![Page 1: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/1.jpg)
Jiří Slíva
Drugs affecting respiratory systemDrugs affecting respiratory system
![Page 2: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/2.jpg)
Absolute number of patients suffering from AB in CZ
Period
Number of patients
http://issar.cenia.cz
![Page 3: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/3.jpg)
Asthma in numbers…
100-150 million worldwide; 180 000 deaths/year
total number of AB patients has doubled during last
decade
Australia: every 6th child suffers from AB
Source: WHO
![Page 4: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/4.jpg)
![Page 5: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/5.jpg)
THE MOST IMPORTANTALERGENES
![Page 6: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/6.jpg)
JANUARY
FEBRUARY
MARCH
APRIL
MAY
1. DEC. 2. DEC. 3. DEC. Pollen situation of„Alnusglutinosa“ in the Europe
![Page 7: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/7.jpg)
![Page 8: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/8.jpg)
![Page 9: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/9.jpg)
![Page 10: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/10.jpg)
DIAGNOSIS
1. ANAMNESIS
3. LABORATORYTESTS
2. CLINICALFEATURES
4. ALLERGOLOGICAL TESTS
![Page 11: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/11.jpg)
pharmacoterapylife style
specific imunotherapy (SCIT vs SLIT)
symptomaticantiinflammatoric
preventive
![Page 12: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/12.jpg)
• sympatomimetics
• anticholinergics
• corticosteroides
• methylxantines
• antileukotriens
• antihistamines
• MABs
Groups of drugs:
![Page 13: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/13.jpg)
![Page 14: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/14.jpg)
Novolizer:
![Page 15: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/15.jpg)
Ventodisk, Turbuhaler:
![Page 16: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/16.jpg)
![Page 17: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/17.jpg)
β-mimetics
- nonselective - adrenaline, isoproterenol, orciprenaline, ephedrine
- selective - metaproterenol, albuterol, salbutamol, terbutalin, fenoterol => more effective via inhalation then p.o.
administration => increase of cAMP
=> SABA, LABA, RABA
Parasympatolytics
ipratropium
Antiasthmatics with rapid effect:
![Page 18: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/18.jpg)
β2-mimetics with long-term effect:
• via inhalation salmeterol • via per os (tbl, susp) clenbuterol, procaterol
![Page 19: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/19.jpg)
Rapid & short-term acting 2- sympatomimetics (RABA)
• fast and short-term bronchodilation after inhalation
• for acute treatment
• onset of action in 5-10 min (inhal.), 15-90 min (p.o.)
• duration of action 4-6 hrs
• salbutamol /Ventolin/
• fenoterol (Berotec)
• terbutalin (Bricanyl)
![Page 20: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/20.jpg)
Long-term acting 2- sympatomimetics (LABA)
• bronchodilation 12 hrs • not suitable for acute treatment, for prophylaxis only • ICS are prefered (20x higher eff. than p.o.,
+ systemic ADRs)• commonly in combination with ICS
• moderate & severe BA in combination with ICS
• salmeterol /Serevent/
• formoterol /Oxis/
• procaterol /Lontermin/
![Page 21: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/21.jpg)
ADRs of 2-mimetics
• muscle tremor (higher doses)
• palpitation, tachycardia, arrhythmia,
sudden death
• headache
• paradox bronchospasm (after inhalation)
• rarely allergy
![Page 22: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/22.jpg)
Action of beta-mimetics…Action of beta-mimetics…
1.1. Smooth muscle rec.Smooth muscle rec.1. bronchodilation
2.2. Other receptors (epitelium, mastocytes Other receptors (epitelium, mastocytes etc.)etc.)
1. mastocytes stabilization
2. inhibition of release mediators from eo, macro, T-cells or neu
3. decreased plasma exsudation to airways
4. etc.
Hanania, 2004
![Page 23: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/23.jpg)
beclometasone
budesonide flunisolide fluticasone triamcinolone
potent antiinflammatory effect
decrease of number of inflammatory potent
cells
inhibition of bronchoconstrictory mechanisms
direct relaxation of smooth muscle cells
Corticosteroids:Corticosteroids:
![Page 24: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/24.jpg)
ICS & beta-mimeticsICS & beta-mimetics
Synergism:Synergism: CS recover bronchial responsivity to beta-2 mimetics CS recover bronchial responsivity to beta-2 mimetics
==>> mechanism (?) mechanism (?)
Mechanism (?):Mechanism (?):
– increased affinity of agonists to receptorsincreased affinity of agonists to receptors
– decreased degradation of receptorsdecreased degradation of receptors
– decreased activity of COMTdecreased activity of COMT
– decreased up-take of mediators to presynaptic decreased up-take of mediators to presynaptic
buttonbutton
…Pauwels, 1985
![Page 25: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/25.jpg)
ADRs of ICSADRs of ICS
![Page 26: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/26.jpg)
Local ADRsLocal ADRs
Most frequent:Most frequent: oropharyngel candidosis dysphonia cough
Prevention:Prevention: mouth washing after admin. use of prodrugs (activation in lungs:
ciclesonide ciclesonide => C C21-des-methylpropionyl-21-des-methylpropionyl-ciclesonideciclesonide)
![Page 27: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/27.jpg)
Systemic ADRs I.Systemic ADRs I.
absorption from lung & GI
no important ADRs after admin. of
budesonide 400 g or its equivalent
GINA, 2006
![Page 28: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/28.jpg)
Frequently discussed:Frequently discussed:
suprarenal supressiondecreased BMDglaucoma & cataracta
Systemic ADRs II.Systemic ADRs II.
![Page 29: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/29.jpg)
theophylline - myotropic influence via inhibition of phosphodiesterase and via antagonism on the adenosine receptors A2
=> bronchodilatation
=> prevention from bronchoconstriction caused by histamine, cholinergic agonists (metacholine) or exertion.
Aminophylline = theophylline + ethylendiamine
Methylxantines:
![Page 30: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/30.jpg)
Antiinflammatory theophyllineAntiinflammatory theophylline
Watanabe S, 2008
![Page 31: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/31.jpg)
Antiinflammatory theophyllineAntiinflammatory theophylline
Watanabe S, 2008
Note: aminoglutethimide = inhibitor of GC synthesis; mifepristone = anta GCR
![Page 32: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/32.jpg)
Mechanism of actionMechanism of action
??? SYNERGISM with ICS ?????? SYNERGISM with ICS ???
- both in vitro & in vivo higher activity of HDAC (histon
deacetylases) in epit. cells & macrophages => higher eff.
of ICS on genes with antiinflammatory properties
Ito K, 2002
![Page 33: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/33.jpg)
Anticholinergics
CNS
bronchialepithelium
bronchial muscle cellsmucus producing cells
parasympat.ganglion
neurokinines
rec. M2 a M3rec. M1 & M3
n. vagus
tiotropium
rec. M1
![Page 34: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/34.jpg)
Anticholinergicsipratropium /Atrovent, in comb. with 2 mimet.
Berodual/• similar structure to atropine• shorter eff. 4-8 hrs, rapid onset: 5‒15 min• for acute use with RABA• for long-term therapy with LABA
tiotropium /Spiriva/• longer eff. up to 48 hrs, slower onset• for long-term therapy of BA or COPD
![Page 35: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/35.jpg)
inhibition of degranulation of mastocytes after exposition to specific agents full effect after 4-6 weeks
Cromones
cromoglycate sodium
nedocromil• similar to cromoglycate in mechanism of action
![Page 36: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/36.jpg)
zafirlukast montelukast
zileuton = inhib. of 5-lipooxygenase
Antileukotriens &
Leukotriene Receptor Antagonists (LTRAs):
![Page 37: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/37.jpg)
Antihistamines:Antihistamines:
![Page 38: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/38.jpg)
Histamine receptors:Histamine receptors:
HH1119661966 smooth muscles, endothelium, smooth muscles, endothelium,
dendritic cells, neu, mono, eo,dendritic cells, neu, mono, eo,
T a B ly, hepato, chondrocytes, T a B ly, hepato, chondrocytes, CNSCNS
HH2219721972 gastric parietal cells, myocardium, gastric parietal cells, myocardium,
uterus, CNSuterus, CNS
HH3319831983 CNS, airways, GITCNS, airways, GIT
HH4420002000 mast cellsmast cells
![Page 39: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/39.jpg)
= sedative antihistamines
inverse agonists of H1 receptor
low selectivity = influence of other receptors
short interaction with the receptor => a need of more frequent
administration (b.i.d. or t.i.d.)
ANTIHISTAMINES ANTIHISTAMINES 11stst generation generation
![Page 40: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/40.jpg)
Common ADRs:Common ADRs:
– antimuscarine eff.
– arrhythmia
– sedation (cross via HEB)
– potentiation of alcohol
– adrenolytic & antiserotonergic eff.
ANTIHISTAMINES ANTIHISTAMINES 11stst generation generation
![Page 41: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/41.jpg)
ANTIHISTAMINES ANTIHISTAMINES 11stst generation generation
ORALORALBisulepineBisulepine
Bilastine Bilastine DimetindenDimetinden
Clemastine Clemastine Promethazin Promethazin KetotifenKetotifen
PARENTERALPARENTERALBisulepin Bisulepin
Promethazin Promethazin
ClemastinClemastin
TOPICALTOPICAL Dimetinden Dimetinden
KetotifenKetotifen
COMBINED PREPARATIONS – COMBINED PREPARATIONS – locallocalSpersallerg – eyeSpersallerg – eye
Sanorin-Analergin – eye, noseSanorin-Analergin – eye, nose
Vibrocil – noseVibrocil – nose
![Page 42: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/42.jpg)
= higher selectivity = better safety profile= higher selectivity = better safety profile
Substances for systemic administration:Substances for systemic administration: acrivastine, cetirizine, loratadine, mizolastineacrivastine, cetirizine, loratadine, mizolastine
Substances for local administration:Substances for local administration: azelastine, emedastine, epinastine, azelastine, emedastine, epinastine,
levocabastine, olopatadinelevocabastine, olopatadine
ANTIHISTAMINES ANTIHISTAMINES 22ndnd generation generation
![Page 43: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/43.jpg)
= active enantiomers (levocetirizine) or metabolites = active enantiomers (levocetirizine) or metabolites (desloratadine or fexofenadine) (desloratadine or fexofenadine)
higher selectivity => better tolerability & safety profilehigher selectivity => better tolerability & safety profile
For systemic administration:For systemic administration: levocetirizine, desloratadine, fexofenadinelevocetirizine, desloratadine, fexofenadine
ANTIHISTAMINES ANTIHISTAMINES 33rdrd generation generation
![Page 44: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/44.jpg)
verapamilenifedipine etc.
inhibition of calcium influx => inhibition of contraction of smooth muscle cells
induction of bronchodilation
used experimentally
Inhibitors of calcium channelsInhibitors of calcium channels
![Page 45: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/45.jpg)
Asthma vs glaucomaAsthma vs glaucoma
![Page 46: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/46.jpg)
Asthma vs. glaucomaAsthma vs. glaucoma
Concomitant glaucoma and AB
- in glaucoma – BBBB = drug of choice (CI: in AB)
- in AB – CSCS = drug of choice (CI: in glaucoma)
![Page 47: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/47.jpg)
„„News“News“
„ULABAULABA“ – „ultra-long acting beta-2 agonists“ -
arformoterol, carmoterol, indacaterol, GSK-159797arformoterol, carmoterol, indacaterol, GSK-159797 …in
clinical praxis from 2010 for AB & COPD (once daily)
omalizumabomalizumab - anti IgE – effective in all. rhinitis as well
bimosiamosbimosiamos – inhalatory pan-selectine anta =>
inhibition of rolling & extravasation of infl. cells
![Page 48: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/48.jpg)
Comparison of numbers of drugs Comparison of numbers of drugs used in therapy of bronchial asthmaused in therapy of bronchial asthma
![Page 49: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/49.jpg)
![Page 50: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/50.jpg)
1) peripheral sensors inhibition - benzonatate, dropropizine
2) afferent signals modulation - prenoxdiazine
3) cough centre inhibition - a) opioid – codein, dextromethorphan - b) non-opioid - butamirate, pipazetate - clobutinol – RC stimulation + cough centre inhibition
4) efferent signals modulation - myorelaxants
5) effector modulation - penthoxyverine - bronchodilation
![Page 51: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/51.jpg)
![Page 52: Jiří Slíva Drugs affecting respiratory system. Absolute number of patients suffering from AB in CZ Period Number of patients](https://reader038.vdocument.in/reader038/viewer/2022110322/56649d345503460f94a0abc8/html5/thumbnails/52.jpg)
Secretomotorics – plant etheric oils - ol. menthae piperitae
Secretolytics - saponines & alcaloids - ipekakuana, primula, NaI, KI, NH4Cl
Mucolytics - acetylcystein, carbocystein, mesna, bromhexin, ambroxol