Okay, welcome to respiratory pharmacology, or we're going to start by looking at the
two topics.
So the first one includes anti-histamines and decongestants nasal steroids and antitussives
and expectorants.
The second section we'll talk about is asthma and anaphylaxis.
So let's start with antihistamines and decongestants.
So first about histamine.
We want to make sure we understand the tale of two receptors.
When does the body release histamine?
Well, when allergens attach to mast cells and basophils, it activates histamine-1
receptors which have to do with vasodilation, vascular permeability, and bronchoconstriction.
Those are the things you think about when you think about an allergic reaction.
On the other side, we have histamine two receptors, which has to do with gastric acid secretion,
which we talked about in the GI section.
So let's first clarify which drugs belong to which camp.
So on the H-1 receptor antagonists, we have first-generation versus second-generation,
the first-generation diphenhydramine or Benadryl.
This is something that would make someone sleepy.
And the improvement from first to the second generation was going to cetirizine or loratadine, which
are Zyrtec and Claritin.
And these don't cause the same kind of sedation that a first generation anti histamine does.
On the other side with the H-2 receptor antagonists, famotidine brand Pepcid and ranitidine
brand Zantac, until ranitidine was pulled from the shelves. Now it's famotidine with two brand names, Pepcid and Zantac.
And notice that the endings are stems are a bit different.
So, you have loratadine, which is -atadine and then -tidine which is an H-2 receptor.
So they sound very similar when you're talking about sounding it out or making a
verbal order.
So you need to be very careful that we're not giving someone who's got nasal allergies,
something for their stomach and something or the reverse, which is somebody
who has stomach acid, not giving them something that's going to help them with their nasal
allergies.
So first-generation antihistamine, and we call it anti-histamine, although it's an H-1
blocker because it was the first one and they didn't know an H-2 was coming down
the line.
So, generally when we say anti-histamine we mean the allergy kind, diphenhydramine or
Benadryl which crosses the blood-brain barrier easily has a high H-1 receptor affinity in the
CNS.
And that causes that.
Drowsiness, indications, well, mild allergy symptoms that runny nose or sneezing, watery
eyes, itching.
Also insomnia, a short term solution if somebody has trouble sleeping, this can help. Though there
is that morning hangover that they just maybe don't feel well rested, although they
may have slept longer than they would have without the drug.
Adverse effects, so drowsiness, a reduced reaction time if they're driving, urinary
retention, these are what are called anticholinergic effects or antimuscarinic effects and first-generation
anti-histamines are notorious for them and they make it very uncomfortable to take them.
So when the second generation came around, they were a welcome relief cetirizine,
brand Zyrtec and loratadine brand Claritin.
They don't cross the blood-brain barrier easily and that reduce those CNS side effects or
that drowsiness.
They also have longer half-lives in the first generation.
So just once daily dosing usually does it.
What kind of indications do we have?
Mild allergy symptoms, runny nose, sneezing, watery eyes and itching.
Obviously, no insomnia indication because they don't really make someone drowsy, but we
did put on the right-hand side.
Sometimes you will get some drowsiness with this, but certainly not to the extent that
you would with diphenhydramine.
Something that gets confused with allergies is sinus congestion, and this is inflamed
sinus blood vessels.
They take up excess fluid and they don't always cause a runny nose.
The treatment is to reduce the sinus inflammation by locally forcing the fluid out of the vessels
through localized vasoconstriction.
-vaso- meaning vessel constriction, meaning tightening.
So a tightening of the vessels.
Pseudoephedrine or brand
Sudafed is the most famous of them.
It's a sympathomimetic action.
And sympathetic is the sympathetic fight or flight system.
And a mime is someone that copies you.
So a sympathomimetic is something that copies the sympathetic nervous system.
It activates those alpha-1 adrenergic receptors.
So it's indicated for allergic rhinitis and nasal and sinus congestion.
Adverse drug reactions, well, CNS excitement, restlessness, insomnia, maybe some anxiety,
cardiovascular, hypertension, tachycardia.
So those are maybe a concern, especially if someone has a cardiovascular disease.
While we're not saying that someone who has controlled high blood pressure should never
use something that's a decongestant, we're saying that certainly a prescriber will want
to look at the case and make sure that it's safe.
Pseudoephedrine is a drug of abuse.
You can manufacture methamphetamine with it.
And because of the combat methamphetamine act of 2005, it's only available behind the
counter.
So you can't just get it off the shelf.
A pharmacist hands it to you, you don't need a prescription, but you may need to scan your
driver's license or something to be put into a database to make sure that you're not going
over the maximum of nine grams per month and 3.6 grams on any one day of medication to
any single person on the other side.
Some states like Iowa has decided have a stronger law and it's 7.5 grams instead of the nine
grams.
So, manufacturers formulated products with phenylephrine, another decongestant that doesn't
have any restrictions on purchasing.
So it has the same actions as pseudoephedrine and all
the same things.
But it doesn't work very well because it has an extensive liver metabolism.
And so when you say, "well I'll just get the PE version over the counter."
It's not quite as good.
Oxymetazoline brand Afrin is a topical decongestant.
We'd give by nasal spray with minimal side effects.
It works within a couple minutes, but we can't use it for more than three days because of
rebound congestion.
That's when you use the medicine.
But it actually comes back worse than it was before.
So just a few days is what we're okay using oxymetazoline for.
It makes sense that with allergy symptoms, one might combine an antihistamine and decongestant.
So loratadine brand, Claritin plus D for decongestant is one combination.
So second-generation antihistamine, that doesn't make you drowsy with a decongestant
or pseudoephedrine.
It treats allergic rhinitis with congestion by reducing that sneezing, runny nose, itchiness,
and that inflammation and congestion.
When someone has seasonal allergies annually, it's really a lot better to use a nasal steroid.
And then we'll also talk about cough, which are the antitussives and expectorants
Triamcinolone or Nasacort 24 hour and it sounds just like it is a nasal corticosteroid.
It's dosed once daily up to two to three weeks to be fully effective.
So it's non for PRN use and that really puts off a lot of people.
They are uncomfortable now.
They don't want to have to take something every day, but this works a lot better than
treating with anti-histamines.
You've got some mild adverse drug reaction, nose drying of the nose, nosebleeds, burning
and itching, sore throat, headache.
But it's really the most effective medicine for the prevention treatment of seasonal allergies.
So if you take it as you should, two or three weeks later, it's going to be a completely
different story.
One antitussive is dextromethorphan, which is the DM in Robitussin DM.
It activates opioid receptors in the brain's cough center and it suppresses that cough
reflex.
It's derived from codeine, but with minimal side effects at normal doses, adverse drug
reactions similar to opioids, but certainly not to the same extent.
Some dizziness, somnolence, fatigue, or possible confusion.
Guaifenesin is an expectorant that increases the respiratory mucous volume and decreases the viscosity.
It's easier to cough out and it's often in combination with antitussives.
So two combinations that we might see are over the counter guaifenesin with dextromethorphan
or that Robitussin DM or the prescription only codeine-based product.
which is Cheratussin AC.
So let's talk about asthma a little bit and we'll first have a graphic that kind of goes
over the big picture and then we'll see how these drugs work in those different pictures.
So it all begins with some kind of allergy and or some kind of trigger.
And then histamine, leukotrienes, these are mediating compounds that get released.
And now we have the two big components of asthma on the left we have inflammation on
the right bronchial hypersensitivity where you have an easily triggered spasm.
Maybe some of the triggers are exercise or cold air or smoke.
Either way, we get this limited airflow or bronchoconstriction and then we have bronchospasm.
So to summarize this, the two things we're really worried about are the asthma symptoms
that result from one chronic inflammation and two bronchoconstrictions.
So we're going to treat the symptoms to prevent this bronchospasm by treating those two components.
We'll start with leukotrienes, they're released in the presence of allergens and they're responsible
for smooth muscle constriction like bronchoconstriction inflammatory responses and recruiting further
inflammatory mediators and montelukast or Singulair.
It's meant to help but very rarely it may cause mood changes, but otherwise, it's very
similar to placebo.
But again, we're seeing these mediator compounds released and we're trying to block that
with this leukotriene receptor blocker, a drug that's more for severe allergy issues
would be something like omalizumab, brand Xolair.
It's a monoclonal antibody and we see the -mab at the end of the word, but it
complexes with the IgE in the blood.
It reduces the amount available to the receptors and mast cells.
So reducing the mediator compound amount release.
It only works for the allergy related asthma, but it's meant to stop the cascade in its
tracks at the mediator.
Step indications, moderate to severe asthma, ages 12 and up.
And then adverse drug reactions and injection site reaction or respiratory infection, maybe
anaphylaxis.
But again, this is not a first-line.
This is certainly for someone that's been struggling and has allergy related condition,
oral glucocorticoids, these are oral steroids that through anti-inflammatory actions.
So, for acute asthma exacerbations rather than chronic treatment, prednisone or methylprednisolone
you can give a short burst and asthma, it's only available
as an oral formulation, whereas methylprednisolone it's a short burst, but you can get it as
an oral tablet. Note that glucocorticoids can raise glucose levels and you can see glucose
and glucocorticoid has the same beginning.
And that's one way to remember the connection.
But once the diabetic patients closely, because if they're on these medications, it's a real
concern.
There are many different inhaler types as there are many different levels of people
that get asthma.
So it was from children to adults to the elderly,
And a lot of times we're choosing it by how easy or hard it is to use something like a
rescue inhaler.
A metered dose inhaler requires a significant amount of dexterity.
So if you have someone that has arthritis or severe arthritis, this can be very difficult
for them.
With a dry powder, they might need a little bit less, it can be activated by the breath or
a Respimat where you've got this pressure.
So the nebulizer, it's really kind of in its own class where if you have a patient that's
bedridden or something like that, you may have to put it in the nebule, it'll
aerosolize it and they might put a mask on or something like that.
So for different inhaler types and ways to get the medicine to the patient.
Let's first talk about the inhaled corticosteroids.
ICS, they're for long-term use with minimal systemic absorption, which means that basically
if you put it directly in the lungs, it's not going to get to the rest of the body.
And the localized anti-inflammatory action in the lungs makes it much safer.
Fluticasone or Flovent HFA
Budesonide is often combined with other agents.
The issue we have is that inhaled corticosteroids can cause oral candidiasis and dysphonia.
So oral candidiasis is thrush or that white tongue, and then dysphonia is being hoarse,
so prevented by rinsing out after using it each time.
On the side of bronchoconstriction, we've got the beta-2 receptor agonists and they
activate these beta-2 receptors in the airways causing bronchodilation and they relieve and
prevent bronchospasm.
Again, beta-1 you have one heart, that affects the heart.
Beta-2, you have two lungs.
This generally affects the lungs and we have it as short and long-acting.
So, if you look at the bottom of the words, short-acting beta two agonists that make SABA
or long-acting beta two agonist, that's LABA.
We could use a beta-2
It's a rescue inhaler really, or albuterol.
And then the long acting are preventative.
These are things you're supposed to take each day, but never alone because a trial showed
that the outcomes were worse.
If someone took it alone, they're going to be in combination with some kind of steroid
anticholinergics or short or long-acting muscarinic antagonists, SAMA or LAMA.
These prevent bronchoconstriction by blocking muscarinic, cholinergic receptors in the lungs.
And those two words mean the same thing.
I just wanted to put them both there so you could see them.
Muscarine was a mushroom and that's how they first discovered it, but then they realized
that acetylcholine was the actual neurotransmitter.
So, then we call it cholinergic.
Now instead of muscarinic, it's usually used more in COPD than asthma.
Chronic obstructive pulmonary disease, and you have ipratropium which is Atrovent
and tiotropium or Spiriva.
And it's up to you to remember that the ipratropium much more short-acting.
And most of us remember it because we'll see it.
Ipratropium with albuterol and knowing albuterol is short-acting ipratropium must be short-acting.
And that combination is very familiar tiotropium, that's long-acting 24 hours as well.
So the combined agents are when you take two and you're going to attack both the inflammation
and the bronchoconstriction.
So which again is for the inflammation, that one that has -sone in it or something like
that.
So, fluticasone, budesonide, and then the salmeterol is the one that's for that bronchoconstriction
that patients have that combats the narrowing of the airway.
On the other side, we could use a SABA and SAMA which is a short-acting beta two agonist
and a short-acting muscarinic antagonist.
So, albuterol and ipratropium.
Okay, so albuterol on the right-hand side we have a SABA and a SAMA.
So albuterol and ipratropium, both affecting bronchoconstriction, call it DuoNeb,
because there's two drugs and it goes in nebulized solution.
Careful, again, using an inhaled corticosteroid must rinse their mouth after use. Anaphylaxis.
is an allergen that can cause a very severe allergic reaction.
It can happen within minutes affecting beta receptors causing vasodilation.
Bronchoconstriction, bronchospasm.
They struggle to breathe and usually we use an Epi-pen or epinephrine which acts rapidly
on its Alpha and Beta receptors throughout the body.
It's given IM or intramuscularly, and we still want to take the patients to the ED
after the epinephrine, dose to ensure safety because the body might eliminate the medication
before the allergen.