Pulmonary Drugs

The sympathomimetics are drugs which bind to adrenergic receptors to stimulate or turn on the receptor to which they have bonded. This translates into the turning on of some cellular process that is mediated by the adrenergic receptor. These drugs are able to turn on an alpha, beta-1, and/or a beta-2 receptor.

Receptor Types : alpha, beta-1, beta-2

alpha Adrenergic Receptors - are responsible for peripheral vasoconstriction
beta-1 Adrenergic Receptors - are responsible for ­ H.R., ­ force of contraction, ­ S.V.
beta-2 Adrenergic Receptors - are responsible for vasodilatation and bronchodilatation

The Mechanism Of Action For The Sympathomimetics On The beta-2 Adrenergic Receptor

1. Drug-receptor complex activates the Gs protein which in turn cleaves an ATP to make cAMP - a second messenger.

2. cAMP blocks the activation of an enzyme called Myosin Light Chain Kinase (MLCK) which would normally phosphorylate myosin (adding a PO4- group) thus activating the myosin head to interact with actin. Since cAMP blocks the activation of MLCK, then myosin light chain (MLC20) cannot be phosphorylated (activated) and thus smooth muscle relaxes because no interaction can occur between actin and myosin. You, therefore get permissive bronchodilation.

Members

Non-Selective
Epinephrine (Adrenaline) - alpha, beta-1, beta-2
Norepinephrine (Levophed) - alpha, beta-1, beta-2
Isoproterenol (Isuprel) - beta-1, beta-2

Selective
Metaproterenol (Metaprel, Alupent) - beta-2
Terbutaline Sulfate (Brethine) - beta-2
Albuterol Sulfate (Ventolin) - beta-2
Isoetharine Hcl (Bronkosol) - beta-2
Pirbuterol (Maxair) - beta-2
Bitolterol Mesylate (Tornalate) - beta-2

Medical Uses Of The Sympathomimetics

1. Bronchodilation - Stimulation of the beta-2 adrenergic receptor
2. Increases In Blood Pressure - Stimulation of the alpha adrenergic receptor
3. Increases In Cardiac Output - Stimulation of the beta-1 adrenergic receptor

Special Medical Uses Of The Sympathomimetics

1. Terbutaline Sulfate (Brethine), Fenoterol, and Ritodrine HCl (Yutopar) are used to inhibit premature labor. They are beta-2 selective sympathomimetics with the effect of relaxing the uterine muscle.

Adverse Side Effects Of The Sympathomimetics :

Nausea, vomiting, headaches, dizziness, irritability, nervousness, seizures, tremors, anxiety, insomnia, hypertension, palpitations, tachycardia, arrhythmias, stroke, cardiac arrest, angina, bradycardia.

Clinical Considerations In Physical Therapy Practice For The Sympathomimetics

1. Clearing Secretions From The Patient’s Lung Fields : Help your patient to clear secretions from their lungs. There are a number of things we can do to assist the patient in this way :

3. Know Your Patient’s Medicines and Medical History : Know which of your patients has chronic obstructive pulmonary disease (COPD) and what medications they are currently using.

4. Medication Side Effects : Know the side effects of those medications.

The Methylxanthines are a group of medications which are largely used to bronchodilate an individual. Members : 1. Theophylline (Theo-Dur, Uniphyl)

• Aminophylline
• Oxtriphylline (Brondecon)
• Theophylline Sodium Glycinate (Asbron G)

Mechanisms of Action For The Methylxanthines

1. Not Clearly Understood
2. May prolong the biological T1/2 life of cAMP
3. May inhibit phosphodiesterase - an enzyme that inactivates cAMP

General Actions Of The Methylxanthines :

1. Bronchodilation
2. Decrease drowsiness
3. Reduces mental and muscular fatigue
4. Stimulates thinking
5. Stimulate the respiratory centers
6. Increases cardiac contractile strength
7. Increases glomerular filtration rate in the kidneys

Medical Uses Of The Methylxanthines :

1. To bronchodilate patients with bronchoconstrictive disorders like COPD
2. To decrease diaphragmatic fatigue
3. To improve airflow mechanics
4. To speed removal of secretions from the lungs

Special Uses Of The Methylxanthines

1. The Treatment Of Neonatal Apnea : The methylxanthines are used to stimulate the respiratory centers in neonates. Caffeine and theophylline are often the drugs of choice.

Adverse Side Effects : Seizures (too much Methylxanthine on board), nervousness, insomnia, headaches, tachycardia, tachdysrhythmias, nausea, anorexia, vomiting, diarrhea.

Clinical Considerations In Physical Therapy Practice For The Methylxanthines 1. Seizures Precautions : Watch the patient for the onset of CNS seizures. These drugs cause patients to have seizures when there is too much of the medication in the blood stream. These drugs have small therapeutic windows. A consciencous physician will do blood titers to make sure that the patient is not getting too much of the drug. 2. Side Effects : Understand the side effects of these drugs. Patients will feel quite “jumpy” and nervous on these medications and may need to be reassured. Also, the patient is frequently irritable and demonstrates some rude behaviors when on these medications. It helps to understand the side effects so that the clinician does not take the patient’s rudeness to heart.

A. Mucolytics

Members :

1. N-Acetylcysteine ( Mucomyst, Airbron)
2. Recombinant Human Deoxyribonuclease I (rhDNase, Dornase)

Mechanisms of Action :

1. N-Acetylcysteine ( Mucomyst, Airbron) breaks the disulfide bonds in mucin thus making the mucin thinner and more easily transported out of the lungs by the MCE.

2. Recombinant Human Deoxyribonuclease I (rhDNase, Dornase) is an enzyme that cleaves DNA left behind by neutrophils in the lungs. When a neutrophil dies, its DNA leaks out of the cell and when it comes into contact with mucin, it makes the mucin very thick and tenacious. This is a particular problem with patients with Cystic Fibrosis. Consequently, when Dornase is inhaled, it cuts apart the neutrophil DNA and makes the mucin thinner and more easily removed by the MCE.

Medical Uses Of The Mucolytics :

1. Mucomyst is used to reduce the secretions in patients with COPD (asthma, bronchitis, bronchiectasis and emphysema).

2. Dornase is used to thin the secretions in patients with cystic fibrosis. This drug is so effective, that the pulmonary function test values in these patients rises dramatically, the incidence of lung infections is reduced dramatically and life is prolonged.

Special Uses Of N-Acetylcysteine (Mucomyst)

1. This medication is given orally to children who have overdosed on Tylenol. Mucomyst binds with Tylenol and prevents it from corrosively destroying the kidney.

Adverse Side Effects Of The Mucolytics :

• N-Acetylcysteine (Mucomyst) : nausea, vomiting
• Dornase : Nausea, sore mucosal membranes in the mouth, irritation of the bronchi

1. Always give these medications by a metered inhaler or by SVN 1 hour prior to other chest PT treatments.

B. Expectorants

Members :

1. Quaifenesin (Robitussin)
2. Iodinated Glycerol (Organidin)

Mechanisms Of Action :

1. Stimulates the mucin secreting cells to hyperactively produce mucin. This mucin is thinner with a higher water content and is, therefore, more easily removed by the MCE.

2. The increased volume of thiiner mucin helps to stimulate coughing.

Members :

1. Triamcinolone Acetonide (Azmacort)
2. Beclomethasone (Beclovent)
3. Flunisolide (Aerobid)
4. Dexamethasone (Decadron)

Mechanisms Of Action :

1. Anti-Inflammatory : Reduce inflammation by blocking the production of leukotrienes, thromboxanes and prostaglandins - the big mediators of inflammation.
2. Reduce Swelling : Improve the airflow mechanics of the bronchi by causing swelling to be reduced. They have the ability to reduce swelling by reducing the leakiness of the capillary bed.
3. Reduces Airway Obstruction : These medications reduce airway obstruction by reducing swelling and excess mucin production. Also, the corticosteroids reduce the destruction of the bronchial and parenchymal tissues.
4. Bronchodilatation : They are believed to have weak bronchodilatory effects.
5. Inhibition of Neutrophils : Inhibit neutrophil migration and thus prevent a lot of indiscriminate destruction - i.e. - neutrophils are not very discriminate in their phagocytotic behaviors. They will kill and phagocytize both good and dying cells.
6. Stabilization Of The Mast Cell : These medications stabilize the mast cell inhibiting it from degranulating and releasing large amounts of histamine - a potent mediator of inflammation.
7. Stabilization Of Lysosomes : Corticosteroids stabilize the membranes of lysosomes so that they will break open and release their lytic enzymes - lipidases, proteases, nucleases, RNAases, DNAases, etc.

Medical Uses Of The Inhaled Corticosteroids

1. Used to reduce inflammation and swelling in the bronchial tubes of patients with COPD - asthma, bronchitis, emphysema, and bronchiectasis.
2. Used to treat inflammation in the lugs of patients with cystic fibrosis.
3. Given to patients with pneumonia to reduce inflammation caused by retention of fluid and secretions.

The Safety And Advantages Of Inhaled Corticosteroids

1. They are delivered by metered dose inhalers or by SVN treatments.
2. These drugs do not cross over into the systemic circulation when taken in therapeutic doses - hence, there are no systemic effects that are negative.
3. The side effects are minimal - some dryness of the mouth, mucosal irritation, horseness, etc.

Adverse Side Effects : Irritation of the mucosal membranes, dry mouth, hoarseness, sore throat, candidal infections of the mouth.

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