Adrenergic Agonists Continued Flashcards
The non selective beta adrenergic agonist drug we will discuss in this class is a catecholeamine called Isoproterenol, what receptors does this drug stimulate?
Stimulates B1 and B2 adrenergic receptors
–action on alpha receptors is insignificant.
What are the cardiovascular effects of isoproterenol?
- -Intense stimulation of the heart (B1)
- -dilates arterioles of skeletal muscle (B2) = decrease in peripheral resistance
- -may increase systolic blood pressure slightly, but it greatly decreases mean arterial and diastolic blood pressure
What are the pulmonary effects of isoproterenol?
-Bronchodilation (B2(
What are additional effects of isoproterenol?
GI Smooth Muscle relaxation
-causes less hyperglycemia than epinephrine, in part because insulin secretion is stimulated by the strong beta adrenergic activation of pancreatic islet cells
What is isoproterenol used for?
–may be used in emergencies to stimulate heart rate in patients with bradycardia or heart block
What are the adverse effects of isoproterenol?
Similar to epinephrine
The next drug to discuss is a beta1 selective adrenergic agonist, dobutamine, explain what that means?
Racemic Mixture
- -consisting of the + and - isomers.
- -the observed clinical result is that of a selective beta1 agonist.
Since dobutamine is a beta1 selective adrenergic agonist, what effect does it have?
Greater inotropic (contraction) than chronotropic (heart rate) on the heart. --heart rate does increase modestly but contractility and cardiac output increase more.
What is dobutamine used for?
Increase cardiac output in the management of acute heart failure
Management of cardiogenic shock
Next drug is a beta2 selective adrenergic agonist, the first two are terbutaline and albuterol, what is the primary use of these?
- -short acting beta2 agonist used primarily as bronchodilators and administered by an inhaler
- -terbutaline is also used to reduce uterine contractions in premature labor
Next drug that is a beta2 selective adrenergic agonist is salmeterol and formoterol, what is the use for these drugs?
Long acting bronchodilators
- -increased duration of action as a result of high lipid solubility
- -slow onset of action after inhalation (not suitable for relief of bronchospasms)
In general what are some adverse effects of B2 agonists?
Excessive activation of b2 receptors
- -tremor is a relatively common effect
- -restlessness, apprehension and anxiety
- -tachycardia when the drug is systemically administered
The next set of drugs is alpha 1 selective adrenergic agonists. What is the general use of these drugs?
—Alpha receptors in the vascular smooth muscle results in an increase in peripheral resistance and thus blood pressure is maintained or elevated
The main alpha 1 selective adrenergic agonist is phenylephrine, what is the use of this drug?
Selective alpha 1 receptor agoniset
- -vasoconstrictor: raises both systolic and diastolic pressures
- -it has no direct effect on the heart, but induces reflex bradycardia
What are some of the uses of phenylephrine?
- Nasal decongestant (decrease resistance to airflow by decreasing the volume of the nasal mucosa)
- -Mydriatic
- -Increasing blood pressure in hypotension
- -used to increase blood pressure and thus terminate episodes of supraventricular tachycardia
The next three drugs to discuss are the alpha 2 selective adrenergic agonists, the first drug is Clonidine, what is the use of this drug?
Partial alpha 2 agonist
–centrally acting antihypertensive agent: active alpha 2 adrenoreceptors in the cardiovascular control centers of the CNS suppressing outflow of sympathetic nervous system activity.
IV infusion of clonidine causes what?
An acute rise in blood pressure, because of activation of postsynaptic alpha 2 adrenoreceptors in vascular smooth muscle (This response is not seen orally)
–this transient vasoconstriction is followed by a more prolonged hypotensive response which results from decreased sympathetic outflow from the CNS
What are adverse effects of clonidine?
Lethargy
Sedation
Xerostomia
The second alpha 2 selective adrenergic agonist is methyldopa, what is the use of this drug?
- -Antihypertensive agent
- taken up by noradrenergic neurons and metabolized to alpha-methylnorepinephrine
- alpha methylnorepinephrine is thought to activate central alpha 2 adrenoceptors and lower blood pressure in a manner similar to that of clonidine
- methyldopa diminishes adrenergic outflow from the CNS, leading to reduced peripheral vascular resistance and decreased blood pressure
Methyldopa is the drug of choice for what condition?
Tx of hypertension during pregnancy due to its effectiveness and safety for both mother and fetus
What are the adverse effects of methyldopa?
Sedation
Menta lassitude
Impaired mental concentration
dry mouth
The last alpha 2 selective adrenergic agonist is brimonidine, what is the use of this drug?
Highly selective alpha 2 agonist administered orally to lower intraocular pressure in glaucoma
–reduces aqueous humor production and increases uveoscleral outflow
The next set of drugs are the indirect acting adrenergic agonists. The first three drugs in this category are your releasing agents, what does releasing agent mean?
–cause release of NE and E from the storage vesicles but blocks up take more and more from the synapse
The first releasing agent drug is amphetamine, what does this drug do?
- displaces endogenous catecholamines from storage vesicles
- -increase blood pressure by alpha 1 agonist action on vasculature as well as Beta1 stimulatory effects on the heart.
What are the behavioral effects of amphetamine?
Central stimulatory action
–increased alertness, decreased fatigue, depressed appetite and insomnia
what are the adverse effects of amphetamine?
Fatigue
Depression
–all following the period of central stimulation
What is the use of amphetamine?
Tx of ADHD
The next releasing agent is methylphenidate, what is the use of this drug?
Used to treat ADHD and narcolepsy
The last releasing agent is tyramine, what is the use of this drug?
Not used clinically
- -by product of tyrosine metabolism
- -normally oxidized by MAO
- -if the patient is taking MAO inhibitors it can precipitate vasopressor episodes
The next three drugs are the uptake inhibitors. The first drug to discuss is cocaine, what are the actions of this drug?
Blocks reuptake of the monoamines in the presynaptic terminal
- -blocks the dopamine transporter (DAT)
- -high contractions block serotonin transporter (SERT) and norepinephrine transporter (NET)
- -both these blocks lead to accumulation of the monoamines in the synaptic spaces resulting in potentiation and prolongation of their central and peripheral action
What are the sympathetic effects of cocaine?
Tachycardia
Hypertension
Pupillary dilation
Peripheral vasoconstriction
Cocaine produces an intense euphoria, what is the mechanism for this?
Inhibition of dopamine reuptake into the neurons of the pleasure centers of the brain
What is the mechanism of a local anesthetic use of cocaine?
Blocks voltage activated sodium channels
What is the main use for cocaine?
topical anesthesia of the upper respiratory tract
The next uptake inhibitor is Atomoxetine, what is the action and use of this drug?
Action: selective inhibitor of the NET
Use: treatment of ADHD
The last uptake inhibitor is Modafinil, what is the action and use of this drug?
Action: inhibits norepinephrine and dopamine transporters, increases synaptic concentrations of norepinephrine, dopamine, serotonin and glutamate and decreases GABA levels
use: tx of narcolepsy
The last category of drugs in the adrenergic agonists are the mixed acting drugs, what is their mechanism of action?
induce the release of norepinephrine and activate adrenergic receptors
There are two drugs for mixed acting adrenergic agonists the first is ephedrine, what is the mechanism of this drug?
Activates alpha and beta receptors, and releases norepinephrine from nerve ending
- -long duration of action
- -excellent absorption orally and does penetrate the CNS
What are the actions of ephedrine?
- Increases systolic and diastolic blood pressure by vasoconstriction and cardiac stimulation
- Causes bronchodilation
- Produces mild stimulation of CNS: increased alertness, decreases fatigue, and prevents sleep and improves athletic performance
- Ephedrine + anticholinesterase = myasthenia gravis effects
What are the uses for ephedrine?
1 Pressor agent, particularly during spinal anesthesia when hypotension frequently occurs
- Tx of allergic disorders such as bronchial asthma
- tx myasthenia gravis
The second mixed acting adrenergic agonist is pseduoephedrine, what is the use of this drug?
Component of many nasal decongestants
–found in combination with a H1 histamine antagonist
