Respiratory Pharmacology (this lecture is huge) Flashcards
What is asthma?
It’s a long term condition in which the airways may unexpectedly and suddenly narrow. This often occurs in response to an allergen, cold air, exercise, or emotional stress. Symptoms include being a wussy kid with glasses and potentially a lisp..
What is COPD (chronic obstructive pulmonary disorder)?
Chronic bronchitis and emphysema are a pair of two commonly co-existing diseases of the lungs in which the airways become narrowed. This leads to a limitation of the flow of air to and from the lungs causing shortness of breath.
Th1 cells lead to _____ while Th2 cells lead to ______.
Cell mediated immunity (cytotoxic t cells)
Humoral immunity
Th2 cells lead to _______ infiltration of the lung.
eosinophil
Asthma typically has an immune response that is slanted towards Th1 or Th2 mediated immunity?
Th2
What are the two types of asthma? Do they require the same treatment?
Eosinophilic asthma
Non-eosinophilic asthma
Different treatments- eosinophilic asthma is treated by the inhalation of corticosteroids and the other one isn’t..
What are three consequences of respiratory inflammation?
Bronchoconstriction
Mucus production
Airway remodeling
What are the three goals of asthma treatment?
relieve or prevent bronchoconstriction
inhibit airway inflammation (prevent mucus production)
prevent airway remodeling
Why does bronchoconstriction happen in asthma versus COPD?
In asthma it’s part of an allergic response. In COPD it’s from a change in vagal tone.
In asthma versus COPD, can normal lung function be achieved?
With asthma, yes. With COPD, nope- airway obstruction is only partially reversible.
I’m only on slide 16
okay
Starting on Slide 67
Okay
ICS stands for?
Inhalation of corticosteroids
What are the things used to treat asthma and COPD?
Beta2 adrenergic receptor agonists- this mediates brochodilation
Corticosteroids
Leukotriene modifiers
Anticholinergics- block M3 which causes bronchoconstriction
Anti-IgE- block the allergic response
T/F a decrease in vagal tone contributes mightily to bronchoconstriction in COPD?
False- and increased vagal tone does this
How does an increase in vagal tone add to bronchoconstriction?
Vagal tone refers to parasympathetics, so act acting on M3 receptors leads to bronchoconstriction
What is a classic muscarinic act receptor antagonist?
Atropine
T/F blockage of M1 and M3 receptors can lead to bronchodilation?
True
What happens when you block the action of ach on muscarinic receptors in the airway?
It inhibits smooth muscle contraction- bronchodilation ensues
Mucus secretion decreases
T/F the only reversible component of COPD is the act-meiated bronchoconstriction?
True
What is the first line of defense to treat COPD? Can this same treatment be used to address asthma?
Anti-cholinergics
It’ll work for asthma- usually used if corticosteroids aren’t working, but not used alone
How does leukotriene affect the airway?
It is a 1000X more potent broncho-constrictor than histamine is in the airway
Leukotriene modifiers do what?
They can block the enzyme that takes arachidonic acid to cysteinyl leukotrienes. These help stop inflammation
Is a leukotriene modifier a good drug to treat asthma?
No, it helps as an adjunctive measure, but these aren’t as effective as inhaled corticosteroids
Anti-IgE’s are super expensive- 10-30k a year.
boom.
What is allergic rhinitis (hay fever)?
It is abnormal inflammation of the membrane lining the nose leading to a bunch of symptoms confined to the eyes, nose and throat
Allergic rhinitis results from what?
From an excessive reaction of the immune system allergens- similar to what happens in asthma.
Are treatments of hay fever and asthma the same? Why or why not?
They aren’t because the nasal passage has a different function and structure than bronchi, so the treatments are a bit different
What are the three purposes of the nasal passage?
- extensive blood flow facilities heat exchange
- nasal mucosa have high secretory capacity
- capillary structure facilitates rapid movement of water through the vascular wall to escape into the airway and humidify the inspired air
Does the characterization of the “snot nosed kid” have any physiological basis?
Indeed it does-
the number of mucous glands you have in your nose remains constant throughout your life. That means that a little baby has as many mucus producing stations as an adult does, just in a smaller nose
How do antihistamines treat allergic rhinitis?
If you use an H1 receptor agonist you get bronchoconstiction- you get inflammation via vasodilation and disruption of the endothelial seal (leaky capillaries result). An H1 receptor antagonist produces vasoconstriction (it’s like stepping on the hose) and restores the capillary seal (stops the leakiness)
There are two “generations” of H1 antagonists. What do first generation H1 antagonists do?
They cross the blood brain barrier. They produce drowsiness. They are also anti-motion sickness
There are two “generations” of H1 antagonists. What do second generation H1 agonists do?
These don’t cross BBB well. They’re more selective and have fewer adverse side effects- dry mouth, fatigue, constipation
Alpha1 adrenergic receptor agonists are use in the respiratory system for what?
As decongestants
What do alpha1 adrenergic receptor agonists do?
They constrict blood vessels and relieve congestion. Mostly just vasoconstriction.
Inflammation in asthma usually involves recruitment of ______ whereas inflammation in COPD involves recruitment of ______.
eosinophils
neutrophils
Asthma drugs work by doing 1 of 4 different things. What are they?
They stymie the allergic response
They diminish the number of immune cells in the lung
They alter the production of bronchoconstrictors
They attenuate the activities of bronchoconstrictors and mucus producers
Beta 2 adrenergic receptor agonists are good for treatment of asthma why?
Because their activation literally causes bronchodilation
Agents that increase Ca++ in smooth muscle will act as ________ and agents preventing Ca++ from increasing in the cell will act as _______.
Bronchoconstrictors
Bronchodilators
Beta 2 adrenergic receptors lead to vasodilation by activating PKA. Why/how does this work?
Well, when PKA is activated it activates K+ channels which leads to hyper polarization of the membrane. This hyper polarization of the membrane leads to a reduction in cellular Ca++. Calcium works on MLCK and if there’s not enough calcium then MLCK gets no love and contraction isn’t happening
There are long and short acting beta agonists. They are called SABA and LABA short or long acting beta agonists.
Great.
How long do SABA’s last? What are they primarily used for?
4-6 hours
Used for rescue- IE albuterol
What are LABA’s used for?
They are not for acute treatment, but rather for maintenance therapy
Why, in a general sense, do corticosteroids work in the treatment of asthma?
Corticosteroids are general immunosuppressant agents- asthma is an overactive immune response, so suppressing that would be beneficial because it would lead to a reductio not eosinophils in the lungs
T/F an important marker of the effe liveness of corticosteroid treatment is the reduction of neutrophils in the lung of an asthmatic after treatment?
False- it should be the reduction of eosinophils that we’re looking for.
Cortisol has a ton of functions. In this lecture they are organized into 6 main points. What are they?
- Carbohydrate and protein metabolism
- Lipid redistribution
- Cardiovascular and respiratory functions- increased expression of adrenergic receptors (both types)
- Increased bone breakdown and weaker skin results
- Has CNS effets on mood and such
- They are anti-inflammatory agents
Inflammation involves immune cells producing and secreting agents that damage tissue at the site. This can be accelerated by agents that recruit immune cells to the inflammatory site or increase the secretion of the harmful agents. Anti-inflammatory agents act by diminishing these processes.
Good to know
Glucocorticoids (like cortisol) have a ton of anti-inflammatory effects. Let’s get a little more specific. What are the three things that they do?
- They weaken leukocyte trafficking so that more leukocytes can’t be recruited to the site
- They have some effects on innate immunity- mostly detrimental to the activity of neutrophils, eosinophils, monocytes/macrophages, and mast cells and basophils
- They suppress the production of inflammatory precursors and vasodilatory peptides.
There is such a thing as a glucocorticoid receptor complex. It can modify gene expression. One of the genes that is transcribed that plays a role in weakening the inflammatory response is what? What does it do?
Annexin-A1 (lipocortin)
It attenuates the innate immune response by decreasing leukocyte adhesion and migration, and increasing leukocyte apoptosis.
It also weakens eicosanoid production
The transcription factor _____ regulates genes responsible for both the innate and acquired immune response.
NFkappaB
How do glucocorticoids block NFkappaB mediated transcription?
By chromatin remodeling
Why are inhalation corticosteroids a good idea?
What are some adverse effects?
It minimizes systemic effects.
You could potentially have some dysphonia, some oropharyngeal candidiasis, maybe a little adrenal suppression
Why do some patients not respond to ICS’s (inhaled corticosteroids)?
Non-Eosinophilic asthma- ICS’s won’t be effective
Glucocorticoid resistance- clearly they won’t work with this going on.
