Lecture 5 - Sympathetic (Adrenergic) Pharmacology Flashcards
1
Q
Two types of cholinergic receptors?
A
nicotinic
muscarinic
2
Q
______: ligand-gated ion channel, membrane depolarization
A
nicotinic
3
Q
What do M1, M3, and M5 do?
A
activates PLC
increases Ca2+
activates PKC
*causes excitation
gastric release, smooth muscle, gladder, etc.
4
Q
What do M2, and M4 do?
A
inhibits AC (adenylate cyclase) activates K+ channels inhibits PKA
*inhibition of cardiac and smooth muscle
5
Q
What do alpha 1 adrenergic receptors do?
A
activates PLC
increases Ca2+
causes smooth muscle contraction (vasoconstriction, sphincter, mydriasis)
6
Q
What do alpha 2 receptors do?
A
INHIBITS THE SYSTEM THAT RELEASES IT
- inhibits AD
- increases K+
- hyperpolarization
this inhibits NE release
this inhibits insulin release
-presynaptic neuron pancreatic B cells ???
7
Q
What do B receptors do?
A
activates AC
increase PKA activation
heart, lung, and energy regulation
Increases:
- heart rate
- contractility
- bronchodilation
- vasodilation
- glyconeogenesis
- lipolysis
8
Q
Parasympathetic:
constrict pupils
A
M3
9
Q
Parasympathetic:
stimulate salivation
A
M3
10
Q
Parasympathetic:
slow heart rate
A
M2
11
Q
Parasympathetic:
constrict airways
A
M3
12
Q
Parasympathetic:
stimulate activity of stomach
A
M3
13
Q
Parasympathetic:
- inhibit release of glucose
- stimulate gall bladder
A
I assume it’s M3
14
Q
Parasympathetic:
stimulate activity of intestine
A
M3
15
Q
M odd = ?
A
stimulatory
16
Q
M even = ?
A
relaxation
17
Q
Parasympathetic:
contract bladder
A
M3
18
Q
Sympathetic:
dilate pupils
A
alpha 1
19
Q
Sympathetic:
inhibit salivation
A
beta
20
Q
Sympathetic:
increase HR
A
B1
21
Q
Sympathetic:
relax airways
A
B2
22
Q
Sympathetic:
inhibit activity of stomach
A
B2
23
Q
Sympathetic:
stimulate release of glucose and inhibit gallbladder
A
B2
24
Q
Sympathetic:
inhibit activity of intestine
A
B2
25
Sympathetic:
| secrete epinephrine and NE
nicotinic
26
Sympathetic:
| relax bladder
B2
27
Sympathetic:
| promote ejaculation and vaginal contraction
alpha 1
28
For pupil opening:
| -sympathetic acts on what muscle ?
radial muscle of iris
contraction (alpha 1)
mydriasis (pupil dilating)
29
For pupil opening:
| -parasympathetic acts on what muscle ?
circular muscle of iris
contraction (M3)
miosis
30
For lens focusing:
| -parasympathetic acts on what muscle?
ciliary muscle
contraction (M3)
near vision
31
Sympathetic effect on glands
| gastrointestinal glands, salivary glands, lacrimal glands, nasal glands
effect from B adrenergic stimulation
-secretion of protein: enzyme and mucus
effect from alpha adrenergic stimulation
- vasoconstriction - decrease water
- decrease and concentrate secretions
Symp:
= fewer secretions
= more concentrated secretions
32
Parasympathetic effect on glands
| gastrointestinal glands, salivary glands, lacrimal glands, nasal glands
effect from M3 muscarinic stimulation
-water secretory product
Parasymp:
= more sections
= less concentrated secretions (more watery)
33
Sympathetic effect on systemic blood vessels
- contraction of skin and splanchnic vessels (alpha 1)
| - relaxation of vessels in skeletal muscle (muscarinic)
34
Parasympathetic effect on systemic blood vessels
endothelial cells release EDRF (M3) - causes vessels to relax
EDRF = endothelial derived relaxing factor (causes vessels to relax)
35
NE mainly stimulates ??
alpha 1 receptors (in vessels)
| -increases BP markedly
36
E has a higher affinity for ??
B receptor (in cardiac muscle)
- increases heart rate and contractility
- less effect on mean arterial pressure
37
NE and E do the same thing in high enough quantities, but in correct quantities: ??
```
NE = alpha 1
E = beta
```
38
Sympathetic effect on GI smooth muscle
GI smooth muscle is relaxed by B2
GI spinchter is contracted by alpha 1
39
Parasympathetic effect on GI smooth muscle
GI smooth muscle is contracted by M3
GI sphincter is relaxed by M2 or M4
40
Describe the baroreceptor reflex
1) heart failure, hypovolemia, hemorrhage, postural changes, etc
2) drop in BP
3) carotid sinus/aortic arch is decreased in firing rate of afferents
4) cardiovascular centre
5) -increase in Symp nerve activity
- decrease in parasymp nerve activity
6) -increase HR
- increase in stroke volume
- arteriolar constriction
7) BP goes back to normal
41
4 types of adrenergic receptors ?
alpha 1
alpha 2
beta 1
beta 2
42
What organs do adrenergic receptors effect?
cardiac muscle
smooth muscle
glands
43
cardiac muscle
smooth muscle
glands
All respond to ??
NE and E
44
___: alpha > beta
NE
45
___: beta > alpha
E
46
Functions of alpha 1 adrenergic receptors
- vasoconstriction
- pupil dilation
- inhibits uterine contractions in pregnancy
- ejaculation
- contraction of bladder neck and prostate
47
What medical purpose does vasoconstriction have?
- nasal decongestant
| - increase BP in trauma/shock pts
48
What medical purpose does pupil dilation have?
eye exams
49
What medical purpose does inhibiting uterine contractions have?
delay birth
*usually a negative side effect of certain medications
50
What medical purpose does ejaculation have?
none yet - but drugs are in development
51
What medical purpose does contraction of bladder neck and prostate have?
it is simply a negative side effect
52
Functions of alpha 2 adrenergic receptors
- inhibits neurotransmitter release thus inhibiting sympathetic (adrenergic) activation
- inhibits it's own neutron from firing
- inhibitor of adrenergic system
53
Where are alpha 2 adrenergic receptors located?
-presynaptic junction
54
alpha 2 receptors are not perfectly opposite of alpha 1
other examples of it's functions are: ?
- cardiac (and other) vasoconstriction
- decreased NE release in brain (a good thing?)
- inhibition of lipolysis and insulin release
55
Primary medical importance of alpha 2 receptors is ??
CNs (neuronal)
| hypertension
56
Functions of Beta 1 receptors
Kidney:
-renin release causes vasoconstriction
Heart:
-increases HR, contractility, velocity of conduction in AV node
57
Functions of beta 2 receptors
- bronchial dilation
- relaxation of uterine muscle
- vasodilation
- glycogenolysis (increase production of glucose)
- glucagon release
58
What is dopamine's function?
dilates renal blood vessels
59
_____ = increases vasoconstriction, pupil dilation, relaxes uterine contraction, contraction of bladder, and prostate neck, ejaculation
alpha 1
60
____ = cardiac vasoconstriction, inhibits NE brain release, inhibits insulin release
alpha 2
61
___ = increase HR and contraction, renin release
beta 1
62
____ = lung bronchi dilation, relaxation of uterus, vasodilation, glucose release
beta 2
63
Pseudophedrine is ??
agonist of alpha 1
64
What does pseudophedrine do?
dry nose up
| increase BP
65
Prazosin is ??
antagonist of alpha 1
66
What does prazosin do?
allows nose to drip
| lowers BP
67
Clonidine is ??
agonist of alpha 2
68
What does clonidine do?
drop BP
| relax prostate
69
Isoproterenol Dobutamine is ??
agonist of beta 1
70
What does isoproterenol dobutamine do?
increases HR
71
Propranolol is a ??
antagonist of Beta 1 and beta 1
72
What does propranolol do?
decrease HR
73
Isoproterenol Terbutaline is ??
agonist of Beta 2
74
see slide 19
okay man
75
distribution of alpha 1
blood vessels
| GI sphincter
76
distribution of alpha 2
presynaptic terminal
77
distribution of beta 1
heart
78
distribution of beta 2
airway, GI, urogenital
79
alpha 1 and beta 2 are antagonistic in some ____ ______
blood vessels
alpha 1 causes constriction
beta 2 causes dilation
*generally B2 dominates where both are found
80
stimulators (sympathomimetic) mimic action of ???
norepinephrine, dopamine, and epinephrine
81
List some uses of adrenergic agonists
- hemodynamic compromise (shock, depressed cardiac rhythm)
- bronchospasms (asthma)
- nasal and sinus congestion
82
Epinephrine stimulates ??
both alpha and beta receptors
83
E is also called ?
adrenaline
84
Epinephrine is mainly given in ______
emergencies:
| -asthma, cardiac arrest, anaphylaxis
85
Why do you give E parenterally or intramuscularly?
GI tract enzymes destroy the drug so it cannot be given orally
86
Why would epinephrine be given with an anesthetic?
it causes vasoconstriction - which allows anesthetic to stay in body longer
87
E = works ____, but ___-acting
works fast
short-acting
88
What are some negative side effects of epinephrine?
- stimulant effects on brain
- hypertension-induced hemorrhage
- cardiac arrhythmia
- hyperglycemia in a diabetic
89
NE is used primarily for?
-treating shock
| increasing BP
90
Pseudoephedrine is used for?
nasal decongestant
91
NE and dopamine are critical for ?
```
mood control
motor control
depression
anxiety
parkinson's disease
```
92
What does cocaine do?
- inhibits reuptake of serotonin, norepinephrine, and dopamine
* it's inhibiting the reuptake - so it is staying in your body longer and making you happier
- non-selective for receptor subtype and organ
- peripheral activation causes side effects (HR increase, sweating, hypertension, etc)
93
How do amphetamines work?
inhibits uptake and increases neurotransmitter release (including serotonin and NE)
-very potent in the CNS and periphery
94
List some types of amphetamines
crystal meth
ritalin
MDMA (ecstasy)
95
Selegiline is a ??
MAOi
| monoamine oxidase inhibitor
96
Selegiline is used in ??
anti-parkinson's disease
97
Selegiline is used with ??
levadopa
98
side effects of seligiline ?
dry mouth
constipation
tachycardia
99
Phenelzine is ??
Monoamine oxidase inhibitor
100
Phenelzine is used as?
anti-depressant
101
side effects of Phenelzine
```
dry mouth
constipation
urinary retention
mydriasis
hyperthermia
sweating
hypertension
```
102
all anti-depressants activate ___
SNS
103
Amitriptyline is a _____
TCA (tricyclic antidepressant)
104
Contraindications of amitriptyline
- urinary retention
- pregnancy
- myocardial infarction
- congestive heart failure
105
is alpha 2 sympathomimetic?
NO
| -because they inhibit sympathetic response
106
Example of an alpha 1 agonist
phenylephrine
107
What do stimulants affect?
adrenergic
108
Examples of stimulants
cocaine, nicotine, caffeine, meth
109
Side effects of stimulants
sweats, manic behaviour, anxiety, paranoia
110
Dobutamine is a
beta 1 agonist
111
how is dobutamine used?
- used in congestive heart failure
| - increases cardiac output (because it is a beta 1 agonist)
112
albuterol (salbutamol, ventolin) is a ??
beta 2 agonist
113
albuterol (salbutamol, ventolin) is used for?
asthma, COPD
| this is a short-acting inhaler
lasts 2 hrs
114
salmeterol is a ??
beta 2 agonist
115
salmeterol is used for?
asthma, COPD
| this is long acting inhaler
lasts 12 hrs
116
what do anti-adrenergic drugs do?
inhibit or block the effects of sympathetic nerve stimulation
117
are anti-adrenergic drugs naturally occurring?
no - only exist as synthetic drugs
118
most anti-adrenergic drugs block ??
alpha 1
beta 1
beta 2
119
alpha 2 agonists are _____ ________
adrenergic antagonists
120
alpha 2 agonists treat _________
hypertension
121
clonidine is an ??
alpha 2 agonist
122
prazosin and doxasin are ?
alpha 1 antagonists
123
what do prazosin and doxasin treat?
they treat hypertension
| -they are competitive blockers of alpha 1 therefore causing decreased blood pressure
124
Tamsulosin is a ??
alpha 1 antagonist
125
what does tamsulosin treat?
prostatic hypertrophy and vasospastic (urinary) problems
*tamsulosin is more selective for alpha 1 A receptors on prostate
126
What is congestive heart failure?
causes decreased preload and after load by decreasing peripheral resistance (through vasodilation)
-this leads to increased cardiac output
127
Explain how you can use two different drugs to treat congestive heart failure
-use a B1 agonist to activate the heart to increase CO
AND
-use an alpha 1 antagonist to inhibit the peripheral vessels to decrease peripheral resistance (makes it easier for the hear to pump to the periphery)
128
What are some side effects of blocking alpha 1 receptors?
- early on, causes massive orthostatic hypotension (fainting when standing) so need to start with low doses
- vertigo
- sexual dysfunction
- reflex tachycardia
- floppy iris syndrome (eye)
129
What are beta blockers used for?
-used to treat rapid pulse arrhythmias, hypertension, MI, other heart problems
130
beta blocker ____ contractility, CO, heart rate, and BP
decreases
131
beta blockers ____ oxygen demand on the heart
decrease
132
beta blocks ____ the conduction through the AV node, and slow down ventricular response
slows
133
how many generations of beta blockers are there?
3
134
___ gen beta blockers are non selective (they act on B1 and B2)
1st
135
___ gen beta blockers are cardioselective (act only on B1)
2nd
136
___ gen beta blockers are partially selective (with alpha 1 inhibition)
3rd
137
What do non selective beta blockers do?
Block both beta 1 (heart) and beta 2 (lung) receptors
138
Propranolol is a ?
non selective beta blocker
| i.e. 1st gen beta blocker
139
Nonselective beta blockers can cause ____
bronchospasms
140
What would propranolol do then?
| If it is a nonselective beta blocker (1st gen beta blocker)
- decrease CO
- peripheral vasoconstriction
- slow decrease in hypertension
- bronchoconstriction
- decreased glycogenolysis and glucagon secretion - this amplifies the effect of insulin on hypoglycaemia
141
Timolol is a ??
non-specific beta blocker
142
What is timolol used for?
used for glaucoma by decreasing production of aqueous humour and intraocular pressure
143
What were 2nd gen beta blockers (B1 specific blockers) developed for?
Developed specifically to avoid bronchoconstriction of B2 receptors
144
What are 2nd gen (B1 specific blockers) used for?
used to treat hypertension
| -reduced pulmonary, vascular, and blood glucose effects
145
Atenolol is a ??
2nd gen (B1 specific) beta blocker
146
How do 3rd gen (partial alpha receptor) beta blockers work?
they cause a reduction in a receptor which leads to reduced peripheral resistance and therefore causes less load on the heart
147
Carvedilol is a ??
3rd generation beta blocker (partial alpha receptor blockage)
148
How does carvedilol work?
It has a higher affinity for B1 and B2, so it reduces HR significantly and may exacerbate asthma
149
Labetalol is a ??
3rd generation beta blocker (partial alpha receptor blockage)
150
How does labetalol work?
it has a higher affinity for alpha 1 so it will reduce BP w/o a large effect on RESTING HR
