Respiratory pharmacology
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respiratory stimulants
antitussive drugs
expectorants
drugs used in asthma
drugs used in pulmonary edema
Respiratory stimulants
-Drugs witch stimulate both respiratory and cardiovasculary center.
Classification
1. Analeptics
- Bemegrid
- Pentetrasol
- Camphor
- Sulphocamphocaine
- Caffeine benzoate natrium
- Ethimizol
- Niketamine
- CO2
2. N-cholinomimetics
- Lobeline
- Cititon
Analeptics are used only in certain specific conditions and stimulate CNS in
subcortical lever and bulb. They have a short duration of action (2-3 hours)
Indications: asphyxia of newborns, chronic bronchitis with obstructive
component, acute respiratory failure, after general anesthesia, intoxication with
barbiturates and narcotic drugs.
Side effects: -cough, nausea, vomiting, agitation, hypertension, tachycardia,
arrhythmias, headache, tremor, and muscular hypertonus, rarely convulsions.
N-cholinomimetics:: stimulate N-cholinoreceptors from sino-carotid zone and
reflector increase activity of respiratory center in bulb.
Duration of action is 2-5 minutes. way of administration is only intravenous.
Indications: respiratory stop caused by trauma or postoperative.
intoxication with barbiturates and narcotic drugs.
Antitussive drugs
The cough-suppressant (antitussive) effect produced by inhibition of the cough
reflex is independent of the effects on nociception or respiration
Classification
1.With central action (opiod or narcotic drugs)
- Morphine
- Ethylmorphine
- Codeine
- Dimemorphan
2. With central action (non opioid drugs)
- Glaucine
- Noscapine
- Oxeladine (Tusuprex)
- Butamirat (Sinecod)
3. With peripheral action
- Prenoxdyazine (Libexin)
- Pronilid (Falimint)
- Pentoxiverine (Sedotusine)
4 With mixed action (central and peripheral action)
- Tipepidine citrate (Bitiodine)
Expectorants
1. Secretostimulants
a) with reflex action
Mucaltine
Licorine
thermopsis infusion
b) with direct action
Potassium iodide
Sodium benzoate
Sodium hydrocarbonate
Oil of eucalypti
Terpinhydrate
Pertusine
2. Secretolitics
1. Proteolytic enzymes
- Trypsine
- Chymotrypsine
- Chymopsine
- Dezoxyribonuclease
2. Thyolitics derivates
- ACC( acetylcicteine)
- Carbocysteine
- Mesna
3. Stimulants of surfactant secretion
- Bromhexine
- Ambroxol
4. Surfactants
Alveofact
Opioid drugs: are used only when cough is dangerous.
Indications: cough after operation, cough that can produce emphysema, TBS,
Cough that facilitate penetration of various infection, cancer with cough ,
pneumatorax, myocardial infarction, aortal aneurysm
Side effects (see opioid drugs.
Codeine phosphate: is synthesized from morphine and inhibits cough center in
the bulb. It is less active than morphine.
Side effects: constipations, nausea, vomiting, dizziness,, somnolence, dysphoria,
bronchospasm, convulsions (children). , tolerance, rarely dependence.
Contraindications: renal failure, cirrhosis, to children till 5 years.
Non opioid drugs with central and peripheral action are indicated in pulmonary
diseases :
-Acute and chronic bronchitis, bronchopneumonia, asthma, emphysema, before
and after bronchoscopy, bronchography.
Prenoxdyazine. Has antitussive action, but it doesn’t inhibit cough center and
doesn’t produce any dependence. It has a local anesthetics and spasmolitic action.
Side effects: rarely, skin eruptions, dyspeptic symptoms, angioneurotic edema.
Expectorants
Remedies that facilitate and dilute expectorations.
1. Secretostimulants with reflex action. In the small doses they irritate gastric
mucousa membrane and increase bronchi secretions.In big doses they stimulate
the emetic center from bulb and produce nausea and vomiting. This remedies are
administrated in the small doses every 2-4 hours.
2. secretostimulants with direct action: are eliminated through respiratory system
and have direct action (stimulate) on the motility of bronchi. Other expectorants
(e.g., hot beverages, potassium iodide, and ipecac) stimulate production of watery
mucus.
3. Secretolitics:: Proteolytic enzymes are used local in aerosol. They break off
peptides polypeptides and fibers of deoxyribonucleic acid. Also they have antiinflammatory action.
Thyolitics derivates: break off S-S groups and bind with them. In this way
decrease viscosity of the bronchi mucus.
Acc (split disulfide bonds in mucus, hence reduce its viscosity and promote
clearing of bronchial mucus.) is used also in intoxication with paracetamol as a
liver protector
Side effects: bronchospasm, nausea, vomiting, diarrhea, anaphylactic reaction
Bromhexine: break off mucopolysaharide and mucoproteic groups..Alo it
stimulates secretion of surfactant.
Side effects: rarely nausea, vomiting, allergy.
Indications for secretolitics: acute and chronic bronchitis, bronchopneumonia,
pneumonia, mucoviscedoses, tracheitis, pleurisies, pre and postoperation,
Drugs used in Asthma
1. simpatomimetics :
- izoprenaline (12)
- orciprenaline (12)
- epinephrine
- terbutaline 2
- phenoterol 2
- salbutamol
- ephedrine 2
- salmetherol
2. Parasimpatholitics (M cholinoblockers)
- Ipratropium bromide
- Oxitropium
- Atropine
- Metacine
- Platyphyline
3. Inhibitors of phosphodiesterase
- Theophylline
- Aminophylline
4. Inhibitors of mast cell. degranulation
- Sodium cromoglycate
- Nedocromil
- Ketotyphen
5. Antihystaminics
- Loratidine
- Astenysol
6. Inhibitors of leucotriene receptors
- Zileutine
- Zafirlukast
7. Inhibitors of thromboxansynthetases
- Ozagrel
8. Glucocorticoids
a) Inhaled: beclomethasone
dexamethasone
b) Systemic: hydrocortisone
prednisolone
methylprednisolone
Bronchial Asthma
Definition: a recurrent, episodic shortness of breath caused by bronchoconstriction arising from
airway inflammation and hyperreactivity. Asthma patients tend to underestimate the true severity
of their disease. Therefore, self-monitoring by the use of home peak expiratory flow meters is an
essential part of the therapeutic program. With proper education, the patient can detect early
signs of deterioration and can adjust medication within the framework of a physician-directed
therapeutic regimen.
Pathophysiology. One of the main pathogenetic factors is an allergic inflammation of the
bronchial mucosa. For instance, leukotrienes that are formed during an IgE-mediated immune
response exert a chemotactic effect on inflammatory cells. As the inflammation develops,
bronchi become hypersensitive to spasmogenic stimuli. Thus, stimuli other than the original
antigen(s) can act as triggers ; e.g., breathing of cold air is an important trigger in exerciseinduced asthma. Cyclooxygenase inhibitors exemplify drugs acting as asthma triggers.
Management. Avoidance of asthma triggers is an important prophylactic measure, though not
always feasible. Drugs that inhibit allergic inflammatory mechanisms or reduce bronchial
hyperreactivity, viz., glucocorticoids, “mast-cell stabilizers,” and leukotriene antagonists, attack
crucial pathogenetic links. Bronchodilators, such as β2-sympathomimetics, theophylline, and
ipratropium, provide symptomatic relief.
First treatment of choice for the acute attack are short-acting, aerosolized β2-sympathomimetics,
e.g., salbutamol, albuterol, terbutaline, fenoterol, and others. Their action occurs within minutes
and lasts for 4 to 6 h. If β2-mimetics have to be used more frequently than three times a week,
more severe disease is present. At this stage, management includes anti-inflammatory drugs,
such as “mast-cell stabilizers” (in children or juvenile patients) or else glucocorticoids.
Inhalational treatment must be administered regularly, improvement being evident only after
several weeks. With proper use of glucocorticoids undergoing high presystemic elimination,
concern about systemic adverse effects is unwarranted. Possible local adverse effects are:
oropharyngeal candidiasis and dysphonia. To minimize the risk of candidiasis, drug
administration should occur before morning or evening meals, or be followed by rinsing of the
oropharynx. Anti-inflammatory therapy is the more successful the less use is made of asneeded
β2-mimetic medication. Severe cases may, however, require an intensified bronchodilator
treatment with systemic β2-mimetics or theophylline (systemic use only; low therapeutic index;
monitoring of plasma levels needed). Salmeterol is a long-acting inhalative β2-mimetic
(duration: 12 h; onset ~20 min) that offers the advantage of a lower systemic exposure. It is used
prophylactically at bedtime for nocturnal asthma. Zafirlukast is a long-acting, selective, and
potent leukotriene receptor (LTD4, LTE4) antagonist with anti-inflammatory/ antiallergic
activity and efficacy in the maintenance therapy of chronic asthma. It is given both orally and by
inhalation. The onset of action is slow (3 to 14 d). Protective effects against inhaled LTD4 last
up to 12 to 24 h.
Ipratropium may be effective in some patients as an adjunct anti-asthmatic, but has greater utility
in preventing bronchospastic episodes in chronic bronchitis.
Asthma
1. β2 adrenomimetics: are bronchospasmolitics. They increase quantity of cAMP and in this way
decrease Ca+ influx .
Form of administration is aerosol.
Side effects: tachycardia, tremor, nervousness, headache, arrhyphmias.
2.M-cholinoblockers: are antagonist of M-cholinoreceptors.
Contraindications: Glaucoma, prostate adenoma etc.
Side effects: hyposecretion, dry mouth, tachycardia, change of accommodation
3.Thiotropium act only M3 cholinoreceptors , has a long duration of action.
Side effects: dry mouth
4.Theophylline: is inhibitor of phosphodiesterase and adenosine at adenosine receptors.
Side effects: headache, vertigo, vomiting, arrhyphmias, irritation, insomnia, convulsions.
5. Sodium cromoglycate: produces mast cell stabilization (depression of release of
neuropeptides, antagonism of tachykinin receptors, inhibition of PAF interaction with platelets
and eosinophils).
Indication: only in prophylaxis of access
Ketotifen: the same mechanism of action plus also inhibition of H1histaminoreceptors.
Indications: - allergic asthma, bronchitis, allergic bronchitis, chronic bronchitis.
Side effects: irritation of the respiratory ways, pruritus, sedative.
Drugs used in pulmonary edema
A. antispume remedies;
1. ethanol 30-40% through mask and 70-80% through catheter
2. antiphosmilat- alcoholic sol. 10%0,6 or 1 ml (inhalations).
B. antidyspnoea:
narcotic analgesics: morphine 1%-1ml
phentanyl 0,005-1-2ml
talamonal 2-3 ml
promedol 1%-1-2 ml
C. Antiarrhythmics: Lidocaine sol. 10%-2 ml
Novocainamide sol 10%-5 ml
Verapamil sol.0,25%-2-4 ml
D. Oxigenotherapy
E. Bronchodilators: Aminophylline
F. Increase of heart capacity: Cardiac glycosides: strophanthine 0,05% or
corglycon 0,06% 0,3-0,5 ml i/v
G. Pulmonary dehydration: Diuretics: frusemide or ethacrynic acid 20-120 and
50-150 mg i/v
H. Decrease of alveolar-capillary permeability
1. Antihistamines (diphenhydramine, suprastin i/v or i/m)
2. Glucocorticoids (hydrocortisone, prednesolone 150-300 and 50-150mg
i/v or perfussion)
I. Decrease of hypoxia and acid-base deregulation.: O2 , Sodium
Bicarbonate 5%
J. Decrease of arterial pressure:
- ganglion-blocking drugs: hexamethonium,
- α-adrenoblockers: phentolamine 0,5%-0,5 ml
- Sodium nitroprusside 50mg
- Blood effusion
K. Antihypotension:
- phenylephrine 1%-0,5 mli/v with 40 ml glucose 40 ml
- dopamine 0,5% - 5 ml with 125 ml NaCl 0,9%
- norepinephrine 0,2% - 2-4 ml