Sympathomimetics Flashcards
Main use of NE
As a potent vasoconstrictor to increase PVR and MAP
1st line vasopresser of choice to treat septic shock?
NE
NE dosage
0.01 to 3μg/kg/min OR 2 to 16μg/min
Why should NE be used cautiously in PTs with right ventricular failure?
They can’t tolerate the increase in pulmonary vascular resistance and/or increase in venous return
NE is a potent A1 agonist that produces intense arteriole and venous constriction in all vascular beds except_____?
Coranry arteries
Why should NE be used with caution in PTs with pulmonary HTN?
NE increases venous constriction in the lungs which further increases pulmonary HTN
NE effect on the following:
1) Afterload
2) SVR
3) DBP
4) MAP
5) SBP
Increases all of them
How can NE cause tissue hypoxia, metabolic acidosis, ischemia, and renal failure?
Excessive peripheral vasoconstriction and decreased perfusion of renal splanchnic beds can lead to hypo perfusion of organ and oliguria leading to renal failure.
How do you prevent renal failure in patients with excessive NE use?
Adequate fluid volume resuscitation
Which receptors do the following bind:
1) NE
2) EPI
3) Dopamine
4) Isoproterenol
5) Phenylephrine
6) Dobutamine
1) NE - A1, A2, B1
2) EPI - A1, A2, B1, B2
3) Dopamine - A1, A2, B1
4) Isoproterenol - B1, B2
5) Phenylephrine - A1
6) Dobutamine - A1, B1, B2
Why is NE never used just for its inotropic effect?
Modest B1 agonist - minimal effect is seen on HR due to activation of baroreflex response.
Effect of NE on coronary arteries?
NE (just like Epi) dilates the coronary arteries which increases coronary blood flow.
NE and hyperglycemia
NE may cause hyperglycemia but is unlikely as it is seen with use of EPI. It is only seen when large doses of NE are given.
Which anesthetic drugs are contraindicated with the use of Levophed, EPI and NE? Why?
Cyclopane and Halothane because they increase cardiac autonomic irritability causing VTACH or VFIB.
Why is use of NE cautioned in PTs taking MAOIs or antidepressants of the Triptyline or Imipramine type?
Can cause severe and prolonged HTN
How is NE extravasation treated?
Phentolamine mesylate (Regitine) 5 to 10 mg diluted in 10mL NaCl injected SQ into the area
MOA of Phentolamine mesylate (Regitine)
Phentolamine is a competitive, non-selective A1 and A2 antagonist
Dopamine role
- Precuror to NE
- Endogenous neurotransmitter in both the PNS and CNS
- Regulates movement in the CNS (i.e. Parkinsons)
Why can’t Dopamine be administered PO?
- It’s not lipid soluble (also can’t cross BBB to cause CNS effects.
- Metabolized by liver, kidney and plasma MAO and COMT enzymes to inactive metabolites
Why must Dopamine be given as a continuous infusion?
It is rapidly metabolized:
- onset of action = 5 mins
- plasma half-life = 2 mins
- duration of action < 10 mins
What would happen if Dopamine is given to a PT on an MAOI?
MAO enzymes metabolize Dopamine, if they are inhibited, the effects of dopamine will be increased.
2 things that inactivate Dopamine
- Alkaline solutions (use D5W instead)
- Light
Why is Dopamine unique among the catecholamines?
It simultaneously increases myocardial contractility, renal blood flow, glomerular filtration rate, sodium excretion and urine output.
Dopamine Doses?
- Dopamine dose - 0.5 to 3μg/kg/min
- Beta dose - 3 to 10μg/kg/min
- Alpha dose - 10 to 20μg/kg/min
Effects of Dopamine dose (0.5 to 3μg/kg/min) of dopamine
- ↑ Renal and splanchnic blood flow = diuresis
- ↓ SPB and DBP causing hypotension
- ↓ Preload and afterload
- ↑ Contractility
Renal Dose of Dopamine
- Same as Dopamine dose (0.5 to 3μg/kg/min)
- Promotes renal blood flow, diuresis and sodium excretion via dopamine1 and dopamine2 receptors
Which drugs antagonize Renal Dose of Dopamine?
Droperidol, haloperidol, and metoclopramide because the bind and block the dopamine2 receptors
Can you use the Renal dose of Dopamine to protect renal PTs?
No! although it has diuretic effects, no evidence show a ↓ of ARF with this dosing.
Hypoxemia effect on Renal Dose of Dopamine?
Attenuates of reduces effect
Effects of Beta dose (3 to 10μg/kg/min) of dopamine
- B1 cardiac effects predominate
- ↑ in NE release from synaptic nerve endings
- ↑ HR, CO, SBP and contractility
Why is Dopamine less reliable at ↑ CO in PTs with chronic cardiac failure?
Because the stores of neurotransmitters might be depleted. Dopamine can no longer stimulate release of NE because there is no more
Effects of Beta Dose of Dopamine on SVR
Usually little change is seen because B1 stimulation dominates and there is little A1 binding to cause vasoconstriction.
Cardiac effects of dopamine
Positive chrono trope, isotrope, dromotrope and lusitrope (rate of myocardial relaxation)
Effects of Alpha dose (10 to 20μg/kg/min) of dopamine
- Predominately stimulates A1 receptors
- ↑ Arterial and venous constriction
- ↑ Afterload and preload
- ↑ SVR, BP, MAP
Effect of High doses ( > 20 μg/kg/min) of Dopamine
- Vasoconstriction compromises circulation in limbs
- B1 cardiac effects get override
- Reversal of renal dilation results in antidiuresis
GI risks of Dopamine
- N and V
- Mesenteric ischemia leading to bacterial translocation and multiple organ dysfunction syndrome
Pulmonary/Ventilation risks of Dopamine
- Depression of ventilation: monitor ABGs and ensure they do not deteriorate
Endocrine risks of Dopamine
- Hyperglycemia possible
- ↓ prolactin, growth, thyroid and pituitary hormone secretion
- Prolonged infusions can deplete NE stores
- Halogenated hydrocarbon anesthetics ↑ of ventricular arrhythmias
- ↑intraocular pressure (be careful with glaucoma PTs)
Isoproterenol’s potency at Beta receptors
Isoproterenol is the most potent activator of all sympathomimetics at Beta receptors. It is a more potent activator at B1 and B2 than Epi and NE
How can Isoproterenol be given?
- Bolus IV injection followed by a continuous infusion
- IM
- SQ
- Intracardiac
- Aerosol
(T/F?) Isoproterenol must be protect from light?
True
Metabolization of Isoproterenol
Metabolized primarily by COMT in the liver
Clinical uses of Isoproterenol
- Heart blocks
- Cardiac arrest until electric shock or pacemaker available
- Bronchospasms during anesthesia (0.01 to 0.02mg diluted in 0.5 to 1 ml NaCl) given via IV
- Adjunct to fluid and electrolyte replacement
Isoproterenol B1 effects @ 1 to 10μg/min continuous IV
- ↑ HR, contractility, automaticity and myocardial oxygen consumption
Isoproterenol B2 effects @ 1 to 10μg/min continuous IV
- ↑ HR and contractility
- ↓ Preload and afterload, PVR, DBP, CO, renal blood flow, and MAP
(T/F?). All sympathomimetics has the potential to cause tachyarrhythmias?
True
Why should you NOT use Isoproterenol to treat septic shock patients?
Potent B2 agonists effects cause systemic vascular resistance to fall which ↓ DBP and impair coronary perfusion pressure.
Classify the sympathomimetic agents based on their chemical structure?
1) Endogenous catecholamines - Epi, NE, and Dopamine
2) Synthetic catecholamines - Isoproterenol and dobutamine
3) Direct Acting Synthetic non-catecholamines - Phenylephrine
4) Indirect Acting Synthetic non-catecholamines - Amphetmines
5) Mixed Acting Synthetic non-catecholamines - Ephedrine
Dobutamine recepter affinity
B1 > B2> A1
Dobutamine is NOT a pure B1 adrenergic agonist! elaborate!
It is a racemic mixture (+) and (-)
(+) is more potent at B1 and B2, and antagonist at A1
(-) is less potent at B1 and B2 and a potent A1 agonist
Dobutamine metabolism
- Rapidly metabolized by COMT
- Plasma half time = 2 mins
- Need a CI at 2.5 to 20μg/kg/min for therapeutic levels
- Onset of action 1 to 2 mins
- Steady state achieved in 10 mins
Why does Dopamine, EPI and Dobutamine have to be dissolved in D5W?
To avoid inactivation of the catecholamine that may occur in alkaline solution
Clinical use of Dobutamine
- Inotropic Support to increase CO
- ↓ Output from organic heart disease or surgical procedures
- Useful if HR and SVR are already increased
When is Dobutamine used with vasodilators
When you want to ↓ afterload in the presence of ↑ SVR
When is Dobutamine used with Dopamine
To ↑ CO and renal perfusion (dopamine)
Cardiovascular effect of Dobutamine
- Positive inotrope with mild effects on HR and BP
- Dose dependent ↑ in CO and SV without increase in HR
- HR ↑ only slightly if dose is < 20μg/kg/min
- LV filling is decreased
- ↓ in pulmonary vascular resistance
- Doesn’t cause release of endogenous NE
High doses ( > 10μg/kg/min) of Dobutamine
may cause tachyarrhythmias but are uncommon
Effects of Dobutamine dose of 2.5 to 20μg/kg/min
- ↓ Preload
- ↓ Afterload
- ↑ Contractility
- Hr or ↑
MOA of Ephedrine
Mixed Acting synthetic non-catecholamine
- Direct acting - ↑ NE release from nerve terminal (Majority of ephedrine effect is this indirect method)
- NonDirect Acting - Weak A1, A2, B1, B2 agonist
2 drugs the block the effect of Ephedrine? How?
Reserpine and Guanethidine - by blocking the re-uptake of NE, which Ephedrine relies on as a mostly non-direct acting synthetic noncatecholamine
Ephedrine characteristics
- Lipid soluble
- Potent CNS stimulant (can cross BBB)
- Can be taken PO, IM and IV
- Metabolized slowly by MAO but not acted on by COMT
- Excreted in urine (t 1/2 = 3 to 6 hrs)
- Can produce mydriasis
- Does not cause hyperglycemia like EPI
Clinical uses of Ephedrine
- Tx hypotension in parturients (10mg to 25mg IV)
- Tx of bronchial asthma
- Nasal decongestant (topical)
- Antiemetic (0.5mg/kg IM)
Cardiovascular effect of Ephedrine
- ↑ Afterload
- ↑ Contractility
- ↑ HR
Effects of PT taking clonidine before they get Ephedrine
Oral Clonidine is an A2 agonist (just like precedex) and will enhance the presser effects of ephedrine.
Ephedrine is subject to tachyphylaxis! Explain
It is an indirect act synthetic non-catecholamine that relies on the endogenous stores of NE, it will stop working after the stores are depleted
Which medical conditions presents with already depleted stores of neuronal catecholamines?
Sepsis and heart transplant - ephedrine won’t work in these PTs
Usual dose of Ephedrine
2.5 to 25μg/kg/min IV or 25 to 50mg IM
Why is Ephedrine NOT a good agent to use to restore BP in women about to give birth?
It lowers umbilical artery pH resulting in fetal acidosis at delivery
How long should you wait to administer Ephedrine after the PT has taken and MAOI?
14 days - Ephedrine is metabolized very slowly by MAOs
(T/F?) All non-catecholamines are less potent than catecholamines?
True
Can Phenylephrine activate Beta receptors?
Although considered and A1 agonist, it has some Beta effects at high doses.
Clinical use of Phenylephrine
- Hypotension associated with anesthetics (usual dose = 50 to 200μg IV)
- Hypotension associated with septic shock (dose = 0.5 to 8μg/kg/min)
- CI at 20 to 50μg/min to sustain BP during carotid endarterectomy
- To relieve drug-induced prism (persistent erection)
- Nasal decongestant (topical)
Phenylephrine Cardiovascular effects
- ↑ Afterload
- Contractility
- ↓ HR
Uterine Effects of Phenylephrine
- Uterine blood flow slightly decreased
- Higher umbilical pH and less fetal acidosis at delivery compared to ephedrine
Amphetamie characteristics
- ↑ NE, DA, and 5HT release from their storage sites in nerve terminals
- Mainly works in CNS
- Lipid soluble (crosses BBB)
- CNS stimulant
- Tachyphylaxis common
- Weak bases (overdose tx is to acidify urine)
Cardiovascular Effects of Amphetamines
- ↑ SBP and DBP
- ↓ HR
CNS effects of Amphetamines
- Apetite supression
- Enhances analgesia produced by opioids
- ↑ Respiration and depth of respiration
- Feeling awake and alert, agitated, dizzy and restless
“Selective B2-Adrenergic Agonists” MOA
- Selective B2 agonists - stimulates activity of adenyl cyclase and ↑ cAMP leading to bronchodilation and inhibition of release of mediators of hypersensitivity from mast cells.
- Relaxation of uterine smooth muscle
Clinical uses for Selective B2-Adrenergic Agonists
- Acute episodes of bronchospasms
- TX of asthma and COPD, chronic bronchitis and emphysema
- Prevent exercise-induced bronchospasm
Tocolytics (i.e. Ritodrine and Terbutaline) - stops premature labor
(T/F?) LABAs should never be used to treat an acute asthma attack or acute bronchospastic attack?
Only SABAs should be used for this
Selective B2-Adrenergic Agonists Adverse Effects
- Tremor
- Tachycardia
- Palpitations
- Nervousness and insomnia
- hyperglycemia and hypokalemia
- Arrhythmias and EKG changes
- Parodoxical bronchospasm
Interaction of Selective B2-Adrenergic Agonists with MAOIs and TCAs
Shouldn’t be administered within 2 weeks of each other because their actions potentiate each other
2 types of Selective B2-Adrenergic Agonists
1) SABAs (onset - < 5 mins, duration - 3-6 hrs)
2) LABAs (onset - < 5 mins, duration > 12 hrs)
* Has nothing to do with the onset of action, only the duration
Types of SABAs
- Albuterol
- Levalbuterol
- Respiclick
- Terbutaline
- Bitolterol
- Metproterenol
- Perbuterol
ALBert’s LEVel of RESpect TERminiate BITter METhodical PERsonalities
The only 2 inhaled SABAs currently available?
Albuterol and Levalbuterol
Characteristics of Albuterol
- Is a racemic mixture (R and S enantiomers) only the R enantiomer can do B2 agonism
- Available as PO tablet or syrup, MDI
Levalbuterol Characteristics
- The R enantiomer of albuterol
- Available as MDI or solution for inhalation
- Cause less tachycardia than Albuterol
Types of LABAs
- Salmeterol
- Formeterol
- Arformoterol
- Indacaterol
- Olodaterol
- Vilanterol
LABAs Characteristics
- Can cause death in asthma patients
- Available as single agent products or combined with inhaled corticosteroids or inhaled anticholinergics
Mybertiq (Mirabegron) MOA
Selective B3 Agonist for Tx of overactive bladder - relaxes detrusor muscle (can cause HTN)
Midodrine
- An A1 adrenergic agonist used as a vasopressor/antihypotensive to treat orthostatic hypotension.
- It is a prodrug
Northera (Droxidopa)
A synthetic amino acid precursor of NE used as an oral agent to treat neurogenic orthostatic hypotension
Northera (Droxidopa) adverse reaction
- Headache
- Nausea
- HTN
