BRONCHIAL ASTHMA

Pharmacology and Clinical Aspects

DEFINITION AB
Asthma bronchiale is chronic
inflammatory disease of airways
connected with bronchial
hyperreactivity and totally or partially
reversible obstruction of airways,
which in the most cases dissapears
spontaneously or with treatment.
AB
1. Extrinsic: often allergy and atopy
2. Intrinsic: non-alergic 10-30%
(more severe, adult-onset)

 daily symptom variability

 family history
 no smoking
 ETIOPATOGENESIS
•  INFLAMMATION  activation of mastocytes, macrophages,
eosinophils, helper Th-lymfocytes => formed and released
inflammatory mediators: histamine, leucotriens, prostaglandins,
bradykinin

bronchoconstriction, mucus secretion, plasma exudation

and bronchial hyperreactivity, airway remodelation

 insufficient anti-inflammatory therapy => progressive destructive

changes  fixing of airway obstruction to emphysematous changes
Triggers of Symptoms and Exacerbations
 allergens
 factors of air pollution (including cigarette smoke)
 respiratory infections, particularly viral (RSV, rhinoviruses,
influenza viruses, chlamydia)
 physical activity and hyperventilation (by osmotic processes)
 wheather changes
 food and drugs (ASA, NSAID, -blockers)
 emotional stress
 gastroesophageal reflux
CLINICAL SYMPTOMS OF AB
 Emphasis on early diagnosis
management begins with right analysis of symptoms

- 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

sy. continuously, attacks PEF  60%N

IV. severe often, physical activity variability of PEF
persistent limited Often 30%
A
sy. daily, attacks PEF = 60-80%N
2/week, influencing activity variability of PEF
III. moderate 30%
 1/week
persistent

sy. 2/week  daily, attacks PEF  80%N

II. mild 2/week, changing activity variability of PEF =
 2/month 20-30%
persistent A

sy. 2/week, only mild or no

attacks, aktivity unchanged PEF  80%N
I. mild intermittent
 2/month variability of PEF
A 30%
Levels of Asthma Control GINA 2011
Assessment of current clinical control (preferably over 4 weeks)
Characteristics Controlled (all of the Partly Controlled (any measure Uncontrolled
following) presented)

Daytime symptoms None (twice or less / More than twice / week Three or more features of
week) partly controlled asthma

Limitations of activities None Yes

Nocturnal symptoms / awaking None Yes

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: persistent airflow obstruction, which can be

reversible or irreversible and slowly progressive →
progressive breathlessness and cough (often
productive and worse in the morning), repeated respiratory
infections, can lead to emphysema

 particularly affects the peripheral airways

 COPD Asthma Bronchiale
Beginning in middle age Beginning in younger age
Symptoms progress slowly Symptoms from day to day
changing

Long anamnesis of smoking Symptoms in the afternoon or

early morning

Dyspnoe at excercise Also allergy, rhinitis, eczema

Larger irreversible restriction Usually reversible restriction

of air flow of air flow bmedzenie

Family history of asthma

 COPD

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

 The most effective contollers of symptoms in chronic

asthma
 Relatively ineffective in COPD
 Mechanism of action: supress inflammation and immune
response
 No bronchodilators
ICS
 AE locally can reduce with the use of attachments and rinsing
the mouth with NaHCO3
 oropharyngeal candidosis
 dysphonia
 seldomly irritation to cough
 risk of systemic AE is , depends on dose ,efficacy and
pharmacokinetic of steroid
  inflammation in airways, bronchial
hyperreactivity and obstruction of airways
  risk of AE (acute exacerbations)
and control symptoms of disease
ICS
 beclomethasone
 budesonide
 fluticasone
 ciclesonide – 1 times per day, minimal syst. AE, prodrug-activation
dirrectly in lungs, the part resorbed is inactive =>  systemic ef. !!!
 mometasone
 Principles of Treatment with ICS
1. ICS need to be administered at each new dg. AB
2. Treatment is essential to start early
3. We administer attack doses of ICS
4. Reduction of dose only after longer stabilisation
(6 months) – than minimal effective dose
5. If not sufficient ICS, we add as the drug of the first choice LABA,
alternatives are leucotriene modifiers ( the first choice add-on therapy for
children younger than 5 years), methylxanthines, slow release β2-agonists
tablets
6. To adult patients are administered max. 200-800 mcg BDP/day and to
children max. 400 mcg BDP/day, than you should start on with add-on
therapy
ICS in the Treatment of AB –
„exacerbations“
 the best to add high dose of ICS to regular maintenance
therapy ICS+LABA

 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

7. Increased appetite and weight gain

8. Osteoporosis (↓ absorption of calcium, ↑ its excretion)
9. Muscle pain, muscle weakness and muscle cramps
(especially ↑ loss of potassium, ↓ calcium level in the
blood)
10. Cataract, increased intraocular pressure, optic nerve
damage, eye infections
11. CNS: irritability, mood and personality changes,
depression, headaches, dizziness
INFLUENCE OF AUTONOMIC NERVOUS SYSTEM
IN THE TREATMENT OF ASTHMA

 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)

 The regular use can enhance Th2

Inflammatory pathways and also down-regulate ß2-
receptors (regular use of ß2-sympathomimetics
without ICS is not advised)
 β2 – SYMPATHOMIMETICS
(LABA and SABA)
speed of effect
rescue treatment
beginning

Fast beginning,

maintanance therapy
Fast beginning,
FAST short duration long duration
inhal. terbutaline,
salbutamol, fenoterol inhal. formoterol,
indakaterol

Slow beginning, Slow beginning,

SLOW
short duration long duration
oral clenbuterol, inhal. salmeterol
salbutamol rtd. cps.

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)

SABA LABA ultraLABA

2x per day 1x per day

Fenoterol Formoterol Indacaterol

Levalbuterol Salmeterol Vilanterol

Salbutamol Abediterol

Terbutaline Olodaterol
Molecular mechanism of positive
interaction ICS and LABA
Corticosteroid ß2-Agonist

ß2-Adrenoceptor

Glucocorticoid
receptor

Anti-inflammatory effect Bronchodilatation

• Effect of corticosteroids on ß2-adrenoceptors

• Effect of ß2-agonists on glucocorticoid receptors
 LABA
 formoterol
 salmeterol

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

Barnes PJ. Eur Respir Rev 1996

INHALED ANTIMUSCARINIC DRUGS
 Mechanism of action:
M3 receptors: mediate bronchoconstriction, mucus secretion
M2 receptors: inhibit cilliary activity, also presynaptic receptors

Ipratropium (non-selective)
Tiotropium (selective for M3 receptors)
INHALED ANTIMUSCARINIC DRUGS

 decrease n. vagus tone

 cause relaxation
 but no bronchoprotective action
 are in general less effective than β2 – mimethics and have a little
slower beginning of action
 advantageous combinations v 1 inhalation system:
 ipratropium
 ipratropium+fenoterol
INHALED ANTIMUSCARINIC DRUGS

SAMA LAMA LAMA

2x per day 1x per day

Ipratropium Aclidinium Tiotropium

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

 with controlled release - p.o.

 aminophylline, theophylline  for using
during day time always + ICS – less effective than
ICS+LABA
 with short-lasting ef. - p.o., i.v.
 aminophylline
 Leukotriene receptor antagonists
 CONTROLLERS, for long-term control of symptoms
 antagonists of leukotriene 1 (CysLT1) receptors
  montelukast, zafirlukast, pranlukast
  inhibitors of 5-lipooxygenase
 zileuton
 taken perorally
 MA: - additive antiinflam. effect to ICS
- reduce tissue eosinophilia
- mild bronchodilation ef.
- bronchoprotective ef.
 Leukotriene receptor antagonists
 role in therapy of AB - still unclear
 are less effective than low doses of ICS
 as additive drugs (in combination with ICS) reduce the need of steroid dose at
severe asthma

 again less effective than standard ICS+LABA

 advantageous – aspirin asthma, by excercise induced asthma, „preschool
wheezing“
  compliance at taking tablet form
A: CONTROLLERS
 inhalatory corticoids  ICS
 long-acting 2-sympathomimetics

(long-acting betaagonists )  LABA, (8-15h.)

 antileukotriens  LTRAs
 leukotriene receptor antagonists
  inhibitors of 5-lipooxygenase (zileuton)
 retard methylxanthines
  cromones
B: RELIEVERS
 inhalatory short-acting 2-sympathomimetics (short-acting

betaagonists )  SABA (till 4-6 h.)

 inhalatory anticholinergics short-acting

 systemic corticoids p.o./i.v. („rescue“ treatment)

 some sources – controllers

 fast acting methylxantines

Management control of asthma GINA 2011 (adults and children older than 5 years)

STEP 1 STEP 2 STEP 3 STEP 4 STEP 5

Asthma education. Enviromental control.
As needed SABA As needed SABA

Select one Select one Select one or more Add either

Low-dose ICS Low-dose ICS + Medium-dose or high- Oral glucocorticosteroid

CONTROLLER LABA dose ICS (lowest dose)
options + LABA
Leukotriene Medium-dose or Leukotriene modifier Anti – IgE treatment
modifier high-dose ICS

Low-dose ICS + Sustained release

leukotriene theophylline
modifier
Low-dose ICS +
sustained release
theophylline
1st May, 2018
ANTIHISTAMINES
Effects of histamine
H1 receptor antagonists (Antihistamines)
 1st generation = sedating antihistamines
 2nd generation = non-sedating antihistamines

 Histamine = local hormone (autacoid) important

important in pathophysiology of allergic reactions
H1 receptor antagonists (Antihistamines)

1st generation 2nd generation

 Non-selective  From the 1980s onwards
 H1, M, 5-HT, Ach, D and other receptors =>  High selectivity for H1 rec.
 ADRs – anticholinergic, sedative...  Less ADRs
 Lipofil, small Mn =>  Lipophobic, relat. big Mn =>
 Little cross HEB
 Easy cross HEB

 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