Pharmacology 7 (Adrenergic Pharmacology)

Front 1

where can substitutions be made on beta-phenylethylamine?

Back 1

1) terminal amino group
2) on the benzene ring
3) alpha or beta carbons

Front 2

what is the effect of making substitutions on catecholamines?

Back 2

changes affinity for alpha and beta receptors

Front 3

what is the effect of increasing the size of the alkyl substituents on the amino group of catecholamines?

Back 3

tends to increase beta receptor activity, decrease alpha receptor activity

Front 4

what do you get when you add a methyl group to the nitrogen of norepinephrine?

Back 4

epinephrine

Front 5

what do you get when you add an isopropyl group to the nitrogen of norepinephrine?

Back 5

isoproterenol

Front 6

what type of drug is phenylephrine?

Back 6

pure alpha agonist

Front 7

what type of drug is methoxamine?

Back 7

pure alpha agonist

Front 8

what is the effect of removing one or both OH groups on the aromatic ring of catecholamines?

Back 8

dramatically decreases the potency of the drug

loss of beta activity

Front 9

why is phenylephrine metabolized so slowly?

Back 9

COMT (catechol-O-methyltransferase) is inactive on phenylephrine, so its half life is prolonged

Front 10

why is methoxamine metabolized so slowly?

Back 10

COMT (catechol-O-methyltransferase) is inactive on methoxamine, so its half life is prolonged

Front 11

what is the effect of complete absence of ring substituents on catecholamine?

Back 11

increases distribution of the molecule into the CNS

Front 12

what catecholamine drugs have a complete absence of ring substituents and substitution on the alpha carbon?

Back 12

ephedrine

amphetamine

Front 13

what is the effect of substitution on the alpha carbon of adrenergic drugs?

Back 13

block oxidation by MAO (monoamine oxidase)

prolong a compound's half-life (especially if the drug is not a catecholamine)

Front 14

how does amphetamine act?

Back 14

mainly by displacing norepi from adrenergic nerve terminals

indirect acting sympathomimetic

Front 15

what is meant by term "pressor drug"?

Back 15

a drug with some ability to raise the blood pressure

Front 16

what type of adrenergic drug is oxymetazoline?

Back 16

alpha agonist

Front 17

what type of adrenergic drug is phenylephrine?

Back 17

alpha agonist

Front 18

what type of adrenergic drug is methoxamine?

Back 18

alpha agonist

Front 19

what is special about oxymetazoline as an alpha agonist?

Back 19

it is very long-acting

Front 20

what type of adrenergic drug is amphetamine?

Back 20

indirect acting sympathomimetic

Front 21

what is the importance of alpha agonists?

Back 21

mainly as pressor drugs or vasoconstrictors (systemically or locally)

Front 22

how are alpha agonists useful for treating paroxysmal atrial tachycardia (PAT)?

Back 22

pressor effects lead to a triggering of baroreceptors causing a large vagal stimulation to the heart which may convert the tachycardia to a normal sinus rhythm

Front 23

what is the problem with using alpha agonists as nasal decongestants?

Back 23

patients experience a horrible "rebound congestion" after they stop taking the drugs

Front 24

how long can alpha agonists be used as nasal decongestants?

Back 24

less than three days

Front 25

how are alpha agonists useful for treating nasal congestion?

Back 25

stimulation of alpha receptors causes a vasoconstriction resulting in decreased secretion

used mainly as a local nasal spray to minimize the systemic effects (increased b.p.)

Front 26

how are alpha agonists useful in conjunction with local anesthetics?

Back 26

constricts surrounding vasculature so that the half life of the local anesthetic (especially in the location) is increased

Front 27

what are the uses for alpha agonists in the maintenance of blood pressure?

Back 27

could be used for shock, but the vasoconstriction caused would only accentuate the already diminished tissue perfusion

could be used for spinal anesthesia where sympathetic tone is lost

Front 28

what is the sole example of alpha agonists not being used as pressor drugs?

Back 28

mydriatic drug (pupil dilator)

used by ophthalmologists in eye exams just as atropine, only here the SNS influence is enhanced

Front 29

how do alpha agonists act as eye drops to get the red out?

Back 29

they constrict the vessels which were causing the redness

Front 30

what is the primary use of beta-2 receptor agonists?

Back 30

bronchodilators to open air passages especially in cases of asthma

Front 31

what is the classic bronchodilator?

what is its major pitfall?

Back 31

isoproterenol

stimulates beta-2 receptors to dilate bronchioles, but also stimulates beta-1 receptors causing powerful myocardial stimulation even if the drug is nebulized to be localized in the lungs

Front 32

what type of adrenergic drug is metaproterenol?

Back 32

selective beta-2 agonist

bronchodilator

Front 33

what type of adrenergic drug is terbutaline?

Back 33

selective beta-2 agonist

bronchodilator

Front 34

what type of adrenergic drug is albuterol?

Back 34

selective beta-2 agonist

bronchodilator

Front 35

what is the other name for albuterol?

Back 35

salbutamol

Front 36

what type of adrenergic drug is isoproterenol?

Back 36

beta-receptor agonist

Front 37

why is the half-life of metaproterenol increased?

Back 37

the hydroxyl groups are on the 3 and 5 carbons rather than the 3 and 4 carbons, which makes it not a substrate for COMT

Front 38

what are the two structure-activity changes in terbutaline?

Back 38

hydroxyl groups on aromatic ring are spread out (3&5 rather than 3&4) - makes COMT inactive on this compound

extra methyl on the N-linked isopropyl group - increases beta-2 specificity

Front 39

what is the main therapeutic action of beta-two agonists in asthma?

Back 39

relaxation of bronchial smooth muscle

Front 40

what are the two uses of beta-2 agonists?

Back 40

relaxation of bronchial smooth muscle in asthmatics

inhibit uterine motility to prevent premature parturition or to delay it

Front 41

what beta-2 agonist is frequently used to prevent premature parturition or delay it?

Back 41

terbutiline

delays premature labor for about two weeks until the patient develops tolerance therefore would have to increase dose to regain effects

Front 42

what type of adrenergic drug is dobutamine?

Back 42

beta-one selective agonist

Front 43

why is the use of dobutamine more advantageous in treating congestive heart failure than isoproterenol?

Back 43

dobutamine is less effective in activating vasodilator beta-2 receptors than isoproterenol, so it may increase the cardiac output with less reflex tachycardia

Front 44

to what receptors does dopamine bind?

Back 44

alpha, beta-1, beta-2, dopamine receptors

Front 45

why is dopamine valuable in the treatment of shock?

Back 45

alpha stimulation results in an increased BP

beta-1 stimulation results in an increased CO

dopamine receptors cause vasodilation and therefore increased blood flow to the kidney

Front 46

where are dopamine receptors of the vasculature found? what is their effect on stimulation?

Back 46

only in the kidney

cause vasodilation upon stimulation, which increases renal blood flow

Front 47

what is the receptor specificity of epinephrine?

Back 47

alpha-1
alpha-2
beta-1
beta-2

Front 48

what are the therapeutic uses of epinephrine?

Back 48

acute asthma

treatment of open-angle glaucoma

anaphylactic shock

increases duration of action of local anesthetics

Front 49

what is the receptor specificity of norepinephrine?

Back 49

alpha-1
alpha-2
beta-1

Front 50

what are the therapeutic uses of norepinephrine?

Back 50

treatment of shock

Front 51

what is the receptor specificity of isoproterenol?

Back 51

beta-1
beta-2

Front 52

what are the therapeutic uses for isoproterenol?

Back 52

cardiac stimulant

Front 53

what is the receptor specificity of dopamine?

Back 53

dopaminergic receptors

alpha-1

beta-1

Front 54

what are the therapeutic uses for dopamine?

Back 54

treatment of shock

treatment of congestive heart failure

Front 55

what is the receptor specificity of dobutamine?

Back 55

beta-1

Front 56

what are the therapeutic uses of dobutamine?

Back 56

treatment of congestive heart failure

Front 57

which adrenergic drugs are catecholamines?

Back 57

epinephrine
norepinephrine
isoproterenol
dopamine
dobutamine

Front 58

which adrenergic drugs are non-catecholamines?

Back 58

phenylephrine
methoxamine
clonidine
metaproterenol
terbutaline
ritodrine
albuterol
amphetamine

Front 59

what is the receptor specificity of phenylephrine?

Back 59

alpha-1

Front 60

what are the therapeutic uses of phenylephrine?

Back 60

nasal decongestant

treatment of supraventricular tachycardia

Front 61

what is the receptor specificity of methoxamine?

Back 61

alpha-1

Front 62

what are the therapeutic uses of methoxamine?

Back 62

treatment of supraventricular tachycardia

Front 63

what is the receptor specificity of clonidine?

Back 63

postsynaptic alpha-2 receptors in CNS

Front 64

what are the therapeutic uses of clonidine?

Back 64

acting at postsynaptic alpha-2 receptors in CNS, clonidine decreases the sympathetic outflow and thereby decreases blood pressure (Tx: HTN)

Front 65

what is the receptor specificity of metaproterenol?

Back 65

beta-2 > beta-1

Front 66

what are the therapeutic uses for metaproterenol?

Back 66

treatment of bronchospasm

Front 67

what is the receptor specificity for terbutaline?

Back 67

beta-2

Front 68

what are the therapeutic uses for terbutaline?

Back 68

treatment of bronchospasm and premature labor

Front 69

what is the receptor specificity for ritodrine?

Back 69

beta-2

Front 70

what are the therapeutic uses for ritodrine?

Back 70

treatment of bronchospasm and premature labor

Front 71

what is the receptor specificity for albuterol?

Back 71

beta-2

Front 72

what are the therapeutic uses for albuterol?

Back 72

treatment of bronchospasm

Front 73

what is the receptor specificity of amphetamine?

Back 73

amphetamine acts indirectly, not on an adrenergic receptor

Front 74

what are the therapeutic uses for amphetamine?

Back 74

CNS stimulant in treatment of children with attention deficit syndrome

Front 75

what are the important descriptors of catecholamines?

Back 75

rapid onset of action
brief duration of action
not administered orally
don't penetrate blood-brain barrier

Front 76

what are the important descriptors of non-catecholamine adrenergic drugs?

Back 76

longer duration of action
all can be administered orally

Front 77

what type of drug is phenoxybenzamine?

Back 77

irreversible alpha adrenergic antagonist

Front 78

how do irreversible alpha adrenergic antagonists work?

Back 78

bind to alpha receptors via covalent binding, so that receptor can no longer be used

maximum effect of agonist is decreased

Front 79

what type of drug is prazosin?

Back 79

competitive alpha-1 selective alpha adrenergic antagonist

Front 80

what type of drug is terazosin?

Back 80

competitive alpha-1 selective alpha adrenergic antagonist

Front 81

what type of drug is doxazosin?

Back 81

competitive alpha-1 selective alpha adrenergic antagonist

Front 82

what type of drug ends in -zosin?

Back 82

competitive alpha-1 selective alpha adrenergic antagonist

Front 83

what type of drug is phentolamine?

Back 83

competitive nonselective alpha adrenergic antagonist

Front 84

how does a competitive alpha adrenergic antagonist work?

Back 84

occludes the alpha receptors from adrenergic agonists

large amounts of agonist will overcome these antagonists

(e.g. phentolamine, -zosins)

Front 85

why is epi reversal noted after administration of dibenamine?

Back 85

dibenamine is an alpha adrenergic antagonist, so it blocks the vasoconstriction caused by alpha stimulation while beta-2-mediated vasodilation still occurs on administration of epi

Front 86

why is the change in blood pressure biphasic upon sympathetic stimulation?

Back 86

initial, sharp component of pressor response is due to local effect of norepinephrine released from sympathetic nerve endings (e.g. in splanchnic vessels)

subsequent slower component of the rise is predominantly due to catecholamines released from adrenal medulla

Front 87

what are the effects of alpha receptor antagonism?

Back 87

epi reversal
decreased blood pressure
reflex increase in heart rate

Front 88

what is the use of alpha antagonists?

Back 88

treatment of benign prostatic hypertrophy

alpha-1 selective antagonists (-zosins) especially, since they will cause less tachycardia than nonselective antagonists

Front 89

why are alpha antagonists useful in treating benign prostatic hypertrophy?

Back 89

blocking alpha receptors on urethra and in prostate leads to better urination

Front 90

describe the effects of nonselective alpha adrenergic antagonists on the arteriole and on the heart

Back 90

arteriole: postsynaptic alpha-1 receptor is blocked, so vasculature dilates; presynaptic, inhibitory alpha-2 receptor is blocked, so there is greater NE release which doesn't matter because the postsynaptic receptor is blocked

heart: presynaptic, inhibitory alpha-2 receptor is blocked, so there is greater NE release; since the postsynaptic receptor is a beta receptor and is not blocked, there is a stronger postsynaptic effect caused by the higher level of NE

inc. HR directly by beta-receptor stimulation and inc. HR indirectly by baroreceptor reflex b/c of decreased TPR

Front 91

describe the effects of alpha-1 adrenergic antagonists on the arteriole and the heart?

Back 91

arteriole: postsynaptic alpha-1 receptor is blocked, so vasculature dilates; presynaptic, inhibitory alpha-2 receptor is not blocked, so there is normal NE release which doesn't matter because the postsynaptic receptor is blocked

heart: presynaptic, inhibitory alpha-2 receptor is not blocked, so there is normal NE release; since the postsynaptic receptor is a beta receptor and is not blocked, there is a normal postsynaptic effect caused by the normal level of NE

inc. HR only indirectly by baroreceptor reflex b/c of decreased TPR

Front 92

why were alpha antagonists thought to be great medications for HTN? why are they no longer used for this purpose?

Back 92

increase HDL
increase glucose sensitivity

this group actually increased mortality

Front 93

describe the following graph: cardiac contractile force vs. time
epi is administered first and then propanolol and then epi

Back 93

this graph has a peak on the first administration of epi due to the beta-1 effect on the heart muscle

on the second administration of epi, there is no peak/change in contractility b/c the beta-1 effect has been blocked

Front 94

describe the following graph: arterial pressure vs. time
epi is administered first and then propanolol and then epi

Back 94

on the first administration of epi, there is a peak which quickly tails off to normal MAP; this is caused by alpha-1 constriction moderated by beta-2 dilation

on the second administration of epi, there is a peak with a longer tail, because the propanolol blocks the beta-2 receptor causing unopposed alpha-1 constriction

Front 95

describe the following graph: heart rate vs. time
epi is administered first and then propanolol and then epi

Back 95

on the first administration of epi, there is a peak, moderated by beta-1 activity at the heart

on the second administration of epi, there is no peak/change because the beta-1 receptors are blocked by propanolol

Front 96

what are the therapeutic uses for beta adrenergic blockers?

Back 96

treatment of angina
treatment of cardiac arrhythmias
treatment of hypertension
treatment of hyperthyroidism
treatment of glaucoma
treatment of migraine
treatment of tremor

Front 97

what type of angina is treated by beta adrenergic blockers?

Back 97

stable angina (chest pain or discomfort that occurs often during activity or stress, caused by a narrowing of the lumen of the coronary arteries)

Front 98

describe stable angina

Back 98

coronary blood flow is impaired in such a way that the heart gets enough oxygen at rest, but not under conditions of increased sympathetic tone to the heart

this causes myocardial ischemia and the pain that goes with it

Front 99

how do beta blockers treat stable angina?

Back 99

they inhibit sympathetic tone to the heart, thus lessening oxygen demand and preventing the angina

Front 100

what drugs act like a "governor," limiting the maximum heart rate?

Back 100

beta receptor antagonists

Front 101

what type of ANS tone predisposes the heart to arrhythmias?

Back 101

sympathetic tone

(inhibition of SNS tone with beta adrenergic antagonists can prevent arrhythmias)

Front 102

what are the two effects of propanolol?

Back 102

blocks beta receptors

exerts a local anesthetic effect (aka "membrane-stabilizing" action) by blocking sodium channels in nerve and heart muscle

Front 103

what is the equation for blood pressure?

Back 103

BP = CO x TPR

BP = blood pressure
CO = cardiac output
TPR = total peripheral resistance

Front 104

what is the effect of sympathetic stimulation on renin levels?

Back 104

SNS stimulation at the beta-1 receptors on the juxtaglomerular cells of the kidney causes the release of renin, which then causes release of angiotensin (which is then converted to angiotensin II by ACE)

Front 105

what is the postulated mechanism for beta-2 adrenergic antagonists treating hypertension?

Back 105

beta-adrenergic antagonists inhibit beta-1 receptors on the juxtaglomerular cells of the kidney, so that renin release is inhibited

Front 106

to what adrenergic effector molecule do beta-2 receptors in the lungs respond?

Back 106

only react to epi, NOT norepi

Front 107

what is the precaution to keep in mind when treating CHF patients with beta-adrenergic antagonists?

Back 107

patients with congestive heart failure have hearts that need help to pump efficiently

the administration of a beta blocker could result in acute decompensation

CO falls -> pulmonary vasculature becomes congested -> pulmonary edema

Front 108

why are beta-blockers contraindicated in asthmatics?

Back 108

asthmatics need beta-2 stimulation to maintain open airways

even the beta-1 (cardioselective) blockers will cause trouble in asthmatics b/c it's only cardioselective at low doses

Front 109

how do beta blockers cause AV blockade?

Back 109

beta blockers increase the PR interval, which can lead to tertiary block

Front 110

why do beta blockers cause poor patient compliance?

Back 110

for patients that exercise, beta blockers make their muscles feel weak and easily fatigued, because they block beta-2 vasodilation in muscles

Front 111

what drugs would you recommend for treating HTN in patients that enjoyed regular physical activity?

Back 111

ACE inhibitor
diuretic

Front 112

what is the effect of beta blockers on glucose metabolism?

Back 112

beta blockers inhibit the beta receptors on the alpha cells, so that glucagon is not released; this decreases glycogenolysis

Front 113

what type of drugs are those with the suffix, -olol?

Back 113

beta blockers

Front 114

what is the prototype of all beta blockers? what was its drawback?

Back 114

propanolol

had to administer 3x daily

Front 115

for what is timolol used?

why?

Back 115

treatment of glaucoma

beta blockers decrease the production of intraocular fluid

Front 116

what beta blockers are cardioselective?

what does this mean?

Back 116

atenolol

metoprolol

means that beta-1 affinity is greater than beta-2 affinity

Front 117

what is the first important advance in beta blockers?

Back 117

cardioselectivity

atenolol
metoprolol

Front 118

what is the second important advance in beta blockers?

Back 118

increased half-life

atenolol
nadolol

Front 119

why do atenolol and nadolol have higher half lives?

Back 119

excreted only by the kidney, which is usually very fast, but since the beta blockers have HIGH lipophilicity their excretion is very slow

***no metabolism by liver***

Front 120

what is the important aspect of pindolol?

Back 120

it has intrinsic sympathomimetic ability (partial agonist activity)

theoretically is safe for asthmatics, but in practice is just as dangerous as other beta-blockers

Front 121

what was the anticipated/hopeful use for labetolol?

Back 121

it was hoped that its ability to block alpha and beta receptors would cause it to be a super antihypertensive

clinically hasn't been any more effective than regular beta-blockers

Front 122

what is the adrenergic receptor specificity of labetolol?

Back 122

alpha blocker
beta blocker

Front 123

how is esmolol unique?

Back 123

it has a very short half-life (5-10 minutes) because it is metabolized by an esterase that is found in red blood cells

Front 124

what is the therapeutic use for esmolol?

Back 124

early treatment of myocardial infarctions

esmolol is administered in IV drip, and if the removal of SNS tone to the heart is too great, the IV infusion can be stopped and the effect is short-lived

Front 125

what medication is good for deciding whether or not to use a beta-blocker in a patient with an MI?

Back 125

esmolol, a short-lived beta-blocker

it can be administered and if its removal of sympathetic tone is too strong, then it can be stopped