriction
Excitation (skel m., CNS)
lacrimination
salivation
sweating
93
Q

Cholinergic Toxicity can occur

A

as a muscarinic toxicity treat with atropine
and AChE toxicity ( too much Ach from blocking too much inhibitor)
antidote: atropine/pralidoxime

94
Q

Muscarinic Agonist Drugs

A 
acetylcholine
carbechol
methacholine
bethanecol
muscarine
pilocarpine
oxotremorine
cevimeline
95
Q

Bethanecol is utilized for

A

treatment of bladder and GI hypotonia

96
Q

Pilocarpine is used for

A

glaucoma

97
Q

Cevimeline is used for

A

sjogen’s syndrome

98
Q

Drug effects of Muscarinic Agonist (parasympomimic)

A 
decrease HR/BP
bronchoconstriction
increased salivation/ lacrimination
increase GI motility
Miosis decrease intraocular pressure, accommodation for near vision
bladder contracts
99
Q

Effects and Clinical use of Muscarinic agonist

A

glaucoma (contract ciliary body, increase aqueous outflow humor)
postop ileus
post op urinary retention
xerostomia (dry mouth)

100
Q

Effects of Muscarinic Agonist Type

A 
salivation
lacrimination
urination
diarrhea
gi upset
emesis
101
Q

Do not use cholinergic drugs if

A 
GI/GU obstruction
CV disease
Respiratory disease (asthma, COPD)
102
Q

Effects of Nicotinic neuron Agonist

A

stimulation of post ganglionic neuronal activity

CNS stimulation

103
Q

Clinical Use of Nicotinic neuron Agonist

A

Smoking cessation

104
Q

Adverse effects of Nicotinic Neuron Agonist

A

CNS stimulation
skeletal muscle depolarization/blockade
HTN, increase HR, N/V and diarrhea

105
Q

Effects of Nicotinic muscle Agonist

A

activation of NM endplates

contraction

106
Q

Clinical Use of Nicotinic NMJ agonist

A

depolarizing skeletal muscle paralysis

107
Q

Muscarinic Antagonist Drugs (nonselective)

A

atropine
glycopyrrate
scopolamine

108
Q

Nicotinic Antagonist (NicotinicN)

A

ganglionic blocker

hexamethonium

109
Q

Nicotinic Antagonist (NaChRM)

A

atracurium, cisatracurium, vecuronium, rocuronium, pancuronium

110
Q

Muscarinic Receptor Antagoinst Effects

A 
increase HR
bronchodilation
decrease GI motility
GU constipation and retention
Decrease sweat and glandular release
pupillary dilation
CNS sedation
111
Q

Clinical Uses of Muscarinic Receptor Antagonist

A 
motion sickness
parkinson's disease
exam requiring mydriasis
cyclopegia
decrease lung secretions
COPD asthma
GI hypermotility
urinary urgency
treatment of bradycardia
anesthetic premed
cholinergic poisoning
achE inhibitor toxicity
112
Q

Atropine Characteristics

A 
tetriary amine
lipophilic
crosses BBB
half-life about 4 hours
injection (IV IM) opthalamic
utilized for opthalmic, bradycardias, antidote vs cholinergic agonist, pre-op inhibits secretions
adjunct for NM block reversal
113
Q

Scopolamine Characteristics

A 
tertiary amine
crosses BBB
CNS effects- amnesia, sedation
half- life 1-4hr (IV) onset 10 mins duration 2 hours
transdermal patch 
injection
uses for motion sickness, post op NV
preop- amnesia, sedation, antiemetic decrease secretions
114
Q

Glycopyrrolate Characteristics

A 
quaternary amine, decreases CNS effects
half life about 1 hour
onset 1 min
duration (7 hours)
IV oral
uses include pre-op, cardiac dysrhythmia (vagal reflex association)
adjunct for NM blockade
115
Q

Muscarinic Antagonist/Anticholinergic Effects

A

Dry as a bone, hot as a pistol, red as a beet, blind as a bat, mad as a hatter

116
Q

Potential concerns of Muscarinic Antagonist/Anticholinergic

A 
hyperthermia
glaucoma
prostatic hypertropy
CV (arrhythmias, ischemia, HF, HTN)
ileus, ulerative colitis
117
Q

Medication classes with anticholinergic effects

A 
antihistamines
antispasmodics
antiparkinson's
skeletal muscle relaxants
antipsychotics
antidepressants
antimuscarinics for urinary incontinence
118
Q

Nicotinic Receptor Antagonist Effects

A

competitive antagonism at skeletal muscle

Non-depolarizing

119
Q

Nicotinic M Receptor Antagonist Clinical Uses

A

Skeletal muscle relaxation for surgical, intubation, ventilation control

120
Q

Nicotinic N Receptor Antagonist Effects

A

Blocks ganglionic output

121
Q

Nicotinic N Receptor Antagonist CLinical uses

A

hypertensive emergency (no longer in use)

122
Q

Mechanisms of Adrenergic drugs

A

indirect
mixed multiple sites of action (release of NE from nerve terminal, activate adrenergic receptors, broader actions)
direct receptor antagonist

123
Q

Alpha 1 second messengers and effectors

A

phospholipase C activation
increase inositol trisphosphate
increase diacylglycerol
increase Ca2+

124
Q

Alpha 1 potency order

A

NE, E, iso

125
Q

Alpha 1 Selective Agonist

A

phenylpherine

methoxamine

126
Q

Alpha 1 Selective antagonist

A

prazosin

doxazocin

127
Q

Alpha 2 second messengers and effectors

A

decrease cAMP, decrease Ca channels, increase K channels

128
Q

Alpha 2 potency order

A

E, NE, ISO

129
Q

Alpha 2 selective agonist

A

clonidine

130
Q

Alpha 2 selective antagonist

A

yohimbine

idazoxan

131
Q

Beta 1/2/3 second messengers and effectors

A

increase cAMP

132
Q

Beta 1 potency

A

ISO>NE>E

133
Q

Beta 2 potency

A

ISO > E> NE

134
Q

Beta 3 potency

A

ISO> NE=E

135
Q

Beta 1 selective agonist

A

dobutamine

xamoterol

136
Q

Beta 1 selective antagonist

A

atenolol

metoprolol

137
Q

Beta 2 selective Agonist

A 
salbutamol
terbutaline
salemetrol
formoterol
clenbuterol
138
Q

Beta 2 selective antagonist

A

butoxamine

139
Q

Beta 3 selective agonist

A

mirabegron

140
Q

Ephedrine

A

displaces/releases stored catecholamine NT
some agonist activity on alpha and beta receptors
noncatecholamine extended duration
herbal source-ma hung

141
Q

Amphetamine

A

displaces/releases stored catecholamine NT
secondary inhibits catetcholamine reuptake (NET, DAT)
uses in ADHD, narcolepsy, appetite suppression

142
Q

Cocaine

A

blocks NE reuptake (inhibits NET & DAT transporters)

Blocks sodium channels- local anesthetic actions

143
Q

Tyramine

A

displaces/releases stored catecholamines

not a drug, in fermentated foods, role in drug food interacitons of MAO inhibitors

144
Q

Tricyclic Antidepresants, SNRI

A

block NE re-uptake (inhibits NET transporter)

145
Q

Monamine Oxidase inhibitors (MAOis)

A

prevents breakdown of catecholamines in presynaptic terminal- catecholamine accumulation in vesicles
MAOA metabolizes NE
MAOB metabolizes DA

146
Q

tranylcypromine and phenelzine

A

nonselective inhibits MAOA and MAOB

147
Q

Selegiline and rasagiline

A

selective MAOB inhibitors

148
Q

Most drugs are non-catecholamines

A

longer acting

oral adminsitration

149
Q

Epinephrine Receptor and Uses

A 
Alpha 1
alpha 2
beta 1
beta 2
beta 3
low doses- beta effects
high doses: alpha effects
Anaphylaxis, w/ local anesthetics, cardiac arrest
150
Q

Norepinpherine Receptors and Uses

A

Alpha 1 and Beta 1

shock

151
Q

Isoproterenol Receptors and Uses

A

Beta 1 and Beta 2

acute asthma, cardiac stimulant

152
Q

Dopamine Receptors and Uses

A

low dose: renal, mesenteric, coronary vascular beds
med doses: beta 1
higher doses: alpha 1
shock, HF and increase blood flow to kidney

153
Q

Dobutamine Receptors and Uses

A

b1 primarily

acute HF

154
Q

Cardiac Effects of NE

A

decrease pulse
increase SBP and DBp
Increases PVR

155
Q

Cardiac Effects of Epi

A

increases HR
increases SBP/ decreases DBP
decreases PVR

156
Q

Cardiac Effect of Isoproterenol

A

increases HR
increases SBP/ decreases DBP
decreases PVR

157
Q

Predominant effects of Adrenergic Receptor agonist

Alpha 1

A 
vasoconstriction
smooth muscle (except GI)
trophic effect (BPH)
GI/GU sphincters contract
Eye-mydriasis
158
Q

Predominant effects of Adrenergic Receptor agonist

Beta 1

A

increase HR, increase contractility
effects on rhythm
kidney renin
trophic effect- hypertrophy

159
Q

Predominant effects of Adrenergic Receptor agonist

Alpha 2

A

decrease NE release (presynaptic)
CNS inhibit sympathetic outflow
platelet aggregation
decrease insulin in pancreas

160
Q

Predominant effects of Adrenergic Receptor agonist

Beta 2

A 
bronchodilation
vasodilation
most smooth muscle (relaxes)
skeletal muscle contracts (tremor)
GI/GU relax
uterine smooth muscle relax
glycogenolysis
161
Q

Alpha 1 agonist effects

A

increase vascular tone, increase PVR/BP and eyes dilate

162
Q

Alpha 1 agonist clinical uses

A

shock

OTC: decongestants, ophthalamic hyperemia

163
Q

Alpha 2 agonist clinical uses

A

hypertension

164
Q

Alpha 2 effects

A

decrease NE release

165
Q

Dexmedetomidine

A

selective alpha 2 receptor agonist (CNS actions)
suppresses sympathetic NS activity
sedative effects
analgesic effects
decrease HR, decrease SVR, decrease BP
Respiratory less RR decrease TV
tolerance, tachyphylaxis, premed, adjunct to general anesthesia,

166
Q

Beta 1 Agonist Effects

A

increase HR, AV node conduction, increase force and renin release

167
Q

Beta 1 Clinical Uses

A

ACUTE heart failure

168
Q

Beta 2 agonist effects

A

relaxation or lung, uterus, vascular and liver

169
Q

Beta 2 clinical uses

A

asthma, COPD, preterm labor

170
Q

Potential concerns with adrenergic agonist

A 
CV disease
cerebrovascular disease
other vasoconstriction related
diabetes (increase blood glucose)
IV extravasation risks
thyroid disease
171
Q

Nonselective alpha adrenergic receptors Blockers

A

phenoxybenzamine

phentolamine

172
Q

Alpha 1 adrenergic receptors Blockers

A

prazosin

173
Q

Alpha 2 adrenergic receptor Blockers

A

yohimibine

174
Q

Nonselective Beta Blocker

A

propanolol

175
Q

Beta 1 Receptor Blocker

A

Metoprolol

esmolol

176
Q

Alpha Receptor Antagonist Effects

A

smooth muscle relaxation, decrease pVR, decrase BP

177
Q

Alpha receptor antagonist Clinical uses

A

hypertension
BPH
pheochromocytoma

178
Q

Adverse Effects of Alpha Receptor Antagonist

A

increase HR, first dose effect

orthostatic HTN and syncopy

179
Q

Beta Receptor Antagonist Effects

A

decrease HE, decrease force of contraction

decrease renin release, anti-rhythmic effects

180
Q

Clinical uses of beta receptor antagonist

A

htn, angina pectoris, arrhythmia, myocardial infaraction, thyrotoxicosis, heart failure, infantile hemangioma, glaucoma, migrane, prophylaxis, anxiety

181
Q

Potential concerns of Adrenergic Antagonist

A

respiratory disease
cardiovascular
diabetes (may potentiate hypoglycemia and mask sign/sym)
thyroid disease

N929 Pharmacology (16 decks)

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