Respiratory system Flashcards
Respiratory is controlled in the….
Medulla
Autonomic nervous system
-controls rate and depth through smooth muscle contraction/relaxation
Sympathetic - noepinephrine –> bronchodilation - B2 adrenergic receptors
Parasympathtic - acethycholine - bronchoconstriction - M3 cholinergic receptors
Mucosal edema, secretions, bronchospasms - they…
increase the resistance to airflow; decrease ventilation and diffusion of gases
Parasympathetic system
- innervation –> smooth muscle and secretory glands
- causes broncho-constriction by activation of muscarinic receptors; increase mucous production
Treatment of COPD
-effectiveness of non-selective anti-muscarinic drug
- not very useful
- inhibit M2 and M3 –> acetylcholine is released –> block on M3 will not be that effective –> competition between blocking agent and acetycholine –> can oppose bronchodilation
-used before the administration of inhalant anesthetics to reduce the accumulation of secretions in the trachea and the possibility of laryngospasms
Sympathetic system
-beta-2-adrenoreceptors in bronchial smooth muscle
short acting beta-2-agonists: acute treatment of asthma symptoms
long acting beta-2-agonists: chronic asthma treatment should only be used in combination with steroids, also COPD
Mechanism of response to inhaled irritants
Provoke bronchoconstriction by:
- trigger the release of chemical mediators from mast cells
- stimulate afferent receptors to initiate reflex bronchoconstriction or to release tachykinins that directly stimulate smooth muscle contraction
Respiratory system - man issues: (4)
- Bronchospasm
- Mucus secretion
- Cough
- Inflammation
Drugs that cause
- Bronchodilation
- Bronchoconstriction
- beta agonists –> increase cAMP
2. Muscarinic antagonists
Asthma (5)
- acute and chronic
- irritants: cold, dry air, exercise-induced, thermally induced
- attacks may be triggered by inflammatory response and/or bronchospasms
- early and late reaction - different mediators in each of them
- treatment: bronchodilators –> increase cAMP
Asthma
-early reaction (5)
- FEV decrease
- allergen bind to mast cell –> degranulation
- bronchoconstriction
- activation of many inflammatory cells - mast cells, T lymphocyte
- different mediators are released - Histamine, IL-4,5, TNF, TGF
Asthma
-late reaction (3)
- edema, mucous hyperesecretion, smooth muscle contraction, increase bronchial reactivity
- cytokines are release which will also activate different inflammatory cells
- cells –> eosinophil, neutrophil
B2-adrenoreceptor agonists
- names
- mechanism of action
-Salbutamol, Salmeterol, Formoterol
- causes bronchodilation –> relieving bronchospasms
- decrease mediator release from mast cells and TNF-a release from monocytes –> increase mucus clearance by an action on cilia
- effect on the early phase
- increase severity of the late reaction –> should be used with inhaled corticosteroids
B2-adrenoreceptor agonists
- unwanted effects
- Short acting beta-2 agonists
- Long acting beta-2 agonists
- tachycardia - if it reaches systemic circulation
- Salbutamol - fast onset and short duration
- Salmeterol - slow onset and long duration
- Formoterol - fast onset and long duration
Other adrenoreceptor agonists
- names
- why are they not used?
-Ephedrine, Adrenaline (epinephrine)
- less suitable, less safe because they could cause arrhythmias and other side effects
- used for emergency treatment
Xanthine derivatives
- name
- pharmacokinetics (6)
-Aminophylline
- well absorbed in the GI tract
- sustained-release tablet
- many drug-drug interactions - plasma clearance varies
- metabolized in the liver
- clearance decrease in viral infections
- narrow therapeutic window
Xanthine derivatives - Aminophylline
- indications
- unwanted effects
-acute and chronic asthma, COPD
- tremulousness, nausea, vomiting, arrhythmias (increase heart rate)
- those effect due to cAMP levels increasing, increase GCMP, adenosine antagonism
Xanthine derivatives
-mechanism of action
- inhibit PDE3 = relaxing smooth muscles –> increase intracellular cAMP
- inhibit PDE4 = decrease release of cytokines and chemokines
- inhibit cell surface receptors for adenosine (adenosine provokes contraction of smooth muscle and histamine release)
- low-dose enhance the effectiveness of corticosteroid treatment
Anti-muscarinic bronchodilators
- names
- mechanism of action
-Ipratropium, Tiotropium
- block the contraction of airway smooth muscle caused by vagus nerve and the secretion of mucus
- block acethycholine –> decrease IP3 –> decrease calcium
- inhibit only that portion of the response mediated by muscarinic receptors, which varies by stimulus
Anti-muscarinic bronchodilators
- effect on which phase?
- indications
- unwanted effects
- NO EFFECT ON EARLY AND LATE INFLAMMATION PHASES
- COPD - long acting, asthma, bronchospasms precipitaded by beta-2-agonists
- dry mouth
Ipratropium
-indication
bronchopasms caysed by bronchitis, asthma, beta 2 agonists, COPD
slow onset of action
short duration of action
Tiotropium
-indication
COPD
slow onset of action
long duration of action
Corticosteroids
- names
- mechanism of action
-Budesonide, Fluticasone
- anti-inflammatory effect –> inhibit the production of inflammatory cytokines
- inhibit the infiltration of airways by lymphocytes, eosinophils, mast cells
- reduce bronchial hyper-reactivity and reduce the frequency of asthma exacerbations
- potentiate the effect of beta receptor agonists - bronchodilation
- effect in EARLY AND LATE RESPONSE
Corticosteroids
- indication
- unwanted effects
- improve all indices of asthma control
- chronic asthma
- acute asthma
- inhaled forms are gold strandard
- oral forms are used only in late stages of the disease - too many side effects
- no general adverse effects
- local effects of inhaled forms: candidiasis of the mouth or throat, hoarseness
Cromoglycates
- names
- mechanism of action
-Cromoglicate
- causes hyperpolarization of the cells –> decrease their activity
- inhibit mast cells and eosinophils activation
- inhibit antigen and exercise induce asthma –> prevents bronchoconstriction
- decrease airway reactivity, decrease symptomatic severity
- inhibit cough
- no effect on airway smooth muscle tone, ineffective in reversing bronchospasm
Cromoglycates
- pharmacokinetics
- indications
- unwanted effects
- inhaled
- not very potent
- inhibit EARLY AND LATE RESPONSES
-prophylaxis of acute asthma attacks
- toxicity minimal
- transient bronchospasm - beta-2-agonist may be inhaled a few minutes before
Leukotriene pathway inhibitors
-names
- Leukotriene receptor antagonist – Montelukast
- 5-Lipoxygenase inhibitor – Zileuton
- inhibit leukotriene type 1 receptor
- inhibit EARLY AND LATE RESPONSES
- decrease sputum eosinophils
- bronchodilation in mild asthma
Why shouldn’t aspirin be used in patients with asthma?
- Aspirin inhibits COX irreversibly
- Shifts arachidonic acid towards another pathway
- LOX levels increase
- Leukotrienes levels increase
Leukotrienes could cause bronchoconstriction, mucous secretion, macrovascular leakage, coudl facilitate chemotaxis
Leukotriene pathway inhibitors
- indications
- unwanted effects
- exercise-induced asthma
- aspirin-induced asthma
- Montelukast - Churg-Strauss syndrome (systemic vasculitis, worsening asthma)
- Zileuton - liver toxicity
Anti-IgE Monoclonal Antibodies
- names
- mechanism of action
-Omalizumab
- decrease the frequency and severity of asthma exacerbations
- inhibits binding of IgE –> does not provoke mast cell degranulation
- inhibit EARLY AND LATE RESPONSES
Anti-IgE Monoclonal Antibodies
- indications
- unwanted effects
-patients 12 years or older with moderate-to-severe allergic asthma
- anaphylaxis
- Churg-Strauss syndrome
Treatment steps of asthma
- short acting beta agonists
- preventing therapy - inhaled corticosteroid
- long acting beta agonists + dose of inhaled corticosteroid may also be increased
- high dose inhaled corticosteroids
- regular oral corticosteroid
Acute asthma attack
-drugs that can be used (5)
- Salbutamol - short acting beta agonists
- Epinephrine - systemic beta agonist
- Aminophylline
- Ipratropium - short acting anti-muscarinic agent
- Corticosteroids
Asthma vs. COPD
ASTHMA
- largely reversible airflow limitation
- corticosteroids are effective
- normally parenchyma is not involved, damage to epithelium
- no abundant mucous secretion
- key cells: eosinophilic inflammation
- large airways - all airways are involved
- thickened b.m due to substances released from eosinophils during the late phase
- therapy- goal –> control symptoms and maintain close to normal pulmonary function, exacerbation can be prevented
COPD
- largely irreversible airflow limitation
- limited effect with corticosteroids
- heavy mucous secretion
- key cells: neutrophilic inflammation
- small airways
- damage is caused in the peripheral part –> alveoli
- late stages –> hard to normalize airflow
- usually in older people
- metaplasia
- high risk factor for pulmonary cancer
- defective response of inflammatory cells
- therapy- goal –> relief symptoms, prevent complications and improve life style
COPD (4)
- limitation of airflow that is not reversible –> progressive
- caused by a mixture of small airway disease and parenchymal destruction
- abnormal inflammatory response of lung to harmful substances
- treatment: no medications can alter the course of the disease. goal is to relief symptoms, prevent complications and improve life style
COPD
-treatment (2)
- Bronchodilators: inhaled therapy is preferred, long- acting ones are more effective
- beta agonists, anti-muscarinic, theophylline
- Corticosteroids - not very effective
- long term treatment is not recommended
- more effective when combined with a long-acting beta agonist
Inhalation devices
-increase delivery of drug to the lungs and decrease deposition of drug on the oropharyngeal mucosa
Anti-tussives - central acting
- names
- mechanism of action
- indications
- adverse effects
- warning
- Codeine
- block central parts of the cough reflex
- dry, hacking, non-productive cough
- respiratory depression
- excessive suppression of the cough reflex
Anti-tussives - peripheral acting
- names
- mechanism of action
- indications
- adverse effects
- contraindications
-Prenoxdiazine
- blocks peripheral parts of the cough reflex
- local anesthetic and broncholytic actibity
- relief dry cough
- allergic reactions, dry mouth
- hypersensitivity to the drug, high bronchial secretions
Expectorants
- names
- mechanism of action
-Guaifenesin
- stimulate the flow of respiratory tract secretions
- increases the efficiency of the cough reflex and facilitate removal of the secretions
- increase the volume and decrease the viscosity of the secretion in the trachea and bronchi
- allow ciliary movement
- muscle relaxant and anti-convulsant properties
Expectorants
- adverse effects
- drug interactions
- nausea, vomiting, diarrhea, kidney stones, allergic reactions, dry mouth, constipation
- paracetamol, aspirin, alcohol, sleep-pills
Mucolytics
-names
Acetylcysteine
Dornase Alfa
Mucolytics - Acetylcysteine
- mechanism of action
- indications
- unwanted effects
- rapidly metabolized to cysteine
- decrease disulphide bonds –> reduce viscosity and elasticity of the mucus
- decrease several inflammatory mediators
- interact directly with oxidants
- paracetamol overdose, mucolytic, COPD, cystic fibrosis
- nausea, vomiting, allergic reactions, fever
Mucolytics - Dornase alfa
- mechanism of action
- indications
- unwanted effects
- enzyme selectively cleaves DNA (non cellular)
- hydrolyzes the DNA present in sputum/mucus and reduces viscosity
- cystic fibrosis
- voice disorders, laryingitis, transient skin rash
Nasal decongestants
- name
- mechanism of action
-Pseudoephedrine, Xylometazoline
- used directly
- for short-term basis: no more than 7 days –> could cause tissue necrosis
- alpha-1-adrenoreceptors agonists
- constrict blood vessels in respiratory tract
Nasal decongestants
- indications
- side effects
- contraindications
- nasal congestion
- allergic rhinitis
- hypotension
- shock
- irritation of the nose
- closed angle glaucoma
