RCP 400
Respiratory Therapy
Pharmacology
Notes Unit #6
Sympathomimetic
Drugs
Sympathomimetic Action
Sympathomimetic
bronchodilator drugs bind with the adrenergic Beta-2 receptors just like
norepinephrine would normally do. When
they bind with the receptor, the enzyme adenylyl
cyclase is activated within the cell. Adenylyl cyclase in turn converts adenosine triphosphate
(ATP) into 3’,5’, cyclic-adenosine monophosphate
(c-AMP). The concentration of c-AMP
inside the bronchial smooth muscle cell when compared to the intracellular
concentration of c-GMP will determine the contraction or relaxation of the
muscle cell. As the concentration of
c-AMP in the cell rises with the binding of sympathomimetic drugs to the beta-2
receptors, the muscles will relax and the airway will dilate.
Sympathomimetic
drugs have the following beneficial effects.
Bronchodilation
Vasoconstriction
Inhibit
release of bronchoconstrictive mediators
Improved
mucocilliary clearance
Routes of Administration
Oral administration of
sympathomimetics has become possible with the introduction of newer,
non-catecholamine drugs. Sulfatase enzymes in the digestive tract inactivate
catecholamines, so they were not effective if administered orally. The oral route has the advantage of being the
most convenient and least expensive route for the administration of any type of
drug. It also has the disadvantage of
significant side effects for drugs administered by the route. Since drugs need to be absorbed systemically
for transport to the desired site of action, the drug also reaches the same
concentration at sites of actions that are not desired. Several of the sympathomimetics are available
in tablet and syrup forms that are taken by adults and children
respectively. For maintenance therapy,
the oral route can be an important adjunct to inhalation. Oral administration of these drugs has no
place in the management or treatment of acute bronchoconstriction.
Subcutaneous
injection
of sympathomimetic drugs is important in the management of acute
bronchoconstriction. When a person is
admitted to the emergency room with acute bronchoconstriction, one of the first
lines of treatment will be the subcutaneous injection of epinephrine or one of
the more specific Beta-2 stimulators like terbutaline. This route of administration will generally
be with a mix of water and lipid soluble forms of the drug. The aqueous drug will be absorbed quickly and
have immediate benefit of relaxation of bronchiolar walls. The lipid portion of the solution will be
absorbed slowly benefit the person in several hours after they have left the
emergency room and decrease the chance of a return visit.
Intravenous administration is generally
limited to the treatment of anaphylaxis.
In all other cases, the beneficial effects of the drug would not offset
the occurrence of side effects from this route.
Inhalation of the drug is generally almost a quick of a way to get the
drug into the lings of the person as intravenous would be.
Inhalation of these drugs is the
preferred route for administration as it has a quick onset of action and since
the drug is delivered directly to the desired site of action, the systemic
distribution of the drug will be minimized and the production of side effects will
be diminished. Inhalation is a
relatively convenient route when using MDI’s and DPI’s and somewhat complicated when using small volume
nebulizers.
Delivery Devices
Respiratory
therapists most often administer medications by small volume nebulizer. Patients often feel they receive greater
benefit from drugs administered from this device. The reason they benefit more is they receive
more medication from the SVN than the MDI.
The typical dose of albuterol administered by SVN is 2.5 mg. At best, about 20% of this dose is retained
in the small airways of the lung. This
means that 0.5 mg of the drug is retained in the airways. When a person used an MDI for administration
of albuterol, the normal dose is two inhalations of the drug. Each activation of the
MDI dispenses 90 mcg (0.09 mg) of the drug.
Two activations administer 0.18 mg of the drug. Again not all of the
drug dispensed is retained in the peripheral airways, so simple math indicates
that a person would need at least 6 activations of the MDI to obtain a similar
amount of drug into the distal airways.
Earlier this term, we spent considerable time discussing ways to improve
the efficiency of the SVN.
HEART
(miniHEART) nebulizers are used in two situations. They are used for the administration of
medications by continuous aerosol and for administration of drugs in-line with
mechanical ventilation when the flow added from a SVN would create too much
change in tidal volume and oxygen concentration. The HEART is used when a large volume of
medication is mixed to be placed in the nebulizer and administered over a
period of several hours for continuous nebulization
of a medication. If the miniHEART is used, it is generally attached to an
intravenous infusion pump to continuously add medication to the nebulizer over
the period of time the medication is to be administered.
When
a typical SVN is used to administer medication in-line with a mechanical
ventilation circuit, the flowrate needed to power the nebulizer will have
significant impacts on the delivered volume in volume cycled modes of
ventilation, the ability of the ventilator to recognize and respond to patient
inspiratory effort and the concentration of oxygen delivered to the
patient. The ideal situation when using
a SVN in-line is to power the nebulizer with a portion of the volume being
delivered to the person by the ventilator.
This is possible with some ventilators like the
1 L x 1000 ml X 1 min = 16.6667
ml / sec
min L 60 sec
At
a flow of 9 LPM this would add 150 ml of tidal volume for each second of
inspiratory time.
Metered
Dose Inhalers
are a portable, convenient device for administration of medications directly to
the airways for those persons who can coordinate their inhalation to the
dispensing of the drug from the device.
As discussed earlier this term, the use of a spacer can aid in the
maximal inhalation of drug from the device.
For individuals whose health care is covered by Medicare, 80% of the
cost of equipment and medications is paid when they use a SVN. If they use MDI’s, none
of the cost is covered as there is currently no prescription drug benefit under
Medicare program. The federal government
has tried to move most persons receiving inhaled medications
from SVN’s to MDI’s
to decrease their expenses for the drugs.
As
Drug companies make changes to reduce the release of chlorofluorocarbons into
the atmosphere, one of the devices that replace MDI’s
are the Dry Powder Inhalers (DPI’s). This device is similar in dosages and
portability to MDI’s.
Indications for Sympathomimetic Bronchodilators
Treatment of bronchoconstriction or bronchospasm from any cause is the reason to administer these drugs. The person may have asthma, COPD, hydrocarbon ingestion or any other cause of constriction of the peripheral airways. This condition is documented by measuring decreased forced expiratory airflows, presence of diffuse wheezing, increased airway resistance or clinical observation of signs of respiratory distress. If a person does not have documented or suspected increases in airway resistance caused by bronchoconstriction, there is no reason they should receive sympathomimetic bronchodilator drugs.
Side
Effects to Sympathomimetic Bronchodilators
Alpha
receptor stimulation
Increased blood pressure
Decreased oxygen delivery
Beta-1
receptor stimulation –
Tachycardia
Palpitation
Arrhythmia – Increased myocardial
oxygen consumption
Dizziness
Headache
Beta-2
receptor stimulation –
Tremor (skeletal muscle receptor)
Nausea / vomiting
Nervousness
Anxiety
Insomnia
Hypotension (peripheral vasodilation)
Hypokalemia
(activation of Na – K pump)
Hypoxemia – Worsened r
Increased blood glucose and insulin levels
Independent
of receptor stimulation –
Bronchoconstriction due to additives
or propellants
Tolerance
Tachyphylaxis
Precautions to the administration of Sympathomimetic Bronchodilators
Solutions will degrade with
exposure to heat, light and oxygen – color change or precipitate indicate these
changes
Bronchoconstriction possible
with any inhaled substance
Contraindications to the administration of Sympathomimetic
Bronchodilators
Heart rate greater than 120 –140 / min
Sensitivity to drug or additives or propellants
Lack of response to administration to the drug
Chemical Structure and Effects of the Drug
The
earliest drugs used to treat bronchoconstriction were catecholamines. The structure of these drugs contains a
benzene ring (6 carbons in a ring shaped structure) with hydroxide groups
attached to the 3rd and 4th carbon atoms and a side chain
containing a nitrogen atom.
OH
H C
C
O OH H
H
C C -
C – N - H
H H
C
C
Catechol nucleus + Amine side chain =
catecholamine
Catecholamines
have two distinct limitations for use.
They have short durations of action due to their similarity to
norepinephrine and they are not effective if administered orally. Sulfatase in the GI
tract inactivates these drugs before they can be absorbed.
To
increase duration of action, the attachments to the benzene ring may be changed
to prevent COMT from degrading the molecule.
The resorcinol drugs have hydroxyl groups on the 3rd and 5th
carbon atoms and therefore the molecule is not affected by COMT. The salignen group
replaces the hydroxyl group on the 3rd carbon atom with methoxyl
group (-OCH3) wile leaving a hydroxyl on the 4th carbon
atom. Both these changes increase the
duration of action by several times over the catecholamines.
Specificity of the drug molecules for the Beta-2 receptor in increased
by adding more carbon atoms (bulk) to the side chain of the molecule. If one compares albuterol to norepinephrine,
one sees the addition of 4 additional carbon atoms. Norepinephrine stimulates alpha, beta-1 and
beta-2 receptors equally well and albuterol is a specific beta-2 stimulator.
Albuterol sulfate
1. Brand names - Proventilâ, Ventolinâ
2. Albuterol is a relatively specific Beta-2 agonist for the autonomic nervous system. Most patients receiving albuterol experience Bronchodilation without cardiovascular side effects. Albuterol binds with the Beta-2 receptor and activates adenylyl cyclase to convert adenosine triphosphate (ATP) to 3’,5’ cyclic-adenosine monophosphate (c-AMP). The cyclic adenosine monophosphate directly results in relaxation of bronchial smooth muscle and the dilation of the airways surrounded by this muscle. Albuterol is a racemic mixture of two isomers of the molecule. These are referred to as the S and R isomers. The R isomer is the one that accomplishes bronchorelaxation.
3. Albuterol is a specific Beta-s receptor stimulator.
4. Albuterol
can be administered by inhalation in the form of a solution for nebulization, a metered dose inhaler and as a dry powder
inhaler. In response to the concern for
chlorofluorocarbon damage to the ozone layer of the atmosphere, one
5. 0.5% liquid for inhalation. Adult dose 2.5 mg (0.5 ml) diluted to 3.0 – 5.0 ml total volume. 0.083% solution (3.0 ml) unit dose, 2.0 mg and 4.0 mg tablets. Adult dose 2.0 – 4.0 mg T.I.D. to Q 4 hour. 4.0 mg and 8.0 mg sustained release tablets. Adult dose 4.0 – 8.0 mg B.I.D. (Q 12 hour). 200.0 mcg (0.2mg) capsules for Rotahaler DPI. Adult dose 200.0 – 400.0 mcg (0.2 – 0.4 mg) Q 4 – 6 hour.
6. See #5
7. Hypersensitivity, tremor, anxiety, nervousness, restlessness, convulsions, weakness, headache, hallucinations, palpitation, hypertension, Hypotension, bradycardia, reflex tachycardia, blurred vision, papillary dilation, nausea, vomiting, muscle cramps, hoarseness
LEVALBUTEROL
1. Brand Name - Xopenexâ
2. Mode of action – how the drug causes the effect it does on the
body
There are two clinically significant isomers in
racemic albuterol. The R and active isomer and an S isomer. Theory has it that the S
isomer is not an inert isomer a, but may have pro-inflammatory effects. By inert, I am referring to a substance which will not chemically react with
anything under normal circumstances. So the makers of Xopenexâ decided to remove the S isomer from racemic
albuterol leaving the R isomer which is the one that confers all the
bronchodilator effects. Thereby making it a “so called” pure form of albuterol.
Basically, the mode of action is the same as racemic albuterol. Activation of the beta2 adrenergic receptors on airway smooth muscle leads to the activation of cyclic AMP activating the protein kinase A which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation.
3. The basic classification of the drug – this may be adrenergic
receptors stimulated or some classification of its action (include the desired
effect of the drug)
Levalbuterol is a Bronchodilator, adrenergic. The desired
effect of course is to dilate the airways.
4. Routes and forms for administration.
inhalation and solution
5. Forms and strengths in which the drug is available.
For inhalation solution dosage form: This medicine is
used in a nebulizer and is taken by inhalation over a period of five to fifteen
minutes. The usual dose is 0.63 milligrams (mg) to 1.25 mg three times a day,
every six to eight hours. Children up to 12 years of age the dose must be
determined by the physician. But there is suggestion from the company that children 6 – 11 years of
age can take 0.31mg TID by neb.
6. Milligram dosage administered to adults.
see question 5
7. Side effects the drug may cause.
More common: Fast heartbeat Less common or rare: Chest pain or
tightness; dizziness; high
or low blood pressure; hives; light-headedness; shortness of
breath; troubled breathing; wheezing
8. Contraindications to administration of the drug
The only one I found is for those who are hypersensitive to Xopenex, albuterol, or HCL
9. Duration of action of the drug along with the minimum time
between doses and maximum days of use if that is indicated... 6 to 8 hours. Can
take the rest of their lives but usually on a PRN basis
I talked to
Salmeterol
1.
Generic Name: salmeterol xinafoate
Brand Name: Sereventâ
2.
Mode of action: Long-acting beta2-adrenoreceptor agonist and
an
analog (similar chemical structure
and action) of albuterol. Stimulation of
beta2-adrenoreceptors relaxes bronchospasm and increases ciliary motility, thus facilitating expectoration. Inhibits the release of
mediators (i.e. histamine) from mast cells, macrophages, and eosinophils.
3.
The basic classification of the drug: autonomic nervous system agent;
beta-adrenergic agonist
(sympathomimetic); bronchodilator; respiratory smooth muscle relaxant
4.
Routes and forms for
administration: inhalation via aerosol or dry powder
5.
Forms and strengths in which the drug is available: 25mcg aerosol;
50mcg powder Diskusâ for inhalation
6.
Milligram dosage administered to adults: 0.042mg (2 inhalations of
aerosol) or 0.050mg (1 powder diskus) b.i.d. approximately 12 hours apart
7.
Side effects the drug may cause: dizziness, headache, tremor,
palpitations, sinus tachycardia, respiratory arrest (rare), rash, tolerance
(tachyphylaxis)
8.
Contraindications to administration of the drug: hypersensitivity to
salmeterol; lactation
9.
Duration of action of the drug: up to 12 hours
Minimum time between doses: 12 hours
Maximum days of use: indefinite; used as maintenance
therapy; monitor liver enzymes periodically with long-term therapy
Metaproterehol Sulfate
Brand
Name: Alupentâ, Metaprelâ
Mode
of action Beta-adrenergic
Classification: Autonomic
Nervous System agent
Desired
effect: Bronchodilator
Route,
Form, & Adult dose Oral 20 mg q6-8h MDI 2-3 puffs q 3-4h wait 10 min
between each puff maximum amount is 12 puffs a day Aerosol 5-10 inhalations of
undiluted 5% solution IPPB 2.5mL of 0.4-0.6% q4-6h
Side
Effects Nervousness,
weakness, drowsiness, tremor, headache, fatigue, tachycardia, hypertension,
cardiac arrest palpitation, nausea, vomiting, bad taste, muscle cramps, throat
irritation, cough, exacerbation of asthma, difficulty in micturition
(urination)
Interactions epinephrine, other sympathomimetic
bronchodilators may compound effects with metaproterenol,
Duration: inhaled 1-5h
oral 4h
Onset inhaled 1
minute,
Peak is one hour all
routes
Terbutaline Sulfate (ter-byoo'te-leen)
Brethaireâ, Brethineâ, Bricanylâ
Classifications: autonomic
nervous system agent; Beta - adrenergic agonist; Bronchodilator
Pregnancy Category: B
Availability: 2.5 mg, 5 mg
tablets; 0.2% aerosol; 1 mg/ml injection
Actions: Synthetic
adrenergic stimulant with selective beta2- and negligible beta1-agonist
(cardiac) activity. Exerts preferential effect on beta2 receptors in bronchial
smooth muscles, inhibits histamine release from mast cells, and increases ciliary motility.
Therapeutic effects:
Relieves bronchospasm in chronic obstructive pulmonary disease(
COPD) and significantly increases vital capacity. Promotes
relaxation of vascular smooth muscle, contraction of GI and urinary sphincters,
increase in retin, pancreatic beta-cell secretion,
and serum HDL-cholesterol concentration. Increases uterine relaxation
(thereby preventing or abolishing high intrauterine pressure)
Uses: Orally or subcutanously as a bronchodilator in bronchial asthma and
for reversible airway obstruction associated with bronchitis and emphysema.
Unlabeled uses: To delay
delivery in preterm labor.
Contraindications: Known
hypersensitivity to sympathomimetic amines; severe hypertension and coronary
artery disease; tachycardia with digitalis intoxication; within 14d of
Cautious use: angina,
stroke, hypertension, diabetes mellitus, thyrotoxicoses.
history of seizure disorders, cardiac arrhythmias,
older adults, kidney and liver dysfunction.
Route and Dosage:
adult-bronchodilator-PO 2.5 mg t.i.d. at 6 hr.
intervals (max: 15 mg/d) SC 0.25 mg q15-30 min up to 0.5 mg in 4 h inhaled 2
inhalations separated by 60 s q4-6h
adult-premature labor-PO 2.5 mg q4-6h
Administration: oral- give
with fluid of pts. choice, tablets may be
crushed. Be certain about recommended
doses,
Store all forms at 15o-30oC
(59*-86* F); protects from light. do not freeze.
Adverse effects (>-1%)CNS: nervousness, tremor, headache, lightheadness, drowsiness, fatigue, seizures, CV-tachycardia, hypotension, palpation, maternal and fetal tachycardia. GI-nausea, vomiting. Body as a whole: sweating, muscle cramps
Interactions: Drug-
Epinephrine-other sympathomimetic bronchodilators may add to effects,
Pharmacokinetics:
absorption- 33%-50% absorbed into GI tract. Onset: 30 min.
Bitolterol
Generic Name - Tornalateâ
Mode of Action - Relaxes bronchial smooth muscle and inhibits the release of
mediators of immediate hypersensitivity from lung tissue cells. Cardiovascular
effects appear to be similar to or less those produced by isoproterenol.
Classification - Autonomic nervous system agent, Beta-Adrenergic Agonist
(Sympathomimetic) Bronchodilator.
Routes and Forms - Inhalation (MDI)
Forms and Strengths - Aerosol
Milligram Dosage for Adults - 2 inhalations spaced 1 - 3 minutes apart every 6
- 8 hours.
Side Effects - Tremors, nervousness, headache, dizziness, light- headedness,
insomnia.
Contraindications - Safety during pregnancy, Lactation, children less than 12
years old has not been established.
Duration - Up to 8 Hours
Onset 3-5 Minutes
Peak 0.5 - 2 Hours
Half-Life 3 Hours
Pirbuterol
Brand:
Maxairâ
Class:
Autonomic Nervous System agent, beta-adrenergic agonist (sympathomimetic);
bronchodilator
Mode
of Action: exhibits preferential effect on beta 2-adrenergic receptors,
lengthened duration of action, relaxes bronchospasm, increases ciliary motion. Activates adenyl
cyclase, enzyme that catalyzes conversion of ATP to cyclic adenosine
monophosphate (cAMP)
Routes:
inhalation
Strengths:
0.2 mg MDI
Side
effects: tremors, nervousness, headache, dizziness, palpitations, tachycardia,
dry mouth, nausea, glossitis, abdominal pain, cramps,
anorexia, diarrhea, stomatitis, cough, tolerance
Contraindications:
hypersensitivity to pirbuterol, or any other
adrenergic agent like epinephrine, albuterol or isoproterenol, pregnancy,
lactation, children<12 years
Cautious
Use: heart disease; irregular heartbeat; hypertension; hx
of stroke or seizures; diabetes; Parkinson's disease; thyroid disease; prostate
disease; glaucoma
Duration:
3-4 hours
Half-Life:
2-3 hours
Onset:
5 minutes
Peak:
30 minutes
Adult
Dose: 2 inhalations (0.4 mg) every 6 hours
Maximum:
12 inhalations per day
Formoterol
Formoterol is also known as Foradilâ
which belongs to the family of medicines knows as, Beta2-agonist. It is used to help treat asthma and prevention of exercise induced asthma. The drugs classifications are autonomic nervous system agent, sympathomimetic, bronchodilators. Formoterol is also used on patients who have COPD and bronchitis. The availability of this drug is 12mcg by oral inhalation every 12 hours. The action of this drug stimulates the production of intracellular cyclic, adenosine monophosphate which causes relaxation of the bronchial smooth muscles. Also inhibits release of mediators of immediate hypersensitivity from the mast cells in the lungs. Formoterol acts locally in the lungs as a bronchodilator, prevents bronchoconstriction. Some contraindication is hypersensitivity to formoterol significantly worsening and actually deteriorating asthma; sever asthmatic attacks, paradoxical bronchospasm. If you have cardiovascular disorders, convulsion disorders, heightened responsiveness to sympathomimetic amines or diabetes you should use caution when taking this drug. Some common side effects that are brought on by this drug are, chills, flu like symptoms, cough or hoarseness, fever, sneezing, sore throat, body aches, chest pain or discomfort, congestion, difficulty breathing, headache, tremors, dizziness, insomnia and wheezing. It is rapidly absorbed into plasma after oral inhalation, onset is 1-3 min, and peak is 1-3 hrs. This medicine should be taking w/ other corticosteroids.
Epinephrine
Brand Name: Adrenalin HCl
Classifications: Autonomic Nervous system agent; Alpha and Beta
Adrenergic Agonist; Bronchodilator
Acts
directly on both alpha and beta receptors; the most potent activator of alpha
receptors. Strengthens myocardial contraction, increases systolic but may
decrease diastolic blood pressure; increases cardiac rate and cardiac output.
Effects: Constricts bronchial arterioles and inhibits histamine release, thus
reducing congestion and edema and increasing tidal volume and vital capacity.
Relaxes uterine smooth musculature and inhibits uterine contractions.
Administration: Inhalation, Instillation, Ophthalmic,
Subcutaneous, and Intravenous
Route and Dosage: Anaphylaxis~ Adult~ SC: 0.1-0.5 ml of 1:1000 q
10-15 min prn; IV: 0.1-0.25 ml of 1:1000 Q 10-15 min
Neonate~
Cardiac
Arrest~ Adult~ IV: 0.1-1 mg q 5
min as needed
Asthma~
Adult~
SC: 0.1-0.5 ml of 1:1000 q 20 min-4 h; Inhalation: 1 Inhalation q 4 h prn
Glaucoma~
Adult/Child~ Instillation: 1-2
drops 0.25-2% solution b.i.d.
Nasal
Hemostasis~ Adult/Child~
Instillation: 1-2 drops 0.1% opthalmic or 0.1% nasal
solution
Topical
Hemostasis~ Adult/Child~
Topical: 1:50,000-1:1000 applied topically or
1:500,000-1:50,000 mixed with a local anesthetic
Side Effects: Nasal burning or stinging, burning of the eyes,
nervousness, tremors, headache, dizziness, dyspnea, anxiety, sleeplessness,
weakness, nausea, vomiting, primordial pain, palpitations, hypertension,
bronchial and pulmonary edema, necrosis with repeated infections, and altered state
of perception and thought.
Contraindications: Hypersensitivity to sympathomimetic amines,
narrow-angle glaucoma, hemorrhage, traumatic or cardiogenic shock, cardiac
dilation, cerebral arteriosclerosis, coronary insufficiency, arrhythmias,
organic heart of brain disease, during second stage of labor, for local
anesthetic of fingers, toes, ears, nose, and genitalia.
Duration of action: Onset~3
to 5 minute; Peak~20minutes; Duration~1-3 hours
Racemic
Epinephrine
The brand name of racemic epinephrine is Miro-nefrinâ and Asthmanefrinâ,
The onset time for this drug is three to
five minutes, its peak time is in five to twenty minutes, and the duration is a
half to two hours.
It’s used either by inhaled aerosol or
direct lung instillation for it’s alpha-adrenergic vasoconstricting
effect, to reduce airway swelling after extubation or during epiglottis, croup,
or bronchiolitis or to control airway bleeding during
endoscopy.
Racemic epinephrine is most commonly given
by a small volume jet nebulizer using a 2.25% solution of 0.25-0.5 ml
(5.63-11.25 mg) qid for an adult.
Racemic epinephrine has a methyl group
attached to the terminal amine group and it activates alpha receptors. This
drug may constrict the bronchial arterioles and inhibit histamine release and
reduce congestion, edema, increase tidal volume and vital capacity. It also
imitates all the actions of the sympathetic nervous system except on arteries
of the face and sweat glands.
The uses of racemic epinephrine is the
temporary relief of bronchospasm, acute asthmatic attack, mucosal congestion,
hypersensitivity, restore cardiac rhythm in cardiac arrest, prolongs action and
delays systemic absorption of local and intraspinal
anesthetics.
The population that should use racemic
epinephrine in caution are older patients, patients
that have hypertension, diabetes mellitus,
Contraindications of racemic epinephrine
include pregnancy, cardiac dilation, coronary insufficiency, arrhythmias,
organic heart and brain disease, and local anesthesia.
Racemic epinephrine is available in many
forms. Some of these forms include:
1:100, 1:1,000, 2.25% solutions for
inhalation (MDI).
Also 0.35 mg, 0.2 mg are available in a spray form.
1:10,000, 1:100,000 concentrations are available in an injection form, and 0.1%
is available in a nasal solution.
Isoproterenol
Brand Names: Isuprel,
Mode of Action:
Synthetic sympathomimetic amine. Acts directly on beta21 and 2-aderergic receptors with little or no
effect on alpha-adrenoceptors. Drug induced stimulation of beta1-adrenergic
receptors results in increased cardiac output and cardiac work by increasing
strength of contraction and, to a slight degree, rate of contraction of the
heart. Stimulation of
beta2-adrenoceptors relaxes bronchospasm and by increasing ciliary
motion, facilitates expectoration of pulmonary secretions. May dilate trachea and main
bronchi past the resting diameter.
Classification:
(In 1940, isoproterenol was reported as a broncholytic
agent.) Beta-adrenergic agonist (sympathomimetic); Bronchodilator; autonomic
nervous system agent;
(relaxes airway smooth muscle)
Routes and Forms of Administration: SVN:
0.5% solution (1:200), 0.25-0.5 ml (1.25-2.5mg) MDI:
qid 103 mcg/puff, 2 puffs qid; IPPB:
0.5ml of 0.5% solution diluted to 2-2.5ml with water or saline over 10-20min
up to 5 times/day; IV: (adult) 0.02-0.06mg bolus, followed by
5mcg/min infusion, (child) 2.5mcg/min or
0.1mcg/kg/min by continuous infusion.
Available Strengths:
0.5%, 1% solution for inhalation; 103mcg aerosol; 0.2mg/ml, 0.02mg/ml
for injection.
Normal Adult
Dose: MDI: 103microg/puff, 2 puffs qid;
IV: 0.01-0.02mg prn or 0.02-0.06mg
bolus followed by 5mcg/min infusion;
SVN: 0.5% solution (1:200),
0.25-0.5ml (1.25-2.5mg)
Side Effects:
headache, mild tremors, nervousness, anxiety, insomnia, excitement,
fatigue, flushing, palpitations, tachycardia, unstable BP, anginal
pain, ventricular arrhythmias, swelling of parotids (seen in prolonged use),
bad taste, buccal ulcerations, nausea, severe
prolonged asthma attack, sweating, bronchial irritation, edema.
Contraindications:
preexisting cardiac arrhythmias associated with tachycardia; tachycardia
caused by digitalis intoxication, central hyper excitability, carcinogenic
shock secondary to coronary artery occlusion an MI; and simultaneous administration
with epinephrine.
Duration of Action: Onset- 2-5min; Peak Effect- 20 min; Duration- 1.5-2 hours. It is classified as an ultra-short-acting drug (< 3hrs).
Isoetherine
Hydrochloride
Bronkosolâ
Autonomic
nervous system agent, Beta-adrenergic agonist, sympathomimetic, Bronchodilator
Desired
effect is bronchodilation.
Synthetic sympathomimeticstimulant with
relatively rapid onset, and long duration. Has
selective affinity for beta2-adreno-receptors on bronchioles.
Given
by inhalation, metered-dose-inhaler, nebulizer
Nebulizer-0.5ml
1% solution diluted 1:3 with ns, 2-4ml 0.125% solution, 2ml
0.25% solution q4 up to 5 times a day.
MDI-1-2
inhalations q4 up to 5 times a day.
Tachycardia,
palpitations, changes in blood pressure, nausea, vomiting, headache, anxiety,
tension, restlessness, insomnia, tremors, cough, bronchial irritation, tachyphylaxis.
Allergies to sulfites, monitor older adults, cardiac arrythmias, pregnancy, trycyclic
antidepressants.
Immediate onset, peak effect in 5-15min. Lasts up to 4 hrs.
Precipitation of Bronchoconstriction
Tachyphylaxis
Allergic
reaction to medication, preservative, propellant
Irritation
from inhaled substances
Some
sympathomimetics are biotransformed into weak beta
blocking chemicals
Hypoxemia Caused by Sympathomimetics
Pulmonary
vasodilation when there is not similar
Bronchodilation
Precipitation
of bronchoconstriction
Unit #6 Sympathomimetics
Sympathomimetic Effects
Bind with adrenergic receptor
Stimulate adenylate cyclase
Increase [c-AMP] in cell
Can stimulate alpha and/or beta receptors depending
on drug
Must bind to produce effects
Routes of Administration
Oral - Convenient but slow and many side effects
Subcutaneous - good for acute bronchoconstriction,
ER use
Intravenous - Anaphylaxis with epinephrine only,
many side effects
Inhalation - best in most situations
Combinations of routes often used
Aerosol Sympathomimetics
Small Volume Nebulizer ,
Metered Dose Inhaler or Dry Powder
Inhaler
Equal doses delivered to airways give equal response
Difficulty is getting drug to airways
Review how to maximize dose with SVN
Review how to maximize dose with MDI
Review how to maximize dose with DPI
Indications
Relief of bronchoconstriction
From any cause
Increased airway resistance without secretion
obstruction
Increased WOB with wheeze
Evidence of small airway obstruction
Decreased Peak Expiratory Flowrate PEFR
Sympathomimetic Beneficial Effects
Vasoconstriction – alpha – decongestion
Bronchodilation (Relaxation) Beta-2 (c-AMP)
Prevent inflammation by blocking mediator release
Improved mucocilliary
clearance
Sympathomimetic Harmful Effects
Tremors
Headache
Nausea and vomiting
Tachycardia
Hypertension
Nervousness
Dizziness
Tolerance (Tachyphylaxis)
Insomnia
Hypokalemia
Worsening V/Q (decreased PaO2)
Toxicity from propellants
Arrhythmias
Increased glucose level (diabetogenesis)
Diaphoresis (sweating)
Side Effects
BETA-2
Nervousness
Tremor
Anxiety
Insomnia
Difficulty urinating
Peripheral vasodilation
Side Effects
BETA-1
Tachycardia
Hypertension
Palpitations
Arrhythmia
Dizziness
Headache
Side Effects
Hypoxemia (V/Q mismatch)
Bronchoconstriction
tachyphylaxis, ingredients, beta
blockade
Tachyphylaxis
Increase Glucose and Insulin levels
Hypokalemia
Nausea and Vomiting
Diaphoresis
Precautions
Solutions prone to breakdown
Oxygen, heat, light degrade
Turn pink then brown
If any precipitate or discoloration do not use
Pink discoloration of secretions or tubes
Contraindications
Sensitivity (allergy) to any ingredient
Preexisting tachyarrhythmias
Lack of response
Heart rate greater than 140
/ min.
Epinephrine
Catecholamine
Quick breakdown by COMT
l- isomer is active
alpha=beta1=beta2
1:100 dilution 0.25 - 0.5 ml (2.5-5.0 mg)
Not often used due to side effects
Primatine mist MDI, Susphrine SubQ
Administer every 4 hours
Active for 1 - 3 hours
Racemic Epinephrine
50% d-isomer - 50% l-isomer
Alpha >>> Beta2 = Beta1
Croup is main use in pediatrics
Post extubation stridor caused by edema in adults
2.25% solution
0.25 - 0.5 ml (5.625 - 11.25 mg)
Continuous till effect or tachycardia
Administer every 4 hours
Active for 10 - 20 minutes
Bitolterol
Prodrug - Not active as
administered
Body converts to Colterol
which is a catecholamine
Colterol
Bitolterol (Colterol)
Broken down by COMT
Longer acting than other catecholamines because
slowly converted to
active
As converted is quickly degraded
0.2% 0.25 -
0.5 ml (0.5 - 1.0 mg)
Available in MDI
Administer every 4 or 8 hours
Effective for 5 - 8 hours
Metaproterenol
Resorcinol - OH on 3 & 5 Carbons
Longer acting as not susceptible to COMT
Beta2 >>Beta 1 >> Alpha
5.0% 0.2 -
0.3 ml (10 - 15 mg)
Administer every four hours
Active for 3 - 4 hours
MDI and tablets available
Albuterol (Salbutamol)
Methoxyl group on 3 OH on 4
Not susceptible to COMT
Longer duration of action
0.5% solution 0.25 - 0.5 ml (1.25-2.5 mg)
Can be taken orally
Several forms available MDI, DPI, Tablets
Active 4 - 6 hours
Administer every 4 - 6 hours
Levalbuterol (Xopenex)
Nonracemic form of albuterol
R-iosmer of albuterol only
S-isomer is thought to be cause of side effects
Two concentrations available
0.63 mg and 1.25 mg each in 3 mL saline
0.63 mg dose gives equal bronchodilation to 2.5 mg
racemic albuterol
with fewer side effects
1.25 mg dose will provide increased bronchodilation
compared with
similar side effects to 2.5 mg racemic albuterol
Beta-2 >>>>Beta-1>>>Alpha
Active 6 – 8 hours
Administer every 6 – 8 hours
Significantly more expensive than racemic albuterol
– should only
use when significant side effects to racemic albuterol
Salmeterol
Second benzene binds with adjacent site
Bind - release - bind repeatedly to same site
Beta2 >> Beta1 >> Alpha
Only available as MDI now
Long term use not acute Bronchospasm
Active 6 - 12 hours
Administer every 12 hours
Pirbuterol
Salignen with Nitrogen in ring
structure
Beta2 >> Beta1 >> Alpha
Long acting 4 - 6 hours
Adminiser every 4 hours
Sympathomimetics
Changes to Benzene ring increase duration
Adding bulk to side chain improves Beta2 sensitivity
Catecholamines not effective orally
Resorcinols and Salignens
effective orally
Salmeterol and formoterol
bind repeatedly at same site
Experimental Sympathomimetics
Fenoterol - Used in
Formeterol - some similarities to
Salmeterol
Bambuterol - Prodrug converts
to Terbutaline
Selection of Sympathomimetics
Route by which administered
Desired onset of action PFT vs. maintenance
Desired duration of action Test vs. treatment
Side effects most want to avoid
Patient knowledge and capabilities MDI vs. nebulizer
Relative Potencies
Epinephrine 2.5
– 5 mg
Albuterol 1.25 - 2.5 mg
Metaproterenol 10 - 15 mg
Levalbuterol 0.63
– 1.25 mg
Bitolterol 0.5
– 1 mg