Therapeutics I Exam VII (Pharmacology of Asthma and COPD Medications) Flashcards
Pharmacology of Asthma and COPD Medications
Define asthma.
Asthma is defined as airway hyperactivity. A trigger will enter the bronchioles and in an asthmatic person, the bronchial tubes tighten and thicken, making the air passages become inflamed and mucus filled.
What are triggers for asthma?
Allergens, airborne particles, drugs (beta antagonists), infection, exercise, stress, and cold temperature.
Define COPD.
COPD is chronic obstructive pulmonary disease. It is the progressive and irreversible disease of limited airflow. There are two types of COPD; chronic bronchitis and emphysema.
What are some causes of COPD?
Smoking, pollution, and genetic predisposition
What is chronic bronchitis COPD?
This is COPD characterized by cilia damage and mucus not longer being sweep upward to clear the airway.
What is emphysema COPD?
This is COPD characterized by alveoli walls being permanently destroyed which leaves spaces too large to produce enough tissue surface area for proper oxygen exchange.
What genetic predisposition/ deficiency is linked to COPD development?
alpha-1-antitrypsin deficiency has been show to increase the risk for COPD.
T or F: Pneumonia is a case/risk factor for COPD.
False
Which 4 classes of drugs are used to relieve bronchial tone/obstruction via direct action on airway smooth muscle?
- Beta receptor agonists (mainly B2 agonists)
- Phosphodiesterase inhibitors
- Adenosine A2B antagonists
- M3 muscarinic acetylcholine receptor antagonists
What are the 5 classes of anti-inflammatory drugs that are used to reduce inflammation/obstruction/ bronchial tone?
- Phosphodiesterase inhibitors
- Corticosteroids
- Mast cell degranulation inhibitors
- Leukotriene modifiers
- Anti-IgE and Anti-interleukine antibodies and antagonists
How does muscarinic activation alter bronchial smooth muscle?
Muscarinic receptor activation in bronchial smooth muscle primarily leads to contraction (bronchoconstriction) and increased mucus secretion through the release of acetylcholine from parasympathetic nerves, activating post junctional muscarinic receptors.
How does muscarinic inhibition/antagonism alter bronchial smooth muscle?
Muscarinic receptor antagonism in bronchial smooth muscle leads to bronchodilation and decreased mucus secretion.
How does phosphodiesterase inhibition alter bronchial smooth muscle?
Phosphodiesterase 4 is the enzyme that breaks down cGMP in the body which decrease the ability for the bronchial to dilate. When we inhibit this enzyme, levels of cGMP are increased which will causes bronchodilation.
In the treatment of asthma and COPD, selective beta 2 agonists are typically used as they are much more selective for the lungs. However, it what situation would non-selective beta agonists like epinephrine and isoproterol be used?
Epinephrine would be used in situation of an emergency wheezing attack. It agonizes B1, B2, and some B3. Isoproterol is a B1 and B2 agonist that is used for rapid reversal of bronchospasms under anesthesia.
What is the MOA for isoproterol (Isoprenaline)?
B1 and B2 agonist
What is the brand name for isoproterol?
Isoprenaline
What is the indication for use of isoproterol (Isoprenaline)?
Rapid reversal of bronchospasms under anesthesia
What is the MOA of epinephrine?
B1, B2, and some B3 agonist
What is the indication for use of epinephrine in terms of asthma and COPD?
Emergency wheezing attack
What is the main issue with using agents like epinephrine and isoproterol chronically for asthma and COPD?
These are short-acting medications and we prefer long-acting medications for chronic treatment of asthma and COPD. Additionally, these medications will cause tachycardia.
Explain beta adrengeric receptor activiation.
A beta agonist will bind to the its g-protein coupled receptor with activates adenylyl cyclase which increase intracellular cAMP and activates protein kinase A.
What are LABAS?
LABAS are long-acting beta-2 receptor agonists
What is the typically dosing regimen for LABAS?
Twice daily dosing
What are the 2 LABAS we need to know?
Salmeterol (servent) and Formoterol (Perforomist)
What is unique about the LABAS, salmeterol?
It has a 12 hour duration of action even though it has a 2-2 hour half-life.
LABAS and SABAS are poor substrates for what 3 reuptake/breakdown enzymes?
COMT, NET, and DAT
This allows these medications to stay active for longer.
Salmeterol is a _____________ drug.
Lipophilic
What is the brand name for salmeterol?
Servent
What is the brand name for formoterol?
Perforomist
What is the half-life of formoterol?
10-12 hours
Salmeterol is a ________ _________ of the beta 2 receptor, allowing it to have a slower onset of action
Partial agonist
What is a unique characteristic of highly lipophilic inhaled medications?
They can leave their receptor and lurk in the lipid bilayer until they can reactivate the receptor.
What are the 2 ultra-LABAS we need to know?
Vilanterol and Olodaterol (Striverdi Respimat)
What is the daily dosing for ultra-LABAS?
Once daily dosing
What are the 3 SABAS we need to know?
Albuterol, pirbuterol, and terbutaline
What is the definition of a SABAS?
Short-acting beta 2 receptor agonists
What is the indication for use of SABAS?
Reversal of asthma symptoms and to provide protection against asthma triggers.
What are some possible side effects associated with SABAS?
Muscle tremors, tachycardia, and hypokalemia
What are the two brand names associated with albuterol?
Ventolin and Proventil
T or F: Corticosteroids are bronchodilators that augment SABAS and LABAS by upregulate the transcription of beta 2 receptors.
False. Corticosteroids do do this, but they are NOT bronchodilators.
Corticosteroids increase the transcription of what receptor?
Beta 2 receptors
What are the 2 adenosine A2B receptor antagonists we need to know?
Theophylline and aminophylline. These drugs are called methylxanthines.
Which medication is more efficacious for asthma and COPD; LABAS, corticosteroids, or adenosine A2B receptor antagonists like theophylline?
LABAS and corticosteroids are more efficacious compared to adenosine A2B receptor antagonists.
The adenosine A2B receptor antagonists, theophylline and aminophylline, are called ________________.
Methylxanthines
Why can adenosine A2B receptor antagonists be used in asthma and COPD?
These drugs block the adenosine A2B receptor so adenosine can not trigger smooth muscle bronchconstriciton.
What are LAMAS?
Long-acting muscarinic receptor antagonists
What are SAMAS?
Short-acting muscarinic receptor antagonists
What are the 3 LAMAS we need to know?
Tiotropium (Spiriva), Umeclidinium (Incruse), and Aclidinium (Tudorza)
LAMAS and SAMAS are less effective compared to LABAS and SABAS for _________ but more effective in _________.
Asthma
COPD
What is the brand name for the LAMA, tiotropium?
Spiriva
What is the brand name for the LAMA, Umeclidinium?
Incruse
What is the brand name for the LAMA, Aclidinium?
Tudorza
What is the one SAMAS we need to know?
Ipratropium (Atrovent)
What is the brand name for the SAMAS, Ipratropium?
Atrovent
What phosphodiesterase subtype is inhibited for asthma and COPD treatment?
Subtype 4
What is the one long-acting PDe4 inhibitor we need to know?
Roflumilast (Daliresp)
What is the brand name for the PDE-i4 inhibitor, Roflumilast
Daliresp
T or F: Roflumilast is a prodrug.
False. It is an active drug when taken but does become more active once converted to roflumilast N-oxide.
T or F: The PDEi4, Roflumilast, is effective in both COPD and asthma.
True
Explain corticosteroid binding.
Corticosteroids binds to their receptor and enter the nucleus, binding to CREB binding protein. The dimer complex between the ICS and its receptor inhibit the CREB binding protein HAT activity meaning the histone is not acetylated so it does not unwind and therefor the inflammation gene is not transcribed.
Corticosteroids suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2).
ICS-GR binds what two things?
- CREB binding protein- stops inflammatory gene expression
- Histone deacetylase enzyme (HDAC2)- shuts down inflammation
What are the 5 big things that inhaled corticosteroids do to airway inflammation and structural cells?
- Inhibit inflammatory cytokine formation and release
- Induce eosinophil apoptosis
- Inhibit inflammatory gene expression in epithelial cells
- Reverse vascular permeability and reduce edema
- Decrease mucus secretion
(NO EFFECT ON AIRWAY SMOOTH MUSCLE OR MAST CELL RELEASE OF MEDIATORS)
What 2 things do inhaled corticosteroids not do?
They do NOT have any effect on airway smooth muscle AND it has NO effect on mediator release from mast cells.
What percentage of inhaled drug actually makes it to the lungs?
Only 10-20%. The other 80-90% is actually just swallowed.
What are the two inhaled corticosteroid prodrugs we need to know?
Beclomethasone propionate (QVAR) and Ciclesonide (Alvesco)
What is the brand name for the ICS, beclomethasone propionate?
QVAR
What is the brand name for the ICS, ciclesonide?
Alvesco
The two ICS prodrugs rely on what enzyme in the lungs to become activated?
Lung esterases
Which ICS was discontinued, but was the first one of its kind on the market?
Beclomethasone propionate (QVAR)
What is the active metabolite of the ICS ciclesonide?
Des-ciclesonide
Is ciclesonide (Alvesco) categorized as a short or long-acting ICS?
Long-acting (6-7 hour half-life)
What are the 4 other inhaled corticosteroids we need to know that are not prodrugs?
Budesonide (Pulmicort), Fluticasone (Flovent), Momentasone (Asmanex), and Triamcinolone (Azmacort)
What is the half-life of the ICS budesonide?
3 hours
What is the half-life of the ICS fluticasone?
12 hours
What is the half-life of the ICS Momentasone?
6 hours
What is the half-life of the ICS triamcinolone?
2 hours
Rank the half-life of the ICSs from longest to shortest.
- Fluticasone (12hr)
- Ciclesonide (6-7hr)
- Momentasone (6hr)
- Budesonide (3hr)
- Triamcinolone (2hr)
Systemic corticosteroids are reserved for ________ cases of asthma and COPD.
Severe
What are the 3 systemic corticosteroids commonly used long-term for those with severe asthma and/or COPD?
Prednisone (Deltasone), methylprednisolone (Medrol Dosepak), and hydrocortisone (Solu-Cortef)
What are the adverse effects of long-term systemic corticosteroid use?
Bone loss, cataracts, thinning of the skin, HYPOKALEMIA, hyperglycemia, insomnia, weight gain, and stunted growth in children
What is the brand name for prednisone?
Deltasone
What is the brand name for Methyprednisolone?
Medrol Dosepak
What is the brand name for hydrocortisone?
Solu-cortef
Which of the 3 systemic corticosteroids is administered via IV?
Hydrocortisone
What is the brand name for the combination inhaler ipratropium and albuterol?
Combivent Respimat
Ipratropium (SAMA)
Albuterol (SABA)
What is the brand name for the combination inhaler olodaterol and tiotropium?
Stiolto Respimat
Olodaterol (LABA)
Tiotropium (LAMA)
What is the brand name for the combination inhaler budesonide and formoterol?
Symbicort
Budesonide (Short acting corticosteroid)
Formoterol (LABAS)
What is the brand name for the combination inhaler fluticasone + salmeterol?
Advair
Fluticasone (long-acting)
Salmeterol (LABAS)
What is the brand name for the combination inhaler fluticasone and vilanterol?
Breo Ellipta
Fluticasone (long-acting)
Vilanterol (LABAS)
What is the brand name for the combination inhaler Fluticasone + Umeclidinium + Vilanterol?
Trelegy Ellipta
Fluticasone (long-acting)
Umeclidinium (LAMAS)
Vilanterol (LABAS)
What is the brand name for the combination inhaler Umeclidinium and vilanterol?
Anoro Ellipta
Umeclidinium (LAMAS)
Vilanterol (LABAS)
What is the brand name for the combination inhaler Momentasone and formoterol?
Dulair
Momentasone (Short-acting)
Formoterol (SHABA)
Corticosteroid binding reduces inflammation via what 3 routes?
- Activate Tristetraprolin (anti-inflammatory)
- Activate Annexin A1 (anti-inflammatory)
- Inhibit NK-FB (proinflammatory)
ICS also block the formation of ____________ and ___________ by indirectly blocking arachidonic acid formation.
Leukotrienes and autacoids
What enzyme cleaves arachidonic acid to make a platelet-activating factor?
Phospholipase A2
Explain COX formation from the plasma membrane.
Phospholipids are used to create arachidonic acid and it converted to LOX (leukotrienes), COX, and platelet-aggrevating factor via the phospholipase A2.
Which drug is a lipoxygenase inhibitor that blocks the formation of leukotrienes?
Zileuton
Which drugs antagonize the leukotriene 1 receptor?
Montelukast, Pranlukast, and Zafirlukast
What is the brand name for the 5-lipoxygenase inhibitor, Zileuton?
Zyflo
What is MOA of Zileuton (Zyflo)?
It stop the conversion of arachidonic acid to leukotrienes by inhibiting 5-lipoxygenase.
Zileuton (Zyflo) is associated with what side effect?
Hepatic problems
What is the brand name for montelukast?
Singulair
What is the brand name for Zafirlukast?
Accolate
What are the two adverse effects associated with the leukotriene cys-LT1 receptor antagonists like montelukast and zafirlukast?
Vasculitis and neuropsychiatric disorders
What are the 5 monoclonal antibodies that are used for severe asthma and COPD?
Benralizumab
Mepolizumab
Reslixumab
Dupilumab
Omalizumab
What is the main function of Omalizumab (Xolair)?
Anti-IgE mab. It blocks IgE from binding to its receptor which stops chronic inflammation.
What is the main function of Dupilumab (Dupixent)?
Anti-IL-4R alpha receptor mab. It blocks IL-4 and IL-13 activation of IL-4 receptor alpha which blocks B cell formation of IgE.
What is the main function of Mepolizumab (Nucala) and Reslizumab (Cinqair)?
These mabs bind and immobilize circulating IL-5 that would otherwise cause eosinophilic inflammation.
What is the main function of Benralizumab (Fasenra)?
Blocks IL-5 activation of IL-5 receptor alpha so eosinophils are not activated.
What is the brand name for Omalixumab?
Xolair
What is the brand name for Dupilumab?
Dupixent
What is the brand name for Mepolizumab?
Nucala
What is the brand name for Reslizumab?
Cinqair
What is the brand name for Benralizumab?
Fasenra
