THE RESPIRATORY SYSTEMTHE RESPIRATORY SYSTEM

Nelia B. Perez RN MSN

Northeastern College

Santiago City

• Anatomy and Physiology• Upper and Lower Respiratory Tract• Respiration

ANTITUSSIVES

• Dry coughs are treated with cough suppressants (antitussives) that suppress the body's urge to cough,

• Codeine is one of the strongest cough suppressants known, along with a number of derivatives such as the dihydrocodeine-hydrocodone subgroup of opioids, and the semi-synthetics and synthetics mentioned below. Codeine is the standard by which all antitussives are measured. It suppresses coughing by direct action on the cough centre in the brain, and also decreases the rate and/or tidal volume of respiration. The below-mentioned semi-synthetics differ from codeine in such ways as lipid solubility and CNS penetration, overall side-effect profile, and duration of action.

• The very popular antitussive dextromethorphan is related to the dextrorotary form of dromoran and is not an opioid but a NMDA antagonist. It is changed to dextrorphan in the liver; this substance is also a NMDA antagonist, not an opioid and pharmacologically active.

• Diphenhydramine and its derivatives are often useful as non-narcotic cough suppressants by themselves and they dry out bronchial secretions, boost the effects of opioids and combat cold/allergy symptoms caused by immune responses which release histamine into the system. Like many of the classical first generation antihistamines, it also boosts the effects of most opioids, with the result that the dose of codeine and other centrally-acting antitussives can be reduced. Because of the drying effect, diphenhydramine may not be ideal for dry coughs and antihistamines of the cyclizine group (Marezine (cyclizine), Dramamine II (meclizine), Atarax and Vistaril (hydroxyzine) and buclizine and others) would be good substitutes for diphenhydramine for use as an opioid potentiator as are cyproheptadine (Periactin) and phenindamine (Nolahist and Thephorin).

DECONGESTANTS

• A decongestant is a broad class of medications used to relieve nasal congestion. Generally, they work by reducing swelling of the mucous membranes in the nasal passages.

• Most decongestants stimulate the adrenergic receptor system, which results in vasoconstriction. Constriction of the blood vessels in the nose, throat, and sinus membranes reduces inflammation and mucous formation. The active ingredients in most ingested decongestants are pseudoephedrine or phenylephrine. Decongestant nasal sprays and eye drops often contain oxymetazoline and are used for topical decongestion. Pseudoephedrine acts indirectly on the adrenergic receptor system while phenylephrine and oxymetazoline are direct agonists. The effects are not limited to the nose and these medicines may cause hypertension (high blood pressure) through vasoconstriction, but most decongestants are not pronounced stimulants due to lack of response from the other adrenoreceptors. Besides hypertension, common side effects include sleeplessness, anxiety, dizziness, excitability, and nervousness.

• Decongestants are normally paired with antihistamines to lessen this effect, but the combination of both classes of drugs do not necessarily cancel the side effects of each other.

• Topical nasal or ophthalmic decongestants quickly develop tachyphylaxis. Long-term use is not recommended since these agents lose effectiveness after a few days.

• These agents are usually administered topically (by the intranasal route) or orally.

• The most common oral decongestants are pseudoephedrine and phenylephrine; phenylpropanolamine (PPA) is another.

ANTIHISTAMINES

• Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the H1 receptor sites, responsible for immediate hypersensitivity reactions such as sneezing and itching. Members of this class of drugs may also be used for their side effects, including sedation and antiemesis (prevention of nausea and vomiting).

PURPOSE

• Antihistamines provide their primary action by blocking histamine H1 at the receptor site. They have no effect on rate of histamine release, nor do they inactivate histamine. By inhibiting the activity of histamine, they can reduce capillary fragility, which produces the erythema, or redness, associated with allergic reactions. They will also reduce histamine-induced secretions, including excessive tears and salivation. Additional effects vary with the individual drug used. Several of the older drugs, called first-generation antihistamines, bind non-selectively to H1 receptors in the central nervous system as well as to peripheral receptors, and can produce sedation, inhibition of nausea and vomiting, and reduction of motion sickness. The second-generation antihistamines bind only to peripheral H1 receptors, and reduce allergic response with little or no sedation.

• The first-generation antihistamines may be divided into several chemical classes. The side effect profile, which also determines the uses of the drugs, will vary by chemical class. The alkylamines include brompheniramine (Dimetapp) and chlorpheniramine (Chlor-Trimeton.) These agents cause relatively little sedation, and are used primarily for treatment of allergic reactions. Promethazine (Phenergan), in contrast, is a phenothiazine, chemically related to the major tranquilizers, and while it is used for treatment of allergies, may also be used as a sedative, the relieve anxiety prior to surgery, as an anti-nauseant, and for control of motion sickness. Diphenhydramine (Benadryl) is chemically an ethanolamine, and in addition to its role in reducing allergic reactions, may be used as a nighttime sedative, for control of drug-induced Parkinsonism, and, in liquid form, for control of coughs. Consult more detailed references for further information.

• The second generation antihistamines have no central action, and are used only for treatment of allergic reactions. These are divided into two chemical classes. Cetirizine (Zyrtec) is a piperazine derivative, and has a slight sedative effect. Loratidine (Claritin) and fexofenadine (Allegra) are members of the piperadine class and are essentially non-sedating.

RECOMMENDED DOSAGE

• Dosage varies with drug, patient and intended use. Consult more detailed references for further information.

• When used for control of allergic reactions, antihistamines should be taken on a regular schedule, rather than on an as-needed basis, since they have no effect on histamine itself, nor on histamine already bound to the receptor site.

• Efficacy is highly variable from patient to patient. If an antihistamine fails to provide adequate relief, switch to a drug from a different chemical class. Individual drugs may be effective in no more than 40% of patients, and provide 50% relief of allergic symptoms.

SIDE EFFECTS

• The frequency and severity of adverse effects will vary between drugs. Not all adverse reactions will apply to every member of this class.

• Central nervous system reactions include drowsiness, sedation, dizziness, faintness, disturbed coordination, lassitude, confusion, restlessness, excitation, tremor, seizures, headache, insomnia, euphoria, blurred vision, hallucinations, disorientation, disturbing dreams/nightmares, schizophrenic-like reactions, weakness, vertigo, hysteria, nerve pain, and convulsions. Overdoses may cause involuntary movements. Other problems have been reported.

• Gastrointestinal problems include increased appetite, decreased appetite, nausea, vomiting, diarrhea, and constipation.

• Hematologic reactions are rare, but may be severe. These include anemia, or breakdown of red blood cells; reduced platelets; reduced white cells; and bone marrow failure.

• A large number of additional reactions have been reported. Not all apply to every drug, and some reactions may not be drug related. Some of the other adverse effects are chest tightness; wheezing; nasal stuffiness; dry mouth, nose and throat; sore throat; respiratory depression; sneezing; and a burning sensation in the nose.

• When taking antihistamines during pregnancy, Chlorpheniramine (Chlor-Trimeton), dexchlorpheniramine (Polaramine), diphenhydramine (Benadryl), brompheniramine (Dimetapp), cetirizine (Zyrtec), cyproheptadine (Periactin), clemastine (Tavist), azatadine (Optimine), loratadine (Claritin) are all listed as category B. Azelastine (Astelin), hydroxyzine (Atarax), promethazine (Phenergan) are category C.

• Regardless of chemical class of the drug, it is recommended that mothers not breast feed while taking antihistamines.

CONTRAINDICATIONS• The following are absolute or relative contraindications to use of

antihistamines. The significance of the contraindication will vary with the drug and dose.

• glaucoma • hyperthyroidism (overactive thyroid) • high blood pressure • enlarged prostate • heart disease • ulcers or other stomach problems • stomach or intestinal blockage • liver disease • kidney disease • bladder obstruction • diabetes

MUCOLYTICS

• A mucolytic agent or expectorant is any agent which dissolves thick mucus and is usually used to help relieve respiratory difficulties. It does so by hydrolyzing glycosaminoglycans, tending to break down/lower the viscosity of mucin-containing body secretions/components. The viscosity of mucous secretions in the lungs is dependent upon the concentrations of mucoprotein, the presence of disulfide bonds between these macromolecules and DNA.

• An expectorant (from the Latin expectorare, to expel from the chest) is a medication that helps bring up mucus and other material from the lungs, bronchi, and trachea. An example of as expectorant is guaifenesin which promotes drainage of mucus from the lungs by thinning the mucus and also lubricates the irritated respiratory tract. Sometimes the term "expectorant" is incorrectly extended to any cough medicine.

• An expectorant increases bronchial secretions and mucolytics help loosen thick bronchial secretions. Expectorants reduce the thickness or viscosity of bronchial secretions thus increasing mucus flow that can be removed more easily through coughing, Mucolytics break down the chemical structure of mucus molecules. The mucus becomes thinner and can be removed more easily through coughing"

DRUGS USED TO TREAT OBSTRUCTIVE PULMONARY DISORDERS

Chronic Obstructive Pulmonary Disease• Includes diseases that cause airflow

obstruction • Chronic Bronchitis• Emphysema• Risk Factors include environmental

exposures and host factors• Primary symptoms are cough, sputum

production and dyspnea

Medication is the cornerstone of asthma treatment and the main way asthma is controlled. Asthma medications can be divided into two basic categories: • Anti-inflammatory medications, also called long-term

controller medications:

• Work slowly and last a long time.

• Reduce the inflammation that makes the bronchial tubes overly sensitive.

• Must be used on a regular basis to be effective. Those with persistent asthma will need to take anti-inflammatory medication daily.

• Are considered a first line of preventive care because they help to prevent asthma attacks from starting. However, they do not immediately stop asthma attacks once they've begun.

Bronchodilators, also called quick-reliever (rescue) medications:

• Work quickly and last for varying periods of time

• Open narrowed airways and relieve bronchoconstriction (spasms of the airways)

• Do little to reduce the chronic inflammation that makes bronchial tubes overly sensitive

• Help stop asthma attacks once they've begun, and are often used on an "as-needed" basis

SYMPATHOMIMETICS

• Sympathomimetic drugs are substances that mimic the effects of the catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), and/or dopamine. Such drugs are used to treat cardiac arrest, low blood pressure, or even delay premature labor, among other things.

• These drugs act at the postganglionic sympathetic terminal,[1] either directly activating postsynaptic receptors, blocking breakdown and reuptake, or stimulating production and release of catecholamines.

Mechanisms of action

• The mechanisms of sympathomimetic drugs can be direct-acting, such as α-adrenergic agonists, β-adrenergic agonists, dopaminergic agonists; or indirect-acting, such as MAOIs, COMT inhibitors, release stimulants, and reuptake inhibitors.

Direct-acting• Adrenergic receptor agonists• Main article: Adrenergic agonist• Direct stimulation of the α- and β-adrenergic receptors can produce

sympathomimetic effects. Albuterol is a very commonly used direct-acting β2-agonist. Other examples include phenylephrine, isoproterenol, and dobutamine.

• Dopaminergic agonists• Stimulation of the D1 receptor by dopaminergic agonists such as

fenoldopam is used intravenously to treat hypertensive crisis.

Indirect-acting• Norepinephrine transporter blockade• Classical sympathomimetic drugs are amphetamines (including

MDMA), ephedrine and cocaine, which act by blocking and reversing norepinephrine transporter (NET) activity. NET is a transport protein expressed on the surface of some cells that clears noradrenaline and adrenaline from the extracellular space and into cells, terminating the signaling effects.

• Inhibition of epinephrine and norepinephrine metabolism• Inhibition of norepinephrine or epinephrine metabolism can produce

sympathomimetic effects. Both are mainly metabolized by the enzyme monoamine oxidase, the monoamine oxidase inhibitor (MAOI) drugs can induce such effects. COMT inhibitors can also decrease metabolism of norepinephrine and epinephrine.

ANTICHOLINERGIC BRONCHODILATORS

• Anticholinergic drugs block the chemical produced by our bodies that normally causes the airways to contract. They also decrease mucous secretions or phlegm.