Asthma bronchiale
COPD
Pharmaceutical care
Timeline:
1. Asthma bronchiale (AB)
2. COPD (Chronic obstructive pulmonary disease)
• Case reports
• Etiology, symptoms, therapy, AB / COPD differences
• Inhalation systems - types, theory, images
• Inhalation systems - practical demonstrations,
training
CASE REPORTS
1. Case report – ASTHMA
Patient: Kateřina, year of birth 1983
Personal history: bronchial asthma, non-smoker, not allergic to
any drugs/medicines, she does not perform self-monitoring
of asthma
Previously used only inhalation salbutamol, she has worsening
of the problem, salbutamol had to be used up to 6 times a
week, started waking up at night once a week because of
dyspnea (shortness of breath) attacks. That's why her
treatment was changed today.
Kateřina
• Medical history:
– Miflonid 400 inh. plv. 1-0-1
– Ventolin Inhaler N 1 to 2 breaths when needed
Prescription analysis
Miflonid 400 inh. plv.
• 1-0-1
• active substance: budesonide
• corticosteroid anti-inflammatory agent, high first pass effect of
drug residues after absorption (local effect)
• Mechanism of action: Reduction of cytokines that activate
eosinophils, inhibition of induction of COX-2 inhibits the formation
of vasodilating PGE2, PGI2 and spasmogenic leukotrienes, thus
reducing the migration of inflammatory elements into the bronchial
tissue
Prescription analysis
Ventolin inhaller N
• 1 to 2 breaths when needed
• active substance: salbutamol
• Beta β2 sympathomimetic, short-acting (SABA),
Dosage:
• acute therapy: 100-200 μg (1-2 breaths) No more than 8 breaths
per 24 hours (800μg), 4 times a day
• chronic therapy: up to 200 μg 4 times a day, each 6 hours
• the onset of action is within 5-10 minutes, duration of effect up to
6 hours
• Dosage only when needed !!
salbutamol had to be used up to 6 times a week, started waking up at night
once a week
Adverse reactions: (Miflonid) - especially oropharyngeal
candidiasis (candidosis) to take before a meal and
then rinse mouth with water ... and spit out - not to get a
systemic effect
• Hoarseness (chrapot), dry mouth, reddening in the throat,
pharyngeal irritation
Self-monitoring AB
• By measuring the PEF (peak expiratory flow), by expirometer,
monitoring asthma symptoms,
• especially when introducing a new drug
• PEF values ​​are recorded daily
• For our patient, self-monitoring can be recommended due to the newly
introduced drug
2. Case report - COPD
• Patient: Martin, year of birth 1958
• Laboratory values: blood pressure 130/84, pulse 102, now
temperature 37.8˚C
• Personal history: COPD, arterial hypertension,
hypercholesterolaemia; indicates that he smoked 25
cigarettes a day (since his 18 years of age), currently
smokes 10-15 cigarettes a day
• He says: he's cold, he starts coughing more often, coughing
at night.
Medical history
• Spiriva 1 – 0 – 0
• Ventolin Every 4-6 hours as needed
1 breath
• Indap 2,5mg 1 – 0 – 0
• Sortis 10mg 0 – 0 – 1
Medical history:
Spiriva 1-0-0 - S: Tiotropium bromide, anticholinergic-
bronchodilators;
MA: selective antagonism of cholinergic M3 receptors prevention
of bronchoconstriction
→ D: ok - inhalation once a day at the same time of day
Ventolin (every 4-6 hours as needed) - S: Salbutamol
IS: bronchodilators, antiasthmatic, betasympatomimetic
MA: agonist activity on β2 receptors - induction of
bronchodilation
→ D: ok - inhalation in an acute case
Indap 2.5mg 1-0-0 S: Indapamide;
IS: antihypertensive, diuretic
MI: inhibition of transport Na + / Cl- in the distal
renal tubule
→ D: ok: once a day in the morning (hypertension controlled)
Sortis 10mg 0-0-1 - S: Atorvastatin;
IS: hypolipidemic
MU: inhibition of HMG-CoA reductase inhibition
of cholesterol synthesis
→ D: ok - once a day, regardless of the time of day and food intake
Differences from AB treatment
• In the treatment of COPD, anticholinergics, β2 agonists,
methylxanthines, inhaled corticosteroids, mucolytics,
ATBs are used
• Habit-breaking is important for smokers!
• in the treatment of AB:
• immunoprophylatics, anti-leukotrienes, H1-receptor
antagonists (allergies) are used
Acute exacerbation of COPD
Basic Clinical Symptoms:
• worsening of dyspnoea
• sputum increase
• the purulent character of sputum
Additional clinical signs:
• High temperature, fatigue (weariness)
• chest pain, chest tightness
• hemoptysis
• fluid retention
• Cold / or exacerbation? can hardly be recognized
!!
Therapy of acute exacerbation
• Increased dose or frequency of bronchodilators administered
• Bronchodilator inhalation: anticholinergics, beta 2 agonists (inh.),
Methylxanthines
• Systemic Corticosteroids: Prednisone, Prednisolone,
Hydrocortisone
• Antibiotics in symptomatic infections
• Mucolytics
• Oxygen therapy - monitoring of respiratory insufficiency
• Healing bronchoscopy - suction of mucous plugs
• Ventilation support, treatment of associated diseases
Therapy of cold, elevated temperature and cough
• Antitussics are contraindicated in COPD! (cough has a
protective role in COPD)
• neopioid analgesics (paracetamol) for colds and elevated
temperature.
• For cough - expectorancia (erdostein, ambroxol, bromhexin,
N-acetylcysteine)
• KI NSAID
If we suspect acute COPD exacerbation, we will send to
the doctor !!!
To facilitate coughing, we recommend a suitable
mucolytic agent
Worsening can be caused by bacterial, viral infections or
other factors whose diagnosis and causal treatment
belongs to the doctor's hands!
Erdostein – No.1
• a muco-modulating agent that acts through its active metabolites
• The metabolites in the structure contain two bound sulfhydryl
groups that are released in hepatic biotransformation and attack
disulfide bridges that bind to each other glycoprotein fibers of
bronchial secretion
• increases the fluidity of the mucus and facilitates its expectoration
from the upper and lower respiratory tract.
• a mucolytic agent with antioxidant action and the ability to
influence the rheological properties of mucus
• an ancillary drug in the therapy of respiratory diseases with mucus
formation or expectoration, acute and chronic bronchitis and
chronic obstructive pulmonary disease (COPD)
Cigarette cessation/substitution therapy
OTC medicines with nicotine: NiQuitin, Nicorette ... etc.
• in the form of chewing gums, lozenges (pastilles), patches, sublingual
tablets, inhalers
ADR: tachycardia, hypertension, dry mouth, nausea
Drugs – prescription needed- do not contain nicotine:
Bupropion (Zyban, Wellbutrin, Elontril)
• selective inhibitor of neuronal reuptake of catecholamines
(noradrenaline and dopamine) released by nicotine
• supression of craving and withdrawal symptoms
Vareniclin (Champix)
• partial nicotinic receptor agonist
• Risk of suicide? ….
Cigarette cessation/habit-breaking therapy
THEORY
AB/COPD
1. Asthma bronchiale
• Worldwide incidence of 1-18% of the population (unknown in
the Czech Republic, children 8%)
• Chronic inflammatory disease of the respiratory tract
• Bronchial hyperreactivity
• Complete / partially reversible airway obstruction = asthmatic
attacks/episodes
• mediators of inflammation are produced that increase the
bronchial reactivity (eosinophils)
• Most patients compensated by therapy
• severe acute condition lasting several hours to days = status
asthmaticus
Triggering factors
Allergens
Infections (viruses)
Environment
Changes of the weather
Physical activity
Food
Emotions
Etiopathogenesis od AB
Inflammation
Activation of
mast cells,
macrophages
eosinophils
Release of
mediators
of
inflammati
on
Histamin,
PG, LT,
bradykinin
Bronchoconstric
tion, mucus
secretion,
plasma exudate,
bronchial
hyperreactivity,
DC change
structure
Predisposition to Asthma
• A necessary combination of genetic predisposition and
external influences
• Polygenic heredity
• Low birth weight
• Mother - a smoker
• Infection in childhood
• Atopic terrain (x COPD)
Division of AB by intensity / difficulty
Asthma - therapy
Indicator Asthma under
control
Asthma under
partial control
Asthma under
insufficient
control
Symptoms during
the day
no
more often
than twice a
week
three or more
indicators
under partial
control
Restriction of
activities
no any
Night symptoms,
awakening
no any
Need for Relief
Medication
no
more often
than twice a
week
Pulmonary function
(PEF, FEV1)
no < 80 %
Exacerbace no 1 or more / year one at a time
Clinical manifestations of asthma
• Cough (unproductive) (x COPD)
• Dyspnoea (night,early morning)
• Chest pressure
• Wheezing during breathing
• Prodromal symptoms before attack (itchy under the chin,
anxiety)
• Symptoms disappear after administration of β2-mimetics (dg .)
Diagnostics
Anamnesis of syptoms
• Functional diagnostics - spirometry
– Vital lung capacity - VC
– Reduced Power Capacity - FEV1 (Forced expiratory volume exhaled
volume)
– Normal VC, 80% reduced FEV1
Allergological examination
• Skin Prick test
– It is necessary to evaluate in the context of clinical
manifestations
– Asthma in children - frequent allergic ethiology
– Specific IgE antibodies
Asthma therapy
Individual therapy settings
A) Relief therapy AB
• Relief therapy inhalation
• Anticholinergic (ipratropium) SAMA
• (tiotropium and others) LAMA first-line drugs for COPD
• The short acting β-mimetic SABA (salbutamol,
terbutaline, fenoterol)
• p.o. xanthine derivatives (theophylline, aminophylline)
• p.o. -β2mimetics
• p.o. systemic corticosteroids (rescue medication,
increased bronchial sensitivity to β-mimetics)
SABA – Short
Acting Beta
Agonist
LAMA – Long
Acting Muscarinic
Antagonist
B) Maintenance therapy AB
• Inhaled corticosteroids
• Long-term beta2mimetics (LABA)
– formoterol, salmeterol, indacaterol
• Leukotriene receptor antagonists
– montelukast (Singulair), zafirlukast (Accolate)
• Cromones nedocromil (Tilade) mast-cell stabilization, more
expensive, rarely used
• Theophylline with long-term effect - PDE inhibitors
• Systemic corticosteroids
• Allergen vaccines
• Biological treatment - Anti-IgE antibodies (omalizumab-Xolair)
LABA – Long
Acting Beta
Agonist
Inhaled corticosteroids
• Basic maintenance treatment
• Treatment of persistent asthma
• Monotherapy, or in combination with ALT, LABA
• Locally anti-inflammatory agents
• Prevention of irreversible remodeling of the bronchial tree
• beclomethasone, budesonide, fluticasone, mometasone,
• ciclesonide (Alvesco) - deesterified in the lungs for the active substance
fluticason/salmeterol (Seretide)
budesonid/formoterol (Symbicort) and generics
fluticason/vilanterol (Relvar) …
Receptor antagonists for leukotrienes
• Acute effects on bronchospasm
• Anti-inflammatory effect
• Glucocorticoids "saving" drugs
• Therapy in children (also against allergic symptoms - rhinitis,
atopic eczema)
• Zafirlukast (Accolate), montelukast (Singulair)
Level 1 Level 2 Level 3 Level 4
Short-term inhaled
β2-SM
X X X X
Degranulation Blockers X
Inhal. glucocorticoid. X X X
Antileukotrienes X X
Xantines X X
β2-SM – p.o. X X
β2-SM – long acting X X
Anticholinergic
inhalation
X X
p.o. glucocorticoids X
How to choose appropriate anti-asthmatic drug
2. COPD
• One of the most common causes of death
• The incidence is about 7.7%, in the Czech Republic it is 700 -
800 thousand patients
• !!!!! Smoking (20-25% of smokers will have COPD)
• Environmental pollution (Si, Cd, oxidants ... bricks production,
asbestos production, coal mines)
• Infections (repeated in childhood ... most commonly viral)
• nutrition, poverty
• increased inflammatory response to risk factors
• restricting airflow in the bronchi (bronchial obstruction) that
is not completely reversible
• imbalance between proteases and antiproteases in lungs pulmonary
emphysema
Symptoms
• Chronic bronchitis
• Long-term mucus expectoration (morning coughing)
• Dyspnoea with a tendency to progression
• Limitation of ability to increase physical activity
• stadium III, IV. - cachexia, muscular atrophy
• Dg: Forced expiratory volume (FEV1) - incomplete
obstruction reversibility
• Depending on the severity of the symptoms of stages
GOLD I to IV
Therapy
• Regular aerobic physical activity - rehabilitation
• Removal of chemicals
• Smoking cessation, habit-breaking
• Vaccination against influenza, pneumococcus
= prevention of infection
Pharmacotherapy - symptomatic
• Oxygen - Long-term Home Oxygen Therapy
• Surgery - bulectomy (removal of bullous emphysema, lung
transplantation)
• Causal COPD therapy does not exist
Therapy
• Long-term beta2mimetics from II. stage
• formoterol, salmeterol (Twice a day)
• indacaterol (Onbrez) (once a day) referred to as ULABA
• olodaterol
• Long-acting anticholinergics (LAMA) from II. stage
• tiotropium (Spiriva)
– improvement of VC of lungs, static functions
– increasing tolerance of effort
• aclidinium (Bretaris, Brimica komb.)
• umeclidinium (Incruse, Anoro komb.)
• glycopyrronium (Seebri, Ultibro komb)
• Inhalation corticosteroids from III. stage
• Long-term p.o. the theophylline derivatives (drugs of 3rd line..)
Bretaris genuair (aclidinium bromid)
• competitive, selective muscarinic receptor antagonist
(anticholinergic) with longer residence times in M3 receptors
than in M2 receptors
• 2x daily
• Powder for inhalation
Seebri Breezhaler (glykopyrronium-bromid)
• a long-acting muscarinic receptor antagonist (anticholinergic) for
maintenance bronchodilator COPD once daily
• Parasympathetic innervation is the major bronchoconstrictive nervous
system in the airway and cholinergic tone is a key reversible component of
airway obstruction in COPD
• blocks the bronchoconstriction effect of acetylcholine on the smooth
muscle cells of the airway, thereby causing airway dilation
• rapid onset of action
Response of asthma and COPD to drug
therapy
INHALATION DEVICES
For proper and effective inhalation
therapy, it is imperative that the patient
knows/does the proper technique of
inhalation
Inhalation therapy
• Local effect
• Different ways of use (application)
• A necessary explanation of the correct inhalation
technique
• Up to 41% of patients do not have the right
technique of inhalation
• Changing from CFC to HFA increases the effect of KS
• (CFC - chlorofluorocarbon = freon propellant, HFA - hydrofluoroalkane)
Inhalation drugs - Benefits
• The drug acts directly on the airways , where it
reaches high concentrations that are practically
unattainable in other routes of administration
• Very fast onset of action (comparable to i.v.)
• Only a small amount of drug is absorbed into the
systemic circulation - a minimum of ADR
General principles of correct inhalation (1)
• When aerosol is inhaled, shake before use, not
necessary when using powder dosage forms
• Before applying the drug deeply breathe out
• Intensive, deep, and rapid inhale (breathing in) is
required to deliver the drug to its place of action the
bronchi (and beyond)
• hold one's breath after application for 10 seconds
• Exhale (breathe out), best by nose
• If inhalation is repeated, wait 30-60 seconds
• After inhaled corticosteroids (ICS), rinse the mouth
with water or clean the teeth to prevent the
possibility of oral candidiasis
• ADR: candidiasis (5-10%), hoarseness (30%), cough (IKS)
• 1. β2-SM 2. ICS
General principles of correct inhalation (2)
Candidiasis (IKS):
• characteristic white coating
that is painful and burning
blisters may develop,
• Occurrence: skin, mucous
membrane
• Local therapy (rinses - nystatin, clotrimazole)
• Systemic therapy (ketoconazole, fluconazole, itraconazole)
1. Inhalers (MDI, metered dose inhalers)
• Liquid vehicle
• Freons are replaced by hydrofluoroalkane (HFA)
– do not cause local mucus cooling
• Shake before use
• It is necessary to synchronize the breath (inhalation)
with the pressing the inhaler
• Patients (children) can use spacer, aerochamber
• "N" water base, no need to shake
• Ventolin N, Ecobec, Ecosal
• Berodual N
How do I know the empty pressure vessel at the inhaler?
a) Dosing aerosol + Spacer
Spacer is an inhalation extension that increases the effect of the metered
aerosol because:
• increases the amount of medicine that gets into your lungs
• reduces the amount of drug stored in the mouth
• co-ordination of breath and pressing is not required
Disadvantages of the inhalation adapter:
• is too big
• necessary regular cleaning
b) Inhalation extension
with mask
(aerochamber)
Procedure:
• Remove the cap, shake the inhaler, and insert it into the extension.
• Put the mask on your face so that it covers your mouth and nose.
• Breathing from the extension must be slow and quiet.
• Press the dispenser container once and inhal several times and exhale.
• Remove the attachment from the face. If you are taking another dose,
• wait for at least 30 seconds.
b) Aerochamber
2. Easi-breathe (BAI, breath-actuated inhalers)
• The dose is released by inhaled air
• Automatic application
• eliminate the issue of hand-inhalation coordination, respectively handbrain
coordination
• Sufficient FEV1 is required (forced expiratory volume in 1
second)
• Ecosal Easi-Breathe
• Beclazone Easi-Breathe
3. Turbuhaler (DPI, dry powder inhalers)
• Active substance in powder form
• It is released from the container after turning
• small inspiration (inspirium) needed
• Pulmicort Turbuhaler, Symbicort Turbuhaler,
Bricanyl Turbuhaler
4. Easyhaler
• Applied substance in powder form
• Simple operation
• Shake before use
• Dose release after pressing the dispenser
• It is possible to inhale the dose several times
• Buventol Easyhaler, Giona ...
• Formoterol Easyhaler
• Beclomet Easyhaler
5. Diskus
• Less number of doses (60-28)
• Doses pre-prepared in a blister (powder form)
– compact shape
– dry, never breathe in
– dose counter to zero (last 5 red)
Seretide Diskus, Flixotide Diskus
6. Aerolizer (spinhaler)
• Patient inserts capsules filled with a dose of the
drug
• Spines in the applicator will disrupt the
packaging and allow the inhalation of the powder
• It is necessary to manipulate with each dose
• Miflonid, Foradil
• Onbrez, Seebri (Breezhaler) applicator included in the package
• Spiriva (HandiHaler) applicator extra
Aerolizer (spinhaler)
Remove the applicator cover
Hold the applicator base firmly
and turn the mouthpiece
Remove the capsule from the blister
and put it in the basement
Turn the mouthpiece back against
direction of the arrow until it fits
with a clear click
Press both brown buttons.
The capsule i opened.
Take a deep breath, close your
lips and inhale deeply.
7. Respimat
• SMI - soft mist inhaler
• The drug solution is transferred to the mist in the
applicator head
• Inhalation of mist formed
• Synchronization with breath needed
• Two doses should always be inhaled
Spiriva Respimat, Spiolto respimat (tioptropium +
olodaterol)
New powder inhalers
Genuair
Bretaris (aclidinium bromid)
• Powder for inhalation
Genuair
Bretaris (aclidinium bromid)
• Powder for inhalation
Ellipta (GSK)
Ellipta (GSK) Relvar, Revinity, Anoro, Leventair, Incruse
vilanterol, umeclidinium…
Spiromax (Teva)
Duoresp 160/320 (budesonid /formoterol)
Forspiro (Sandoz)
Airflusan (salmeterol/fluticason)
Cleaning of applicators
• Different depending on the type of construction
• Remove everything you can
• Rinse with lukewarm or hot water
• Let it dry in the air
• Dry by the hair dryer
• Do not dry with a dry cloth - static electricity is generated
but dry powder forms, e.g. Easyhaler
• Clean mouthpiece at least once a week with dry cloth, do not
use water, Easyhaler powder is sensitive to moisture
• If the inhaler is accidentally pushed or pushed more than
once, remove the powder from the mouthpiece by tapping
against the table or palm
Cases %
He does not understand the instructions for use 33, 0 %
He thinks another dose is better for him 24, 8 %
He thinks another drug is better for him 13, 3 %
He thinks he's already cured 10, 5 %
He forgot to use the medicine 5, 7 %
He thinks the cause of his illness is a cure 4,7 %
He feels resistance to the drug 3, 8 %
He thinks the medicine damages him at work 1, 0 %
The patient has lost or is physically unavailable 1, 0 %
Various other causes 2, 2 %
Non-compliance of patients with AB - the role of pharmacist
„Ten Commandments“ of asthma treatment
(dle MUDr. Milan Teřl,PhD., FN Plzeň)
1. Each asthma patient should be informed about the chronic course of the
disease and know the difference between the preventive and
maintenance medication
2. Each should be equipped with both types of prevention and relief
3. Whenever possible, the inhalation form is preferred
4. Effect of preventive drugs is not immediate
5. The relief medication should be used exceptionally - except SMART
(Single Maintenance and Reliever Therapy) - fixed combination
6. Type of drug to choose by type of patient - skill, age, vision, experience,
intelligence, socio-economic status
7. All inhalation drugs should preferably be in the same or similar system
8. Prescription = presentation of the inhalation technique, dispensing in
the pharmacy = verbal instructions
9. Do not drop off tretament/drugs without consulting your doctor (even
during pregnancy)
10. Compliance and inhalation monitoring regularly