BRONCHOPNEUMONIA

1. BRONCHOPNEUMONIA

2. Bronchopneumonia • = acute inflammatory process in the area of respiratory bronchioli, alveolar structures and/or lung interstitium • caused by espec. infectious agent • complications: pleuritis, parapneumonic empyema, lung abscess, lung gangrene and sepsis • risk factors: age, CV and respiratory comorbidities, smoking, immunodeficiency • = mortality over 70 yr. to 25%! • Division according to agent: viral bacterial mycotic parasite • Division of clinical terms: CAP – community HAP – hospital acquired pneumonia

3. Clinical signs of disease • = may start suddenly with chills and fever, especially when bacterial etiologic agent • in viral diseases - development is slower, it may follow inflammation of the upper respiratory tract • temperature in children usually relatively high, in elderly subfebrileto afebrile • cough - first dry, irritable, and later with various expectoration.At the inflammatory response on the pleura, is manifested chest pain linked to cough and breathing • tachypnoea and dyspnoea in children alarm breathing and cyanosis

5. Therapy of Bronchopneumonia • immediately begin initial empirical anti-infective therapy, with the spectrum of effect covering the most prevailing pathogens, also taking into account individual risk factors • knowledge of the epidemiological situation + resistance of respiratory pathogens to antibiotics in the region • antimicrobial therapy should be directed = necessity to determine etiology and sensitivity of microorganisms to antibiotics /after identification of the pathogen, initial therapy adequately adjusted / + bronchodilators mucolytics expectorances antitussics + rest in bedfluid intakecalories intake vitamin intake

6. LUNGS respiratory viruses Str. pneumoniae H. influenzae S. aureus Klebsiella speciei M. pneumoniae Str. pyogenes Chl. psittaci BRONCHI respiratory viruses Str. pneumoniae H. influenzae Str. pyogenes S. aureus Escherichia coli Etiologic Agents according to Frequency of Occurance

7. Antimicrobial Drugs • with targeted mechanism affect the structure or function of microorganism cells, and thus they either kill - bactericidal effect, or inhibit their growth and multiplication - bacteriostaticeffect/immunodeficiency and cachect. patients! / • selective action on the cells of microorganisms:effect on the synthesis of cell wall - bactericideffect on protein and NA synthesis + inhibition of metabolic procedures – bacteriostatic

8. Division of Antimicrob. Substances • chemical – according to similar structure, substance with the same mechanism of action have usually the same AE • baktericid:ß-laktamic ATB, aminoglycosides, bacitracin, isoniazid, metronidazole, quinolones, vancomycin, teicoplanin, rifampin • bacteriostatic:macrolides, tetracyclines, chloramphenicol, sulfonamides, trimetoprim, linkomycin, klindamycin, ethambutol, nitrofurantoin

9. Ideal Antibiotic • Wide spectrum • Rapid action • Bactericidal • High selectivity, without AE, not causing allergy • Not to occur resistance • High biologiavailability, good penetration to tissues, long biolog. half-life • Low price

10. Ideal antibiotic drug absorption distribution elimination ADR price Which available ATB is close to ideal? ß-lactams Macrolides Quinolones Tetracyclines Cotrimoxazol Choice of Antimicrobial Substance

11. Principles of Antimicrob. Therapy for Respiratory Diseases • racional indication • take into account the nature and severity of infection • take into consideration the clinical condition of the patient • Individual choice of drug • prevent the increase in resistance due to : • incorrect prescription • incorrect dosage • not keeping the optimal length of therapy

12. Choice of the Right Antibiotic • Targeted administration on the basis of identification of causative agent of infection • Consider pharmacokinetic properties • Choosing the most appropriate route of administration and site of administration. At severe infections we begin with parenteral therapy. At limited function of elimination organs we reduce the dose or prolong dosing interval • Reducing the risk of administration by revealing of predisposing factors such as drug allergy • Determination of the risk groups of patients

13. Problematic of ATB Resistance • = the ability of the bacterial population to survive inhibitory concentration of the given antimicrobial drug, becomes a significant problem nowadays 1. Primary resistance = natural resistance of microbial species, which are outside the range of ATB action /missing are „mechanisms“ (receptors) for the effect of antimicrobial drugs/ absolut resistance + relevant resistance /mikroorganism not sensitive to antibiotic concentrations reachable in human organism, but sensitive to high concentration of antibiotic reached in vitro 2. Secondary resistance occurs during antibiotic therapy, when initially sensitive bacterial population during antibiotic treatment become resistant to them.

14. Resistance to ATB mechanism of resistance: - productions of enzymes, which change structure of antimicrob. substance the way that it looses antimicrobial effect - mutation changes on the level of intracelular recep. /betalact. ATB – structure change of binding place for PNC/ - preventing penetration of ATB through cell wall /making impossible binding of ATB to the site of action on intracel.rec./ - change of metabolic pathway

15. Possibilities of Slowing Down Resistance Appearance • the right choice of antimicrobial drug • optimal and enough long administration • right dose • in special cases stable combinations /treatment of TBC/

16. Development of Actual Resistance • Penicillin resistant pneumococs (PRP) • Meticillin resistant staphylococs (MRSA) • CA-MRSA (Community-Associated Methicillin-Resistant Staphylococcus Aureus) • Streptococcus pyogenes/macrolides • Quinolone resistant E. coli

17. Agents Causing Pneumonia of Adults lobal: S. pneumoniae, H. influenzae, K. pneumoniae bronchopneumonia: S. pneumoniae, S. aureus, L. pneumophilla atypical: influensa virus, RSV, adenoviruses, HZV, Mycoplasma pneumoniae, Chlamydia pneumoniae

18. Pharmacotherapy of Bronchopneumonia Caused by Streptococcus pneumoniae • Aminopenicillins at high doses • Aminopenicillins protected with inhibitors of betalactamases /ampicillin-sulbactam, amoxicillin-clavulanic acid/ • Cephalosporins III. generation • Fluoroquinolones /levofloxacin, moxifloxacin/ = advantage is higher concentration in the site of action /alveol. fluid, macrophages/ than in plasma!

19. Betalactamic Antibiotics - in structure betalactamic circle • bactericid • inhibit synthesis of cell wall of mikroorganisms in the last phase of its consolidation with peptidoglycan • hydrophil • low direct toxicity • low occurance of AE • spectrum of effect depends on substance • here belong PNC cephalosporins monobactams carbapenems

20. Penicillins • absorption of peroral PNC after p.o. administration better from empty stomach • G-penicillin, meticillin, karboxypenicillin, ureidopenicillin – unstable in acid environment of stomach - administration parenteral • don´t cross intracelullarly, metabolised a little, excreted through kidneys through glom. filtr. and also tubul. secretion, high concentrations reached in urine • minimal AE, also in high doses not toxic, allergy 5-8% • resistance: enzyme type – betalactamases + mutations – not letting to recognise of recept. site

21. PNC with Narrow Spectrum Benzylpenicillin – natural PNC, acidolabile, only parent. mainly g+, streptococci, pneumococci, meningococci medium serious inf. caused mailnly by betahaemol. streptococci serious infections – high plasmat. concentrations of Na or K salts of crystalic PNC i.v. /renal diseases!/ depot preparations – i.m.- Procain PNC– 2 times per day 1g Penicillin V – biosynthet.,acidostable, g+ microorg., identical effect spectrum, lower plasm. concentration – mild streptoc. infections and their healing Penamecillin– prolonged effect, á 8h. Oxacillin, cloxacillin, dicloxacillin, meticillin antistaphylococcal, resistant against betalactamases produced by staphylococci, very narrow spectrum, peroral also perenteral administration, á 4 till 6 h.

22. PNC with Broader Spectrum - also G- microorg./E. coli, salmonellas, shigellas, H. influensae/ Aminopenicillins - ampicillin, amoxicillin /=better penetration, higher plasm. conc./ acidostable, aren´t resistant againstnie betalactam. uncomplic. infections of urinary,airway and gallbladder pathways mainly in combination with inhibitors of betalactamases, peror. also parent. admin. Carboxypenicillins /carbenicillin, tikarcillin/ semisynthet. PNC, also Pseudomonas aeruginosa, Proteus - at syst. infections alone or in combination with aminoglykosides acidolabile – parenter. adm., tikarcillin in comb. with inh. of betalactamases Ureidopenicillins /azlocillin, mezlocillin, piperacillin/ acidolabile, good penetration to tissues, more intensive on Proteus, Pseudomonas aeruginosa, piperacillin also to some anaerobes, the highest effectivity, reserved to serious infections

23. Cephalosporines • similar mechanism of action as PNC • wide use, in pediatria and geriatria • good efficacy and low toxicity • good penetration to tissues • excretion through kidneys by glom. filtr., tub. secretion • according to pharmacodynamic – spectrum of efficacy, ability to penetrate to cells, stability against betalactamases - 4th generation

24. Cephalosporins of 1st and 2nd Generation 1st generation cefalotin, cefazolin, cephalexin,cefradil narrow spectrum, against G+/also staphylococci/, G-sticks, airway, urinary and skin infections 2nd generation cefoxitin, cefaclor, cefamandol expanded spectrum to G-bact., resistant against betalactamases, act against H. influenzae + some anaerobes, less against staphylococci

25. Cephalosporins of 3rd and 4th Generation 3rd generation cefotaxime, ceftazidime, ceftriaxon, empir. treatment of severe life threatening infections targeted treatment of microorg. resist. to PNC and ceph. of lower gen. - parent. adm. - oft aplication infections of airways – p.o. – 1 times per day 4th generation cefepime, cefpirom intensified effect against staphyloc., streptococci and pseudomonads severe nosocomial infections

26. Rezistance of Pneumococci to Antibiotics • increase of rezistance to pneumococci to natural penicillins, also to cephalosporins, macrolides, doxycycline = drug-resistant Streptococcus pneumoniae • risk factors of occurance: age over 65 years ATB therapy in last 3 months immunodeficiency comorbidities

27. Fluoroquinolones • chemotherapeutic with high ATB activity • baktericid effect – select. inh. of bacterial gyrase activity, which catalyses creating of loops and by twisting allows the sdepositing of DNA in the cell nucleus • rezistance – mutation of DNA gyrase • fluor – increased efficacy, better kinetic properties – use at systemic infections, also serious, serious nosocomial pneumonias, uroinfections, gynecol. infections, GIT infections, infections of airways • good absorption after peror. administration, some also parenter. administration /ciprofloxacin/, possible parenteral. starting therapy, than peroral administration • good penetration to soft tissues, bones and lungs

28. Levofloxacin • high bioavailability • good penetration to bronchial mucosa and lung parenchyma • at middle serious and serious inf. of airways, complic. uroinfections, inf. of skin and soft tissues • interactions at absorption are occuring at simultaneous administration of iron salts, or antacides containing magnesium and alluminium • „respiratory quinolone“ – effect on G+ causative agents of respiratory infections • AE: nausea, diarrhoea, increases hepatic enzymes

29. Moxifloxacin • fast perfect absorption after peroral administration, quickly distributed to extravasc. space • at metabolism doesn´t undergo oxidation, that´s why not showing signs of interaction with other substances, which are metab. through cytochrome P-450 • excretion by faeces, less by urine • „respiratory quinolone“ – effect on G+ causative agents of respiratory infections

30. Bronchopneumonia Caused by Pseudomonas aeruginosa • risk factors of occurance: structural changes of airways and lungs, systemic therapy with glucocorticoids, wide-spectrum ATB therapy in the last month, malnutrition • antipseudomonad betalactamic ATB: cefepime, piperacillin-tazobactam / both also effective on pneumococci/, at allergy to betalactams monobactam aztreonam always combined therapy with aminoglykosides /gentamicin/ and antipseudomonad fluoroquinolone /ciprofloxacin/

31. Atypical Bronchopneumonia • disease development and a mild physical symptoms does not correspond to significant signs on X-ray of lungs, but some of them have severe acute development with the possible occurance of serious complications / ARDS / • 30 – 40% of bronchopneumonias • causative agents = intracelular parasits /Mycoplasma pneumonie, Chlamydia pneumoniae, Legionella pneumophila, Coxiella burnetii/ + respiratory viruses • occurance mainly in societies of young people • ATB therapy which penetrates intracelullarly and interferes with proteosynthesis of atypical microorganisms

32. Occurance of Bronchopneumonias Caused by Mycoplasmas according to Age

33. Pharmacotherapy of Atypical Pneumonias • Macrolides /erythromycin, klarithromycin, azithromycin/ • Tetracyclines /doxycycline/ • Fluoroquinolones /antipneumococcal/

34. Macrolides • bakteriostatic effect – inhibit proteosynthesis of microorganisms • spectrum mainly G+ bacterias, H. influenzae, some anaerobic bacterias • penetration to cells and influence on intracel. pathogens /M. pneumoniae, chlamydias/ • good penetration to tissues • metabolis. in liver by cytochr. P-450 interactions: increases plasmat. conc. of theophylline, digoxin, anticoagulants. Interaction with antihistaminics causings severe ventricular arrhytmia

35. Macrolides slower and lower development of resistance • stability in acidic surrounding • longer biologic half-life • high concentration in tissues and serum • 2nd generation /erythromycin+spiramicin/ roxithromycin, azithromycin, clarithromycin = better pharmacokinetics and tollerability/ • little toxic, good tolleration • AE: GIT + liver functions

36. Clarithromycin • semisyntetic • verry good tollerance • biotransformation to antimicrobically more effective 14-OH-clarithromycin • typical, atypical, intracelular and ß-laktamase producing pathogens • 8 times more effective as erythromycin to Chl. pneumoniae and M. pneumoniae • very good at infections caused by Legionella pneumophilla and Moraxella catarrhalis

37. Tetracyclines • bakteriostatic, strong occurance of resistance • infections caused by mykoplasmas, chlamydias, rickettsias • resorption at fasting good, not with milk, antacids, Fe 3+, which prevent their resorption • good penetration to tissues except to CNS • at renal diseases needed dose reduction • 2nd generation: tetracyclin doxycyclin – better pharmacokin. properties /higher bioavailability, longer half-life = administratio 1-2 times per day/ • AE: oft but not severe, GIT, disorders of bones and teeth by calcium chelation = contraindic. at children

38. 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: • antitussives with central effect and with the structure of opioids 2. antitussives with central effect and peripheral effect with different structure

39. 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

40. 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

41. FOLCODINE = 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

42. 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 not at patients with bronchial asthma!

43. 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 /

44. EXPECTORANTS = getting rid of viscous mucus from airways • Mucolytics and secretolytics – lower viscosity of mucus, resp. increase production of mucus CAREFUL AT SIMULTANEOUS ADMINISTRATION OF ANTITUSSÍVE 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 2. Secretomotorics – are increasing activity of cilliar epithelium /β-sympathomimetics, eteric oils/