drugs used to treat respiratory disease
DESCRIPTION
Drugs used to treat respiratory disease. A. Kohút. Bronchial asthma. ASTHMA Asthma - syndrom with recurrent reversible obstruction of the airways in response to stimuli. The patient has intermittent attacks of : dyspnoea, wheezing, cough disorder of breathing - PowerPoint PPT PresentationTRANSCRIPT
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Drugs used to treat respiratory disease
A. KohútA. Kohút
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Bronchial asthmaBronchial asthma
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ASTHMA
Asthma - syndrom with recurrent reversible obstruction of the airways in response to stimuli.
The patient has intermittent attacks of :dyspnoea, wheezing, cough disorder of breathing Its pathologic features are: • contraction of airway smooth muscle . mucosal thickening from edema . cellular infiltration, viscid plugs of mucus
- airway obstruction, contraction of smooth muscle is most easily reversed by BRONCHODILATORS - edema and cellular infiltration requires sustained treatment with ANTI-INFLAMMATORY AGENTS
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Causes of asthma
- allergens – pollen and household dust
- air pollutants – burning leaves, solvents
- respiratory infection
- stress – exercise in dry & cold climates
- chemicals – drugs (aspirin)
- food – shellfish & nuts
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PathologyPathology
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Submucosa
Mucosa
Inflammatory
cells
Hypertrophied smooth muscle
Mononuclear cellOedema
Mast cell
Mucus plug witheosinophils desquamatedepithelial cells
Thickened basementmembrane
Eosinophil
Dilated blood vessels
Schematic diagram of a cross-section of a bronchiole showing the changes that can occur with severe chronic asthma.
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airway obstruction, contraction of smooth muscle is most easily reversed by BRONCHODILATORS
1. Methylxanthines2. Sympathomimetic agents3. Muscarinic antagonists4. New bronchodilators - edema and cellular infiltration requires
sustained treatment with - ANTI-INFLAMMATORY AGENTS
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cAMPATPbronchodilation
adenyl cyclase
stimulation: mimetics
BRONCHODILATORS
5´AMP
phosphodieste-rase
inhibition:methylxanthins
cGMP GTP
Smooth musclecontraction
guanylyl cyclase
M2
inhibition:parasympatholytics
ACH
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Antiasthmatic agents are often used by :
inhalation
- aerosol- dry powder
orally i.v.
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Early phase
bronchoconstriction
Late phase
inflammation
bronchodilators antiinflamatory drugs
Two phases of asthma
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ANTIINFLAMMATORY DRUGS
BRONCHODILATORS
DRUGS FOR ASTHMA TREATMENT
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ANTIINFLAMMATORY DRUGS
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ANTIINFLAMMATORY DRUGS Corticosteroids
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Corticosteroids
work by inhibiting or otherwise modifying the
inflammatory response in airways
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1. Systemic corticosteroids p.o. or i.v.
prednisone
Because of severe adverse effects are generally
reserved for patients:
who do not improve adequately with
inhalatory corticosteroids
Treatment: oral dose of 30-60 mg of per day
In most patients, systemic corticosteroids can
be discontinued in a week or 10 days
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Systemic adverse effects of glucocorticoids administered p.o. or i.v.
- hyperglycemia- hypertension- immunosuppresion- adrenal suppresion- osteoporosis- growth retardation in children- cataract- glaucoma
CUSHING SYNDROM
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2. Corticosteroids administered by inhalation (ICS)
- the most effective method of decreasing systemic adverse effects
- are currently the most effective long-term preventive medications
- long-term treatment with minimal daily doses of ICS
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Corticosteroids for inhalations are: beclomethasone, budesonide, fluticasone with minimal systemic absorption reduced adverse effects
An average daily dose - from 100-2000 g/day inhalation according to asthma severity
Systemic steroid effects are minimal if compared with those of the oral prednisone: oropharyngeal candidiasis - mouth washes can alleviate this problem
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ICS the growth in children
Long-term retrospective studies proved that
treatment with ICS (BUD 200-800 g/day) does not
significantly influenced the growth
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Chronic use of inhaled corticosteroids:
- effectively reduces symptoms and
improves pulmonary function in patients
- reduces bronchial hyperreactivity
- the maximal reduction may not be achieved
until the ninth to twelfth months of therapy
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INHIBITORS OF MAST CELL DEGRANULATION
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Sodium cromoglycate- inhibition of mast cell degranulation
- inhibition of inflammatory cells
- very good effectivity in children
- 4-6 week of therapy
- in prevention
Clinical use:
- reversible bronchospasm
- bronchial asthma (allergic)
- allergic rhinitis, conjuctivitis
Unwanted effects:
Rare: cought, bad taste, headache
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Sodium nedocromil- inhibition of mast cell degranulation
- inhibition of inflammatory cells (IC)
- inhibition of IC cummulation in bronchial mucosa
- prevention of immediate an late bronchoconstr.
- decrease of bronchial hyperreactivity
Clinical use:
- prevention of astma (allergic, non-allergic)- excersise induced asthma
Unwanted effects:
- bad taste, headache
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New drugsCysteinyl leukotriene-receptor antagonistsMontelucast prevents antigen-induced and exercise- induced asthma. It relaxes the airways
in mild asthma, its effects are additive with 2-
adrenoceptors agonists
5-lipoxygenase inhibitors
Zileuton prevents the production not only LTC4
LTD4 but also LTB4, a chemotaxin that recruits
leukocytes into the bronchial mucosa then activates them
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1. sympathomimetic agents
2. methylxanthines
3. muscarinic antagonists
BRONCHODILATORS
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Sympathomimetic agents
Nonselective
Adrenaline is an effective, rapidly acting
bronchodilator when injected s.c. (1:1000 solution) or
inhaled as a microaerosol
maximal bronchodilation is achieved 15 min after
inhalation lasts for 60-90 min
Adverse effects: tachycardia, arrhythmias,
worsening of angina pectoris
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2-selective agonists
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2-selective agonist
the most widely used drugs for the treatment of asthma
a. Salbutamol, terbutaline, fenoterol bronchodilation begins in 5 minutes, is maximal by 30-60 min persists for 2 h Terbutaline is also prepared in tablet form one tablet 3 times daily is the usual regimen Salbutamol, terbutaline Salbutamol, terbutaline are used to prevent are used to prevent premature labourpremature labour
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. .
Bronchial deposition depends on the particle size. Even with particles in the optimal size range of 2-5 m, 70-50% of the total dose is deposited in the mouth or pharynx
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b. Newer 2-selective agonists
developed for an increased duration of action (12 h or more) vs. older 2 agonists (4-6 h):
f o r m o t e r o l , s a l m e t e r o l (for inhalation) c l e n b u t e r o l , p r o c a t e r o l (p.o.)
are prescribed in prevention of attacks because
- Their high lipid solubility permits them to dissolve in the smooth muscle cell membrane and reach high concentration (slow release depot) that provides the drug available to -receptors over a long period
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Adverse effects of -agonists
- cardiac arrhythmias from β1-receptor stimulation
- muscle tremor
- headache and insomnia
- flushing
- tolerance
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Notice Notice
With high doses, certain beta-2-agonists showed With high doses, certain beta-2-agonists showed muscular anabolic properties. muscular anabolic properties.
It is the case of It is the case of clenbuterolclenbuterol, released on the , released on the market in some countries as a bronchodilator, market in some countries as a bronchodilator, which was used in animal diet and also by which was used in animal diet and also by athletes to induce muscular development. Its athletes to induce muscular development. Its principal adverse effects are tremors and principal adverse effects are tremors and tachycardia. tachycardia.
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Methylxanthines
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Methylxanthines Theophylline, theobromine, caffeine
(alkaloids from tea, cocoa, coffee)
Actions :
central nervous system effects
cardiovascular effects
effects on the GIT
effects on kidney
effects on smooth muscle
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Central nervous system effects increased alertness, tremor nervousness, stimulant
effects on respirationCardiovascular effects stimulation of the heart (possitive chronotropic inotropic
actions) Effects on the GIT spasmolytic action, increase in HCl secretionEffects on kidney weak diuretic effect, involving both increased GF
reduced reabsorption in the tubulesEffects on smooth muscle vasodilation, bronchodilation
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Clinical use of methylxanthines
Theophylline is used as a saltaminophylline, which contains 86% of theophylline
Improvements in theophylline preparations:
anhydrous theophylline in a microcrystalline form
in which the increased surface area facilitates
solubilization for complete rapid absorption
after oral administration
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Theophylline blood level should be m o n i t o r e d
Therapeutic toxic effect of theophylline are related to the plasma concentrations of the drug.
- 5-20 mg/L plasma concentration - improvement in pulmonary function- greated than 20 mg/L - anorexia, nausea, vomiting, abdominal discomfort, headache anxiety become common at concentrations- higher levels (> 40 mg/L) may cause seizures or arrhythmias,
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Drug-drug interaction
the half-life of theophylline
- is increased by erythromycin, cimetidine
ciprofloxacin, oral contraceptives
- is decreased by concurrent use of
phenytoin, carbamazepine, rifampicin,
phenobarbital
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several sustained-release preparations with
aminophylline theophylline
are available and can produce therapeutic blood
levels of theophylline for up to 12 or 24 h
These preparations offer the advantages of
- less frequent drug administration
- less fluctuation of theophylline blood levels
- more effective treatment of nocturnal
bronchospasm
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Muscarinic antagonists
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Muscarinic antagonists
- muscarinic antagonists competitively
inhibit the effect of ACh at M-receptors
- ipratropium bromide - short-acting drug is
used for patients with heart disease or
thyreotoxicosis in whom -agonists are
unsuitable
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Treatment of status asthmaticus1. Oxygen1. Salbutamol by nebuliser in a dose of 2.5-5 mg over
about 3 min. Repeted in 15 min. Terbutaline 5-10 mg is an alternative.
2. Prednisolone 30-60 mg by mouth, or Hydrocortisone i. v. to very sick patient.
No sedatives of any kind. If life-thretening features are present:1. Ipratropium 0.5 mg add to the Salbutamol or
Terbutaline.2. Aminophylline 5mg/kg over 20 min. i.v.
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Antitussives
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Cough physiology
Cough reflex- induces coughing expectoration
- initiated by irritation of sensory receptors in the respiratory tract
To remove secretions or foreign objects
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Two basic types of cough
- productive cough
removes excessive secretions
- nonproductive cough
dry cough
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Coughing
- most of the time, coughing is beneficial
removes excessive secretions
removes potentially harmful foreign
substances
In some situations, coughing can be harmful,
such as after hernia repair surgery
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Definition
- drugs used to stop or reduce coughing
Antitussive drugs
- opioid nonopioid
Used only for nonproductive coughs!
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Mechanism of action - opioids
- suppress the cough reflex by acting on the cough center in the medulla
- examples:
– codeine – hydrocodone– pholcodine
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Mechanism of action - nonopioids
- suppress the cough reflex by preventing the cough reflex from being stimulated
examples:
- benzonatate
- dextromethorphan
- butamirate
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Indications
Used to stop the cough reflex when the
cough is nonproductive and/or harmful
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Side effects
benzonatate
- dizziness, headache, sedation, nausea,
dextromethorphan
- dizziness, drowsiness, nausea
opioids
- sedation, nausea, vomiting, constipation,
urinary retention
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Expectorants
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Definition
by increasing the production of respiratory
tract fluids, expectorants reduce the
thickness, adhesiveness surface tension
of mucous, making it easier to clear from the
airways
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Mechanism of action - direct stimulation
- the secretory glands are stimulated directly to increase their production of respiratory tract fluids
Examples: iodine-containing products such as iodinated glycerol and potassium iodide
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Mechanisms of action – reflex stimulation
- agent causes irritation of the GI tract
- secretions occur in response to this irritation
Example: guaifenesin
Final result of both mechanisms:
- thinner mucus that is easier to remove
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Indications
- used for the relief of coughs from:
colds, minor bronchial irritation,
bronchitis, influenza, sinusitis,
bronchial asthma, emphysema, other
respiratory disorders
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Common side effects
guaifenesin– nausea, vomiting, gastric irritation
iodinated glycerol– GI irritation, rash, enlarged thyroid gland
potassium iodide– nausea, vomiting, bad taste
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MUCOLYTICSMUCOLYTICS
- act directly on mucous, breaking down
sticky, thick secretions so they’re more
easily eliminated
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MUCOLYTICS
Bromhexine
- potent mucolytic mucokinetic agent
- depolymerises mucopolysaccharides directly or by liberating of lysosomal enzymes – network of fibres in tenacious sputum is broken
- side effects: lacrimation, rhinorrhea, gastric irritation, hypersensitivity
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MUCOLYTICSMUCOLYTICS
Ambroxol
– metabolite of bromhexine
- simmilar effects side effects
Acetylcysteine
- it opens disulfide bonds in mucoproteins present in sputum
- it has to be administered directly into respiratory tract
- antidotum in paracetamol overdose
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DRUGS INFLUENCING COUGH
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