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Systemic Pharm I > Modulation of the Sympathetic Nervous System > Flashcards

Modulation of the Sympathetic Nervous System Flashcards

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1
Q

What substance mediates the ultimate effects of sympathetic stimulation?

A

norepinephrine

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2
Q

Norepinephrine is released from ____ and epinephrine is released into ____ from _____

A

nerve terminals, blood, adrenal medulla

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3
Q

T/F sympathomimetics can be direct or indirect

A

true

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4
Q

What do direct sympathomimetics do?

A

directly interact with receptors

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5
Q

What do indirect sympathomimetics do?

A

enhance action of endogenous neurotransmitters

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6
Q

What are the four adrenergic receptors?

A

alpha 1 and 2, beta 1 and 2 all are g protein coupled

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7
Q

What is true of receptor selectivity?

A

many agonists have selectivity for one of the major subtypes of receptors but not specificity aka at high concentrations will be non-selective

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8
Q

What is desensitization?

A

repeated exposure to agonist causes a receptor to be less responsive to the agonist

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9
Q

What are the five consequences of alpha 1 activation?

A

vasoconstriction, increased peripheral resistance, increased blood pressure, pupil dilation, and increased closure of internal sphincter of the bladder

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10
Q

What are the three consequences of alpha 2 activation?

A

inhibition of norepinephrine release, inhibition of acetylcholine release, inhibition of insulin release

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11
Q

What are the four consequences of beta 1 activation?

A

tachycardia, increased lipolysis, increased myocardial contractility, increased release of renin

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12
Q

What are the six consequences of beta 2 activation?

A

vasodilation, decreased peripheral resistance, bronchodilation, increased muscle and liver glycogenolysis, increased release of glucagon, and relaxed uterine smooth muscle

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13
Q

What does vasoconstriction do to heart rate?

A

decreases heart rate

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14
Q

What is the structure of most sympathomimetics?

A

most drugs contain a benzene ring with an ethylamine side chain

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15
Q

T/F substitutions on benzene ring, amino group, or alpha carbon effect the kinetic properties of a drug

A

true

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16
Q

What do changes to drug structure result in?

A

changes in bioavailability, receptor activity and duration of action

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17
Q

What is true of the cardiovascular system’s handling of sympathomimetics?

A

the net effect of any sympathomimetic will be a combination of its direct effect on a receptor and a counteraction by compensatory mechanisms so the body can maintain homeostasis

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18
Q

What does the activation of alpha 1 do to the cardiovascular system?

A

arterial and venous vasoconstriction, increase in peripheral resistance, increase in blood pressure (reflex decrease in heart rate)

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19
Q

What does activation of alpha 2 do to the cardiovascular system?

A

inhibition of sympathetic tone which leads to a decrease of blood pressure

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20
Q

What does activation of beta 1 do to the cardiovascular system?

A

increased cardiac contractility and heart rate, increases cardiac output and increases blood pressure

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21
Q

What does activation of beta 2 do to the cardiovascular system?

A

vasodilation except in skin and brain which decreases blood pressure

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22
Q

What does a nonselective beta agonist have a net effect of?

A

decreasing blood pressure (technically increasing systolic and decreasing diastolic

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23
Q

What does beta 2 activation do to the respiratory system?

A

bronchodilation

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24
Q

What does the activation of alpha 1 do to the eye?

A

pupil dilation/mydriasis from contraction of the pupillary dilator muscle

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25
What does activation of alpha 2 do to the eye?
decrease in aqueous production, increase in uveoscleral outflow
26
What does activation of beta 2 do to the eye?
relaxation of the ciliary muscle, production of aqueous, insignificant pupil dilation
27
What does alpha 1 activation do to the urinary system?
constriction of bladder base and prostate leading to urinary retention
28
What does activation of beta 1 do to metabolism?
increase lipolysis-- breakdown of fat to increase energy reserves
29
What does activation of beta 2 do to metabolism?
increased glycogenolysis (breakdown of glycogen into glucose) and increased glucagon release (increased breakdown of glycogen in the liver)
30
What are the three endogenous sympathomimetics?
epinephrine (adrenaline), norepinephrine, and dopamine
31
What is epinephrine?
nonselective endogenous sympathomimetic that is a potent vasoconstrictor and cardiac stimulant that is dose dependent and increases blood flow
32
What is norepinephrine?
a nonselective sympathomimetic with little effect on beta 2 that causes an intense increase in peripheral resistance and blood pressure
33
What is dopamine?
a precursor to NE
34
Phenylephrine
alpha 1 selective, vasoconstriction --> mydriatic and decongestant
35
Midodrine
alpha 1 selective, treatment of orthostatic hypotension
36
Clonidine
alpha 2 selective, decrease in blood pressure, used in emergency
37
Isoproterenol
nonselective beta agonist, potent vasodilator that increases cardiac output and decreases blood pressure
38
Dobutamine
beta 1 selective but some isomers have alpha 1 so in summary direct acting agonist
39
Albuterol
beta 2 selective, bronchodilation, inhaler for asthma
40
What are the clinical cardiovascular uses of sympathomimetics?
acute hypotension, chronic orthostatic hypotension, cardiac arrest, hypertension, local vasoconstriction
41
What are clinical pulmonary uses of sympathomimetics?
treatment of asthma by beta 2 selective agonists
42
How can sympathomimetics be used for anaphylaxis?
epinephrine IM injection
43
What are the ophthalmic uses of sympathomimetics?
pupil dilation, glaucoma, identification of horners
44
What is horners syndrome?
interruption of sympathetic innervation to the face
45
What are the signs of horners?
ptosis, miosis, anhydrosis caused by a pre or post ganglionic lesion of sympathetic fibers
46
How can you confirm a horner's diagnosis?
1 % apraclonidine produces dilation of the abnormal pupil and cocaine produce dilation of the normal pupil because it prevents re-uptake of norepinephrine
47
What do you do after a horner's diagnosis to locate the lesion?
hydroxyamphetamine drops are used, dilation=pre-ganglionic and no dilation= post-ganglionic lesion
48
T/F alpha 1 and 2 antagonists are more clinically relevant that beta blockers
false
49
What is the MOA of alpha antagonists?
bind to alpha receptors and prevent binding of agonist, can be reversible or irreversible
50
What are cardiovascular effects of alpha antagonists?
decrease arteriolar and venous tone which lowers peripheral vascular resistance and blood pressure
51
What are side effects of alpha antagonists?
tachycardia and orthostatic hypotension
52
What are other effects of alpha antagonists?
miosis, nasal stuffiness, increased urine flow
53
Phenoxybenzamine
alpha 1> alpha 2 antagonism, blocks histamine, acetylcholine, and serotonin receptors, causes attenuation (stoping vasoconstriction) of sympathetic vasoconstriction aka adverse effect of orthostatic hypotension and tachycardia
54
Phentolamine
non selective, reduces peripheral vascular resistance and causes cardiac stimulation, adverse effects of severe tachycardia, arrhythmias, and myocardial ischemia, not available in US
55
Prazosin, Terazosin, Doxazosin
alpha 1 antagonist, less tachycardia (because no blocking of alpha 2), relax vascular smooth muscle... can be used in chronic hypertension but not usually
56
Which alpha 1 antagonist has a longer half life?
doxazosin
57
Tamulosin and afluzosin
highly selective for alpha 1a/d and has a much higher effect on prostate smooth muscle, causes floppy iris syndrome so caution with cataract surgery
58
Yohimbine
alpha 2 selective, promotes norepinephrine release as well as NO, increases central sympathetic activation and peripheral vasodilation, used for erectile dysfunction
59
Pheochromaocytoma
tumor of adrenal medulla or sympathetic ganglion cells, excessive secretion of norepinephrine and epinephrine can be treated with phenoxybenzamine or phetolamine before operation to control hypertension
60
What can be used in hypertensive emergencies?
alpha antagonists or labetalol
61
What can be used in urinary obstruction from BPH?
alpha antagonists cause partial reversal of smooth muscle contraction in an enlarged prostate, tamsulosin and alfuzosin have fewer effects on blood pressure
62
What are beta blockers?
drugs that occupy beta receptors and prevent binding by agonists, competitive antagonism
63
T/F some beta antagonists are partial agonists
true
64
How does the partial agonist thing work for beta antagonists?
inhibit activation in presence of high agonist concentration but moderately activate receptor in absence of endogenous agonists
65
What is the affect of beta antagonists on cardiovascular system?
decrease in blood pressure, slow atrioventricular conduction, oppose b2 mediated vasodilation
66
What to beta antagonists decrease blood pressure in patients with hypertension?
due to decrease in renin release
67
How do beta antagonists slow atrioventricular conduction?
decrease heart rate and cardiac output
68
How do beta antagonists oppose B2 mediated vasodilation?
acute effect of increasing blood pressure, decreases with chronic administration of drug
69
What is the effect of beta antagonists on the respiratory tract?
increases airway resistance-- DO NOT GIVE BETA BLOCKER TO ASTHMATIC PATIENT
70
What is the effect of a beta antagonist on the eye?
decrease aqueous humor production aka decrease IOP
71
What is the effect of a beta antagonist of metabolism?
impairs recovery from hypoglycemia, increases VDLV and decreases HDL cholesterol
72
Which nonselective beta blocker has a longer duration of action?
nadolol
73
What beta blocker is used for glaucoma?
timolol and betaxolol
74
Which beta blockers also have alpha 1 antagonist activity?
carvedilol and labetalol
75
Why do some beta blockers have alpha 1 antagonist activity as well?
to oppose the vasoconstriction caused by blockage of beta 2 receptors and decrease blood pressure without major effect on the cardiovascular system
76
Which beta blocker is most highly selective and causes vasodilation?
nebivolol
77
Which beta blocker is very short acting?
esmolol, ten minute half life
78
What drug class can be used to improve survival rate after a heart attack?
beta blockers, timolol, propranolol, metoprolol
79
How do beta blockers help in ischemic heart disease?
regulate heart beat which reduces the oxygen demand
80
Do beta blockers treat hypertension?
yes but usually in combination with a diuretic or vasodilator
81
T/F heart condition may worsen with first dose of a beta blocker?
true, dose is increased gradually
82
T/F topical beta blockers can be absorbed systemically
true
83
T/F beta agonist treat hyperthyroidism
false, beta blockers do
84
How do beta blockers affect neurologic disease?
reduce frequency and intensity of migraine and reduce tremors (like eyelid twitch), prevent anxiety as well
85
What are adverse effects of beta blockers?
bradycardia, mild sedation and or depression, worsening asthma or airway obstruction, cardiac decompensation, and hypoglycemic episodes
86
Why should you measure the heart rate of patients on beta blockers?
they can decrease heart rate
87
T/F beta blockers are the first line drug for hypertension
false
88
What are the major clinical uses of beta antagonists?
ischemic heart disease, arrhythmia, hypertension, hyperthyroidism, and glaucoma

Systemic Pharm I (13 decks)

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