Asthma and COPD treatment

1. Asthma and COPD treatment

Drugs acting on pulmonary system

2. Indacaterol

Selective prolinged beta2agonist (24 hrs)
Adenylatcyclaze catalyzing ATP to cyclic AMP
transformation
Increase of CAMP leads to bronchodilation
Action on beta2 receptors 24 times more than
beta1 and 20 times more than beta3

3.

FEV elevation for 24 hrs
Acts 5 min post inhalation (comparable to
salbutamol)
Maximal action 2-4 hrs
Decreases hyperinflation (increase of volumes
at the end of spontaneous expiration) in
midsevere and severe COPD
Decrease of risk of COPD exacerbations and
demand of short time beta2 agonists,
ipmrovement of life quality

4.

Cmax reached in 15 min post inhalation
Bioavailability 43%
Systemic exposition due to absorbtion in
lungs and intestine increases as dose increase
(from 150 to 600 mcg)
Excreted with urine – 2% of dose; in oral intake –
90% through intestine
T1/2 45,5 - 126 ч. T1/2, basing on the cumulation
after repeated use – 40-56 days

5. Indication

Prolonged treatment in COPD
Contraindication
Hypersensitivity, pregnancy, brestfeeding, age
< 18
Limitations
Cardiovascular diseases, convulsive disorders,
thyrothoxicosis, diabetes, QT prolongation
(congenital or drug induced), inadequate
response to beta mimetics in case history

6. Side effects

Most – mild degree
Nasopharyngitis, upper respiratory infections,
,muscular spasm, sinusitis
Hypersensitivity
Cough, throat pain, rhinorrhea, rare – paradoxal
bronchospasm
Rash, itching
Dizziness, paresthezy
IHD, palpitation, Afib, tachycardia
Dry mouth
Hyperglycemia/onset of diabetes
Peripheral edema, non cardiogenic chest pain

7. Interactions

With drugs causing QT prolongations – arrhytmias
With sympathomimetics –higher risk of systemic
actions
With drugs causing K decrease – hypokaliemia
(incl.with GCS, methylxantines)
With beta blockers – decrease of action (accurately
selectives can be used)
With inhibitors of CYP3A4 and P-glycoprotein –
with verapamil and erythromycin Cmax increases
1.2 times

8. Overdosage

After single use of the dose 10 times higher than
therapeutic in COPD patients – moderate increase
of heart rate, BP, QTc prolongation

9. Dosage

150, 300 mcg capsels
Onbrez breezhaler
150 once daily usual dose, 300 mcg daily
maximal dose

10. Olodaterol

High selectivity beta2 mimetic
QT prolongation with no influence on the heart
rate or rhythm disorders
5 mcg once daily leads to significant
improvement of FEV1 during 5 min after first
dose

11.

Cmax 10–20 min after inhalation
Bioavailability 30%
CYP2C9 and CYP2C8 of cytochrome Р450 are
participating in metabolism
T1/2 45hrs
No significant changes in aged and
concomitant diseases

12. Indications

Prolonged treatment of COPD
Possibility of use in asthma was not studied

13. Contraindications and Limitations

Contraindications: age <18 (not studied),
individual intolerance
Limitations: unstable course of IHD, QT
prolongation and rhythm disorders,
obstructive CMP, AH, hyperthyrosis, crapms,
in patients with recent MI or heart failure
decompensation (last year), paroxysmal
tachycardia, heart rate > 100/ min

14. Side effects

Nasopharyngitis, cough
Dizziness
Hypertension
Rash
Back pain and arthralgia
Pneumonia; lung cancer was observed in 0,7%,
0,3% и 0,2% of patients receiving 10 mcg, 5 mcg
and placebo
Hyperthermia
Diarrhea, constipation

15. Interactions

Same as Indacaterol
Interaction with ketaconazol – increase Cmax
1.7 times

16. Infortispir Respimat

5 mcg once daily (inhalation)

17. Salmeterol

Prolonged bronchodilation (12 hrs)
Prevents histamine, LT and PGD2 deliberation
from mast cells
Antiinflammatory properties

18. Indications

Asthma, COPD
Contraindications
Intolerance, age <4 yrs
Limitations
Thyrotoxicosis, arrhythmia, IHD, uncontrolled
hypertension, hypoxial pheochromocytoma,
pregnancy, breastfeeding, aged

19. Side effects

Increase SBP/decrease DPB, rhythm disorders
(SVT, PAC, Afib)
Diarrhea, abdominal pain, vomiting, viral
gastroenteritis, mucosal irritation of throat
Dizziness, headache, tremor, anxiety
Paradoxal bronchospasm (drug to be cessated),
cough
Arthralgia, hypokaliemia, allergy rhinitis, laryngitis

20. Serevent®

2×25 mcg twice daily
Maximal dose 4×25 mcg 2 times daily

21. Formoterol

High selective
QT prolongation
Cmax 5 min
T1/2 10 hrs

22. Indications

Asthma, COPD
Contraindication – intolerance
Limitations – coronary insufficiency AH,
cramps, thyrotioxicosis, preganncy, breast
feeding, age <5yrs

23. Side effects

Tremor, dizziness, insomnia
Pulmonary infections, dyspnoe, tonsillitis,
dysphonia
Viral infections, chest pain, rash

24. Foradil®

Capsels 12 mcg for inhalation
12–24 mcg 2 times daily

25. Oxis® Turbuhaler®

4,5 mcg in one inhalation
1-2 inhalations 1-2 times daily

26. Fenoterol

Start of action 5 min
Maximal 30–90 min
Duration 3–6 hrs
T1/2 – for 30% of drug 11 min, for 70% - 120
min
100 mcg

27. Side effects

Tremor, nervousness, headache, dizziness,
accomodation disorder, psychical changes in rare
cases
Tachycardia, palpitations, rare SBP increase DBP
decrease, arrhtytmia
Rare cough, pharyngitis, paradoxal bronchospasm
Nausea, vomiting
Rare rash angioedema urticaria
Hypokaliemia, weakness, cramps, urine retention

28. Salbutamol

T1/2 — 3,8 hrs, circulation at therapeutic level in
blood 2-9 hrs
Excreted with urine and bile
Maximal effect at 4–5 min, increases to 20 min
and reach maximal at 40-60 min, duration 4-5
hrs
Maximal effect in 2 doses inhalation

29. Ventolin®

100 mcg

30. Aclidinium bromide

Selective
M3 receptors longer than M2 (M3 in smooth
muscles of bronchi)
FEV1 improvement 30 min after 1st dose,
maximal 1-3 hrs, lasts more than 12 hrs
No influence on QT
Cmax 5-15 min (healthy and COPD)
T1/2 2-3 hrs

31. Indications

COPD
Contraindications – individual intolerance, age
<18, lactose intolerance

32. Side effects (rare)

Headache
Nasopharyngitis
Angioedema , rash
Dizzinesss
Palpitations, tachycardia
Dry mucosa
Urine retention, worsening of glaucoma

33. Overdosage

No symptoms in healthy after 6000 mcg

34. Accurately

Asthma – not to be used (no experience)
Accurately with recent MI, rhythm disorders,
HF III-IV class
Dry mouth may lead to caries

35. BRETARIS GENUAIR

322 mcg
One inhalation 2 times daily

36. Glycopyrronium bromide

Seebri Breezhaler - 50 mcg (once daily)

37. Tiotropium bromide Spiriva® 18 mcg

High selective to M3
Effect is due to local, not systemic action, and
lasts 24 hrs
Bioavailability (systemic) 19.5%
Minimal biotransformation
T1/2 5–6 days

38. Indications

COPD
Contraindications – 1st trimester of pregnancy,
<18

39. Side effects

Mild dryness in mouth, constipation
Cough, local irritation, bronchospas,
Tachycardia, urine retention in males with
predisposing factors
Angioedema
Vision disorder, acute glaucoma

40. Dosage

One capsule inhaled once daily

41. Ipratropium bromide)

M-blockers
Minimally absorbed
Bronchodilative effect 5-10 min, lasts 5-6hrs
Dilates mostly large and medium bronchi
Decreases mucus secretion
For tachycardia 500 doses needed
10% reaches bronchiols and alveols

42. Side effects

Headache, dry mouth
Tachycardia, accomodation disorders, decreased
perspiration, GI motorics disorder, urine retention
Cough, rare paradoxal bronchospasm
Rask, urticaria, angioedema, rare anaphylaxia
Glaucoma exacerbation

43. Atrovent®

2 doses 2 times daily
0.021 mg in one dose

44. Beclometasone)

Decreases cells migration and activation
Decreases mucus secretion
Dilates smooth muscles and normalizes its
sensitivity to adrenomimetics
Increases number of active beta receptors
Effect starts in 4-5 days and reachs maximum
for several weeks

45. Side effects

Hoarse voice
Laryngitis, sneezing, cough, paradoxal
bronchospasm, eosinophilic pneumonia,
candidosis (>400 mcg daily)
In dose >1.5 mg daily – systemic effects

46. Beclazone Eco

50 mcg, 100 mcg, 250 mcg

47. Budesonide

25% of dose comes to alveoli
90% of dose in GI is destroyed during first
passage (bioavailability 10% of all drug passed
to intestine)

48. Side effects

Dysphonia, throat pain, rare – candidosis,
nausea, pharyngitis

49. Pulmicort®

250 mcg, 500 mcg (suspension for nebulizer)
Pulmicort®Turbuhaler®
100 and 200 mcg

50. Ciclesonide

Alvesco
Low affinity to receptors
Pulmonary esterases transform it to
desciclesonide which has proinflammatory
activity
Less pharyngeal and systemic side effects
Active metabolite is metabolized with use of
CYP3A4 in liver

51. Indications

Asthma
Contraindication <6yrs old
Accurately in active TB, in pulmpnary
infections

52. Side effects

Diarrhea, dyspepsia
Angioedema, paradoxal bronchospasm
Oral candidosis – equal to placebo
Exema, rash

53. Dosage

Mild to moderate asthma – 160-640 mcg daily,
640 mcg should be separated to 2 intakes
Severe – maximal 1280 mcg
In one dose 40, 80, 160 mcg

54. Combinations

Aclidinium bromide + Formoterol (COPD only)
Budesonide + Salbutamol Biasten
Budesonide + Formoterol Symbicort Turbuhaler®Foradil
Combi
Vilanterol + Umeclidinium bromide ANORO ELLIPTA®
(22 + 55 mcg /dose – once daily)
Vilanterol + Fluticasone furoate Relvar Ellipta (40+200
mcg) – asthma, COPD
Glycopyrronium bromide + Indacaterol Ultibro Breezhaler
Mometasone + Formoterol (Zenheyl (200 mcg+5 mcg)
Olodaterol + Tiotropium bromide Spiolto® Respimat®
Salmeterol + Fluticasone Seretide®
Ipratropium bromide + Fenoterol Berodual®

55. Zafirlukast

Blocks leucotrien receptors and prevents
smooth muscles contraction (LTC4, LTD4 , LTE4)
Cmax 3 hrs
Т1/2 10 hrs
Excreted by fects 89%, urine and breast milk
10%

56. Indications

Mild and midsevere asthma
Contraindications – liver failure, cirrhosis, age
< 5 yrs

57. Side effects

Insomnia, headache, weakness
Rare hemabomas after traumas, hypermenorrhea,
decreased platelets, rare agranulocytosis
Nausea, vomiting, abdominal pain , rare hepatitis,
liver failure and fulminant hepatitis

58. Interactions

ASA – 1.5increases blood levels
Erythromycin, theophyllin – decrease 40% and
30%
If used with warfarin, prothrombin time
increases 35%
In smokers clearance in s20% increased

59. Accolate 20 mg

20 mg 2 times daily
No age correction

60. Montelukast)

Specifically inhibits CysLT1- receptors of LTC4,
LTD4, LTE4
воспаления, поддерживающего
гиперреактивность бронхов при бронхиальной
астме.
Cmax 2–3 hrs, bioavailability 64–73%.
Decreases bronchial spasm and edema, Eo and
macrophages migration, improves mucociliar
transport
Effect develops in one day

61.

Possibility of extremities abnormalitis in fetus (if taken by
pregnant)
Hallucinations, agressions, insomnia, paresthesia, hedache,
cramps
Nausea, vomiting, dyspepsia, diarrhea, abdominal pain
Myalgia, arthralgia
Anaphylaxy, angioedema, rash, urticaria, rare liver
eosinophilic infiltrates
Trend to increased bleeding
Palpitations
ASAT ALAT increase, hepatitis incl fulminant
Flu like syndrome
Edemas

62. Singulair®

10 mg daily (once, in the evenling)