Asthma/COPD Pharmacology (Young)

Drug treatment for asthma and COPD aims to relieve/prevent bronchoconstriction, inhibit airway inflammation, prevent airway remodeling, and manage asthma/COPD. However, it does not aim to cure asthma/COPD. Asthma and COPD are chronic conditions that currently do not have a known cure. The goal of drug treatment is to control symptoms, improve lung function, and prevent exacerbations, but it cannot completely eliminate the underlying condition.

Beta-2-agonists are medications that relax the muscles in the airways, making it easier to breathe. They are commonly used to treat conditions such as asthma and chronic obstructive pulmonary disease (COPD). One of the side effects of beta-2-agonists is tremors, which are involuntary shaking movements. Headaches can also occur as a side effect. Tachycardia, or a rapid heart rate, is another potential side effect. However, bradycardia, which is a slow heart rate, is not typically associated with beta-2-agonists. Hypertension, or high blood pressure, can also occur as a side effect.

Anticholinergics are believed to be more effective in managing COPD than asthma because they block muscarinic receptors on bronchial smooth muscle, preventing muscle contraction and reducing mucus production. This helps to alleviate the symptoms of COPD, such as bronchoconstriction and excessive mucus production. In asthma, on the other hand, bronchodilation is needed to relieve symptoms, which anticholinergics do not provide as effectively. Therefore, anticholinergics are considered more beneficial in the management of COPD compared to asthma.

Allergic rhinitis, or hay fever, is caused by an inflammatory response triggered by the activation of mast cells. Histamine is a primary mediator released by mast cells during this process, causing symptoms such as itching, sneezing, and nasal congestion. Leukotrienes are secondary mediators that are also released by mast cells and contribute to the inflammatory response, leading to symptoms such as nasal congestion and inflammation. Therefore, the correct answer is Primary: Histamine, Secondary: Leukotriene.

Roflumilast and cilomilast are specific phosphodiesterase 4 (PDE4) inhibitors. PDE4 is an isoform of phosphodiesterase enzyme that is involved in the breakdown of cyclic adenosine monophosphate (cAMP) in the cells. By inhibiting PDE4, roflumilast and cilomilast increase the levels of cAMP, which can have anti-inflammatory effects. Therefore, the correct answer is PDE4.

First-generation H1 receptor antagonists are known to have a side effect profile that includes short half-lives and the ability to cross the blood-brain barrier. This means that these anti-histamines are quickly metabolized and eliminated from the body, and they are also able to enter the brain, which can lead to sedation and other central nervous system effects. Therefore, the given answer correctly identifies the side effect profile associated with first-generation anti-histamines.

Alpha-1 antagonists are not drugs that stimulate beta-2 sympathetic receptors. Alpha-1 antagonists work by blocking the alpha-1 adrenergic receptors, which are involved in vasoconstriction. They are used to treat conditions like high blood pressure. On the other hand, sympathomimetics, adrenergics, and beta-2 agonists are all terms used to describe drugs that stimulate the beta-2 sympathetic receptors. Catecholamines are a type of sympathomimetic drug that includes substances like epinephrine and norepinephrine.

All of the options listed in the question are routes of administration for beta-2-agonists. This means that beta-2-agonists can be administered through inhalation solutions, long-acting oral agents, intravenous agents, and inhaled dry powders. Therefore, the correct answer is that all of the above are routes of administration of beta-2-agonists.

Omalizumab (Zolair) is a unique treatment of asthma that uses humanized monoclonal antibodies to target against IgE, which is an immunoglobulin involved in allergic reactions. The most worrisome side effect of this drug is anaphylaxis, a severe and potentially life-threatening allergic reaction.

Levalbuterol is the R-enantiomer of albuterol, which means it is a specific form of the drug that has a higher affinity for the B2 receptor. This higher selectivity for the B2 receptor leads to fewer side effects compared to the racemic mixture of albuterol. Therefore, the correct answer is "higher; B2."

Anticholinergics exhibit all of the listed actions, including decreasing vagal tone, decreasing transmission of airway ganglion, decreasing mucus production, and decreasing neurokinin release and inflammation. Therefore, the correct answer is that all of the above are actions of anticholinergics.

Ephedrine and isoproterenol are the non-selective beta-2-agonists because they bind to both beta-1 and beta-2 adrenergic receptors. Albuterol and pirbuterol are selective beta-2-agonists, as they primarily target the beta-2 adrenergic receptors. Salmeterol and formoterol are also selective beta-2-agonists commonly used as long-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD).

Oropharyngeal candidiasis is a fungal infection that can occur in the mouth and throat as a side effect of using inhaled corticosteroids (ICS). It is characterized by white patches or lesions in the mouth and can cause discomfort and difficulty swallowing. However, with proper inhaler use and education, patients can minimize the risk of developing this side effect. This may include rinsing the mouth after each use of the inhaler and using a spacer device to ensure the medication is delivered directly to the lungs and not deposited in the mouth.

Beta-2 adrenergic agonists primarily alleviate bronchoconstriction. In addition to this, they have several additional benefits. They can reduce plasma exudation, increase ciliary action, stabilize mast cells, and reduce bacterial adherence to epithelial cells. Therefore, all of the given options are actually additional benefits of beta-2 agonists.

Methylxanthines like theophylline prevent the breakdown of cAMP. cAMP is a secondary messenger that plays a crucial role in various cellular processes, including the regulation of MLCK (myosin light chain kinase). By inhibiting the breakdown of cAMP, methylxanthines increase the levels of cAMP in the cell, leading to the inhibition of MLCK. MLCK is responsible for the phosphorylation of myosin, which is necessary for muscle contraction. Therefore, by preventing the breakdown of cAMP, methylxanthines indirectly inhibit MLCK and ultimately relax smooth muscles.

Beta-adrenergic stimulation by agonists increases the production of cyclic adenosine monophosphate (cAMP). In this case, the increase in cAMP leads to the activation of protein kinase A (PKA). PKA then inhibits myosin light chain kinase (MLCK), which is responsible for the phosphorylation of myosin light chain (MLC). By inhibiting MLCK, PKA prevents the phosphorylation of MLC and thereby inhibits smooth muscle contraction. This explains why the correct answer is PKA inhibiting MLCK.

When using intravenous formulations of beta-2-agonists, a larger dose is necessary compared to inhaled formulations. This is because intravenous administration bypasses the lungs and delivers the medication directly into the bloodstream, requiring a higher dose to achieve the desired effect.

Anticholinergics act by blocking muscarinic acetylcholine receptors, which leads to a decrease in intracellular calcium concentration. This decrease in calcium concentration ultimately results in a decrease in stimulation of MLCK (myosin light chain kinase).

The correct answer states that all of the mentioned features are desired in inhaled corticosteroids (ICS) for the long-term treatment of COPD and asthma. This means that ICS should have a high affinity for the glucocorticoid receptor, minimal systemic absorption, high serum protein binding, and rapid systemic inactivation. These features are desired because they allow for targeted delivery to the lungs, reducing the risk of systemic side effects and maximizing the therapeutic effects of the medication.

The cysteinyl receptor is a G-coupled protein receptor, and the inhibition affects the ion Ca++. This inhibition of Ca++ prevents muscle contraction and eosinophil chemotaxis.

Quaternary ammonium is the unique structural feature of anticholinergics that is responsible for its minimum systemic effects. This feature refers to a positively charged nitrogen atom bonded to four alkyl or aryl groups. This structural arrangement allows the anticholinergic to have limited penetration into the central nervous system, reducing the risk of side effects such as sedation or confusion.

Oral decongestants, like pseudoephedrine, work by stimulating alpha-1 adrenergic receptors. This stimulation causes vasoconstriction, which reduces swelling in the nasal passages and helps to relieve congestion. Muscarinic acetylcholine receptor antagonists, glucocorticoid receptor agonists, and H1 histamine receptor agonists do not accurately describe the mechanism of action of decongestants.

The catalytic subunits of PKA phosphorylate MLCK (Myosin Light Chain Kinase) to inhibit airway muscles. MLCK is responsible for phosphorylating myosin, which leads to muscle contraction. By phosphorylating MLCK, the catalytic subunits of PKA inhibit its activity, preventing the phosphorylation of myosin and ultimately leading to muscle relaxation. This mechanism of action is important in regulating airway smooth muscle tone and controlling bronchial constriction.

Long acting beta agonists (LABAs) have a unique structural feature of long hydrophobic carbon tails. This feature allows them to bind tightly to the beta-adrenergic receptors in the lungs, resulting in a prolonged duration of action. The hydrophobic nature of the carbon tails allows LABAs to remain in the lipid-rich cell membrane for an extended period, leading to sustained activation of the receptors and a longer-lasting bronchodilator effect. The other options, such as hydrophilic OH groups, highly water soluble nitrogen atom, and hydrophobic phenolic rings, may have their own roles in drug activity but do not specifically contribute to the long-acting property of LABAs.

Theophylline and aminophylline have very narrow therapeutic windows, meaning that the range of serum concentrations at which they are effective is very close to the range at which they can cause side effects. In this case, a patient would be expected to exhibit minor side effects such as N&V, nervousness, and insomnia at serum concentrations of 15-25 mcg/ml. This range is higher than the previous options, indicating that a higher concentration of the drug is needed to cause these side effects.

Studies using human and mouse cys-LT receptors have shown that LTD4 is the most important leukotriene ligand in the use of leukotriene inhibitors to treat asthma. This suggests that blocking LTD4 specifically can be more effective in managing asthma symptoms compared to blocking other leukotriene ligands such as LTB4, LTC4, or LTE4. The answer also indicates that leukotriene inhibitors do not block these ligands with the same affinity, further emphasizing the significance of targeting LTD4 specifically.

Cortisol is a hormone that follows a diurnal pattern, meaning its production varies throughout the day. It typically rises in the morning, with its peak occurring around 8 AM. This aligns with the natural sleep-wake cycles of the body. Additionally, cortisol production can be triggered by bursts throughout the day in response to stress or other stimuli. However, cortisol levels do not decrease with caffeine and exercise. In fact, both caffeine and exercise can stimulate cortisol production. Therefore, the correct answer is "decreases with caffeine and exercise."

Palpitations are the sensation of a rapid or irregular heartbeat. Beta 2 receptors are primarily found in the smooth muscle of the bronchioles and blood vessels. While beta 2 receptors can cause relaxation of smooth muscles, they are not directly responsible for palpitations. Palpitations are more commonly associated with the activation of beta 1 receptors, which are located in the heart. These receptors increase heart rate and can lead to palpitations. Therefore, the pairing of palpitations with beta 2 receptors is incorrect.

The correct answer is "Salmeterol causes more side effects, tachycardia and muscle tremor, that lead to death." This is because the question asks for the reason that is NOT attributed to the asthma-related deaths. The other options provided in the question are all valid reasons that can contribute to asthma-related deaths caused by Salmeterol.

Tiotropium is considered a more potent agent than ipratropium because it has tighter binding to the target receptor (M3) and slower dissociation from it. This means that tiotropium stays bound to the receptor for a longer time, leading to a more prolonged and effective action. The tighter binding and slower dissociation contribute to the increased potency of tiotropium compared to ipratropium.

R112 is shown to be effective in allergic rhinitis by blocking the mast cell activation pathway. This suggests that R112 is an inhibitor of Syk, as Syk is a key protein involved in mast cell activation. By inhibiting Syk, R112 can prevent mast cell activation and subsequently reduce the symptoms of allergic rhinitis.

The correct answer is Cholesterol; StAR. Hormone synthesis in the adrenal cortex begins with cholesterol, which is transported into the inner mitochondrial membrane with the help of the StAR (Steroidogenic Acute Regulatory) protein. StAR plays a crucial role in the transfer of cholesterol from the outer to the inner mitochondrial membrane, where it is converted into pregnenolone, the precursor for various adrenal hormones.

The mast cell degranulation pathway and the mast cell eicosanoid synthesis pathway share all the steps mentioned in the options except for Syk activating the PLC-gamma, cleaving PIP2 into IP3 and DAG.

Methylxanthines have several additional benefits for asthma/COPD, including being an antagonist of adenosine, inhibiting the secretion of inflammatory mediators, and strengthening the diaphragm. However, they do not inhibit PKA (protein kinase A), which is a key enzyme involved in many cellular processes. Therefore, the correct answer is "Inhibition of PKA."

Cortisol's anti-inflammatory effects are due to the inhibition of two enzymes: PLA2 and PGH2 synthase (COX 1 and 2). PLA2 is an enzyme that releases arachidonic acid from cell membranes, which is a precursor for the production of inflammatory mediators. By inhibiting PLA2, cortisol reduces the availability of arachidonic acid and subsequently decreases the production of inflammatory mediators. PGH2 synthase, also known as cyclooxygenase (COX), is responsible for the synthesis of prostaglandins, which are potent mediators of inflammation. Cortisol inhibits both COX 1 and COX 2, further reducing the production of inflammatory prostaglandins.

Exogenous glucocorticoids are synthetic forms of cortisol that are used as medications to reduce inflammation and suppress the immune system. Sustained elevation of exogenous glucocorticoids can lead to induced hypertrophy, which refers to an increase in the size of cells or tissues. This is because glucocorticoids can stimulate protein synthesis and promote the growth of muscle fibers. On the other hand, prolonged exposure to exogenous glucocorticoids can lead to induced atrophy, which refers to a decrease in the size of cells or tissues. This is because glucocorticoids can inhibit protein synthesis and promote the breakdown of muscle fibers.