PHARMACOLOGY - medsyllabus.org · Cough is a protective reflex – occur due to stimulation of...
Transcript of PHARMACOLOGY - medsyllabus.org · Cough is a protective reflex – occur due to stimulation of...
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PHARMACOLOGY
Drugs acting on Respiratory System
TOROKHTIN ALEXANDERprofessor, doctor of medical science
biochemistry, pharmacology and physical treatment methods chair-chief
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AGENDA: Drugs acting on Respiratory System
Drug for cough and Bronchial Asthma
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Cough is a protective reflex – occur due to stimulation of mechano- and/or chemoreceptors of throat,
respiratory passages or stretch receptors in the lung
сough may be useful or useless
Useless (nonproductive) cough should be suppressed. Useful (productive) cough – serves do drain the
airway, its supрression is not desirable, may even be harmful –
so should be stimulated.
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Apart from specific remedies – targeted reason of cough reflex – cough, as a symptom may be treated as
a symptom by nonspecific therapy – acting on concomitant pathologic processes
But cough is not the only one symptom occur during lung an respiratory tract pathology –
ventilation disorders – are signals for reasons searching…
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Chronic obstructive pulmonary disease (COPD) an inflammatory disease characterized by progressive
bronchiolar fibrosis and alveolar destruction (emphysema) which can occur in variable proportions
The expiratory airflow limitation does not fluctuate markedly over long periods of time, but there are
exacerbations precipitated and provoked by respiratory infections, and/or pollutants. Loss of bronchiolar
elasticity leads to closure of smaller air tubes during expiration. The airway obstruction is accentuated
during exercise causing shortness of breath.
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Pharyngeal demulcens
Lozenges
Cough drops
Tinctures containing syrup, glycerine, liquorice
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Drugs acting on Respiratory System are classified as
-analeptics – which stimulate autonomic nerve system (acting on respiratory centre);-antitussive drugs;
-lung air flow improving remedies:--broncholitics (anti-asthmatic drugs);
--agents acting on bronchial drenage function (expectorants);-drugs preventing, treating lung oedema (acute pathology of
lung tissue);-antibacterial (if infection is detected);
-oncologic (anti tumoral).
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1.Direct analeptics
bemegrid 0,5%-5ml in isotonic solution of NaCl (acting on respiratory centre of medulla oblongata)
aethimizolum a1-1,5%-5ml (acting on medulla oblongata)coffeinum t0,1; a10%-1ml (acting on cerebral cortex
providing general analeptic effect)
strichnini nitras 0,1%-1ml (acting on medulla spinalis – by stimulating transmission of reflector impulses)
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1.2.Indirect (reflectoric) analeptics
-lobelinum hydrochloridum 1%-1ml-citisinum 0,15%-1ml = cititon (Н-cholinergicm, acting in
synocarotid region > activate medulla oblongata > finaly provide analeptic effect);
-solution of ammonium causticum – NH4OH – integrative act on peripheric nerve receptors with final functional activation of respiratory organs function (like reaction of defence).
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1.3.mixed action analeptics
solutio camphorae oleosae 20%-1-2mlsolutio sulfocamphocaini 10%-2mlcordiaminum = solution 25% bisaethylamid of nicotinic acid
carbogen= O2 - 93-95%+CO2 - 5-7%
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Antitussive (Cough centre supressants)a.Opioids
Codein, Ethylmorphineb.Nonopioids
Noscapine, Dextromethorphan, Chlophedianolc.Antihistamine
Chlorpheniramine, Diphenhydramine, Promethazined.Peripherially acting
Pronoxdiazine
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opioid antitussive
codeinum t0,015 {6-methylmorphine} κώδεια, κοδεια – head (Papaverus somnipherus)
codeini sulphas max=0,1 maxD=0,3aethylmorphini hydrochloridum {6-ethylmorphine}max=0,03
maxD=0,1morphini hydrochloridum 1%-1ml
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nonopioids narcotic antitussive remedies1Noscapine [narcotine] – an opium alkaloid of
benzoisoquinoline. It depresses cough but has no narcotic, analgetic or dependence inducing properties. Dose: 0,015-0,03
Dextromethorphan – synthetic (central N-methyl D-aspartate receptor antagonist) d-isomer has antitussive action while l-isomer is analgetic. Doea not depress mucociliary function. The antitussive action has been rated equivalent to codein. Dose: 0,01-0,02
Chlophedianol – centrally acting antitussive with slow onset and longer duration. Dose: 0,02-0,04
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nonopioids narcotic antitussive remedies2
glaucini hydrochloridum t0,04-0,05]
{alkaloid of – Glaucinum flavum}[glauvent, tussiglaucin] t0,05A componente of various
anti-cough mixtures: “bronchlitin”
Glaucium Flavum Crantz.
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synthetic antitussive remedies
libexin t0,1] [prenoxdiazine] (cough reflexogen zone blocker) oxeladini citras t0,01 syrup 1мл=0,01 [tusuprex, paxeladine]butamirate citrate dr0,005 [stoptusin, sinecod, intusin] atussin [dextromethorphan 0,015 + ascorbinic acid)
2.3.combined non nonkpioid antitussive remediesfalimint [dragee]clophedanol
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Peripherally acting antitussives
Prenoxdiazine [Prenoxid] – desensitizes the pulmonary strech receptors and reduce tussal impulses originating in the lungs. Indicated in cough of bronchial origin. Dose: 0,1-0,2
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Expectorants (Mucokinetics)a.bronchial secretion enhancers
Sodium/Potassium citrateSodium/Potassium hydrocarbonate
Potassium iodideGuaiphenesine (Glyceryl guaiacolate)
Balsame of ToluVasaka
Ammonium chloride b.mucoliticsBromhexineAmbroxol
Acetyl cysteineCarbocisteine
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Differently acting drugs (list)Antitussive-expectorant combinations
3.1. remedies acting on sol-stratum of sputum (local rehydratant and secretolotic) as inhalation
iso- and hyper-tonic solution of sodium chloride [NaCl], sodium bicarbonate [NaHCO3], sodium bensoate, amonia chlorid
[NH4Cl]3.2.bronchial gland stimulants (direct acting)
potassium iodidum [KJ], sodium iodidum [NaJ]3.3.Gastropulmonal mucokinetic – vagus reflex activators
3.3.1.emetins (vomitus starting)3.3.2.saponins (radicorum et rhizomata extracts)
3.3.aetheric oils (folia eucalipti, bud трава чебрецю, плоди анісу, листя евкаліпту, бруньки сосни)
3.4.detergents (surface-active remedies: glycerol, propilenglycol)4.4.combined pharmacologic expectorant remedies
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Adjuvant to antitussive drugs (indirect action)
bronchodilators (acting through adrenergic receptors)SalbutamolTerbuthalin
bronchodilators (acting through cholinergic receptors) Ipratropium bromide Oxytropium bromideTiotropium bromide
MethylxantinesTheophyllineTheobromine
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3.1. Local broncholitics, rehydratantsSodium chloridum [NaCl]
sol. natrii chloridis isotonica/hypertonica
Sodium bicarbonic [NaHCO3] hydrocarbonatenatrii bicarbonatis p0,5
Sodium bensoas [C6H5COONa]natrii bensoas p0,2
Amonii chloridum [NH4Cl]
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Bronchial mucousal glands (direct) stimulants
Sodium/Potassium iodidum (KJ) (NaJ) solutio natrii/kalii iodidum 1%-180ml; 0,3-0,5-1,0 ad usum cum lactis vacci
Ammonia chloridum [NH4Cl] s0,5% ad usum internum
Sodium bicarbonatis [NaHCO3]
sodium hydrogencarbonas pulveris 0,25-0,5
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3.3.Gastropulmonal mucokinetic – n.vagus reflex activators
–acting through stomach mucous, it leads to bronchial secretion increasing, insreases ciliar apparatus activity of bronchial epithelium
–also acting on autonomic nerve ganglia (chromafin celles of suprarenal glands and on synocarotide reflectoric zone)
3.3.1.emetins (vomitus inducing) indirect actingherba thermopsidis lanceolata [inf-1:300][contains citisin (Mixtura sicca contra tussim pro adult)
infusum ex 0,6 – 180 ml; extractum siccum t0,01]radix ipecacuanae
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Indirect acting on respiratory tract through due to chemical compounds
Saponin containig plantsradix althaeae officinalis; inf.1:30 {ex 6,0 – 180 ml} (Mixtura sicca
contra tussim pro infantibus)mucaltinum t0,05 – herba althea (polysaccharides)radix glycyrrhyza (солодка) inf.1:30radix polemonium (синюха) inf.1:30radix inula (оман) inf.1:30radix polygala (істод) inf.1:30 folia tussilago farfara (підбіл звичайний) inf.1:30herbae thymus serpillum (чебрець) inf.1:30herbae viola tricolor (фіалка триколірна) inf.1:30
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Aetheric oils
herba Thymi serpilli; [pertusin = 12 чебрецю +1 KBr +82 syrupi sacchari +5spiritus eathylicum]
liquor ammonii anisatus = [olei anisati 2,8m1 sol. Ammonii caustici 15ml, spiritus aethylicus 90% ad 100ml]
folium eucaliptituriones pini (паростки бруньки сосни )terpinum hydratum pt0,25 [para-menthandiol-1,8-hydrate]
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Mucoactive remedies
4.1. Mucoactive remedies, acting on synthesis of sputum secretion
4.2. Mucoactive remedies, acting on polymeric bonds of sputum
4.3.detergents (surface tention decreasing agents (secretoroics – decrease adgesive properties of
sputum) (sorbetol, sodium bicarbonic)4.4.bronchial mucousalglands blocking agents
4.5.surfactant acting and related drugs
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Cystein derivatescystein
With ammonia blocked group priventes peptid bond condensation which form mucoproteins and mucopolycarbohydrates
acetylcysteinum [ACC, mucosolvin]t0,2-0,4-0,6 a10-20%-2-10ml
Carbocystein (lysinic salt), aethylcystein, methylcystein
acethyl cystein
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synthetic mucolitics (tiolitics)
Stepronin
mesna2-MercaptoEthane Sulfonate Na (mistabron)
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synthetic mucolitics (tiolitics)
Letostein
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mucolytics (direct acting on bronchial secret – solving bronchial secret
[if increased adgesity]) 4.2.1.Proteolitic enzymestrypsinum a0,005chimotrypsinum f0,005ribonucleasum f0,005desoxyribonucleasum (pulmosim) f0,005(lizozym, streptokinaza, α-amilasa) 4.2.2.Drugs acting like hydratants of bronchial secret
(mucohydrants) inorganic compounds of iodine – potassium and sodium [KJ, NaJ], hypertonic salt solutions of NaCl
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Detergents
4.3.detergents – decreases surface tension of bronchial secretbronchorhoics – are decrease adgesivity of secret -glycerol-propilenglycol-sodium bicarbonatis pro inhalationes
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4.5.acting on surfactant4.5.1.surfactant synthesis stimulators
bromhexynum (bisolvin, solvin, phlegamin) t0,008; a0,004ambroxol (lasolvan, mucobron, ambroxan, ambrobene, ambrohexal) t0,03 a0,75%-2ml [ambroxol-retard t0,075]
4.5.1.surfactant substitutorsalveofact purifide surfactant suspension for intratracheal
instillationexosurf (distress syndrom at newly born child)
sucrim
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4.4.drugs acting on bronchial secretion activity. Mucousoactive agents.
4.4.1.alkaloid derivates bromhexin
ambroxol (syrup 0,015/5ml = sol 0,3%)
(ambroxol is a metabolit of bromhexin)
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Drugs for bronchial asthmaapproaches to treatment
1.prevention of antigen-antibody reaction (if antigen can be identified)
2.Neutralization of IgE (reaginic antibody)3.Suppression of inflammation and bronchial hyperreactivity
4.Prevention of release of mediators (mast cell stabilizers)5.Anthagonism of released mediators (leucotriene antagonists,
antihystamines platelet activating factor (PAF) antagonists6.Blockade of constrictor neurotransmitter (anticholinergics)
7Mimicking dilator neurotransmitter (sympathomimetics)8Directly acting bronchodilators
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Adrenomimetics
5.1.1.α- and β-adrenomimeticsadrenalini hydrochloridum 0,1%-1ml
Indirect acting adrenomimeticsephedrine hydrochloridum 5%-1ml, t0,05
5.1.2. β1+ β2-adrenomimeticsisadrinum t0,001; a1%-25ml
orciprenalini sulfas [alupent, aspopent]
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Bronchodilators
β2 SympathomimeticsSalbutamolTerbutalineBambuterolSalmeterolFormoterolEphedrine
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β2-agonists5.1.3. β2-adremomimetics (β2-agonists)
-short acting (duration of acting in hours)Phenoterol (4-6) [phenoterolum dose=0,0002] (berotek) Salbutamol (4-6) [salbutamolum] (ventonil, combivent)
Terbutalin (4-6) [terbuthalinum] (bricanil)Levosalbutamol (6-8)
-long acting (duration of acting in hours)Formoterol (12+)
Arformoterol (12+)Indecaterol (24)
Salmaterol (12+) [salmeterol]=serevent [clenbuterol]
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Bronchodilators
Methylxantines
Theophylline (anhydrous)Aminophylline
Choline theophyllinateHydroxyethyl theophylline
Theophylline ethanolate of piperazineDoxophylline
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Bronchodilators
MethylxantinesTheophylline (1,3 Dimethylxanthine) Theobromine (3,7 Dimethylxanthine) Caffeine (1,3,7 Trimethylxanthine)
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source alkaloid content in beverage in an average cup
Thea sinensis Caffeine 0,05 (Tea leaves) Theophylline 0,001
Coffea arabica Caffeine 0,075(coffee seeds)
Theobroma cacao Theobromine 0,2(cocoa, chocolate) Caffeine 0,004
Cola aciminata Caffeine 0,03(Guru nuts) (in 200 ml bottle of cola drink)
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Euphylline (solution 2,4% and 24%)
[euphylline is a mixture of theophylline 80% and 1,2 – ethylendiamin 20%]
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Anticholinergics
(also blocking tromboxan А2)
atropini sulfas Aer0,0001-0,00025; amp:0,1%-1mlplatiphillini hydrotartras amp:0,2%-1ml
metacinum amp: 0,1%-1ml
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Anticholinergics
short actingIpratropium bromide (6-8 hours)
[atrovent aerosol 15ml 1 dose=0,0002]
Oxytropium bromide (6-8 hours)
long actingTiotropium bromide (24+ hours)
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Combined Bronchodilators
BERODUALFenoterol + Ipratropium bromid
inhalator (200μg/80μg)nebulizer (1,25μg/0,5μg)
Salbutamol + Ipratropium bromidInhalator (75μg/15μg)
nebulizer (0,75μg/0,5μg)
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Corticosteroids
a.SystemicHydrocortizone
Prednisolone
b.InhalationalBeclomethasone dipropionate
BudesonidFluticasone propionate
FlunisolideCiclesonide
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Combined bronchodilators
β2-agonists long lasting effect + corticosteroids
Formoterol + Budesonidinhalator(4,5μg/160 μg)
Salmeterol + Flutikasone propionatinhalator(50 μg /100 μg)
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Leucotriene antagonists
MontelucastZafirlucast
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Mast sell stabilizers
Sodium cromoglycateKetotifen
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Inti-IgE antibody
Omalizumab
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Choice of treatment (asthma)1.Mild episodic asthma
(symptoms less then one daily, normal in between attacks: inhalation of short acting β2-adrenagonist)
2.Seasonal asthma(low-dose inhalation of steroids 200-400μg/day
cromoglycate 3-4 weeks before anticipated seasonal attacks)
3.Mild chronic (persistent) acthma with occasional exacerbrations
(symptoms one daily, subnormal ventilatory perfomence – regular low-dose inhalation of steroids
100-500μg/day)
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4.Moderate asthma with frequent exacerbation(attack more than one daily – inhalation of steroids up
to 800μg/day + long acting β2-adrenagonist)
5.Severe asthma(continuou symptoms, activity limitation, frequent
exacerbation - inhalation of steroids up to 800-2000μg/day + long acting β2-adrenagonist twice
daily)
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6.Status asthmaticus/Refractory asthma(hydrocortisone hemisuccinate 100 mg
nebulized salbutamol 2.5-5 mgipratropium bromide 0.5 mg
high flow humidified inhalation of O2salbutamol/terbutalin 0.4 mg i.m./s.c.intubation and mechanical ventillation
correct dehydratationsol.bicarbonat infusion)
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Antihistamin acting drugs and
Antibiotics
will be discussed and observed separately
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Thank YOU for ATTENTION