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