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test 4 Flashcards

1
Q

How are adrenoceptors activated?

A

Through norepi or epi

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2
Q

What do adrenoceptors act on?

A

Act on neurons that release norepi

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3
Q

What does administration of epi cause?

A

Produces similar effects of stimulation of sns

Sympathetic response

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4
Q

What do alpha 1 receptors act on?

A

Vascular smooth muscle
Genitourinary smooth muscle
Intestinal smooth muscle
Heart
Liver

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5
Q

What do alpha 1 receptors do to the vascular smooth muscle?

A

Contraction

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6
Q

What do alpha 1 receptors do to the genitourinary smooth muscle?

A

Contraction

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7
Q

What do alpha 1 receptors do to the intestinal smooth muscle?

A

Relaxation

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8
Q

What do alpha 1 receptors do to the heart?

A

Increase intropy and excitability

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9
Q

What do alpha 1 receptors do to the liver?

A

Glycogenolysis and gluconeogenesis

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10
Q

What do alpha 2 receptors act on?

A

Platelets
Pancreatic beta cells
Nerves
Vascular smooth muscle

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11
Q

What do alpha 2 receptors do to platelets?

A

Aggregation

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12
Q

What do alpha 2 receptors do to the pancreatic beta cells?

A

Decrease insulin secretion

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13
Q

What do alpha 2 receptors do to nerves?

A

Decrease NE release

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14
Q

What do alpha 2 receptors do to vascular smooth muscle?

A

Contraction

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15
Q

What do Beta 1 cells act on?

A

Heart
Renal juxtaglomerular cells

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16
Q

What do beta 1 cells do to the heart?

A

Increase chronotropy and intropy
Increase AV node conduction velocity

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17
Q

What do beta 1 cells do renal juxtaglomerular cells?

A

Increase renin secretion

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18
Q

What do beta 2 cells act on?

A

Smooth muscle
Liver
Skeletal muscle

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19
Q

What do beta 2 cells do to smooth muscle?

A

Relaxation

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20
Q

What do beta 2 cells do to liver?

A

Glycogenolysis
Gluconeogenesis

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21
Q

What do beta 2 cells do to the skeletal muscle?

A

Glycogenolysis and K+ uptake

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22
Q

What receptor is the main cause of ateriole constriction and eye muscle contraction?

A

Alpa 1

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23
Q

What receptor causes the heart to increase rate and force?

A

Beta 1

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24
Q

What receptor causes the lungs to relax?

A

Beta 2

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25
What receptor is responsible for decreased activity of intestines and dilation of skeletal muscle?
Beta 2
26
What are alpha 1 agonists used for?
Shock/hypotension Nasal decongestant
27
What are alpa 1 antagonists used for?
Antihypertensives BPH
28
What are alpha 2 agonists used for?
Antihypertensives Glaucoma Analgesia Sedatives
29
What are alpha 2 antagonists used for?
We do not use them clinically
30
What are Beta 1 agonists used for?
There are none
31
What do we use Beta 1 antagonists for?
Antihypertensives Antiarrhythmics
32
What are beta 2 agonists used for?
Bronchodilators Glaucoma
33
What are beta 3 agonists used for?
Weight loss
34
What are beta 2 antagonists used for?
They are not used clinically
35
What does stimulation of the alpha 1 receptor cause?
Vasoconstriction Increased peripheral resistance Increased blood pressure Mydriasis Closure of the sphincter of bladder
36
What does stimulation of the alpha 2 receptor cause?
Inhibition of norepinephrine release Inhibition of ACH release Inhibition of insulin release
37
What does stimulation of the beta 1 receptors cause?
Tachycardia Increased lipolysis Increased myocardial contractility Increased release of renin
38
What does stimulation of the beta 2 receptors cause?
Vasodilation Decrease of peripheral resistance Bronchodilation Increased glycogenolysis Increased release of glucagon Relaxed uterus
39
What happens to catechols when they are exposed to air?
They are oxidized and the solution darkens to a highly colorized product
40
How are catechols metabolized?
By COMT
41
What are the non selective alpha 1 agonists?
Norepi and epi
42
Why arent NE and E used clinically alot?
They have limited clinical uses due to selectivity issues and oral bioavailability
43
Which is used more often? EPi or NOrEpi
EPI
44
Why is epi used?
For trauma (stimulation of the Beta 1 - heart muscle) - hypotension
45
What are the selective alpha 1 agonists?
Phenylephrine Metaraminol Methoxamine Tetrahydrozoline Oxymetazoline
46
Why do selective alpha 1 agonists have limited cardiac stimulation?
They are selective so they have little cardiac activity
47
What are alpha 1 selective agonists used for?
Nasal decongestants Red eye
48
Why do selective alpha 1 agonists last longer in the body than E and NE?
They have a longer duration of action due to less catechol activity
49
What are alpha 2 agonists mainly used for?
Hypertension, sedative, and epidural enhancer
50
What are the alpha 1 selective agonists?
Clonidine, apraclonidine, brimonidine, Tizanidine, Guanfacine, Guanabenz, Methyldopa
51
What are apraclonidine and brimonidine used for?
Glaucoma and have little systemic effect
52
What is methyldopa used for?
Antihypertensive during pregnancy (metabolized into active compound = methylnorepinephrine)
53
What are the beta 1 agonists?
Dopamine and its analogues
54
What does Beta 1 agonism do?
Increased contractile force of the heart Cardiac stimulation We want to avoid this
55
When are beta 1 drugs used?
As a cardiac stimulant post surgery
56
What are Beta 2 agonists used for?
Bronchodilation Short acting and long acting Asthma COPD
57
What kind of drug is isoproterenol?
Beta 2 short acting agonist
58
Why is isoproterenol not used?
It has beta 1 type side effects due to an isopropyl group as the amine side chain Has a catechol that makes it unstable
59
What kind of drug is albuterol?
Short acting beta 2 agonist
60
Why is levalbuterol 4 times more potent than albuterol?
It is the pure isomer and not the racemic mixture but it is more expensive and time consuming to make
61
What kind of drug is salmeterol with flucticasone (Advair)?
Long acting Beta 2 agonists
62
What makes a beta 2 agonist long acting?
Much higher LogP due to a long lipophilic side chain
63
What kind of drug is formoterol with budesonide (symbicort)?
Long acting beta 2 agonist 4 times more potent than advair
64
What makes a drug a mixed acting sympathomimetic?
It is a drug that acts both directly and indirectly (directly activates receptor and causes release of NE)
65
What are mixed acting sympathomimetics used for?
Nasal decongestant (Sudafed)
66
What drugs are alpha 1 selective antagonists?
Prazosin, Terazosin, Tamsulosin, Doxazosin, Alfuzosin, Sildosin
67
What do alpha 1 A receptors do?
Decrease smooth muscle contraction of the prostate while B is vasculature
68
What kind of drug is Yohimbe?
Alpha 2 agonist
69
What does yohimbe do?
induce hypertension Increase heart rate No clinical use but can be used for impotence and orthostatic hypotension
70
What do Beta 1 antagonists do?
Decrease contractile force and decrease blood pressure
71
What is the difference between olols and alols?
Olols are for aryloxypropanolamines Alols are for arylethanolamines
72
What do beta blocker do to decrease blood pressure?
They compete with catecholamines for Beta 1 and 2 binding to treat hypertension
73
What are olols used for?
Glaucoma and hypertension
74
What are the ADRs of non selective beta blockers?
Fatigue Bronchoconstriction Sexual dysfunction Arrhythmias from withdrawls
75
What pneumonic device can you use to see if the beta blocker is selective "clean" or not?
BEAM (if they start with these letters they are clean as well as Nebivolol and except Metipranolol)
76
What enzyme converts tyrosine to L DOPA
Tyrosine hydroxylase
77
What molecule inhibits tyrosine hydroxylase?
Alpha methyl tyrosine
78
What enzyme converts LDOPA to dopamine
Dopa decarboxylase
79
What molecule inhibits dopa decarboxylase?
Carbidopa
80
What enzyme converts dopamine to norepinephrine?
Dopamine beta hydroxylase
81
What takes up dopamine into vesicles?
VMAT
82
What inhibits VMAT?
Reserpine
83
Why do you need to transport dopamine into a vesicle?
MAO will degrade the dopamine in the cell
84
What enzyme converts NE to E?
Phenylethanolamine N Methyl transferase
85
What produces E?
adrenal medullary cells
86
What are the two ways to terminate catecholamine neurotransmission?
Reuptake Diffusion away from synapse
87
What is the major way to terminate catecholamine neurotransmission?
Presynaptic reuptake
88
What blocks reuptake of catecholamines?
Cocaine and antidepressants and amphetamines
89
What does COMT do?
Metabolizes NE, E, and DA and is excreted into the urine and not reuptaked
90
What kind of G protein is alpha 1?
Gq
91
What kind of G protein is alpha 2?
Gi
92
What kind of G protein is beta?
Gs
93
What does alpha 2 activation do inside of the cell?
Inhibits adenylate cyclase (decrease PKA and CAMP and increase K+ so it hyperpolarizes the cell to inhibit it)
94
What does alpha 1 activation do inside the cell?
Increase phospholipase C (Increase IP3, DAG, Ca2+ from ER)
95
What is unique of the beta 2 variant of agonist potency?
Beta 2 - epinephrine has much greater effect than NE unlike others where they are the same
96
What does systolic tell you?
Strength and volume of cardiac output
97
What does diastolic tell you?
Peripheral vascular resistance
98
What does mean arterial pressure tell you?
Tissue perfusion pressure Monitered by baroreceptors
99
Heterologous
PKA
100
Homologous
Beta arrestin BARK
101
What class is epinephrine and norepinephrine in?
Nonselective adrenergic neurotransmitters
102
What does reserpine do?
Blocks VMAT VMAT takes up neurotransmitters into vesicles so they are not degraded by MAO so this would reduce the amount of neurotransmitters available
103
What class of drug is amphetamine?
Indirect acting sympathomimetic
104
Why is NE and E not typically used in clinical settings?
They have selectivity issues and oral bioavailability issues
105
Which is used more, E or NE?
E
106
When is epi used?
During trauma situations (trauma based hypotension
107
What class of drug is Phenylephrine?
Alpha 1 selective agonist
108
What is phenylephrine used for?
Nasal decongestant Sudafed PE
109
What class of drug is Tetrahydrozoline?
Selective alpha 1 agonist Visine
110
What is tetrahydrozoline?
Reduce red eye
111
What class of drug is oxymetazoline?
Selective alpha 1 agonist Afrin
112
What does oxymetazoline do?
Used as a nasal decongestant
113
Why do selective alpha 1 agonists have little or minimum cardiac stimulation?
Because they are not selective to the beta receptors (beta1) that stimulates the heart
114
Why do selective alpha 1 agonist have a longer duration of action compared to E and NE?
Because they do not have catechols so are not sucseptible to COMT
115
What class of drug is clonidine?
Selective alpha 2 agonist Catapres
116
Why is clonidine considered a flag ship compound?
It was used as an alpha 1 nasal decongestant but they noticed a significant reduction in blood pressure so they found alpha 2 activation
117
What do alpha 2 receptors primarily do when stimulated?
Decrease the amount of NE released into the cleft
118
What class of drug is apraclonidine?
Selective alpha 2 agonist Iopidine
119
What is apraclonidine used for?
eye drops for glaucoma
120
What class of drug is brimonidine?
Selective alpha 2 agonist Alphagan P
121
What is brimonidine used for?
Glaucoma
122
What class of drug is Guanfacine?
Selective alpha 2 agonist Tenex, Intuiv
123
What class of drug is alpha methyldopa?
Selective alpha 2 agonist Aldomet
124
What is alpha methyldopa used for?
Antihypertensive during pregnancy It is metabolized into methylnorepinephrine
125
What class of drug is Dobutamine?
Beta 1 agonist
126
What is dobutamine used for?
Only used as a cardiac stimulant post surgery
127
What do you need for beta 2 selectivity?
A t butyl or greater group on the amine an OH on the beta carbon
128
What class of drug is Isoproterenol?
Short acting beta 2 agonist
129
Why is isoproterenol not a good drug?
It has beta 1 side effects due to the isopropyl group on the amine It has a catechol so it is not stable
130
What class of drug is albuterol?
short acting beta 2 agonist Proventil, Ventolin, ProAir
131
What class of drug is levalbuterol?
Short acting beta 2 agonist Xopenex
132
What is the difference between levalbuterol and albuterol?
albuterol is a racemic mixture levalbuterol is the pure active isomer which makes it 4 times for potent as a bronchodilator
133
What is albuterol and levalbuterol used for?
it is a rescue inhaler so for acute symptoms
134
What class of drug is salmeterol?
Long acting beta 2 agonist With fluticasone = Advair Without = serevent
135
What is Salameterol used for?
Chronic or daily use for asthma and COPD NOT FOR ACUTE SYMPTOMS
136
What class of drug is formoterol?
LABA
137
What makes a beta 2 agonist long acting?
It has a lipophilic long side chain that interacts with the exosite so the drug can keep interacting over and over with the binding site or active site
138
What is the main difference between formoterol and salmeterol?
faster onset for formoterol
139
What class of drug is pseudophedrine?
Mixed acting sympathomimetic
140
What is the main side effect of pseudophedrine?
Increase in blood pressure from indirect activity
141
What class of drug prazosin?
Alpha 1 selective antagonist Minipres
142
What is Minipress used for?
Hypertension and BPD (not FDA approved for BPH)
143
What is the difference between alpha 1 A and alpha 1 B?
Alpha 1 a has selectivity for the prostate (used for bph) Alpha 1 B has selectivity for the vasculature (hypertension)
144
What is the USAN for quinazolines?
Azosin
145
What class of drug is terazosin?
Selective alpha 1 antagonist Hytrin
146
What is Hytrin used for?
Hypertension and BPH
147
What class of drug is tamsulosin?
Selective alpha 1 antagonist Flomax
148
What is tamsulosin used for?
BPH
149
What class of drug is doxazosin?
Selective alpha 1 antagonist Cardura
150
What does doxazosin treat?
BPH mainly
151
What class of drug is Alfuzosin?
Selective alpha 1 antagonist Uroxatral
152
What is alfuzosin used for?
BPH
153
What class of drug is silodosin?
Selective alpha 1 antagonist
154
What is silodosin used for?
BPH
155
What class of drug is yohimbine?
Alpha 2 antagonist Herbal not FDA approved
156
What does yohimbine treat off label?
Impotence orthostatic hypertension
157
What do selective beta 2 blockers treat?
Glaucoma and hypertension
158
What is added to the drug for it to be an antagonist?
A bulky side chain
159
What are the adr's of selective beta blockers?
Fatigue Bronchoconstriction Sexual dysfunction Arrhythmias upon withdrawls
160
what pneumonic device is used to see clean beta blockers?
BEAM Plus Nebivolol
161
What is the rate limiting step for making neurotransmitters?
Tyrosine to LDOPA through tyrosine hydroxylase
162
How do you get from LDOPA to Dopamine?
DOPA decarboxylase
163
How do you get from dopamine to Norepinephrine?
Dopamine Beta Hydrolase
164
How do you get from NE to E?
Phenylethanolamine N methyl transferase
165
What are the two ways to terminate catecholamine neurotransmission?
Reuptake (presynaptic is major) Diffusion away from the synapse
166
What drugs block reuptake?
Antidepressants and Cocaine
167
What metabolizes E, NE, and DA and excretes it in the urine?
COMT
168
Why is alpha 2 receptor considered an autoreceptor?
it is inhibitory and is on the presynaptic neuron unlike the others which are on the postsynaptic neuron
169
How do alpha 2 receptors create an inhibitory response?
Increase K currents to hyperpolarize the cell
170
What kind of G coupled receptor is alpha 1?
Gq
171
What does Gq alpha 1 receptor do in the cell?
Increase IP3, DAG, Ca2+, and turns on phospholipase C
172
What kind of G coupled receptor are the beta receptors?
All are Gs
173
Which has a greater effect on beta 2, E or NE?
E
174
What does systolic pressure measure?
Cardiac output
175
What does diastolic pressure measure?
PVR
176
What is mean arterial pressure?
Tissue perfusion pressure monitered by baroreceptors
177
Why does phenylephrine help with nasal decongestion?
The mucosal membranes are highly vascularized and if you constrict the vasculature, it reduces the pressure in the nose
178
What are two off label uses for clonidine?
Sedative Epidural enhancer
179
What kind of spacer does clonidine and its derivatives have?
An N and C spacer
180
What are the three major determinants of action of a drug?
Relative potency of amine or drug (is it alpha or beta) Dominant tone Reflex and other homeostatic adjustments
181
What is the main difference between reuptake 1 and 2?
Reuptake 1 has a high affinity for NE but is slow Reuptake 2 has a low affinity for NE but is fast (protective mechanism if there is too much NE in the cleft)
182
What are the two ways a receptor can be desensitized?
Changes in the receptor or receptor coupling Receptor sequestration (tachyphylaxis)
183
What is inotropic?
Contractile force
184
What is chronotropic?
Increase in hr and conduction velocity
185
What is the core drug structure of sympathomimetics?
Phenylethanolamine
186
What kind of drug is amphetamine?
Indirect acting sympathomimetic
187
How does amphetamine cause an increase in calcium release?
Taken in by VMAT and moves NE out into the cytosol. It is a weak MAO inhibitor so it also inhibits the break down of NE and E
188
What is the main difference between amphetamine and tyramine?
It is Calcium independent it is metabolized by MAO
189
What kind of drug is methylphenidate?
Psychostimulant | Indirect agonist
190
What kind of drug is Concerta?
Psychostimulant | indirect agonist
191
How does concerta work in terms of delayed release?
Causes osmotic release Immediate release and then the device delays release to different compartment
192
What is phentermine (adipex P) used to treat?
Obesity
193
What drug is a mydriatic agent but wont cause cycoplegia (cilliary muscle constriction)?
Phenylephrine | Alpha receptors are not on the cilliary muscle
194
What drug causes an increase of blood pressure and reflex bradycardia?
Phenylephrine
195
How do you stop reflex bradycardia from phenylephrine?
Add a ganglionic blocer | no ACh on heart so no reflex bradycardia
196
What class of drug is midodrine (orvaten)?
Alpha 1 agonist
197
What is midodrine used to treat?
Orthostatic hypotension
198
What class of drug is hydroxyamphetamine and tropicamide (Paremyd)?
Alpha 1 agonist
199
What does hydroxyamphetamine and tropicamide (Paremyd) treat?
It is a mydriatic agent so glaucoma
200
What class of drug is Droxidopa (Northera)?
Alpha 1 agonist
201
What is Droxidopa used to treat?
Orthostatic hypotension (neurogenic) | Prodrug of NE and E, Metabolized into neurons by the DOPA decarboxylase
202
What kind of drugs are imidazolines?
Alpha 1 agonist
203
What are the main side effects of clonidine?
Dry mouth
204
What kind of drug is Precedex/dexmedetomidine?
Alpha 2 agonist | Sedative for ICU

MPT (5 decks)

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