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1- Abstract
2- The pathogenesis of COPD
3- Examples of medications
4- Mechanism of action
5- Dose
6- Side effects
7- Risks
8- Drug – Drug interaction
9- Drug – food interaction
10- Monographs
1- Abstract
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.
2- The pathogenesis of COPD
Under the stimulation of cigarette smoke, pathogen infection and other factors, oxidative stress is induced and the pulmonary inflammatory cells (neutrophils, CD8 T lymphocytes, macrophages) accumulate, resulting in a large number of reactive ROS. The inflammatory cells are activated by the NF-κB, p38MAPK and PI3K signalling. Inflammatory cells (mainly neutrophils) migrate from the circulation to the inflammatory site under sequential regulation involving cytokines and adhesion molecules such as selectin. Proteases are involved in tissue remodelling, inflammation and ECM degradation, thereby participating in the pathological process of COPD. Inflammatory cytokines and chemokines, such as LTB4, IL-8 and TNF-α, and other mediators are secreted into the lungs to aggravate the lung tissue damage and promote inflammatory responses. PDE4 decreases cAMP levels in inflammatory cells and promotes inflammatory cell activity and the release of inflammatory factors. Chronic inflammation stimulates the increase of EGFR and TGF-β1. Activated EGFR is involved in the proliferation of the airway epithelial goblet cells and mucus production. TGF-β1 chemoattracts neutrophils, macrophages and mast cells, and activates PI3K/Akt and/or p38MAPK signalling to induce pulmonary fibrosis and EMT. Endothelin-1 (ET-1) produced by endothelial cells, stimulates the contraction and proliferation of vascular smooth muscle cells and the liver to produce more CRP, and it also induces the synthesis.
3- Examples of medications
Bronchodilators
Bronchodilators are medications that usually come in inhalers — they relax the muscles around your airways. This can help relieve coughing and shortness of breath and make breathing easier. Depending on the severity of your disease, you may need a short-acting bronchodilator before activities, a long-acting bronchodilator that you use every day or both.
Examples of short-acting bronchodilators include:
Albuterol (ProAir HFA, Ventolin HFA, others)
Ipratropium (Atrovent HFA)
Levalbuterol (Xopenex)
2.Examples of long-acting bronchodilators include:
Aclidinium (Tudorza Pressair)
Arformoterol (Brovana)
Formoterol (Perforomist)
Indacaterol (Arcapta Neoinhaler)
Tiotropium (Spiriva)
Salmeterol (Serevent)
Umeclidinium (Incruse Ellipta)
Inhaled steroids
Inhaled corticosteroid medications can reduce airway inflammation and help prevent exacerbations. Side effects may include bruising, oral infections and hoarseness. These medications are useful for people with frequent exacerbations of COPD. Examples of inhaled steroids include:
1- Fluticasone (Flovent HFA)
2- Budesonide (Pulmicort Flexhaler)
4- Mechanism of action
Beta 2 adrenoceptor agonists (B2-agonists)
Mechanism of action B2 adrenergic receptors (B2AR) are present in high density in airway smooth muscle cells. B2 agonists act by binding to the B2AR (Fig. 1). Interaction of the receptor with intracellular G proteins stimulates the production of intracellular cyclic adenosine monophosphate (cAMP). This leads to activation of protein kinase A, which results in phosphorylation of various targets mediating smooth muscle relaxation. The exact targets are unknown but probably involve myosin light chain kinase and calcium dependent potassium channels.
Indacaterol is an ultra-long acting, once daily LABA; it is the only agent of this type currently on the market, although others are in development, including vilanterol.34 It is a partial B2 agonist which exhibits high intrinsic efficacy at the B2AR, more than two fold that of salbutamol and salmeterol.35 Partial agonists can exhibit antagonist behavior in the presence of an agonist with higher receptor efficacy, which could potentially result in inhibitory action of rescue medication, an effect which has been shown with salmeterol but not indacaterol.35 Studies using indacaterol have demonstrated a relatively rapid onset of action (5 minutes) with peak effect occurring at 15 minutes and lasting 24 hours.35 The rapid onset of action and length of duration of action is related to both the high affinity of indacaterol to the lipid raft domains within the B2AR membrane and its intrinsic efficacy at the receptor level.35 Following administration, the bioavailability of indacaterol is 43%, with a steady state reached after 12 to 14 days. It is primarily metabolized to a hydroxylated derivate by the CYP3A4 enzyme, and subsequent to this, to phenolic O glucuronides and other metabolites. Elimination occurs via the fecal route, with less than 2% being excreted unchanged in the urine.
5- Dose
Budesonide
Budesonide is usually taken as one dose per day, often in the morning, and can be taken with or without food, with a glass of water.
Budesonide is usually used rectally twice a day, in the morning and evening, for two weeks.
2- albuterol
1 to 2 puffs are usually taken as needed to relieve symptoms
1 to 2 puffs may be taken about 15 minutes before exercise or exposure to a trigger substance to prevent symptoms
Do not used more than 2 puffs every 4 hours up to a maximum of 4 times (up to 8 puffs) in 24 hours
If your inhaler does not relieve your symptoms for at least 3 hours then contact your healthcare provider.
3- Beclomethasone
Recommended dose for adults: two inhalations (200 mcg salbutamol with 100 mcg beclomethasone) three or four times a day.
Recommended dose for children: One or two inhalations (100 or 200 mcg salbutamol with 50 or 100 mcg beclomethasone) two, three or four times a day.
6- Side effects
Gastrointestinal Diarrhea
nausea
Musculoskeletal
Arthralgia Nervous System
Headache
Respiratory Nosebleeds
nervousness or tremors
headache
throat or nose irritation
muscle pain
While more serious side effects - although less common - include increased heart rate, called tachycardia, or a feeling of fluttering or oscillations, called heart palpitations.
7- Risks
Air pollution
Exposure to air pollution over a long period can affect how well the lungs work and some research suggests it could increase your risk of COPD.
But the link between air pollution and COPD is not conclusive and research is continuing.
Genetics
You're more likely to develop COPD if you smoke and have a close relative with the condition, which suggests some people's genes might make them more vulnerable to the condition.
People with alpha-1-antitrypsin deficiency can go on to develop COPD. Alpha-1-antitrypsin is a substance that protects your lungs. Without it, the lungs are more vulnerable to damage.
People who have an alpha-1-antitrypsin deficiency usually develop COPD at a younger age – particularly if they smoke.
Smoking
Smoking is the main cause of COPD and is thought to be responsible for around 9 in every 10 cases.
The harmful chemicals in smoke can damage the lining of the lungs and airways. Stopping smoking can help prevent COPD from getting worse.
8- Drug – Drug interaction
(Abametapir) The serum concentration of Beclomethasone dipropionate can be increased when it is combined with Abametapir.
(Abatacept ) The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Abatacept.
(Abemaciclib) The metabolism of Abemaciclib can be increased when combined with Beclomethasone dipropionate.
(Acalabrutinib) The metabolism of Acalabrutinib can be increased when combined with Beclomethasone dipropionate.
(Acarbose) The risk or severity of hyperglycemia can be increased when Beclomethasone dipropionate is combined with Acarbose.
(Beclomethasone) inhaled has serious interactions with the following drugs:
aldesleukin
BCG intravesical live
BCG vaccine live
echinacea
hyaluronidase
leflunomide
macimorelin
natalizumab
pimecrolimus.
9- Drug – food interaction
Take beclomethasone in the morning so the levels in your body are lowest at bedtime. Avoid having a big meal, smoking, or drinking alcohol, tea or coffee in the evening.
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