Neuropharmacology Flashcards
1
Q
What do the nervous system and endocrine system do?
A
coordinate the regulation and integration of body functions
2
Q
Endocrine system
A
various levels of blood-borne hormones
3
Q
nervous system
A
transfer signals via the transmission of electrical impulses over nerve fibers to effector cells, which release neuromodulator substances
4
Q
Central Nervous System
A
brain and spinal cord
5
Q
Peripheral Nervous System
A
neurons located outside the brain and spinal cord
6
Q
efferent nervous system
A
efferent neurons deliver signals away from the CNS to the peripheral tissues
autonomic nervous system and somatic nervous system
7
Q
Afferent nervous system
A
afferent neurons deliver signals from the peripheral tissues to the CNS
provide sensory info to regulate the function of the efferent division through neural pathways
8
Q
Somatic Nervous System
A
voluntary functions
contraction of skeletal muscles, essential for locomotion
9
Q
Autonomic nervous system
A
involuntary functions
vital bodily functions without consciousness
require sensory input from peripheral structures to provide information on the current state of the body
includes the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system
10
Q
ganglion
A
collection of neuron cell bodies in the PNS
functions for communication
11
Q
Where are preganglionic neurons located
A
in the CNS
12
Q
Where are postganglionic neurons located?
A
distal/posterior to a ganglion
13
Q
Functions of the sympathetic nervous system
A
adjust to stressful situations
incr heart rate and blood pressure
incr blood flow to skeletal muscles and the heart
divert flow from the skin and internal organs
dilate pupils and bronchioles
14
Q
Functions of parasympathetic nervous system
A
maintain homeostasis within the body, essential bodily functions
opposes/balances the actions of the sympathetic division
15
Q
Sympathetic has wide distribution and parasympathetic has x
A
short distribution
16
Q
Hormones
A
endocrine cells secrete hormones into the circulation, traveling throughout the body, initiating effects on target cells
17
Q
Local mediators
A
cells secrete chemicals that act on nearby cells
rapidly destroyed, don’t enter circulation
18
Q
Neurotransmitters
A
communications between nerve cells occurs via chemical signals released from the nerve terminals
triggered by arrival of action potential at the nerve ending
19
Q
How are neurotransmitters signals mediated?
A
by binding to receptors on the cell surface of target organs
20
Q
Types of neurotransmitters in the autonomic nervous systems
A
ACh
NE
Epi
21
Q
Sympathetic innervation of adrenal medulla
A
preganglionic neuron releases ACh
it binds to nicotinic receptor on adrenal medulla
Epi and NE released into blood
they bind to adrenergic receptor
22
Q
Sympathetic path
A
preganglionic neuron releases ACh
it binds to the nicotinic receptor
postganglioni neuron releases NE
NE binds to adrenergic receptor
23
Q
parasympathetic path
A
preganglionic neuron releases ACh
binds to nicotinic receptor
postganglionic neurons release ACh
binds to muscarinic receptor
24
Q
M1, M3, M5
A
stimulators of muscarinic receptors in parasympathetic nervous system
Gq-PLC-IP3/ DAG- Ca^2+
25
M2, M4
inhibitory muscarinic receptors in parasympathetic nervous system
inhibits adenylyl cyclase and regulates specific ion channels
26
Synthesis and Release of ACh from cholinergic neuron
1. Ach is made
2. taken up into storage vesicles
3. released in to synaptic cleft
4. binds to nAChR
5. AChE degrades ACh
6. Choline is take back up by the neuron
27
muscarinic receptors
cholinoceptors
weak affinity for nicotine
GPCR
28
nicotinic receptor
cholinoceptors
weak affinity for muscadine
iontropic receptor
29
What does ACh do to the cardiovascular system?
vasodilation
decr heart rate, cardiac conduction velocity in AV-node, and force of contraction
effects mediated by M2 receptors:
incr K^+ current
decr L type Ca^2+ current
decr cAMP
inhibition of NE release form sympathetic nerve terminals
30
What does ACh do to the respiratory tract?
bronchoconstriction
increased tracheobronchial secretion
effects mediated by activation of M3 receptors
31
What does ACh do to the urinary tract?
detrusor muscle contraction
incr urinary voiding pressure
ureteral peristalsis
effects mediated by M2 and M3 receptors
32
What does ACh do to the GI tract?
incr tone of GI muscle, muscle contraction, secretory activity of stomach and intestine
effects mediated by M2 and M3 receptors
33
What secretory and ocular effects is ACh responsible for?
glandular secretion
mitosis
effects mediated by M1 and M3 receptors
34
What effects does ACh have on the CNS?
cognition
motor control
appetite regulation
nociception
arousal
effects mediated by all 5 muscarinic receptors
35
Acetylcholine
muscarinic agonist
direct acting
used topically to induce miosis during eye exams or ophthalmic surgery
ganglionic blocker - arousal and cognitive enhancement
36
Methacholine
muscarinic agonist
used as an inhalant to diagnose bronchial airway hypersensitivity in patients with subclinical asthma
37
Bethanechol
muscarinic agonist
directs acting
used for treating urinary retention & inadequate emptying of bladder postoperatively
used to stimulate GI tract peristalsis and increase LES pressure
38
Pilocarpine
muscarinic agonist
direct acting
used to treat xerostomia following head and neck irradiation and Sjogren syndrome
used topically to treat glaucoma and as a miotic agent
reduces intraocular pressure in open and narrow angle glaucomas
uncharged tertiary amine that can penetrate the CNS
39
Contraindications of Muscarinc Agonists
asthma
COPD
urinary/GI obstruction
acid-peptic disease
cardiovascular disease
hypotension
hyperthyroidism
40
Adverse Effects of Muscarinic Receptor Agonists
Diaphoresis
NVD, abdominal cramps
blurry vision
hypotension
41
Muscarinic Receptor Antagonists
Prevents effects of ACh by binding to muscarinic receptors
little effect on nicotinic receptors
42
Ipatropium [Atrovent]
muscarinic receptor antagonist
used in respiratory tract to treat COPD, frequently in combo with inhaled long-acting beta 2 adrenergic receptor agonists
43
Tiotropium [Spriva]
muscarinic receptor antagonist
derivative of atropine, bronchodilator
used in respiratory tract to treat COPD, frequently in combo with inhaled long-acting beta 2 adrenergic receptor agonists
44
Oxybutynin [Ditropan]
muscarinic antagonist
used in the genitourinary tract to treat overactive bladder; relaxes detrusor muscle of the bladder
synthetic atropine-like drug
adverse effects: xerostomia, blurred vision, constipation and dyspepsia, drowsiness and confusion
45
Atropine
muscarinic antagonist
binds competitively and prevents ACh from binding to muscarinic receptors
used in GI tract to treat irritable bowl and increased tone, and to decrease GI motility
used in the cardiovascular system to reduce the degree AV-block that results from overactive parasympathetic tone
used in anesthesia to block vagaries responses to surgical manipulation of visceral organs
used to treat
- AChE poisoning from use of pesticides and nerve gas agents
- Spastic disorders of the GI tract
- organophosphate poisoning
- suppress respiratory secretions prior to surgery
- bradycardia
46
Homatropine [Ispto Homatropine]
muscarinic antagonist
administered topically to the eye to induce mydriasis and cycloplegia
47
Scopolamine [Transderm Scop]
muscarinic antagonist
used for the CNS
admin as a transdermal patch prophylactically to treat motion sickness
peripheral effects similar to atropine
greater actions in the CNS and longer duration of action compare to atropine
adverse effects: dry mouth, drowsiness, blurred vision i
48
Benztropine Mesylate [Cogentin]
muscarinic antagonist
used for the CNS
used to treat extrapyramidal side effects of antipsychotic drugs
49
Contraindications of Antimuscarinic agents
urinary tract/ GI obstruction
50
Adverse effects of antimuscarinic agents
xerostomia
constipation
blurred vision
dyspepsia
cognitive impairment
51
AChE inhibitors
enhance cholinergic tone by selectively blocking AChE
acts at cholinergic neuroeffector junctions
52
There are no vascular adverse effects with AChE because there is not x on the muscarinic receptors on the endothelium of blood vessels
cholinergic nerve fibers
53
Categories of AChE inhibitors
Reversible inhibitors
carbamylatipm inhibitors
organophosphate inhibitors
54
What kind of binding do reversible AChE inhibitors have?
non-covalent
55
Donepezil [Aricept]
AChE reversible inhibitor
used to treat the symptoms of Alzheimer’s disease
has not been shown to reduce healthcare costs/delay institutionalization
can be used with memantine in moderate to severe disease
56
What kind of binding do carbamylatipm inhibitors have?
Immediate duration covalent binding (15-30 min)
57
Neostigmine [Prostigmin]
indirect acting reversible muscarinic agonist carbamylatipm AChE inhibitor
used to treat myasthenia gravis, urinary retention without blockage and paralytic ileus
prevents postoperative abdominal distention
used as an antidote for competitive neuromuscular blockers
has intermediate duration of action 0.5-2hrs
58
What kind of binding do organophosphate inhibitors have?
long duration covalent binding (hours-permanent)
59
Malathion, and insecticide, and sarin, a nerve gas, are both examples of?
organophosphate AChE inhibitors
60
What effects do AChE inhibitors have on the body?
eye- miosis
GI Tract- enhanced gastric contractions, increased secretion of gastric acid, increased activity of small and large bowel
increased glandular secretion
increased contraction of smooth muscle of bronchioles and ureters decreased cardiac output
bradycardia
61
What are the symptoms of AChE inhibitor overdose?
salivation
lacrimation
urination
defecation
62
Nicotine
nicotinic agonist
acts at the neuromuscular junction
in PNS - transited stimulation followed by depression of autonomic ganglia and neuromuscular junction leading to paralysis
in CNS- stimulation, weak analgesia, tremors leading to seizures at toxic doses, excitation of respiration, nausea and vomiting
used in smoking cessation
63
Varenicline [Chantex]
nicotinic agonist
acts at the neuromuscular junction
partial agonist at nicotinic receptor
used in smoking cessation
adverse effects: mood and behavior changes
64
Pancuronium [Pavulon]
competitive nicotinic receptor antagonist
induces muscle paralysis by blocking nicotinic receptors at the neuromuscular junction
used for muscle relaxation during general anesthesia
used in the lethal injection cocktail
65
Direct acting muscarinic agonists
acetylcholine
bethanechol
carbachol
pilocarpine
nicotine
66
Indirect acting reversible muscarinic agonist
edrophonium
physostigmine
neostigmine
pyridostigmine
ambenonium
donepezil
rivastigmine
galantamine
67
indirect acting irreversible muscarinic agents
ecothiphate
68
Which muscarinic agonist reactivates AChE?
pralidoxime
69
Antimuscarinic agents examples
atropine
ipratropium
tiotropium
tropicamide
cyclopentolate
benztropine
trihexyphenidyl
darifenacin
fesoterodine
oxybutynin
solifenacin
tolterodine
trospium chloride
70
Which muscarinic antagonist is a ganglionic blocker?
nicotine
71
What are the 2 types of neuromuscular blockers?
nondepolarizing and depolarizing
72
Adrenergic agonist direct acting agents
epinephrine
norepinephrine
isoproterenol
dopamine
fenoldopam
dobutamine
phenylephrine
clonidine
albuterol
terbutaline
salmeterol
formoterol
mirabegron
73
indirect acting adrenergic agonists
amphetamine
cocaine
74
mixed action adrenergic agonists
ephedrine
pseudoephedrine
75
adrenergic antagonists: alpha blockers
phenoxybenzamine
phentolamine
prazosin
terazosin
doxazosinn
tamsulosin
alfuzosin
Yohimbine
76
Adrenergic Antagonists: Beta blockers- nonselective
propranolol
nadolol
timolol
77
Adrenergic antagonists: beta 1 blockers- selective
acebutolol
atenolol
betaxolol
bisprolol
esmolol
metaprolol
nebivolol
78
adrenergic antagonists: beta blockers with partial agonist activity
acebutolol
pindolol
79
adrenergic antagonists: beta blockers- antagonists of both alpha and beta adrenoreceptors
labetalol
carvedilol
80
Which adrenergic antagonist affects neurotransmitter uptake or release?
reserpine
81
physostigmine
indirect acting reversible muscarinic agonist
increases intestinal and bladder motility
reverses CNS and cardia effects of tricyclic antidepressants
reverses CNS effects of Atropine
uncharged tertiary amine that can penetrate the CNS
82
Rivastigmine
indirect acting reversible muscarinic agonist
first line treatment for Alzheimer’s disease
not been shown to reduce healthcare costs/delay institutionalization
can be used with memantine in moderate to severe disease
83
Galantamine
indirect acting reversible muscarinic agonist
first line treatment for alzheimer’s disease
has not been shown to reduce healthcare costs/ delay institutionalization
can be used with memantine
84
What do antimuscarinic agents do?
blocks the muscarinic receptor and inhibits muscarinic function
85
What do ganglionic blockers do?
blocks the entire output of ANS at the nicotinic receptor
86
What do neuromuscular blockers do?
block cholinergic transmission between motor nerve endings and the nicotinic receptors on the skeletal muscles
87
Ipatropium
muscarinic antagonist
derivatives of atropine, bronchodilator
used to treat COPD
88
Tropicamide
muscarinic blocker
duration of action is shorter than atropine
in ophthalmology used to produce mydriasis and cycloplegia prior to refraction
89
Cyclopentolate
muscarinic blocker
duration of action is shorter than atropine
in ophthalmology used to produce mydriasis and cycloplegia prior to refraction
90
Benztropine
muscarinic blocker
adjuncts with other antiparkinsonian agents
used to treat Parkinson’s disease
91
Trihexyphenidyl
muscarinic blocker
adjuncts with other antiparkinsonian agents
used to treat Parkinson’s disease
92
Darifenacin
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
93
Fesoterodine
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
94
Solifenacin
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
95
Tolterodine
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
96
Trospium Chloride
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
97
Adverse effects of muscarinic antagonists
blurred vision
confusion
mydriasis
constipation
urinary retention
98
Dopamine
ganglionic blocker
pleasure
appetite suppression
catecholamine
alpha 1 and beta 1 receptors
treats shock and congestive heart failure
raises blood pressure
increased cardiac output, increased blood flow
99
Norepinephrine
ganglionic blocker
arousal
appetite suppression
100
Glutamate
ganglionic blockers
learning + memory enhancement
NMDA receptors- calcium and sodium channels
in the brian
neuronal excitation
synaptic plasticity
excitotoxicity
101
Serotonin
ganglionic blocker
mood modulation
appetite suppression
5HT3 receptor
excitatory; gates sodium, potassium, and calcium ions
in the CNS and PNS
nauesea and vomiting, anxiety, seizure propensity, pro-nociception
102
Beta Endorphin
ganglionic blocker
anxiety and tension reduction
103
GABA
ganglionic blocker
anxiety and tension reduction
receptor is inhibitory and gates Cl^-
major inhibitory transmitter in the CNS
hyperpolarizes cell membranes
decreases neuronal fibrin rate
in the CNS
anxiolytic, anticonvulsant, amnesic, sedative, hypnotic, muscle relaxant
104
Blocking sympathetic ganglion means
reduction in norepinephrine release
reduction in heart rate and blood pressure
105
Blocking parasympathetic ganglion means
reduction in ACh release
increase in heart rate
106
Nondepolarizing competitive neuromuscular blocking drugs
pancuronium, vecuronium, cistracurium, rocuronium
highly polar compounds that are poorly absorbed from the GI tract; preferred parenteral admin
low doses competitively block ACh at the nicotinic receptors
high doses block the ion channels of the motor endplate, leads to weakening of neuromuscular transmission, resulting in decrease of the ability of AChE inhibitors to reverse nondepolarizing blocker’s action
used for muscle relaxation during general anesthesia and in the lethal injection cocktail
safe with minimal side effects
107
Depolarizing neuromuscular blocking agents
succinylcholine
binds to the nAChR and acts like ACh to depolarize the junction
rapid onset
used for rapid endotracheal intubation during the induction of anesthesia, electronvulsive shock treatment
adverse effects: hyperthermia, apnea, hyperkalemia
108
Adrenergic drugs affect receptors stimulated by
norepinephrine and epinephrine
109
Sympathomimetics
adrenergic drugs activating adrenergic receptors
110
Sympathy lyrics
drugs blocking the activation of adrenergic receptors
111
What does DOPA stand for?
dihydroxyphenyalanine
prodrug
112
What does COMT stand for?
catechol-O-methyltransferase
113
What does MOA stand for?
monoamine oxidase
114
What does SNRI stand for?
serotonin-norepinephrine reuptake inhibitor
115
Steps for the release of norepinephrine from the adrenergic neuron
1. hydroxylation of tyrosine makes dopamine
2. uptake into storage vesicles and converted to norepinephrine
3. Norepinephrine is released into the synaptic cleft
4. Norepinephrine binds to receptors
5. norepinephrine is taken back up into the neuron
6. norepinephrine is methylated by COMT and. oxidized by MAO
116
alpha1 adrenoreceptors
on postsynaptic membrane of the effector organs
leads to constriction of smooth muscle
GPCR- generates IP3 and DAG which turns on cytosolic proteins and releases calcium ions
117
alpha 2 adrenoreceptors
on presynaptic nerve endings
decreases NE release and inhibits cAMP production
inhibits release of ACh
118
What are the effects of alpha1 receptors?
vasoconstriction
increased peripheral resistance
increased blood pressure
mydriasis
increased closure of internal sphincter of the bladder
119
What are the effects of alpha2 receptors?
inhibition of norepinephrine release
inhibition of ACh release
inhibition of insulin release
120
What are the effects of beta1 receptors?
tachycardia
increased myocardial contractility
increased release of renin
121
What are the effects of beta 2 receptors?
vasodilation
decreased peripheral resistance
bronchodilation
increased muscle and liver glycogenolysis
increased release of glucagon
relaxed uterine smooth muscle
increase plasma glucose concentration
122
What are the effects of beta 3 receptors?
increased lipolysis
relaxation of detrusor muscles
123
Catecholamines
compounds containing a 3,4-dihydroxybenzene group
high potency to activate receptors
rapid inactivation due to metabolism by COMT and MOA
polar -> poor penetration into the CNS
brief duration of action
not admin orally
epinephrine
norepinephrine
isoproterenol
dopamine
124
Noncatecholamines
compounds w/o catechol hydroxyl groups
longer half lives since they are not inactivated by COMT
poorly metabolized by MOA
increased lipid solubility -> greater access to CNS
phenylephirine
ephedrine
amphetamine
125
Epinephrine
alpha 1 and alpha 2, beta 1 and beta 2 receptors
catecholamine
treats acute asthma and anaphylactic shock
used to treat cardiac arrest, bronchodilation, bronchospasm
used in local anesthetics to increase duration of action
increases heart rate and blood pressure
126
Norepinephrine
catecholamine
alpha 1, alpha 2, and beta 1 receptors
used in the treatment of shock
increases heart rate, blood pressure, and vascular resistance
127
Isoproterenol
catecholamine
beta 1 and beta 2 receptors
cardiac stimulant
increase cardiac output
peripheral vasodilation, bronchodilation
128
Dobutamine
catecholamine
beta 1 receptor
treats acute heart failure
129
Oxymetazoline
Noncatecholamine
alpha 1 receptor
nasal decongestant
130
Phenylephrine
noncatecholamine
alpha 1 receptor
nasal decongestant
raise blood pressure
treats paroxysmal suprventricular tachycardia
131
Clonidine
noncatecholamine
alpha 2 receptor
treatment of hypertension
132
Albuterol
noncatecholamine
beta 2 receptor
treatment of short acting bronchospasm
133
Terbutaline
noncatecholamine
beta 2 receptor
treatment of short acting bronchospasms
134
Salmeterol
noncatecholamines
beta 2 receptor
treatment of long acting bronchospasms
135
Formoterol
noncatecholamine
beta 2 receptor
treatment of long acting of bronchospasm
136
Amphetamine
noncatecholamines
alpha and beta receptors, CNS
treats kids with ADD and narcolepsy
helps with appetite control
137
Ephedrine
Noncatecholamine
alpha and beta receptors, CNS
nasal decongestant
raises blood pressure
138
Pseudoephedrine
Noncatecholamine
alpha and beta receptors, CNS
nasal decongestant
raises blood pressure
139
Adverse effects of adrenergic agonists
arrhythmias
headache
hyperactivity
insomnia
nausea
tremors
140
Adrenergic antagonists
adrenergic blockers
sympatholytics
reversible/irreversibly bind to adrenergic receptor
prevent receptor activation by endogenous catecholamines
primarily used to relieve complications of cardiovascular disease
141
Alpha adrenergic antagonists
blockade of alpha adrenergic receptors
inhibit vasoconstriction of blood vessels
decrease peripheral vascular resistance
decrease blood pressure
142
Phenoxybenzamine
nonselective alpha adrenergic agonist
non competitive
143
Phentolamine
nonselective alpha adrenergic antagonist
competitive
144
Adverse effects of alpha adrenergic antagonists
provoke reflex tachycardia
syncope
orthostatic hypotension
tachycardia
dizziness and headache
sexual dysfunction
145
Prazosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
146
Terazosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
147
Doxazosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
148
Alfuzosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
149
Tamsulosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
150
Yohimbe
alpha adrenergic antagonist
selective alpha 2 blocker, competitive
treats erectile dysfunction
increases sympathetic outflow from the CNS to the periphery
151
Blockade of beta adrenergic receptors
inhibit NE release
decreased heart rate, heart contractility, cardiac output, renin activity
152
Which receptors do nonselective Beta adrenergic antagonists act on?
both beta 1 and beta 2
153
Propranolol
adrenergic antagonists
Beta 1 and Beta 2 receptor
used to treat hypertension, migraine, hyperthyroidism, angina pectoris, myocardial infarction
154
Nadolol
adrenergic antagonist
Beta 1 and beta 2 receptors
treats hypertension
155
Pindolol
adrenergic antagonist
Beta 1 and beta 2 receptors
treats hypertension
156
Timolol
beta adrenergic antagonists
beta 1 and beta 2 receptors
used to treat hypertension and glaucoma
157
Atenolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
158
Bisoprolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
159
Esmolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
160
Metoprolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
161
Acebutolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension
162
Nebivolol
beta adrenergic antagonist
beta 1 receptor, increased nitric oxide
treats hypertension
163
Carvedilol
beta adrenergic antagonist
alpha 1, beta 1, and beta 2 receptors
treats hypertension
164
Labetalol
beta adrenergic antagonist
alpha 1, beta 1, and beta 2 receptors
treats hypertension
165
Adverse effects of Beta adrenergic antagonists
fatigue
bronchoconstriction
sexual dysfunction
arrhythmias
166
How many distinct ion channels do humans express?
200
167
Ion channels regulate the passive diffusion of these through cell membranes:
sodium, potassium, calcium, and chloride
168
What are the types of ion channels?
voltage activated
ligand activated
store activated
stretch activated
temperature activated
169
Where are ion channels that generate action potential?
excitable tissues
170
Where are ion channels that trigger cellular biochemical and secretory events?
non-excitable tissues
171
Sodium
binds to voltage gated ion channels
inhibits peripheral neurotransmission- local anesthetics
involved in transmission of myocardial action potential- class 1 antiarrhythmic drugs
172
Potassium
expressed in nerve, cardiac and smooth muscle tissues
regulates resting membrane potential
class 3 antiarrhythmic drugs prolong repolarization of cardiac action potentials
173
Where is calcium widely distributed in?
nerves- stimulates release of neurotransmitters
myocardium- class 4 antiarrhythmic drugs, depolarization of pacemaker, modification of shape and duration of myocardial action potential
smooth muscle- calcium channels regulate vascular tone, calcium channel blockers dilate blood vessels
174
Acetylcholine ligand-gated ion channels: somatic neuromuscular transmission
agonist- carbachol
antagonist- pancuronium, alpha bungarotoxin
175
Acetylcholine ligand-gated ion channels: sympathetic and parasympathetic autonomic ganglia
agonist- nicotine
antagonist- trimetaphan
176
Acetylcholine ligand-gated ion channels: CNS
3 subtypes involved in attention, addiction, and cognition
agonist- nicotine
antagonist- bupropion
177
Bicuculline
antagonist at GABA binding sites
178
Allosteric agonist modulators of GABA
barbiturates
ethanol
benzodiazepines
propofol
179
What are the agonists of glutamate?
glutamic acid and glycine
180
What are the antagonists of glutamate?
ketamine, Mg^2+, memantine
181
What are the agonists of serotonin ?
ethanol
ibogaine
182
What are the antagonists of serotonin?
ondansetron, clozapine
183
Glycine receptor
involved in sensory and motor function
binds the inhibitory neutrotransmitter glycine; gates chloride channels
in the CNS
184
What are the glycine receptor agonists?
glycine and taurine
185
What are the glycine receptor antagonists?
picrotoxin
strychnine
186
If the G protein heterotrimer forms a complex with GDP there is no?
ligand present
187
What binds to and regulates effectors?
GTP bound G alpha subunit and beta gamma dimer
188
GTP is inactivated by
hydrolysis
189
Prolonged stimulation of GPCR can lead to
downregulation of the receptor
190
G protein receptor kinases
phosphorylate the C terminal tail on the receptor and recruit proteins known as arrestins
191
Arrestins
binds to the receptor on the internal surface, displace g proteins and inhibit signaling
192
GPCR Gi
inhibition of adenyly cyclase and decrease in cAMP
193
Adenosine, melatonin, opioids, and acetylcholine all bind to which type of GPCR receptor?
Gi
194
GPCR Gq
second messengers
IP3- binds to and releases Calcium ions from the endoplasmic/ sarcoplasmic reticulum
DAG- activates kinase PKC
Ca^2+ -binds to and activates intracellular proteins and enzymes
PKC- phosphorylates and activates/deactivates intracellular enzymes
pharmacological response to receptor activation by the agonist
195
Agonists that activate Gq GPCRs
NE- alpha 1- vascular smooth muscle contraction
Thromboxane A2 - platelet aggregation
ACh- M3- smooth muscle contraction and glandular secretion
