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125 Cards in this Set
- Front
- Back
where can substitutions be made on beta-phenylethylamine?
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1) terminal amino group
2) on the benzene ring 3) alpha or beta carbons |
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what is the effect of making substitutions on catecholamines?
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changes affinity for alpha and beta receptors
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what is the effect of increasing the size of the alkyl substituents on the amino group of catecholamines?
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tends to increase beta receptor activity, decrease alpha receptor activity
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what do you get when you add a methyl group to the nitrogen of norepinephrine?
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epinephrine
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what do you get when you add an isopropyl group to the nitrogen of norepinephrine?
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isoproterenol
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what type of drug is phenylephrine?
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pure alpha agonist
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what type of drug is methoxamine?
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pure alpha agonist
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what is the effect of removing one or both OH groups on the aromatic ring of catecholamines?
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dramatically decreases the potency of the drug
loss of beta activity |
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why is phenylephrine metabolized so slowly?
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COMT (catechol-O-methyltransferase) is inactive on phenylephrine, so its half life is prolonged
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why is methoxamine metabolized so slowly?
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COMT (catechol-O-methyltransferase) is inactive on methoxamine, so its half life is prolonged
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what is the effect of complete absence of ring substituents on catecholamine?
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increases distribution of the molecule into the CNS
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what catecholamine drugs have a complete absence of ring substituents and substitution on the alpha carbon?
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ephedrine
amphetamine |
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what is the effect of substitution on the alpha carbon of adrenergic drugs?
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block oxidation by MAO (monoamine oxidase)
prolong a compound's half-life (especially if the drug is not a catecholamine) |
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how does amphetamine act?
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mainly by displacing norepi from adrenergic nerve terminals
indirect acting sympathomimetic |
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what is meant by term "pressor drug"?
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a drug with some ability to raise the blood pressure
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what type of adrenergic drug is oxymetazoline?
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alpha agonist
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what type of adrenergic drug is phenylephrine?
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alpha agonist
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what type of adrenergic drug is methoxamine?
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alpha agonist
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what is special about oxymetazoline as an alpha agonist?
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it is very long-acting
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what type of adrenergic drug is amphetamine?
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indirect acting sympathomimetic
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what is the importance of alpha agonists?
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mainly as pressor drugs or vasoconstrictors (systemically or locally)
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how are alpha agonists useful for treating paroxysmal atrial tachycardia (PAT)?
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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
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what is the problem with using alpha agonists as nasal decongestants?
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patients experience a horrible "rebound congestion" after they stop taking the drugs
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how long can alpha agonists be used as nasal decongestants?
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less than three days
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how are alpha agonists useful for treating nasal congestion?
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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.) |
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how are alpha agonists useful in conjunction with local anesthetics?
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constricts surrounding vasculature so that the half life of the local anesthetic (especially in the location) is increased
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what are the uses for alpha agonists in the maintenance of blood pressure?
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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 |
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what is the sole example of alpha agonists not being used as pressor drugs?
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mydriatic drug (pupil dilator)
used by ophthalmologists in eye exams just as atropine, only here the SNS influence is enhanced |
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how do alpha agonists act as eye drops to get the red out?
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they constrict the vessels which were causing the redness
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what is the primary use of beta-2 receptor agonists?
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bronchodilators to open air passages especially in cases of asthma
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what is the classic bronchodilator?
what is its major pitfall? |
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 |
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what type of adrenergic drug is metaproterenol?
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selective beta-2 agonist
bronchodilator |
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what type of adrenergic drug is terbutaline?
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selective beta-2 agonist
bronchodilator |
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what type of adrenergic drug is albuterol?
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selective beta-2 agonist
bronchodilator |
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what is the other name for albuterol?
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salbutamol
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what type of adrenergic drug is isoproterenol?
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beta-receptor agonist
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why is the half-life of metaproterenol increased?
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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
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what are the two structure-activity changes in terbutaline?
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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 |
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what is the main therapeutic action of beta-two agonists in asthma?
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relaxation of bronchial smooth muscle
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what are the two uses of beta-2 agonists?
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relaxation of bronchial smooth muscle in asthmatics
inhibit uterine motility to prevent premature parturition or to delay it |
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what beta-2 agonist is frequently used to prevent premature parturition or delay it?
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terbutiline
delays premature labor for about two weeks until the patient develops tolerance therefore would have to increase dose to regain effects |
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what type of adrenergic drug is dobutamine?
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beta-one selective agonist
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why is the use of dobutamine more advantageous in treating congestive heart failure than isoproterenol?
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dobutamine is less effective in activating vasodilator beta-2 receptors than isoproterenol, so it may increase the cardiac output with less reflex tachycardia
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to what receptors does dopamine bind?
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alpha, beta-1, beta-2, dopamine receptors
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why is dopamine valuable in the treatment of shock?
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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 |
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where are dopamine receptors of the vasculature found? what is their effect on stimulation?
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only in the kidney
cause vasodilation upon stimulation, which increases renal blood flow |
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what is the receptor specificity of epinephrine?
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alpha-1
alpha-2 beta-1 beta-2 |
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what are the therapeutic uses of epinephrine?
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acute asthma
treatment of open-angle glaucoma anaphylactic shock increases duration of action of local anesthetics |
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what is the receptor specificity of norepinephrine?
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alpha-1
alpha-2 beta-1 |
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what are the therapeutic uses of norepinephrine?
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treatment of shock
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what is the receptor specificity of isoproterenol?
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beta-1
beta-2 |
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what are the therapeutic uses for isoproterenol?
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cardiac stimulant
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what is the receptor specificity of dopamine?
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dopaminergic receptors
alpha-1 beta-1 |
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what are the therapeutic uses for dopamine?
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treatment of shock
treatment of congestive heart failure |
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what is the receptor specificity of dobutamine?
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beta-1
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what are the therapeutic uses of dobutamine?
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treatment of congestive heart failure
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which adrenergic drugs are catecholamines?
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epinephrine
norepinephrine isoproterenol dopamine dobutamine |
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which adrenergic drugs are non-catecholamines?
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phenylephrine
methoxamine clonidine metaproterenol terbutaline ritodrine albuterol amphetamine |
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what is the receptor specificity of phenylephrine?
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alpha-1
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what are the therapeutic uses of phenylephrine?
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nasal decongestant
treatment of supraventricular tachycardia |
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what is the receptor specificity of methoxamine?
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alpha-1
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what are the therapeutic uses of methoxamine?
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treatment of supraventricular tachycardia
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what is the receptor specificity of clonidine?
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postsynaptic alpha-2 receptors in CNS
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what are the therapeutic uses of clonidine?
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acting at postsynaptic alpha-2 receptors in CNS, clonidine decreases the sympathetic outflow and thereby decreases blood pressure (Tx: HTN)
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what is the receptor specificity of metaproterenol?
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beta-2 > beta-1
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what are the therapeutic uses for metaproterenol?
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treatment of bronchospasm
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what is the receptor specificity for terbutaline?
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beta-2
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what are the therapeutic uses for terbutaline?
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treatment of bronchospasm and premature labor
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what is the receptor specificity for ritodrine?
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beta-2
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what are the therapeutic uses for ritodrine?
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treatment of bronchospasm and premature labor
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what is the receptor specificity for albuterol?
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beta-2
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what are the therapeutic uses for albuterol?
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treatment of bronchospasm
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what is the receptor specificity of amphetamine?
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amphetamine acts indirectly, not on an adrenergic receptor
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what are the therapeutic uses for amphetamine?
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CNS stimulant in treatment of children with attention deficit syndrome
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what are the important descriptors of catecholamines?
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rapid onset of action
brief duration of action not administered orally don't penetrate blood-brain barrier |
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what are the important descriptors of non-catecholamine adrenergic drugs?
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longer duration of action
all can be administered orally |
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what type of drug is phenoxybenzamine?
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irreversible alpha adrenergic antagonist
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how do irreversible alpha adrenergic antagonists work?
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bind to alpha receptors via covalent binding, so that receptor can no longer be used
maximum effect of agonist is decreased |
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what type of drug is prazosin?
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competitive alpha-1 selective alpha adrenergic antagonist
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what type of drug is terazosin?
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competitive alpha-1 selective alpha adrenergic antagonist
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what type of drug is doxazosin?
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competitive alpha-1 selective alpha adrenergic antagonist
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what type of drug ends in -zosin?
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competitive alpha-1 selective alpha adrenergic antagonist
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what type of drug is phentolamine?
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competitive nonselective alpha adrenergic antagonist
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how does a competitive alpha adrenergic antagonist work?
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occludes the alpha receptors from adrenergic agonists
large amounts of agonist will overcome these antagonists (e.g. phentolamine, -zosins) |
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why is epi reversal noted after administration of dibenamine?
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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
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why is the change in blood pressure biphasic upon sympathetic stimulation?
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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 |
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what are the effects of alpha receptor antagonism?
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epi reversal
decreased blood pressure reflex increase in heart rate |
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what is the use of alpha antagonists?
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treatment of benign prostatic hypertrophy
alpha-1 selective antagonists (-zosins) especially, since they will cause less tachycardia than nonselective antagonists |
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why are alpha antagonists useful in treating benign prostatic hypertrophy?
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blocking alpha receptors on urethra and in prostate leads to better urination
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describe the effects of nonselective alpha adrenergic antagonists on the arteriole and on the heart
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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 |
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describe the effects of alpha-1 adrenergic antagonists on the arteriole and the heart?
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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 |
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why were alpha antagonists thought to be great medications for HTN? why are they no longer used for this purpose?
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increase HDL
increase glucose sensitivity this group actually increased mortality |
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describe the following graph: cardiac contractile force vs. time
epi is administered first and then propanolol and then epi |
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 |
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describe the following graph: arterial pressure vs. time
epi is administered first and then propanolol and then epi |
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 |
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describe the following graph: heart rate vs. time
epi is administered first and then propanolol and then epi |
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 |
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what are the therapeutic uses for beta adrenergic blockers?
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treatment of angina
treatment of cardiac arrhythmias treatment of hypertension treatment of hyperthyroidism treatment of glaucoma treatment of migraine treatment of tremor |
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what type of angina is treated by beta adrenergic blockers?
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stable angina (chest pain or discomfort that occurs often during activity or stress, caused by a narrowing of the lumen of the coronary arteries)
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describe stable angina
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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 |
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how do beta blockers treat stable angina?
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they inhibit sympathetic tone to the heart, thus lessening oxygen demand and preventing the angina
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what drugs act like a "governor," limiting the maximum heart rate?
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beta receptor antagonists
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what type of ANS tone predisposes the heart to arrhythmias?
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sympathetic tone
(inhibition of SNS tone with beta adrenergic antagonists can prevent arrhythmias) |
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what are the two effects of propanolol?
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blocks beta receptors
exerts a local anesthetic effect (aka "membrane-stabilizing" action) by blocking sodium channels in nerve and heart muscle |
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what is the equation for blood pressure?
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BP = CO x TPR
BP = blood pressure CO = cardiac output TPR = total peripheral resistance |
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what is the effect of sympathetic stimulation on renin levels?
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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)
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what is the postulated mechanism for beta-2 adrenergic antagonists treating hypertension?
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beta-adrenergic antagonists inhibit beta-1 receptors on the juxtaglomerular cells of the kidney, so that renin release is inhibited
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to what adrenergic effector molecule do beta-2 receptors in the lungs respond?
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only react to epi, NOT norepi
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what is the precaution to keep in mind when treating CHF patients with beta-adrenergic antagonists?
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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 |
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why are beta-blockers contraindicated in asthmatics?
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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 |
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how do beta blockers cause AV blockade?
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beta blockers increase the PR interval, which can lead to tertiary block
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why do beta blockers cause poor patient compliance?
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for patients that exercise, beta blockers make their muscles feel weak and easily fatigued, because they block beta-2 vasodilation in muscles
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what drugs would you recommend for treating HTN in patients that enjoyed regular physical activity?
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ACE inhibitor
diuretic |
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what is the effect of beta blockers on glucose metabolism?
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beta blockers inhibit the beta receptors on the alpha cells, so that glucagon is not released; this decreases glycogenolysis
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what type of drugs are those with the suffix, -olol?
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beta blockers
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what is the prototype of all beta blockers? what was its drawback?
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propanolol
had to administer 3x daily |
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for what is timolol used?
why? |
treatment of glaucoma
beta blockers decrease the production of intraocular fluid |
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what beta blockers are cardioselective?
what does this mean? |
atenolol
metoprolol means that beta-1 affinity is greater than beta-2 affinity |
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what is the first important advance in beta blockers?
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cardioselectivity
atenolol metoprolol |
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what is the second important advance in beta blockers?
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increased half-life
atenolol nadolol |
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why do atenolol and nadolol have higher half lives?
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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*** |
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what is the important aspect of pindolol?
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it has intrinsic sympathomimetic ability (partial agonist activity)
theoretically is safe for asthmatics, but in practice is just as dangerous as other beta-blockers |
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what was the anticipated/hopeful use for labetolol?
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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 |
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what is the adrenergic receptor specificity of labetolol?
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alpha blocker
beta blocker |
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how is esmolol unique?
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it has a very short half-life (5-10 minutes) because it is metabolized by an esterase that is found in red blood cells
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what is the therapeutic use for esmolol?
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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 |
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what medication is good for deciding whether or not to use a beta-blocker in a patient with an MI?
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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 |