Pharm Ch. 18 Adrenergic Drugs
what do ophthalmics do?
-temporarily relieve conjuctival congestion by causing arteriolar vasoconstriction -can also be used to decrease intraocular pressure (useful in treatment of open-angle glaucoma) -can dilate the pupils (mydriasis) which is useful for eye exams
what are the TOXIC effects of adrenergic drugs?
-toxic effects are an extension of their common adverse effects -seizures from excessive CNS stimulation -hypotension or hypertension -dysrhythmias -palpitations -nervousness -dizziness -fatigue -malaise -insomnia
vasoactive adrenergic used to treat
-treat failing heart or shock -treat orthostatic hypotension -wide range of effects on alpha and beta-adrenergic receptors
when is epinephrine used?
-used in emergency situations -primary drug used in ACLS (cardiac arrest) -also used to treat acute asthma attacks and anaphylactic shock because of bronchodilatory effects
the cardiovascular adrenergics are referred to as?
-vasoactive sympathomimetics -vasoconstrictive drugs (also known as vasopressive drugs, pressor drugs, or pressors) -inotropes -cardioselective sympathomimetics
what are the alpha-adrenergic agonist responses?
-vasoconstriction -CNS stimulation
what happens to blood vessels when alpha1 receptors are stimulated? beta2?
-vasoconstriction for alpha1 -vasodilation for beta2
when are adrenergics used for the cardiovascular system?
during cardiac failure and shock
Adrenergics can be selective for what receptors?
either alpha- or beta-adrenergic receptors
if death occurs from adrenergic toxicity, it is usually the result of what?
either respiratory failure or cardiac arrest
what happens when alpha1 receptors on the penis are stimulated?
ejaculation
what vasoactive adrenergic is an endogenous vasoactive catecholamine that acts directly on alpha and beta-adrenergic receptors?
epinephrine (Adrenalin)
what are examples of nonselective adrenergics?
epinephrine and norepinephrine
what vasoactive adrenergic is indicated for parenteral use to lower BP?
fenoldopam (Corlopam)
midodrine is indicated primarily for what?
for symptomatic orthostatic hypotension
what happens when alpha1 and beta2 receptors on the liver are stimulated?
glycogenolysis
what are the adverse effects of alpha-adrenergics?
headache, restlessness, excitement, insomnia, euphoria chest pain, palpitations (dysrhythmias), tachycardia, vasoconstriction, hypertension loss of appetite, dry mouth, nausea, vomiting, taste changes (rare)
anesthetic drugs and interaction with adrenergic
increase cardiac dysrhythmias
antihistamines and thyroid preparations interaction with adrenergic
increase effects of adrenergic drugs
what is the result of a positive inotropic effect?
increase in the force of contraction
tricyclic antidepressants and interaction with adrenergic
increase vasopressor effects = acute hypertensive crisis
what happens when the beta1 receptors on cardiac muscle are stimulated?
increased contractility
what happens when beta1 receptors on AV and SA node are stimulated?
increased heart rate is the result
what kind of relationship is there between epinephrine and norepinephrine activation and the response of the cell?
inverse relationship -activity (muscle tone) or the cell is decreased
when any of the adrenergic drugs are given, what area does it have an effect on?
it bathes the area between the nerve and the effector cell (the synaptic cleft) -once there, the drug has the opportunity to induce a response
when should midodrine be given?
last dose of day should not be given after 6 pm
MAOIs and interaction with adrenergic
life-threatening hypertensive crisis
where are beta2 receptors located?
located in smooth muscle of the bronchioles, arterioles, and visceral organs (beta two lungs)
where are alpha2-adrenergic receptors located?
located on presynaptic nerve terminals (the nerve that stimulates the effector cells)
where are alpha1-adrenergic receptors located?
located on the postsynaptic effector cells (the cell, muscle, or organ that the nerve stimulates)
where are beta1 receptors located?
located primarily in the heart (beta one heart)
what is the duration of action for noncatecholamine adrenergic drugs compared to other catecholamines?
longer duration of action than either the endogenous or synthetic catecholamines
dopamine may have what effects?
may have dopaminergic, beta1, or alpha2 effects depending on the dose
what is a vasoactive prodrug that is converted in the liver to its active form?
midodrine (ProAmatine) -its active form is desglymidodrine
what are the adverse effects of beta-adrenergics?
mild tremors, headache, nervousness, dizziness increased heart rate (positive chronotrophy), palpitations (dysrhythmias), fluctuations in BP sweating, nausea, vomiting, muscle cramps
the selective adrenergics only affect what?
only affect one receptor subtype
the alpha 1 and 2 and beta 1 and 2 receptors are part of which system?
part of the sympathetic division of the autonomic nervous system (in the PNS)
what are examples of selective adrenergics?
phenylephrine (Neo-Synephrine) and clonidine
ophthalmic adrenergics stimulate what?
stimulate alpha-adrenergic receptors located on the small arterioles in the eye
low doses of epinephrine do what?
stimulate beta1 adrenergic receptors (increasing force of contraction and HR)
what drug is used to stop premature labor? (causes relaxation of uterine smooth muscle)
terbutaline
noncatecholamine adrenergics are structurally dissimilar to what?
the endogenous catecholamines
the effects of adrenergics (aka catecholamine drugs) are similar or mimic the effect of what system?
the sympathetic nervous system (SNS)
adrenergics stimulate what receptor sites located where? what usually occurs?
-stimulate alpha1 adrenergic receptor sites located on smooth muscles -usually results in vasoconstriction
norepinephrine stimulates what receptors? this leads to what?
-stimulates alpha-adrenergic receptors, which leads to vasoconstriction -direct stimulating beta-adrenergic effects on the heart (beta1-adrenergic receptors)
what are the examples of noncatecholamine adrenergic drugs?
-Phenylephrine (Neo-Synephrine) -metaproterenol -albuterol
what are common bronchodilators classified as beta2-selective adrenergic drugs?
-albuterol -ephedrine -formoterol -terbutaline
onset of action for vasoactive adrenergics
-all have rapid onset (except midodrine) and effects will cease once administration is stopped
what are the three receptors for the sympathetic neurotransmitters?
-alpha-adrenergic receptors -beta-adrenergic receptors -dopaminergic receptors: respond only to dopamine -it is at these receptor sites that adrenergic drugs bind and produce their effects
dobutamine (Dobutrex) is available in what forms?
-available only in IV form (preferably through a central line) and is a continuous infusion
a direct-acting sympathomimetic binds directly to what? what's an example of this drug?
-binds directly to the receptor and causes a physiologic response -epinephrine is an example
what are the beta-adrenergic agonist responses?
-bronchial, GI, and uterine smooth muscle relaxation -glycogenolysis -cardiac stimulation
a mixed-acting sympathomimetic both directly and indirectly stimulates the receptor how? what's an example of this drug?
-by binding to it and indirectly stimulates the receptor by release of neurotransmitter stored in vesicles at the nerve endings -ephedrine is an example
how is a response enacted once the drug reaches the synaptic cleft?
-by direct stimulation -by indirect stimulation -or by a combination of the two (mixed-acting)
monitoring needs to happen with vasoactive adrenergics
-careful monitoring of vitals and ECG are required -therefore patients require ICU monitoring for these drugs
an indirect sympathomimetic causes what? what are examples of this drug?
-causes the release of the catecholamine from the storage sites (vesicles) in the nerve endings -it then binds to the receptors and causes a physiologic response -amphetamine and other anorexiants are examples
what is a common medication error that happens with a cardiovascular adrenergic?
-common medication error is confusion between norepinephrine and the brand name for phenylephrine, which is Neo-Synephrine
what happens when alpha1 and beta2 receptors on the uterus are stimulated?
-contraction for alpha1 -relaxation for beta2
what happens when alpha1 receptors in the pupils are stimulated?
-dilation (mydriasis)
what are common vasoactive adrenergic drugs?
-dobutamine (Dobutrex) -dopamine (Inotropin) -ephedrine -epinephrine (Adrenalin) -fenoldopam (Corlopam) -midodrine (ProAmatine) -norepinephrine (Levophed) -phenylephrine (Neo-Synephrine)
what are the 2 synthetic neurotransmitters?
-dobutamine (Dobutrex) -phenylephrine (Neo-Synephrine)
what are examples of nasal decongestants?
-ephedrine -naphazoline -phenylephrine
stimulation of beta1 receptors causes what 3 things?
-increased force of contraction (positive inotropic effect) -increased heart rate (positive chronotropic effect) -increased conduction through AV node (positive dromotropic effect)
dobutamine (Dobutrex) does what to the heart?
-increases cardiac output by increasing contractility (positive inotrophy) -increases stroke volume especially in patients with heart failure
high doses (e.g., IV drip) of epinephrine do what?
-it stimulates mostly alpha-adrenergic receptors, causing vasoconstriction -this elevates blood pressure
what is the HALF-LIFE like for adrenergic compounds?
-majority of adrenergic compounds have very short half-lives, and thus their effects are short-lived -therefore, when these drugs are taken in overdose or toxicity develops, stopping the drug causes the toxic symptoms to subside in a relatively short period of time
how do you treat adrenergic toxicity?
-manage the symptoms and support the patient -aimed at supporting the respiratory and cardiac systems - intracranial bleeding caused by blood pressure elevation can be treated by used rapid acting sympatholytic drug ex: esmolol
activation of beta2 adrenergic receptors produces what in the bronchi, uterus, and liver?
-produces relaxation of the bronchi (bronchodilation) -produces relaxation of the uterus -also increases glycogenolysis (glucose release) from the liver
binding to these alpha1 receptors can also cause what?
-relaxation of GI smooth muscle (decreased motility -contraction of the uterus -constriction of the bladder sphincter -male ejaculation -contraction of pupillary muscles of eye (dilated pupils-mydriasis)
which vasoactive adrenergic drugs are titrated to the desired physiologic response?
ALL doses
what is a naturally occurring catecholamine neurotransmitter that acts a vasoactive adrenergic?
dopamine (Intropin) -potent dopaminergic, beta1 and alpha1-adrenergic receptor activity
fenoldopam (Corlopam) induces arteriolar vasodilation mainly through stimulation of what receptors?
D1 receptors
what is the preferred route of dopamine?
IV infusion only preferably through a central line
what are the 3 endogenous neurotransmitters?
Norepinephrine (NE) epinephrine (EPI) dopamine -also known as catecholamines
nonselective agonists act as what receptors?
act as both alpha and beta receptors
where are beta-adrenergic receptors all located?
all located on possynaptic effector cells
which alpha receptors control the release of neurotransmitters?
alpha2-adrenergic receptors
how are adrenergic drugs classified?
also classified as selective or nonselective
in what ways is epinephrine available?
available in two strengths for IV use -this has led to many medication errors -*read the label closely before administering
which adrenergics are helpful in treating conditions such as asthma and bronchitis?
beta2 agonists
alpha-adrenergic receptors are differentiated by what?
by their location on nerves
what does intranasal application of certain adrenergics cause?
can cause constriction of dilated arterioles and reduction in nasal blood flow, which decreases congestion
at the highest doses of dopamine what can happen?
can cause vasoconstriction
low doses of dopamine can do what?
can dilate blood vessels in the brain, heart, kidneys and mesentery
high doses of dopamine can do what?
can improve cardiac contractility and output
adrenergic drugs are also known as what?
catecholamine drugs, adrenergic agonists, or sympathomimetics
stimulation of beta1 receptors in the kidney causes what?
causes an increase in renin secretion
stimulation of dopaminergic receptors causes what where?
causes dilation of the following blood vessels, resulting in increased blood flow (renal, mesenteric, coronary, cerebral)
what is one of the benefits of giving epinephrine in high doses via IV drip?
causes vasoconstriction which increases BP
what happens when alpha1 receptors on sphincters in the GI tract are stimulated?
constriction of sphincters
what drug is sometimes used in low doses to increase perfusion to the kidneys for patients with acute renal failure?
dopamine
what happens when beta2 and alpha receptors are stimulated on the GI muscle?
decreased motility
what happens when beta2 receptors on bronchial muscles are stimulated?
dilation
what drug provides an extra "squeeze" in patients with cardiac decompensation (pts with CHF, pts post cardiac surgery)?
dobutamine (Dobutrex) -beta1-selective vasoactive adrenergic
dopaminergic receptors are stimulated by what?
dopamine
fenoldopam (Corlopam) is used for what conditions?
used for severe hypertension and positive benefits on renal function due to increasing renal blood flow
potency of vasoactive adrenergics
very potent, quick-acting, injectable drugs
desglymidodrine is responsible for the primary action of midodrine which is what stimulation? causes what?
which is alpha1 adrenergic receptor stimulation -causes constriction of arterioles and veins resulting in peripheral vasoconstriction
how do the topical nasal decongestant adrenergics work?
work by stimulating alpha1-adrenergic receptors and have little or no effect on beta-adrenergic receptors
are the 3 endogenous hormones available in synthetic forms?
yep
