Download Free Medical Drugs Acting on Respiratory System PowerPoint Presentation

Drugs Acting on Respiratory System PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Drugs Acting on Respiratory System", to know about the drugs acting on respiratory system.

Tags : Pharmacology, Drugs, Acting, Respiratory System

Published on : Jul 18, 2021 | Views : 3593 | Downloads : 22

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Drugs Acting on Respiratory System Assoc. Prof. Ivan Lambev e-mail: itlambev@mail.bg (Summary)
Slide 2-

I. Drug Therapy of Bronchial Asthma The term asthma is derived from the Greek word meaning difficulty in breathing. Asthma is a chronic inflammatory allergic disease: the patients suffer with reversible episodes of airways obstruction due to bronchial hyper-responsiveness. In the early (acute) phase there are smooth muscle spasm and excessive bronchial secretion of mucus. In the late (chronic or delayed) phase, inflammation continues, accompanied by fibrosis, oedema and necrosis of bronchial epithelial cells.
Slide 3-

FACTORS THAT EXACERBATE ASTHMA
Slide 4-

The cardinal symptoms of asthma are breathlessness wheezing, cough and chest tightness with worsening of these symptoms at night. In the acute attack there are ra- pid respiratory rate and tachycardia. The majority of patients suffer with atopic extrinsic asthma, which is associated with exposure to specific allergen (pollen or house-dust mite) . In non-atopic extrinsic asthma the attack may be stimulated with some non-specific stimulus, e.g. chemical irritants. In such cases, IgG and Ig antibodies circulate in the blood but are not attached to the mast cells or basophils. Neutrophils destroy these antigen-antibidy complexes. As a result, the liberated lysosomal enzymes
Slide 5-

can digest the remaining mucoproteins. Drugs which stabilize the lysosomal membrane, e.g. GCS provide relief to these patients. In contrast, the many patients who acquire asthma after the age of 40 years have no identifiable external precipitating factor or immunological basis for asthmatic attack. This can be described as intrinsic asthma. Many patients suffer from both extrinsic and intrinsic forms of asthma. In comparison with intrinsic asthma, extrinsic asthma is episodic and less prone to develop into status asthmaticus. Status asthmaticus is a severe acute asthma, which is a life-threatening condition involving exhaustion, cyanosis, bradycardia, hypotension, dehydration and metabolic acidosis.
Slide 6-

Cardiac asthma is a bronchospasm precipitated by uncompensated congestive heart failure. Pathophysiology of Asthma Antigens (pollen and house-dust mites) sensitize patients by eliciting the production of IgE type of antibodies, which remain either circulating in the blood or become attached to the mast cells of nasal or bronchial tissues and basophils. On re-exposure the same antigen, the resulting antigen- antibody reaction in the early phase causes degranulation of the lung mast cells and releasing of the powerful bronchoconstrictors: histamine, 5-HT, PGD2 and cysteinyl leucotriens (LTB4, LTC4 and LTD4).
Slide 7-

Lung mast cells also release ILs (IL-4, IL-5 and IL-13). In the late (delayed) phase of asthma, these mediators activate additional inflammatory cells (eosinophils, basophils, and alveolar macrophages) which also release LTs and ILs. Other mediators of inflammation, in delayed phase, are: adenosine (causing bronchconstriction), neuropeptides (SP, causing mucus secretion and increase in vascular permeability; neurokinin A, causing bronchoconstriction), PAF etc. The normal tone of bronchial smooth muscle is influenced by a balance between parasympathetic, sympathetic and non-adrenergic–non-cholinergic (NANC) mediators activity.
Slide 8-

Activation of M3-receptors by the release ACh results in increase in cGMP levels and leads to bronchoconstriction and increase in mucus secretion. β2-receptor stimulation leads to an increase of cAMP levels which results in bronchodilation. The main NANC inhibitory neurotransmitter is NO. The main NANC excitory transmitters are neuropeptides (neurokinin A and SP), released from unmyelinated sensory C-fibres when stimulated by inflammatory mediators and irritant chemicals (SO2, cigarette smoke).
Slide 9-

ppt slide no 9 content not found
Slide 10-

Classification of Antiasthmatic Drugs 1. Bronchodilators Selective β2-agonists: Clenbuterol, Salbutamol, Fenoterol, Indacaterol, Levosalbutamol, Salmeterol, Terbutaline Nonselective β-agonists: Epinephrine, Isoprenaline, Orciprenaline; Ephedrine M-cholinolytics: Ipratropium, Tiotropium, Oxitropium Methyl Xanthines: Theophylline, Aminophylline, Theotard 2. Mast Cell Stabilizers: Sodium Cromoglycate, Ketotifen, Nedocromil
Slide 11-

3. Glucocorticosteroids (GCS) Oral: Prednisone, Methylprednisolone Parenteral: Methylprednisolone, Betamethasone Inhalational: Beclomethasone, Budenoside, Fluticasone, Triamcinolone 4. Inhalational β2-agonists/Glucocorticosteroids Seretide® (fluticasone/salmeterol) Symbicort® (budenoside/formoterol) 5. Leukotriene Modulators 5-Lipoxygenase Inhibitor: Zileuton LTD4-antgonists: Zafirlukast, Montelukast 6. Monoclonal Anti-IgE Antibody: Omalizumab 7. Miscellaneous: NO-donors, Calcium antagonists
Slide 12-

Bronchodilators – relievers (β-agonists, M-cholinolytics, Methyl Xanthins) provide a rapid sympto- matic relief but they do not control the disease process. Selective β2-agonists activate β2-receptors present on airway smooth muscle and mast cells too. These agents relax airway smooth muscle, inhibit the release of bronchoconstricting mediators from the adipocytes and increase the mucociliary transport by increasing the mucociliary activity. ADRs: tremor, tachycardia, desensitization/down-regulation. of β2-receptors that results in diminished responsiveness.
Slide 13-

Adrenaline (b1&b2) Gs AC ATP cAMP PKA Effects Ex In (+)
Slide 14-

ppt slide no 14 content not found
Slide 15-

Short acting beta-2 agonists: the onset of effect (per inhalation) begins after 3 to 5 min and continues 4–6 h: Salbutamol (albuterol) Fenoterol, Terbutaline Highly lipid, soluble long-acting agents (t1/2 12 h) Effect: after 15–20 min, duration 12 h: Salmeterol, Formoterol Beta-2-agonists are available as metered-dose aerosol.
Slide 16-

ppt slide no 16 content not found
Slide 17-

Selective β2-adrenomimetics with tocolytic effect Fenoterol (Partusisten: tab. 5 mg) Hexoprenaline Salbutamol (Salbupart) Terbutaline
Slide 18-

Primarily, the site of bronchodilation action of inhaled β2-adrenergic agonists is mainly the bronchiolar smooth muscle. Atropinic drugs cause bronchodilation by blocking cholinergic constrictor tone, act primarily in large airways. Anticholinergics in asthma Ipratropium Tiotropium
Slide 19-

Methyl Xanthines (Theophylline, Aminophylline, Theotard): a) inhibit phosphodiesterase III (present in airway muscle) and IV (present in eosinophil and mast cells), the two specific isoenzymes responsible for the degradation of cAMP; b) block the adenosine-1-receptors on airway muscle and adenosine-3-receptors, present on mast cells. The main use of methyl xanthins is in the management of asthma and COPD (Chronic Obstructive Pulmonary Disease), usually as combination therapy with beta-2-agonists.
Slide 20-

Glucocorticosteroids provide long-term stabilization of the symptoms due to their anti-inflammatory effects. Inhaled GCS, along with beta-2-agonists are the first choice drugs for chronic asthma. GCS inhibit the release of PGs and LTs and thus prevent smooth muscle contraction, vascular permeability and airway mucus secretion. GCS produce eosinopenia which prevents cytotoxic effects of the mediators released from eosinophils. GCS enhance beta-2-adrenergic response by up-regulating the beta-2-receptors in lung cells and leuckocytes. Several hours are required for DNA transcription and RNA translation to occur after administering GCS.
Slide 21-

The anti-inflammatory actions of GCS are mediated by stimulation of synthesis of lipocortin, which inhibits pathways for production of PGs, LTs and PAF. These mediators would normally contribute to increased vascular permeability and subsequent changes including oedema, leucocyte migration, fibrin deposition.
Slide 22-

ppt slide no 22 content not found
Slide 23-

Hydrocortisone Prednisolone Nonfluorinated prednisolones Fluorinated prednisolones Methylprednisolone Betamethasone, Dexamethasone Fluticasone, Triamcinolone The most used glucocorticoids
Slide 24-

Cushing’s syndrome Osteoporosis Tendency to hyperglycaemia Negative nitrogen balance Increased appetite Increased susceptibility to infections Obesity etc. Adverse effects of GCS Cushing’s syndrome
Slide 25-

Leukotriene Modulators Metabolism of arachidonic acid via 5-lipoxigenase pathway yields the cysteinyl LTs – C4, D4 and E4, which activate cysteinyl leukotriene receptors to cause bronchoconstriction, stimulate mucus secretion and increase capillary permeability, leading to pulmonary oedema. Zileuton (p.o.) inhibits the 5-lipoxigenase and blocks synthesis of LTs. Zafirlukast, Montelukast and Pranlukast (new agent) block cysteinyl LT-receptors and used with inhaled GCS in poorly respond asthmatic patients.
Slide 26-

Arachidonic acid 5-Lipoxigenase Leukotrienes (LTs) LTC4- receptor LTD4- receptor LTE4- receptor Montelukast, Zafirlukast (–) (–) (–)
Slide 27-

Cromoglycate – per inh. (Cromolyn – USAN) Ketotifen (p.o.) Nedocromil – per inh. Mast cell stabilizers prevent transmembrane influx of calcium ions, provoked by antigen-IgE antibody reaction on the mast cell membrane. They prevent degranulation and release of histamine and other autacoids from mast cells. They also inhibit leukocyte activation and chemotaxis. Indications: prophylactic treatment of asthma.
Slide 28-

Monoclonal Anti-IgE Antibody Omalizumab is a recombinant humanized monoclonal antibody. (1) It inhibits the binding of IgE to mast cells and basophils; (3) it inhibits the activation of IgE already bound to mast cells and prevents their degranulations; (3) it down-regulates Fc epsilon receptor-1, present on mast cells and basophils. Omalizumab is indicated for asthmatic patients who are not adequately controlled by inhaled GCS and who demonstrate sensitivity to aero-allergens.
Slide 29-

Treatment of Status Asthmaticus It is a potentially life-threatening acute attack of severe asthma needing immediate treatment. Most often hospitalization is necessary. A high concentration (40–60%) of O2 is administered. High doses of inhaled short acting beta-2-agonist. High doses of systemic GCS (p.o./i.v.) Ipratropium through inhalation.
Slide 30-

II. Drug Therapy of Cough The cough is a physiological useful protective reflex that clears the respiratory pathway of the accumulated mucus and foreign substances. Many times it occurs as a symptom of an underlying disorder and needs treatment. The cough may be non-productive (dry) and productive. The productive cough is characterized by the presence of excessive sputum and may be associated with chronic bronchitis and bronchiectasis.
Slide 31-

1. Antitussive Agents are used for the treatment of non-productive cough which increases discomfort to the patients. Centrally Acting Antitussives (supress the cough center that mediates the cough reflex) Codeine (methylmorphine) Dihydrocodeine Dextrometorphan Glaucin (Glauvent®) Perpheral Acting Antitussives Prenoxidiazine (Libexin® – tabl. 100 mg) Poppy
Slide 32-

2. Expectorants These drugs increase the volume or/and decrease the viscosity of the respiratory secretions and facilitate their removal by ciliary action and coughing. Mucokinetic Expectorants stimulate the flow of respiratory tract secretions by stimulating the bronchial secretory cells (to increase the volume) and the ciliary movement (to facilitate their removal). Essential oils (oil anise, oil eucalyptus) Syrup of Ipecacauanha (in sub-emetic doses) Infusum of Radix Primulae Ammonium chloride, Sodium citrate Guaiacol and Guaifenasin (obtained from creosote wood)
Slide 33-

Mucolytic Expectorants decrease the viscosity of mucus by splitting the disulfide (–S–S–) bonds of mucoproteins. This action is further facilitated by alkaline pH (7–9). Ambroxol Acetylcystene (used also for the treatment of paracetamol intoxication) Bromhexine Dornase-alfa Mesna (used also for protection of cancerogenic activity of cyclophosphamide and ifosphamide too)