Respiratory Pharmacology Part 1 (Rhinitis & Cough)
Here we'll learn about medications used to treat rhinitis and cough; although we'll single out specific drugs and their actions, keep in mind that many over-the-counter medications comprise various combinations of drugs.
Rhinitis: the nasal passages are inflamed, causing a "runny" and/or "stuffy" nose, sneezing, and sinus congestion; may be caused by allergies (IgE-mediated) or viral pathogens or irritants.
Decongestants
Alpha-adrenoreceptor agonists that promote vessel constriction in the nasal mucosa, which reduces edema and swelling.
Epinephrine and
oxymetazoline are nasal sprays. Afrin is the name-brand version of oxymetazoline, which is also used in Visine for itchy, red eyes.
Phenylephrine is available in both sprays and tablet formulas.
Pseudoephedrine comes in tablet form. Because it can be used to create methamphetamine, it has largely been replaced by phenylephrine in over-the-counter drugs.
Pseudoephedrine acts on both alpha and beta receptors, and is therefore associated with more systemic effects.
Adverse effects of alpha-adrenoreceptor decongestants are due to sympathetic activation, which particularly affects the central nervous and cardiovascular systems (again, this is especially true for pseudoephedrine).
If patients experience serious adverse effects, including irregular heart beat, shaking, or anxiety, they should stop using these medications.
Rhinitis medicamentosa: Although nasal sprays are better tolerated due to their localized effects, patients should not use them for more than 3-5 days at a time, as they can cause rhinitis medicamentosa, which is a form of rebound congestion.
Avoid or use caution in prescribing alpha-adrenoreceptor agonists to patients with
heart disease, hypertension, thyroid disease, diabetes, enlarged prostate, pregnancy, or those who have used monoamine oxidase inhibitors in the last two weeks.
Glucocorticoids
Available as nasal sprays; glucocorticoids bind to intracellular glucocorticoid receptors and downregulate the inflammatory response by up-regulate anti-inflammatory genes and suppressing pro-inflammatory genes.
Very effective against allergic rhinitis with discharge and blockage; antihistamines are added to some formulas.
Cromolyn sodium
Blocks mast cell release of histamine and other inflammatory mediators that cause rhinitis; it is occasionally used in asthma, as well.
However, because cromolyn has to be used multiple times a day and is generally less effective than other available drugs, it is not a first-line treatment.
Antihistamines
Antihistamines are used to treat allergic rhinitis.
Histamines cause nasal vessel dilation and edema, which produces the increased watery discharged associated with a "runny" nose.
Anti-histamines block the action of histamines:
H1 antihistamines are inverse agonists that keep H1 receptors in their inactive states, which prevents mast cell degranulation and NF-kB (nuclear factor kappa B) activation.
Thus, these drugs reduce nasal discharge; antihistamines are also used to treat allergic inflammation and itching of the eyes and skin.
Additionally, some H1 antihistamine drugs also have other, non-histamine receptor effects (for example, some have anti-tussive effects).
Use caution when prescribing antihistamines to pregnant patients and those with cardiovascular disease, hypertension, urinary retention, and elevated ocular pressure.
First-generation antihistamines include diphenhydramine (aka, Benadryl), chlorpheniramine, brompheniramine, and hydroxyzine.
First-generation antihistamines readily cross the blood-brain barrier, and often cause sedation; headaches and weigh gain are also reported.
Additionally, these drugs have anticholinergic effects: blind as a bat, hot as a hare, mad as a hatter, dry as a bone, red as a beet.
First-generation antihistamines are also used as sleep aids and to prevent or treat motion sickness
Second-generation antihistamines include loratadine (Claritin), cetirizine (Zyrtec), azelastine, and olopatadine (the last two are available in eye and nasal sprays).
Second generation formulas were designed to cause less sedation and have fewer anticholinergic side effects; they do not cross the blood-brain barrier as readily as the first-generation antihistamines.
Third generation antihistamines include fexofadine, desloratadine, and levocetirizine.
These drugs are metabolites of the second generation H1 antihistamines, and, like those drugs, cause less sedation and fewer anticholinergic effects than first-generation antihistamines, and do not readily cross the blood-brain barrier.
Saline
Found in over-the-counter sprays and nasal irrigation systems.
Saline solutions flush away mucus and nasal irritants and sooth nasal membranes.
Cough suppressants
Aka, anti-tussives
Target the medullary cough center.
They are NMDA receptor antagonists and Sigma-1 receptor agonists (NMDA stands for N-Methyl-D-aspartate).
These medications suppress cough caused by bronchial irritation due to flu and cold viruses, but are not used for chronic cough caused by smoking and lung disorders such as emphysema.
Dextromethorphan Is a common over-the-counter anti-tussive drug.
Adverse effects are rare and include GI upset, drowsiness, and dizziness.
This should not be used by patients who have taken an MAOI in the last two weeks, nor should it be prescribed to children under four years old.
Furthermore, beware of dextromethorphan abuse; when taken at high dosages, it can cause euphoria, but it can also cause brain damage, seizures, and cardiovascular events.
Opioids, including codeine and hydrocodone also suppress the cough reflex.
Because of the potential for addiction and abuse, they are contraindicated in children and are not first-line therapy in adults.
Mucoactive agents
These are drugs that modify the production, secretion, or components of mucus, or that act on the respiratory cilia to facilitate easier mucus removal from the bronchi.
Guaifenesin (the main ingredient in Mucinex) is an expectorant: it increases the volume of watery mucus to facilitate productive coughing.
N-acetylcysteine is a mucolytic: it breaks down mucus components to reduce overall mucus viscosity.
It is sometimes used by patients with
COPD.
In IV form, can be used to treat acetaminophen overdose.
Ambroxol is a mucokinetic drug: it increases the transportability of mucus by acting on the respiratory epithelium cilia.
Anticholinergic agents act as mucoregulators: they reduce mucus hypersecretion.
For full references, please see our full tutorial on Respiratory Pharmacology.
