| General Medication Information | |
The goal of respiratory pharmacology is to prevent or relieve the pathologic triad discussed at the beginning of this CEU module: bronchospasm, airway inflammation or mucosal edema, and retained secretions. The medicating agents used to relieve these symptoms can be referred to as the “treatment triad.” The pathologic triad and treatments include:
Pathologic Condition Treatment
Bronchoconstriction Bronchodilator (e.g., albuterol)
Airway edema Decongestant (e.g., racemic epinephrine)
Retained secretions Hydration or mucolytics
The actions of the various categories of pharmacologic agents used to relieve the pathologic triad can be briefly summarized as:
· Bronchodilators increase airway patency by relaxing the bronchial muscle spasm triggered by disease or irritation.
· Decongestants cause contraction of the muscle fibers of the arterioles and small arteries, triggering a reduction of blood flow to the affected area and lowering of hydrostatic pressure that permits fluid to move into the tissues.
· Mucokinetics facilitate loosening and mobilization of secretions.
Throughout this part of the course we will present information regarding individual drugs. Some will contain more information than others. Regarding some of the medications, we will include the full text of what can be found in drug reference books such as the Physicians Desk Reference or in other texts which go into respiratory medications in great. For the purposes of this CEU, will not do so for every drug mentioned as to do so would turn this into a textbook rather than what it is: a continuing education unit. Regarding other drugs, in order to present you with more information, we will present you with examples of published articles about those drugs. Again, published articles will not accompany every drug mentioned.
There are a wide variety of patient circumstances that can necessitate the modification of recommended dosage or frequency of medications administered to pulmonary patients. Following administration, most drugs go through several steps in a well-defined sequence before being excreted from the body, including:
1. Absorption from the site of administration
2. Distribution via the circulatory system
3. Metabolism
4. Excretion from the body
Metabolism, also known as biotransformation, is the step in which a drug circulating in the bloodstream is transformed from its original active form to a less active form. While other organs participate to a limited degree in the metabolism process, the liver is the principal site of drug metabolism. Drugs absorbed through the mucous membrane of the stomach or intestines, enter the bloodstream via the portal vein. Before this vein empties into the general circulation system, it passes through the liver where the drugs carried by the vein are exposed immediately to metabolism by liver enzymes.
Because the liver plays such a key role in the metabolism of most drugs, a decreased rate of drug metabolism can occur in patients with liver diseases or hepatitis. Drug dosages for these patients need to be adjusted in order to avoid toxicity, and to compensate for the prolonged pharmacologic action of unmetabolized drug in the blood stream.
The kidney is the principal organ involved in the excretion of drugs from the body. Poor renal function can significantly prolong the effects of some drugs, and altered pH levels can inactivate some drugs, such as bronchodilators. Since mechanical ventilation can affect kidney function by decreasing perfusion pressure, drug dosages may need to be modified for patients on ventilation.
Also, since many patients are being treated with more than one drug at a time, drug interaction and synergism needs to be taken into account when setting dosages and administration frequencies. All of these factors contribute to making the task of prescribing proper dosage of medications for respiratory patients a more complex undertaking.
Most drug effects are mediated through the agency of a receptor, which is special protein molecule on the cell membrane that is specifically designed to interact with natural body chemicals, and it also interacts with drugs.
There are many types of receptors throughout the body. For example, andrenergic receptors are part of the sympathetic nervous system and are activated by the natural neurotransmitters epinephrine, norepinephrine, and dopamine, or by drugs. There are three types of andrenergic receptors (alpha, beta1, and beta2). Cholinergic receptors are part of the parasympathetic nervous system, and are activated by the natural neurotransmitter acetylcholine.
The G protein-linked receptors mediate both bronchodilation and bronchoconstriction in the airways, in response to endogenous stimulation by neurotransmitters epinephrine and acetylcholine. These same airway responses can also be elicited by andrenergic bronchodilator drugs, or blocked by acetylcholine blocking (anticholinergic) agents.
Bronchodilators relax the smooth muscle that surrounds the bronchi, thereby increasing airflow. This dilation of the bronchi is due either to stimulation of beta2 receptors in the smooth muscle of the bronchi, the release of epinephrine which itself stimulates beta2 receptors, or to inhibition of acetylcholine at cholinergic receptor sites in the smooth muscle.
Andrenergic bronchodilators are the most widely used of all medications in respiratory therapy. The name andrenergic comes from their ability to act like adrenaline on the beta sites and cause smooth muscle relaxation.
At the effector site, the bronchial smooth muscle cell, the stimulation of the beta site results in the stimulation of adenyl cyclase, which in turn catalyzes the formation cyclic 3’,5’ adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). The presence of cAMP causes the smooth muscle to relax, leading to bronchodilation. cAMP is inactivated by the enzyme phosphodiesterase into AMP, losing the bronchodilatory effect. Stimulation of the bronchial smooth muscle beta site, whether by sympathetic system or by sympathomimetic drug, increases the level of 3’5’ AMP, and results in dilation.
The bronchodilating action of the adrenergic drugs is primarily caused by stimulation of beta2 receptors located on bronchial smooth muscle. In addition, some adrenergic bronchodilators can stimulate alpha and beta1 receptors. The clinical effects of these stimulations include:
· Alpha receptor stimulation causes vasoconstriction and a vasopressor effect; in the upper airway (nasal passages) this can provide decongestion.
· Beta1 receptor stimulation causes increased myocardial conductivity, increased heart rate, and increased contractile force.
· Beta2 receptor stimulation can cause:
1. relaxation of bronchial smooth muscle
2. inhibition of inflammatory mediator release
3. stimulation of mucociliary clearance
The general indication for the use of andrenergic bronchodilators is relaxation of airway smooth muscle to reverse or improve airflow obstruction. They are used clinically to reverse bronchoconstriction seen with asthma, acute and chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, and other obstructive airway diseases.
The sympathomimetic bronchodilators are all either catecholamines or derivatives of catecholamines. Catecholamines, or sympathomimetic amines, mimic the actions of epinephrine fairly precisely, causing tachycardia, elevated blood pressure, smooth muscle relaxation of bronchioles and skeletal muscle blood vessels, glycogenolysis, skeletal muscle tremor, and central nervous system stimulation.
| General Medication Information | |