Drugs for Respiratory Tract Flashcards
Antiinflammatory Drugs
Corticosteroids: Beclomethasone Triamcinolone Budesonide Fluticasone
Mast cell stabilizers:
Cromolyn Sodium
Lodoxamide
Nedocromil
Leukotriene inhibitors:
Montelukast
Zafirlukast
Zileuton
Phosphodiesterase type 4 inhibitors:
Roflumilast
Corticosteroids - MoA
-Suppress the activation of T-lymphocytes by interleukins and nuclear factor KB
-Suppress production of cytokines by activated T-cells
-Decrease the release of histamine, prostaglandins and leukotrienes by increased transcription of annexin-1
(–>inhibit phospholipase A2)
-Stabilize lysosomal membranes of neutrophils
-Cause vasoconstriction by inhibiting phospholipase A2 (prostacyclin’s)
-They decrease activation of macrophages
Corticosteroids - Clinical use
Asthma
Allergic rhinitis
(long term basis to prevent asthmatic attack rather than treatment of acute bronchospasm)
Corticosteroids - Adverse effects
Oral candidiasis (thrush) Growth retardation
Mast cell stabilizers - MoA
They block calcium influx into mast cells and thus stabilize the plasma membranes of mast cells and eosinophils and thereby prevent degranulation and release of histamine, leukotrienes, and other substances that cause airway inflammation. They do not interfere with the binding of IgE to mast cells or with the binding of antigen to IgE.
Cromolyn Sodium - Clinical use
Asthma,
Allergic rhinitis and
Seasonal (Vernal) conjunctivitis.
Given orally to treat mastocytosis, ulcerative colitis and food allergy.
(Long-term prophylaxis of asthmatic bronchoconstriction and allergic reactions, but have no role in treatment of acute bronchospasm)
Cromolyn Sodium - Adverse effects
Throat irritation
Cough
Bronchospasm (Administration of beta2 agonist can prevent this)
Lodoxamide and Nedocromil - Clinical use
Ophthalmic solution to treat ocular allergies;
-Seasonal (vernal) keratitis and conjunctivitis
Lodoxamide and Nedocromil - Adverse effects
Ocular discomfort
Montelukast and Zafirlukast
- MoA
Cysteinyl leukotrienes C4, D4, and E4 activate the type 1 cysteinyl leukotriene receptor (CysLT1) and thereby increase recruitment of leukocytes, stimulate mucus secretion, increase vascular permeability increase collagen, and cause smooth muscle proliferation and contraction. These effects lead to airway inflammation and to sustained bronchoconstriction. These drugs compete with cysteinyl leukotrienes for the CysLT1 receptors and inhibit both early and late phases of bronchoconstriction induced by antigen challenge. However, they do not block the effect of leukotriene B4, which appear to be important in severe asthma and asthma exacerbation.
Montelukast and Zafirlukast
- Clinical use
Allergic asthma including
Aspirin-sensitive asthma, and prevention of
Exercised-induced asthma (Less potent than corticosteroids, but may be given to pt that are unable/unwilling to take steroids, or not adequately controlled by inhaled steroids alone)
Montelukast and Zafirlukast
- Adverse effects
Allergic granulomatous vasculitis (Churg-Strauss syndrome)
Hypersensitivity reactions
Liver injury
Zafirlukast - Interactions
Zafirlukast inhibits CYP enzyme and may elevate plasma level of phenytoin, warfarin, felodipine, lovastatin, and triazolam.
Zileuton - MoA
Inhibits 5-lipoxygenase and blocks the formation of all leukotrienes, including LTB4. Because the CysLT1 receptor antagonists do not block the leukocyte chemoattractant and other effects of LTB4, zileuton might be more effective in severe cases of asthma.
Zileuton - Clinical use
Prophylaxis and treatment of asthma in adults and children above 12 years.
Zileuton - Adverse effects
Flulike syndrome Headache Drowsiness Dyspepsia Elevated hepatic enzyme levels (patients should be monitored for hepatitis)
Zileuton - Interactions
Inhibits CYP enzymes and may elevate plasma levels of theophylline and warfarin
Roflumilast - MoA
Selective inhibitor of type IV phosphodiesterase in lung tissue (which degrades cAMP), thereby increasing intracellular levels of cAMP.
Roflumilast - Clinical use
Reduce the risk of COPD exacerbations in pt with chronic bronchitis who have a history of exacerbations (it is not bronchodilator and has no utility in acute episodes).
Roflumilast - Adverse effects
Diarrhea Nausea Weight loss Anxiety Insomnia Depression
Roflumilast - Interactions
It is metabolized by CYP enzymes and strong inducers (rifampin) and inhibitors (erythromycin) may affect its therapeutic effect/toxicity.
Bronchodilators
B2-Adrenoceptor agonists: Albuterol Salmeterol Terbutaline Indacaterol Formoterol Arformoterol Fenoterol Levalbuterol
Muscarinic receptor antagonists: Tiotropium Ipratropium Umeclidinium Aclidinium
Methylxanthine drug:
Theophylline
B2-Adrenoceptor agonists - MoA
Increase cAMP concentrations in smooth muscle and cause it to relax. Selective ones only affect smooth muscle without affecting the heart.
B2-Adrenoceptor agonists - Clinical use
Acute bronchospasm
(Primary bronchodilators used for asthma)
Salmeterol and formoterol are LABAs used to prevent nocturnal asthmatic attacks.
Arformoterol (active isomer of formoterol) is used to treat bronchoconstriction in pt with COPD.
Indacaterol is ultralong-acting and used for COPD.
B2-Adrenoceptor agonists - Adverse effects
Tachycardia
Tremor
Nervousness
Muscarinic receptor antagonists - Clinical use
Primarily used for COPD
Allergic and viral rhinitis
Less useful in asthma
Theophylline - MoA
Nonspecific inhibitor of PDE isozymes in bronchial smooth muscle and inflammatory cells, thereby increasing cAMP levels and leading to bronchodilation and antiinflammatory effects. Might also inhibit T-lymphocyte proliferation and cytokine production. In patients with asthma, theophylline reduces the number of eosinophils, lymphocytes and monocytes that infiltrate the airway epithelium. Other effects include; blockade of adenosine receptors, inhibition of calcium influx, and enhancement of catecholamine secretion.
Theophylline - Clinical use
Treatment of COPD, asthma, Neonatal apnea, and
Obstructive sleep apnea
Theophylline - Adverse effects
GI distress,
CNS stimulation (Headache, anxiety, restlessness, insomnia, dizziness, seizures), and
Cardiac stimulation.
(Hypotension, bradycardia, premature ventricular contractions, and tachycardia)
Theophylline - Interactions
Cimetidine and erythromycin inhibit metabolism and may increase theophylline levels.
Others that elevate concentration of theophylline include; Quinolones, isoniazid and verapamil
Drugs for Cystic fibrosis
Mucolytics:
Dornase alfa
CFTR modulators:
Ivacaftor
Lumacaftor
Dornase alfa - MoA
It is a mucolytic agent that targets and cleaves the extracellular DNA from invading neutrophils to decrease mucus viscosity.
Ivacaftor - MoA
Potentiates the effect of CFTR protein in patients with certain mutations
Lumacaftor - MoA
Brings the defective CFTR protein to the cell surface so Ivacaftor can potentiate its effect
Drugs for Eosinophilic asthma
Benralizumab - IL-5
Mepolizumab - IL-5
Reslizumab - IL-5
Omalizumab - IgE
