Flashcards in Airway Pharmacology Deck (22):
Name 5 of the most common drugs used in respiratory diseases.
• Salbutamol + Salmeterol
• Ipratropium + Tiotropium
• Theophylline (aminophylline) – don’t use as much as makes people vomit
Describe the parasympathetic innervation of our airways leading to bronchoconstriction.
Muscarinic (Ach) receptors cause bronchoconstriction and mucus secretion. Pre-ganglionic fibres -> Ach at ganglia -> post-ganglionic fibres -> release Ach at smooth muscle/gland -> bronchoconstriction/mucus release.
Describe the parasympathetic innervation of our airways leading to bronchodilation.
Parasympathetic fibres that release NO at smooth muscle which causes bronchodilation. So, there is generally a balance with your airways sitting at a constant level of tone.
Name two anti-muscarinic drugs which can be inhaled.
Ipratropium: Short acting (3hr)
Tiotropium: Long acting (24hr)
These drugs are not very well absorbed into the blood stream, which is good because we don’t want anti-muscarinic effects all over the body.
**Drugs are routinely used in COPD because they have combined bronchodilator and anti-mucus effect, but with regards to asthma we only use it for severe acute asthma.
Humans have no sympathetic innervation to their airway smooth muscle. The smooth muscle does contain ****** receptors.
Beta 2. Adrenaline gets to this via the blood causing bronchodilation.
Why is frightening someone a good remedy for asthma?
Because of the adrenaline released acting on beta receptors leading to bronchodilation.
He also noticed a very strong cup of coffee is a good remedy for asthma attack, this is because it contains theophylline.
**Discovered by Henry Hyde Salter
What are the mediators that mediate Bronchoconstriction and which pathway is triggered?
Acetylcholine, histamine, leukotrienes, prostaglandins, endothelins and others. AKA the inflammatory soup. Cause contraction via DAG+PLC causing increased Ca2+.
What does the inflammatory soup mean for the treatment for brochoconstriction?
You can’t possibly block all their receptors, so it is easier to give a drug that causes relaxation of airway smooth muscle (rather than blocking everything that causes bronchoconstriction).
The last thing you want during an asthma attack is increased demand of O2 by the heart. Therefore, we use β2 selective agonists, as β2 are in the lungs while β1 are in the heart.
How does giving adrenaline (a β2 agonist) cause airway relaxation?
Increased stimulation of Adenylate cyclase and increase in cAMP -> More PKA -> PKA/cAMP inhibits MLCK -> relaxation (by reducing Ca2+ and decreasing sensivity to Ca2+).
Name one long and one short acting β2 agonist.
Salbutamol – short acting (3hrs) – generally all asthmatics will carry this.
Salmeterol – Long acting (12hrs) – could be dodgy as if airways permanently dilated things such as inflammation could be getting worse but you wouldn’t notice the symptoms.
What type of inhibitor is Theophylline?
Theophylline inhibits the breakdown of cAMP by phosphodiesterase (i.e. it is a phosphodiesterase inhibitor).
How does Theophylline cause airway relaxation?
Usually adenylate cyclase gets ATP and converts it to cAMP which causes relaxation. The cAMP is then broken down to AMP by phosphodiesterase. If we stop the breakdown of cAMP then cAMP levels will rise.
What is a common problem with Theophylline?
Theophylline has a narrow therapeutic window, i.e. short space of dosage for treatment between there being no clinical effect and vomiting and headaches.
What, other than bronchconstriction, does the inflammatory soup trigger?
Also causes mucus secretion, stimulate other inflammatory cells (e.g. mast cells which release more mediators). Also cause plasma leakage (permeability), this causes swelling which narrows airways. Also, there is more sensitive nerve activation (nerves more sensitive), so there is more cough.
How do Glucocorticosteroids inhibit the expression of inflammatory genes?
They stop the transcription of these genes for inflammatory mediators so this stops inflammation.
However, this takes a while. People just stick to the instant relief bronchodilators.
A downside is that you could also reduce the effectiveness of your immune system. This is immunosuppression.
**Mainly used in asthma
What are leukotrienes?
Mast cells are a rich source of inflammatory mediators. Leukotrienes are a family of such mediators.
What is a leukotriene antagonist? Give an example.
inhibit/block some of these mediators using Leukotriene antagonists e.g. Montelukast.
It showed to be useful prophylactically (to prevent disease) in some patients (sub-types of asthamatics), e.g. exercise induced asthma.
Outline the guidelines for treating someone with asthma.
Guidelines run from being very easy to treat on one end i.e using a short acting β2 agonist (step 1) to more severe (hospital + Anti IgE and specialist care) step 5. What you’re always trying to do is wean people back to the easy to treat end, being aware of the fact they may flare up at times e.g. in winter. As we progress to the more severe steps we add inhaled Corticosteroids, LABA's, Oral CS and leukotriene antagonist.
Why is COPD harder to treat than asthma?
It is a mixture of emphysema – which nothing can be done about, you can’t do much about the fact they lost a lot of lung structure and surface area, the bronchitis – causing inflammation in their airways tends to be resistant to steroids.
What are the recommended medications for patients with COPD?
SABA or SAMA (short acting muscarinic antagonist) and see what happens, if patient comes back having taken the SABA and didn’t like it then give them the SAMA and vice versa.
What happens when symptoms of COPD persist?
If FEV1 is greater than 50%, so lungs aren’t in severe condition, we can think of adding a LABA (long acting beta2 agonist) or a LAMA (long acting muscarinic antagonist) depending on what they liked previously.
If their lung function is poor, we can think of adding a corticosteroid to a beta agonist drug or we could add the LAMA.