Lecture 2 Flashcards
What drugs are used in replacement therapy for the treatment of severe allergic reactions, asthma, rheumatoid arthritis and some cancers and how?
Glucocorticoids, it inhibits NF and suppresses both B and T cell function by decreasing transcription of many cytokines. Induced T cell apoptosis
what are glucocorticoids used for (other than replacement therapy)
adrenal insufficiency, asthma, CLL, cushings, cataracts.
adrenal insufficiency may occur if the drug is stopped abruptly after chronic use
what are the short acting glucocorticoids
hydrocortisone
cortisone
what are the intermediate acting glucocorticoids
prednisone
prednisolone
methylprednisolone
triamcinolone
what are the long acting glucocorticoids
betamethasone
dexamethasone
what are mineralocorticoids
fludrocortisone
adverse effects of rheumatoid arthritis,
rheumatoid arthritis: daily dose of prednisone is the strongest predictor of occurrence of adverse effects.
averse effects of osteoporosis
the glucocovrticosteroids can suppress the intestinal Ca2+ absorption, inhibits bone formation and decrease sex hormone synthesis.
osteoporosis: take calcium and vitamin D
bisphosphonates can be used to treat glucocorticoid induced osteoporosis.
if we have long term corticosteroid therapy / replacement what can we expect ( adverse effects)
- cushings like syndrome
- cataracts
- hyperglycaemia which can develop into diabetes mellitus
- topical therapy can cause skin atrophy, ecchymosis and purple straie.
what can occur if we have a discontinuation of the corticosteroid drugs.
if patient has suppression of HPA axis then it can be serious, so we have to do an abrupt removal of corticosteroids.
the disease associated with this is Addisons disease. (abdominal pain, nausea, vommiting, shock)
waterhouse friderichsen syndrome-> adrenal haemorrhage in the setting of sepsis
what are some respiratory disorders
Asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis are commonly encountered respiratory disorder
chronic inflammatory disease characterised by by bronchial hyper responsiveness causes what symptoms
Chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic exacerbation (asthma attacks), and reversible airflow obstruction; manifests with reversible cough, wheezing, and dyspnea
what is acute asthma
Acute asthma exacerbation: a reversible worsening of the clinical features of asthma that develops over a short period of time and can progress to life-threatening asthma; may be the first manifestation of asthma in some patients.
what is the most common type of asthma
Allergic asthma: the most common type of asthma; begins with intermittent symptoms in childhood and is usually associated with atopy (e.g., eczema, rhinitis) and a good response to treatment.
what is allergic rhinitis
Allergic rhinitis is a common chronic disease and is characterized by itchy, watery eyes, runny nose, and a nonproductive cough that can significantly decrease quality of life.
ethology and risk factors for asthma
The exact etiology of asthma remains unknown.
Risk factors for asthma include:
Family history of asthma
Past history of allergies
Atopic dermatitis
Low socioeconomic status
what is asthma
obstructive lung disease usually triggered by allergens. It is linked to atopy (a genetic tendency toward allergic diseases) and is characterized by reversible airway obstruction due to bronchoconstriction, inflammation, and mucus production.
A specific form called NSAID- or aspirin-exacerbated respiratory disease (AERD) is associated with asthma, nasal polyps, and a reaction to COX inhibitors (part of Samter’s triad).
Intermittent episodes of dyspnea (shortness of breath), coughing, wheezing, and rapid breathing (tachypnea).
Type I hypersensitivity reaction: A fast immune response that causes inflammation
Asthma is reversible: Unlike other chronic lung diseases, asthma symptoms improve with bronchodilators.
what are some non allergic asthma triggers
cold air
stress
aspirin/ NASIDS
exercise
pathophysiology of asthma
Asthma is an inflammatory disease driven by T-helper type 2 (Th2) cells in genetically predisposed individuals.
Three main pathophysiologic processes:
- Bronchial hyperresponsiveness (airways overreact to triggers).
- Bronchial inflammation (immune cells cause swelling and mucus production).
- Bronchial obstruction due to smooth muscle contraction and lack of supportive cartilage.
Th2-cell overexpression leads to:
- Cytokine release (IL-3, IL-4, IL-5, IL-13) → Activates eosinophils and stimulates IgE production by B cells.
Inflammation and smooth muscle contraction → Leads to bronchiolar collapse and breathing difficulties.
Pathophysiology of Endobronchial Obstruction
Increased Parasympathetic Tone → Leads to reversible bronchospasm and increased mucus production.
Mucosal Edema & Leukocyte Infiltration → Causes hyperplasia of goblet cells, leading to excess mucus.
Hypertrophy of Smooth Muscle Cells → Thickened airway walls contribute to airflow obstruction.
types of asthma
Allergic Asthma (IgE-mediated Type 1 Hypersensitivity)
Triggered by a specific allergen (e.g., pollen, dust mites).
Mast cell degranulation releases histamine after prior sensitization.
Leads to bronchoconstriction, inflammation, and mucus production.
2. Non-Allergic Asthma
Irritant-Induced Asthma:
Triggered by pollutants, smoke, cold air, or chemicals.
Causes neutrophil activation → submucosal edema → airway obstruction.
Aspirin-Induced Asthma (NSAID-Exacerbated Respiratory Disease - NERD):
Part of Samter’s Triad:
Asthma
Chronic rhinosinusitis with nasal polyps
Aspirin/NSAID sensitivity
Mechanism:
COX-1 inhibition → ↓ PGE2 (which normally inhibits inflammation) → ↑ leukotrienes → inflammation & submucosal edema → airway obstruction
asthma symptoms
Persistent, dry cough that worsens at night, with exercise, or on exposure to triggers/irritants (e.g., cold air, allergens, smoke)
End-expiratory wheezes
Dyspnea (shortness of breath)
Chest tightness
Prolonged expiratory phase on auscultation
Hyperresonance to lung percussion
how do we treat asthma
Drugs that Promote Bronchodilation (Airway Relaxation)
1) Beta-agonists (e.g., Albuterol, Salmeterol)
Stimulate adenylate cyclase (AC) → increases cAMP → relaxes bronchial smooth muscle.
Short-acting (SABA): Used for acute attacks (Albuterol).
Long-acting (LABA): Used for maintenance therapy (Salmeterol, Formoterol).
Theophylline (Methylxanthine class)
Inhibits phosphodiesterase (PDE) → prevents cAMP breakdown → increases bronchodilation.
Also blocks adenosine, which normally causes bronchoconstriction.
2) Drugs that Prevent Bronchoconstriction (Airway Constriction)
Muscarinic Antagonists (e.g., Ipratropium, Tiotropium)
Block acetylcholine (ACh) receptors → prevent bronchoconstriction and mucus secretion.
Leukotriene Antagonists (e.g., Montelukast, Zafirlukast)
Block leukotrienes, which normally cause inflammation and airway constriction.
asthma drug classes and mechanisms
β₂-agonists (e.g., Albuterol, Salmeterol) → Activate AC → Increase cAMP → Bronchodilation.
Muscarinic Antagonists (e.g., Ipratropium, Tiotropium) → Block ACh → Prevent bronchoconstriction.
Leukotriene Inhibitors (e.g., Montelukast, Zafirlukast, Zileuton) → Block leukotrienes → Reduce inflammation.
Glucocorticoids (e.g., Fluticasone, Budesonide) → Inhibit phospholipase A2 → Prevent inflammation.
Anti-IgE Therapy (Omalizumab) → Binds IgE → Prevents mast cell activation.
IL-5 Inhibitors (Mepolizumab, Reslizumab, Benralizumab) → Reduce eosinophil activation in severe asthma.
asthma treating drugs summary
Asthma treatment includes bronchodilators (β₂-agonists, Theophylline, Muscarinic Antagonists) and anti-inflammatory drugs (Glucocorticoids, Leukotriene Inhibitors, Monoclonal Antibodies).
Short-term relief: SABAs (Albuterol), Anticholinergics (Ipratropium).
Long-term control: ICS (Fluticasone), LABAs (Salmeterol), LTRAs (Montelukast), Biologics (Omalizumab, Mepolizumab).
explain the SYMPATHOMIMETIC AGENTS as a treatment for asthma
Adrenoceptor agonists are mainstays in the treatment of asthma.
Their binding to β-adrenergic receptors—abundant on airway smooth muscle cells—stimulates adenylyl cyclase and increases the formation of intracellular cAMP thereby relaxing airway smooth muscle and inhibiting release of bronchoconstricting mediators from mast cells
In general, β-adrenoceptor agonists are best delivered by inhalation
what are β2-adrenergic agonists used for
Inhaled β2-adrenergic agonists directly relax airway smooth muscle.
They are used for the quick relief of asthma symptoms, as well as adjunctive therapy for long-term control of the disease.
short-acting β2 agonists (SABAs)
short-acting β2 agonists (SABAs) have a rapid onset of action (5 to 30 minutes) and provide relief for 4 to 6 hours.
They are used for symptomatic treatment of bronchospasm, providing quick relief of acute bronchoconstriction.
Direct acting β2-selective agonists
Direct acting β2-selective agonists include albuterol and levalbuterol
Salmeterol and formoterol are long-acting β2 agonists (LABAs)
LABAs should be used only in combination with an asthma controller medication
adults and adolescents with moderate persistent asthma can use what
Although both LABAs are usually used on a scheduled basis to control asthma, adults and adolescents with moderate persistent asthma can use the ICS/formoterol combination for relief of acute symptoms.
COPD long-acting β2 agonists (LABAs)
Salmeterol, formoterol, indacaterol, and vilanterol are long-acting β2 agonists (LABAs), but indacaterol and vilanterol are currently approved only for COPD.
adverse effects of β2 agonists (LABAs)
Adverse effects, such as tachycardia, hyperglycemia, hypokalemia, hypomagnesemia, and mediated skeletal muscle tremors are minimized with inhaled delivery versus systemic administration.
what are the inhaled β2 agonists and what can it cause
albuterol (short acting) , salmeterol, formeterol (long acting) - relaxes bronchial smooth muscle. can cause tremor and arrhythmia and
what corticosteroid is the drugs of choice for long-term control in patients with any degree of persistent asthma
ICS are the drugs of choice for long-term control in patients with any degree of persistent asthma .
what is the mechanism for corticosteroids for asthma and what are some examples of it
Corticosteroids inhibit the release of arachidonic acid through phospholipase A2 inhibition, thereby producing direct anti-inflammatory properties in the airways.
Inhalational treatment is the most effective way to avoid the systemic adverse effects of corticosteroid therapy
The introduction of ICS such as beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone has made it possible to deliver corticosteroids to the airways with minimal systemic absorption.
what is a problem caused by inhaled topical corticosteroids.
and what is ciclesonide.
Special problem caused by inhaled topical corticosteroids is the occurrence of oropharyngeal candidiasis.
Ciclesonide, a prodrug activated by bronchial esterases, is comparably effective to other inhaled corticosteroids and is associated with less frequent candidiasis.
Hoarseness can also result from a direct local effect of ICS on the vocal cords.
LEUKOTRIENE PATHWAY INHIBITORS
Leukotrienes (LT) B4 and the cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are products of the 5-lipoxygenase pathway of arachidonic acid metabolism and part of the inflammatory cascade
5-Lipoxygenase is found in cells of myeloid origin, such as mast cells, basophils, eosinophils, and neutrophils
LTB4 is a potent chemoattractant for neutrophils and eosinophils, whereas the cysteinyl leukotrienes constrict bronchiolar smooth muscle, increase endothelial permeability, and promote mucus secretion.
Zileuton -a 5-lipoxygenase inhibitor block leukotriene receptors (CysLT1). Especially good for aspirin-induced and exercise-induced asthma
Zafirlukast and montelukast are selective antagonists of the cysteinyl leukotriene-1 receptor and they block the effects of cysteinyl leukotrienes
Cromolyn
Cromolyn is a prophylactic anti-inflammatory agent that inhibits mast cell degranulation and release of histamine.
It is an alternative therapy for mild persistent asthma and is available as a nebulized solution.
Because cromolyn is not a bronchodilator, it is not useful in managing an acute asthma attack.
Due to its short duration of action, this agent requires dosing three or four times daily, which affects adherence and limits its use.
Adverse effects are minor and include cough, irritation, and unpleasant taste
Cholinergic antagonists
Muscarinic antagonists competitively inhibit the action of acetylcholine at muscarinic receptors and are therefore sometimes referred to as “anticholinergic agents”
In the airways, acetylcholine is released from efferent endings of the vagus nerve, and muscarinic antagonists block the contraction of airway smooth muscle
Greater bronchodilation, with less toxicity from systemic absorption, is achieved with a selective quaternary ammonium derivative of atropine, ipratropium bromide
Longer-acting antimuscarinic agents, including tiotropium,aclidinium, and umeclidinium, are approved for maintenance therapy of COPD.
