Asthma Drugs Flashcards
The bronchial smooth muscle has innervation ONLY from which portion of the nervous system? PNS or SNS?
PNS assumes the dominant role in the modulation of bronchial smooth muscle tone. The SNS does not directly act on bronchial smooth muscle.
If SNS stimulation doesn’t work on bronchial smooth muscle, how the hell does it work?
Hetero-receptors. Remember that stimulation of one branch of the autonomic nervous system simultaneously inhibits the other branch via heteroreceptors located on the other branch’s neurons. Example: Epinephrine is released. It not only binds to and stimulated a1, and B1 receptors on catecholaminergic neurons, it also binds to B2 receptors on the presynaptic membrane of PNS neurons. This inhibits the release of Ach, helping the SNS signal potentiate. So we don’t directly cause the relaxation of smooth muscle by giving Allopurinol, we just prevent the parasympathetic tone from constricting it.
The vagus nerve sends efferent signals to parasympathetic effector neurons in the lungs. What happens?
PNS controls bronchial smooth muscle tone and glandular secretions. Contraction and hypersecretion of mucus. = Asthma.
What type of neuroendocrine receptors are part of the parasympathetic system?
Muscarinic
Which subtype of muscarinic receptors is responsible for hypersecretion of mucus?
M1, M3
What subtype of muscarinic receptors of responsible for bronchial smooth muscle tone?
M1
What do M2 receptors do?
THey’re autoreceptors on the presynaptic membrane of PNS effector neurons. When stimulated they prevent the release of more Ach.
Why do we care about the specificity of muscarinic receptors and what they do? Explain it in the context of Atropine.
Atropine is a muscarinic antagonist. We learned about it in Cardio, where it is used to treat paroxysmal SVT. It blocks the stimulation of M2 and M3 receptors (nonspecific receptor antagonism). This produces a Jekyl and Hyde effect in the lungs. At first, it causes bronchial relaxation, but when the M2 receptor is inhibited as well, more endogenous Ach is allowed to be released, offsetting the bronchodilatory effects of the M3 receptor blockade.
What effect does a muscarinic antagonist have on mucus production?
Drying up, decreasing secretions.
Explain the paradox of B2 antagonist administration, and how it is the balance of opposing forces.
No clue. Look it up.
Do B agonists have an effect on cilia?
They increase the beat frequency of cilia, facilitating mucociliary clearance.
At high concentrations, what adverse effects can a B-agonist produce?
CV stimulation (high doses) QT prolongation, esp in the presence of hypokalemia Arterial dilation Muscle spasm
You prescribe your patient a B-agonist for their asthma, and they develop weird muscle twitches. Explain this.
B2 stimulation in skeletal muscle causes increased action of the Na+/K+ ATPase. Apparently it makes them more sensitive to stimuli, and membrane depolarization. Leads to increased intracellular K+ and decrease in serum K+, promoting QT prolongation.
Your patient is on Propofenone for a congenital arrhythmia, and has recently developed adult-onset asthma. Can you give them B2 agonists? What other drugs can you not co-prescribe Allopurinol with?
Nope. Also Loop diuretics/Thiazdes –> cause Hypokalemia anyway Non-specific B blockers like Propranolol –> removes the ability to treat bronchospasm.
M1 and M3 parasympathetic receptors are coupled to what type of G protein? M2? B2?
M1, M3 = Gq M2 = Gi B2 = Gs (adenylyl cyclase)
Some patients that frequently use their rescue inhaler experience a loss of drug potenty/effectiveness. Explain this. What cool thing can you do to make them drug-sensitive again?
Overstimulation of the B2 receptor causes downregulation of it. Give the patient corticosteroids that increase transcriptional activity of new functional B2 receptors, restoring drug sensitivity. He doesn’t say how this works.
How do corticosteroids prevent asthma attacks?
They reduce the inflammation that is the root of the exacerbations. Inflammation causes the epithelial damage, which hypersensitizes the bronchial epithelium to irritants. Corticosteroids have no immediate effect on exacerbations, but serve as a preventative measure.
Name all the ways Albuterol helps treat asthma.
- Stimulates B2 receptors, resulting in the relaxation of bronchial smooth muscle 2.Inhibits the release of inflammatory mediators 3. Stimulates mucociliary clearance
What are some side effects of albuterol? What analog of albuterol has fewer side effects?
- Skeletal muscle tremor 2. CV effects: Decreased BP, tachycardia, hypokalemia, arrhythmias. LEVALBUTEROL has fewer side effects.
Name the 2 non-selective adrenergic antagonists. Which can you get OTC? What’s it called?
Isoproterenol Epinephrine (called Primatene Mist)
Name the 2 LABAs used most often.
SALMETEROL FORMOTEROL
Explain the buffalo hump syndrome that sometimes comes as a side effect of oral corticosteroid use.
Cushings Syndrome: Moon face, weight gain, buffalo hump, with thinning legs and arm muscles. Increased acne, facial hair growth, scalp hair loss Acanthosis (neck darkening)
