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

Modulation of the Sympathetic Nervous System Flashcards

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
Q

What does activation of alpha 2 do to the eye?

A

decrease in aqueous production, increase in uveoscleral outflow

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26
Q

What does activation of beta 2 do to the eye?

A

relaxation of the ciliary muscle, production of aqueous, insignificant pupil dilation

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27
Q

What does alpha 1 activation do to the urinary system?

A

constriction of bladder base and prostate leading to urinary retention

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28
Q

What does activation of beta 1 do to metabolism?

A

increase lipolysis– breakdown of fat to increase energy reserves

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29
Q

What does activation of beta 2 do to metabolism?

A

increased glycogenolysis (breakdown of glycogen into glucose) and increased glucagon release (increased breakdown of glycogen in the liver)

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30
Q

What are the three endogenous sympathomimetics?

A

epinephrine (adrenaline), norepinephrine, and dopamine

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31
Q

What is epinephrine?

A

nonselective endogenous sympathomimetic that is a potent vasoconstrictor and cardiac stimulant that is dose dependent and increases blood flow

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32
Q

What is norepinephrine?

A

a nonselective sympathomimetic with little effect on beta 2 that causes an intense increase in peripheral resistance and blood pressure

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33
Q

What is dopamine?

A

a precursor to NE

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34
Q

Phenylephrine

A

alpha 1 selective, vasoconstriction –> mydriatic and decongestant

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35
Q

Midodrine

A

alpha 1 selective, treatment of orthostatic hypotension

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36
Q

Clonidine

A

alpha 2 selective, decrease in blood pressure, used in emergency

37
Q

Isoproterenol

A

nonselective beta agonist, potent vasodilator that increases cardiac output and decreases blood pressure

38
Q

Dobutamine

A

beta 1 selective but some isomers have alpha 1 so in summary direct acting agonist

39
Q

Albuterol

A

beta 2 selective, bronchodilation, inhaler for asthma

40
Q

What are the clinical cardiovascular uses of sympathomimetics?

A

acute hypotension, chronic orthostatic hypotension, cardiac arrest, hypertension, local vasoconstriction

41
Q

What are clinical pulmonary uses of sympathomimetics?

A

treatment of asthma by beta 2 selective agonists

42
Q

How can sympathomimetics be used for anaphylaxis?

A

epinephrine IM injection

43
Q

What are the ophthalmic uses of sympathomimetics?

A

pupil dilation, glaucoma, identification of horners

44
Q

What is horners syndrome?

A

interruption of sympathetic innervation to the face

45
Q

What are the signs of horners?

A

ptosis, miosis, anhydrosis caused by a pre or post ganglionic lesion of sympathetic fibers

46
Q

How can you confirm a horner’s diagnosis?

A

1 % apraclonidine produces dilation of the abnormal pupil and cocaine produce dilation of the normal pupil because it prevents re-uptake of norepinephrine

47
Q

What do you do after a horner’s diagnosis to locate the lesion?

A

hydroxyamphetamine drops are used, dilation=pre-ganglionic and no dilation= post-ganglionic lesion

48
Q

T/F alpha 1 and 2 antagonists are more clinically relevant that beta blockers

A

false

49
Q

What is the MOA of alpha antagonists?

A

bind to alpha receptors and prevent binding of agonist, can be reversible or irreversible

50
Q

What are cardiovascular effects of alpha antagonists?

A

decrease arteriolar and venous tone which lowers peripheral vascular resistance and blood pressure

51
Q

What are side effects of alpha antagonists?

A

tachycardia and orthostatic hypotension

52
Q

What are other effects of alpha antagonists?

A

miosis, nasal stuffiness, increased urine flow

53
Q

Phenoxybenzamine

A

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
Q

Phentolamine

A

non selective, reduces peripheral vascular resistance and causes cardiac stimulation, adverse effects of severe tachycardia, arrhythmias, and myocardial ischemia, not available in US

55
Q

Prazosin, Terazosin, Doxazosin

A

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
Q

Which alpha 1 antagonist has a longer half life?

A

doxazosin

57
Q

Tamulosin and afluzosin

A

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
Q

Yohimbine

A

alpha 2 selective, promotes norepinephrine release as well as NO, increases central sympathetic activation and peripheral vasodilation, used for erectile dysfunction

59
Q

Pheochromaocytoma

A

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
Q

What can be used in hypertensive emergencies?

A

alpha antagonists or labetalol

61
Q

What can be used in urinary obstruction from BPH?

A

alpha antagonists cause partial reversal of smooth muscle contraction in an enlarged prostate, tamsulosin and alfuzosin have fewer effects on blood pressure

62
Q

What are beta blockers?

A

drugs that occupy beta receptors and prevent binding by agonists, competitive antagonism

63
Q

T/F some beta antagonists are partial agonists

A

true

64
Q

How does the partial agonist thing work for beta antagonists?

A

inhibit activation in presence of high agonist concentration but moderately activate receptor in absence of endogenous agonists

65
Q

What is the affect of beta antagonists on cardiovascular system?

A

decrease in blood pressure, slow atrioventricular conduction, oppose b2 mediated vasodilation

66
Q

What to beta antagonists decrease blood pressure in patients with hypertension?

A

due to decrease in renin release

67
Q

How do beta antagonists slow atrioventricular conduction?

A

decrease heart rate and cardiac output

68
Q

How do beta antagonists oppose B2 mediated vasodilation?

A

acute effect of increasing blood pressure, decreases with chronic administration of drug

69
Q

What is the effect of beta antagonists on the respiratory tract?

A

increases airway resistance– DO NOT GIVE BETA BLOCKER TO ASTHMATIC PATIENT

70
Q

What is the effect of a beta antagonist on the eye?

A

decrease aqueous humor production aka decrease IOP

71
Q

What is the effect of a beta antagonist of metabolism?

A

impairs recovery from hypoglycemia, increases VDLV and decreases HDL cholesterol

72
Q

Which nonselective beta blocker has a longer duration of action?

A

nadolol

73
Q

What beta blocker is used for glaucoma?

A

timolol and betaxolol

74
Q

Which beta blockers also have alpha 1 antagonist activity?

A

carvedilol and labetalol

75
Q

Why do some beta blockers have alpha 1 antagonist activity as well?

A

to oppose the vasoconstriction caused by blockage of beta 2 receptors and decrease blood pressure without major effect on the cardiovascular system

76
Q

Which beta blocker is most highly selective and causes vasodilation?

A

nebivolol

77
Q

Which beta blocker is very short acting?

A

esmolol, ten minute half life

78
Q

What drug class can be used to improve survival rate after a heart attack?

A

beta blockers, timolol, propranolol, metoprolol

79
Q

How do beta blockers help in ischemic heart disease?

A

regulate heart beat which reduces the oxygen demand

80
Q

Do beta blockers treat hypertension?

A

yes but usually in combination with a diuretic or vasodilator

81
Q

T/F heart condition may worsen with first dose of a beta blocker?

A

true, dose is increased gradually

82
Q

T/F topical beta blockers can be absorbed systemically

A

true

83
Q

T/F beta agonist treat hyperthyroidism

A

false, beta blockers do

84
Q

How do beta blockers affect neurologic disease?

A

reduce frequency and intensity of migraine and reduce tremors (like eyelid twitch), prevent anxiety as well

85
Q

What are adverse effects of beta blockers?

A

bradycardia, mild sedation and or depression, worsening asthma or airway obstruction, cardiac decompensation, and hypoglycemic episodes

86
Q

Why should you measure the heart rate of patients on beta blockers?

A

they can decrease heart rate

87
Q

T/F beta blockers are the first line drug for hypertension

A

false

88
Q

What are the major clinical uses of beta antagonists?

A

ischemic heart disease, arrhythmia, hypertension, hyperthyroidism, and glaucoma

Systemic Pharm I (13 decks)

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