Professional Documents
Culture Documents
- to them belong:
dyspnoe
cough (in younger people may be the only
symptom, mostly at night)
chest tightness
wheezing
Clasification of Asthma according to clinical symptoms and lung
function:
DEGREE OF SYMPTOMS DURING DAY SYMPTOMS LUNG FUNCTION
GINA SERIOUSNESS
DURING
2002 NIGHT
Daytime symptoms None (twice or less / More than twice / week Three or more features of
week) partly controlled asthma
Need for reliever / rescue None (twice or less / More than twice / week
inhaler week)
Lung function / (PEF or FEV1) Normal < 80 % predicted or personal best (if
known)
Assessment of future risk (risk of exacerbation, instability, rapid decline in lung function, side effects)
Poor clinical control, frequent exacerbations in past year, ever admission to critical care for asthma, low FEV1, exposure to
cigarette smoke, high dose medications
GINA
2006
CLINICAL SIGNS OF AB
depends on the stage of asthma
intermittent attacks of expiration type dyspnoe, ich
worsening at night and at dawn
wheezing: intermittent, more significant at expiration
cough: usually not productive, can be basic sign
anxiety, pressure, chest tightness, dyspnoe
sputum production usually little, if than deep mucus
prodromal signs prior attack: itching under the chin, discomfort
between shoulder, fear, anxiety
typical is vanishing of signs after b-dilators or
antiinflammatory therapy, unsuccessful ATB th.
DIAGNOSIS
PRINCIPLE: simple examinations made repeatedly are more
usefull than complete examinations made at one time or during
long intervals limitation of expiratory flow at asthma has
variable character findings may vary from completely normal to
absolutely pathological
Functional diagnostics
Allergologic diagnostics
Specifying of inflammation markers
EXAMINATIONS AT AB
• SPIROMETRY
• BRONCHODILATION TESTS (BDT)
– it verifies the degree of obstruction reversibility
• BRONCHOPROVOKING TEST (BKT)
– BKT with histamine, ACh, adenosine, excercise, cold...
– negative BKT excludes dg. of AB (absence of bronchial
hyperreactivity...)
• PEF variability by výdychomerom (self monitoring)
• ARTERIAL BLOOD GASES (at exacerbation)
• Determination of NO in exhaled air (early marker of asthmatic
inflammation)
• SPUTUM EXAMINATION
– eosinophils and their effective products, Curshmann´s spirals,
Charcot-Leyden´s crystalls
SPIROMETRY • simple, reproductible
• gives informations about
restriction of air flow
• – FVC (forced vital
capacity)
– FEV1 (sec. vital cap.)
– FEV3 (forced expiratory flow at
50% expiration)
– FEV1/VC – Tiffaneau´s index
(FEV3/VC)
– PEF (peak expiratory flow
in l/min)
DIFERENTIAL DIAGNOSIS
chronic obstructive pulmonary disease
asthma cardiale at older adults
viral bronchiolitis at children
hyperventilatory syndrom
fixed obstacles in the airways (tumors, extramural compression,
foreign particles)
diffuse interstitial lung processes
pneumothorax
chest wall diseases (kyphoscoliosis, neuromuscular diseases)
COPD
95% are or have been cigarette smokers
less common causes: exposure to air polution, inherited
alfa1-antiprotease deficiency
Symptoms
Pulmonary
functions
ASTHMA
Pulmonary
Symptoms
functions
GOALS of Optimal AB Control
- elimination or significant reduction of symptoms
- prevention of exacerbations
- maintaining lung functions closest to physiological values
- maintaining normal physical and living activity
- absence of treatment adverse effects
- prevention of irreversible bronchial obstruction (remodelation of
lower airways)
- preventing asthma mortality
THERAPY OF AB
• Nonpharmacological
– Patients´ education
– avoiding risk factors and triggers-
• Pharmacological
– A NT I I N F L A M M AT O RY
• relieves inflammation and bronchial hyperreactivity
• regular, long-term use
– B R O N CH O D I L A T O R Y
• eliminates the symptoms of expiratory flow limitation
• rescue therapy in exacerbation
Administration of Drugs at
AB
peroral
parenteral
by inhalation
directly to the site of action
fast beginning of action
maximum efficacy
lower therapeutic doses = minimalise risk of AE
limitations from the site of patient (technique of
inhalation, cooperation...)
inspiratory resistance, needs to be overcomed
THERAPY OF AB
A: CONTROLLERS
– preventive drugs, controlling inflammation
– are taken regularly,long time to maintain control
antiinflammatory drugs
long acting inhalatory bronchodilators
B: RELIEVERS
substances releasing bronchospasm
relieving = fast acting bronchodilators
C: OTHER ANTIASTHMATIC DRUGS
– Monoclonal Ab against IgE = omalizumab (50 pat. in SR)
– Monoclonal Ab against IL-5 = mepolizumab
– ketotifen
– Imunosupressives (MTX, CysA...)
INHALED CORTICOIDS ICS
the most effective antiinflammatory antiasthmatics
to long-term use at all forms of AB
Mechanism of action:
1. inhibition of cytokine transcription antiinflam. ef.
2. inhibition of mediators of inflam. release
3. decrease of airways reactivity
4. restriction of vasodilation antioedematic ef.
5. affect synthesis of eikosanoids
6. control activation of adhesive molecules
7. increase of susceptibility resp. protection of 2 receptors
against down-regulation at long-term treatment with 2 mimetics
ICS
at severe AE systemic CS
Adverse effects of systemically
administered corticosteroids
1. Infections
2. The long-term use may increase blood pressure,
cause fluid retention and salt retention in the body
(oedema), increased excretion of calcium and
potassium
3. Worse and longer wound healing
4. Rash and acne
5. Hyperglycaemia
6. They increase the risk of gastrointestinal perforation
Adverse effects of systemically
administered corticosteroids
ß2- SYMPATHOMIMETICS
ANTICHOLINERGICS
ADMINISTRATION BY INHALATION
ß2- sympatho Anti M -
MIMETICS cholinergic
= SM = PsL
activate block
sympathic parasympa
NS thic NS
dilate
bronchi dilate
bronchi
Localisation of Receptors
cholinergic adrenergic
(parasympathic)
(sympathic)
ß2- SYMPATHOMIMETICS
Mechanism of action = agonistic, activating influence on ß2
receptors of sympathic NS
1. Long-acting ß2SM
(long-acting betaagonists ) = LABA
Controllers – to long-term,regular bronchodilation
2. Short-acting ß2SM
(short-acting betaagonists ) = SABA
Relievers – to short-term, acute management of exacerbation
ß2- SYMPATHOMIMETICS
Mechanism of action:
Influence of ß2-receptors in lungs (↑cAMP, aktivation of
PKA, phosphorylation of proteins that regulate smooth
muscle tone)
Fast beginning,
maintanance therapy
Fast beginning,
FAST short duration long duration
inhal. terbutaline,
salbutamol, fenoterol inhal. formoterol,
indakaterol
duration of action
SHORT LONG
SABA LABA
SABA
basic relievers
used ad hoc to relieve or to remove symptoms
no reason for regular administration
salbutamol (Ventolin)
fenoterol /Australia – deregistered for AE CVS/
LABA
the best, fast and intense acting b-dilatans
duration of action >12 hours
MA: Bronchodilation through β2 => relaxation of smooth muscle
Improve mucociliar clearens
Lower vascular permeability
Modulate release of mediators from mastocytes a bazophils
Provide long-term safety against bronchoconstriction
Length of this bronchodilation effect at long-term regular administration
decreases sign of tollerance for down regulation of β2 receptors =>
inhibition = concomitant administration of ICS
LABA in long-term therapy of asthma never can administer lonely, without
ICS!
β2 – SYMPATHOMIMETICS
(LABA, SABA, ultraLABA)
Salbutamol Abediterol
Terbutaline Olodaterol
Molecular mechanism of positive
interaction ICS and LABA
Corticosteroid ß2-Agonist
ß2-Adrenoceptor
Glucocorticoid
receptor
Monotherapy LABA:
effectivity of LABA vs. ICS
improving sleeping, but without effect to pulmonary
functions
discontinuation ICS and adding LABA at persistent asthma
loosing control
good controlled patient with asthma with persistent asthma at
low dose ICS replacement by LABA loosing control
( eNo and Eo in sputum)
without effect on inflam. in airways (biopsia)
ß2- SYMPATHOMIMETICS - ADRs
Fine skeletal muscle tremor
Tachycardia and arrhythmias (high doses, oral or parenteral
administration)
Hypokalaemia with high doses
Paradoxical bronchospasm
Headache
Tolerance (avoids use of ICS)
FDA – LABA drug safety
communication 2011
In February 2010, the agency announced it was requiring
manufacturers to revise their drug labels because of an
increased risk of severe exacerbation of asthma symptoms,
leading to hospitalizations, in pediatric and adult patients, as
well as death in some patients using LABAs for the treatment
of asthma.
FDA – LABA drug safety
communication 2011
The new recommendations in the updated labels state:
Use of a LABA alone without use of a long-term asthma control medication, such as an inhaled
corticosteroid, is contraindicated (absolutely advised against) in the treatment of asthma.
LABAs should not be used in patients whose asthma is adequately controlled on low or medium
dose inhaled corticosteroids.
LABAs should only be used as additional therapy for patients with asthma who are currently taking
but are not adequately controlled on a long-term asthma control medication, such as an inhaled
corticosteroid.
Once asthma control is achieved and maintained, patients should be assessed at regular intervals and
step down therapy should begin (e.g., discontinue LABA), if possible without loss of asthma
control, and the patient should continue to be treated with a long-term asthma control medication,
such as an inhaled corticosteroid.
Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid
should use a combination product containing both an inhaled corticosteroid and a LABA, to ensure
adherence with both medications.
INHALED ANTIMUSCARINIC DRUGS
Relievers of the second choice, at AE
competitive antagonists on M1, M2 and M3
receptors of parasympathicus
cholinergic tonus
Division:
with short-lasting effect: ipratropium bromide
with long-lasting effect: tiotropium bromide (CHOPD)
FDA – LABA drug safety
communication 2011
In February 2010, the agency announced it was requiring
manufacturers to revise their drug labels because of an
increased risk of severe exacerbation of asthma symptoms,
leading to hospitalizations, in pediatric and adult patients, as
well as death in some patients using LABAs for the treatment
of asthma.
FDA – LABA drug safety
communication 2011
The new recommendations in the updated labels state:
Use of a LABA alone without use of a long-term asthma control medication, such as an inhaled
corticosteroid, is contraindicated (absolutely advised against) in the treatment of asthma.
LABAs should not be used in patients whose asthma is adequately controlled on low or medium
dose inhaled corticosteroids.
LABAs should only be used as additional therapy for patients with asthma who are currently taking
but are not adequately controlled on a long-term asthma control medication, such as an inhaled
corticosteroid.
Once asthma control is achieved and maintained, patients should be assessed at regular intervals and
step down therapy should begin (e.g., discontinue LABA), if possible without loss of asthma
control, and the patient should continue to be treated with a long-term asthma control medication,
such as an inhaled corticosteroid.
Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid
should use a combination product containing both an inhaled corticosteroid and a LABA, to ensure
adherence with both medications.
Muscarinic receptorys in
airways
Pre-ganglionic
nerve
Nicotinic receptor (+)
Parasympathetic
ganglion M1 receptor (+)
Post-ganglionic
nerve
M2 receptor (–)
ACh
M3 receptor (+)
Smooth muscle
Ipratropium (non-selective)
Tiotropium (selective for M3 receptors)
INHALED ANTIMUSCARINIC DRUGS
Glycopyrronium
Umeclidinium
Methylxanthines
CONTROLLERS, to long-lasting control of symptoms
Improvement of clinical symptomatology
bronchodilation - without signif. increase of FEV1/ improvement of
lung function parameters through inhibition of fosfodiesterase I. to IV.
=> cAMP
antiinflam., immunomodulatory effects
positive effect on phenomenon of „corticoid resist.“
AE: cephalea, nausea, vomiting, tachycardia, palpitations,
plasm. conc. (TDM) arrhytmias, epileptic spasms even death
potential toxicity, profile of AE BRONCHODILATORS OF
THE THIRD CHOICE
Methylxanthines
Proven benefit bring only drug forms providing long-lasting action
with controlled release
Cetirizine (Zyrtec)
Bisulepine (Dithiaden)
Loratadine (Claritine)
Dimetindene (Fenistil)
Modern antihistamines:
Moxastine (Kinedryl)
Desloratadine (Aerius)
Promethazine (Protazín)
Fexofenadine (Fixit)
Ketotifen (Zaditen)
Levocetirizine (Xyzal)
Cyproheptadine (Peritol) Bilastine (Omarit)
Tietylperazine (Torecan) Rupatadine (Rupafin)
Topical antihistamines
EYES, NOSE
Azelastine (Allergodil)
Levocabastine (Livostin)
Olopatadine (Opatanol)
ANTITUSSIVES
MUCOLYTICS
ANTITUSSIVES
cough = reflex. protective mechanism, with witch airways are
getting rid of any foreign materiala, and also secretory products
complete cough supression is unwanted and unreal
but long-lasting cough cand weaken patient and strained
breathing muscles are painful, that´s when are indicated
antitussives
antitussives we use only when we know ethiology of cough and
when we treat causally given disease!
Division:
1. antitussives with central effect and with the
structure of opioids (not recommended at patients with
bronchial asthma and COPD)
2. antitussives with central effect and peripheral effect with
different structure
ANTITUSSIVES OF CODEINE TYPE
(CODEINE)
= decreases sensitivity of center for cough
properties similar to morphine, less effective
p.o. administered good absorption from GIT, metabolis.
in liver to morphine and norcodeine, excreted by kidneys unchanged
or as glucuronide, transfer to breast milk = supress of child´s
breathing
interactions: + IMAO, thymoleptics, physostigmine,
neostigmine
- naloxone, nalorphine, pentazocine
= increases analgetic effect of analgetics-antipyretics
= potentiation of suppressive effect of other CNS drugs
= with opioid analgetics – deepening depression of CNS and breathing
center
ANTITUSSIVES OF CODEINE TYPE
(CODEINE)
indication: symptomat. supressing of irritating non-
productive cough of known etiology in combination with
causal therapy of given disease
contraindications: difficult expectoration, mainly at
advanced stage of bronchopulmonal disease,
hypersensitivity to drug, prohibition of alcohol /strongly
increases depressive effect on CNS/!
dose: 15 – 30 mg 3 times per day
ANTITUSSIVES OF CODEINE TYPE
(PHOLCODINE)
= derivate of codeine with bigger efficacy, doesn´t decrease
bronchial secretion, isn´t usually cause of dependence,
supresses cough reflex inhib. by inhibition of centrum for
cough in medulla
- therapy of dry irritating cough
- increases depressive effect of substances supressing CNS and
also alcohol
dosage: 10 – 20mg 3 times per day
ANTITUSSIVES OF CODEINE TYPE
Etylmorphine = derivate of morphine similar to codeine,
stronger analgetic and antitussic effect
at dry irritating cough at acute inflammation of airway
system, TBC, spontaneous pneumothorax and before
diagnostic procedure
long-lasting aplication in pregnancy = abstinent signs at
newborn, passes to milk!
Dextromethorphan = antitussive drug without analgetic.
effect, doesn´t supress breathing center, minimal risk of
dependence, minimal AE
ANTITUSSIVES OF NONCOD. TYPE
central effect: pentoxyverine /one-third effect of
codeine, lower effects, at antitus. doses proven no
depressive influence on breathing center/, butamirate
/effective antitussic used in pediatria, minimum AE/,
clobutinol /contraindicated in pregnancy and at breast
feeding/
peripheral effect: benzonatate, dropropizine /strong
antitussive with properties similar to butamirate, mild
antihistaminic effect, minimal effect on on breathing
center/
MUCOLYTICS and EXPECTORANTS
= getting rid of viscous mucus from airways
Mucolytics and secretolytics – lower viscosity of mucus, resp. increase
production of mucus
Secretomotorics – are increasing activity of cilliar epithelium
/β2-sympathomimetics, eteric oils/
CAREFUL AT SIMULTANEOUS ADMINISTRATION OF ANTITUSSIVE AGENTS!
BROMHEXINE – increasing proportion of liquid bronchial mucus and reduces its viscosity by
reduction of transversal bonds of acid mucopolysaccharides, promotes secretion of mucus,
improves cilliar function, pharmaco-therapeutically active is metabolite ambroxol
AMBROXOL – mukolytic and secretolytic effects, activation of cilliar epithelium
N-ACETYLCYSTEINE - cleaves disulfidic bridges connecting mucopolysacharid fibers in
sputum, at difficult expectoration, at chronic bronchitis and mucoviscidosis, also
prophylactically
ERDOSTEINE – newer, decreases the sputum viscoelastic properties and bacterial adhesion to the
cell membrane
GUAIFENESIN – helps thin and loosen mucus in the lungs
PREPARATIONS OF HERBAL ORIGIN – coltsfoot, thyme, plantain, mint and others, well
tolerated with a low incidence of adverse reactions; do not administer in suspicion of bronchial
asthma