Respiratory System Flashcards
(87 cards)
1
Q
Drugs used to treat asthma
A
useful in the prophylactic or curative treatment of
bronchial asthma, being effective for the control of various clinical forms of asthma.
2
Q
In the production and maintenance of respiratory inflammation, bronchospasm and viscous bronchial hypersecretion (components incriminated in asthma), multiple pathogenic mechanisms are involved;
A
1) agglomeration of various inflammatory cells and chemical produced by them,
2) epithelial lesions,
3) increased permeability of capillaries,
4) neurovegetative imbalances.
3
Q
in the treatment of asthma mainly substances with ____ are used
A
1) bronchodilator action and
2) substances with anti-inflammatory action at bronchial level
In addition to such substances, in asthma, depending on the clinical situation, various therapeutic measures may be useful:
1) avoiding exposure to allergens and trigger factors,
2) specific desensitization,
3) administration of antibiotics,
4) administration of expectorants,
5) oxygen therapy,
6) treatment of acidosis.
4
Q
Substances with bronchodilator action currently used can be divided, according to the mechanism
of action, into:
A
1) sympathomimetic bronchodilators,
2) parasympatholytic bronchodilators and
3) musculotropic bronchodilators.
5
Q
With anti-inflammatory action, ____are mainly used in the treatment of asthma.
______are used in the prevention of asthma attacks
A
1) Glucocorticoids
2) Mast cell degranulation inhibitors
To these therapeutic groups are added leukotriene receptor antagonists and lipoxygenase inhibitors.
6
Q
Calcium channel blockers, nitric oxide-releasing compounds or potassium channel-releasing
compounds :
A
are currently being studied for possible bronchodilator effects.
7
Q
sympathomimetics
A
are among the most active substances in the treatment and prophylaxis of asthma attacks. Such compounds are included in most antiasthmatic treatment protocols
8
Q
The therapeutic benefit in asthma is mainly due to
sos
A
The stimulation of β2 adrenergic receptors that
cause bronchodilation.
Also, at the pulmonary level, β2 adrenergic stimulation also produce :
1) increased mucociliary clearance,
2) inhibition of cholinergic neurotransmission,
3) maintenance of small vessel integrity as well as
4) inhibition of mast cell degranulation.
The formation and / or release of
histamine,
leukotrienes,
prostaglandins from mast cells, basophils and, possibly, other lung cells is prevented.
However, these actions do not significantly influence the chronic background inflammation.
9
Q
Beta2-adrenergic effects are produced as a result of :
MOA
A
adenylate cyclase stimulation and
consequent increase in intracellular cAMP.
Cyclic adenylate via a protein kinase increases
Na +, K + - membrane ATPase activity and
decreases cytoplasmic Na + levels.
Consecutively, the Na + / Ca2 + exchange is activated, with the decrease of the available intracellular Ca2 +. Decreased intracellular Ca2 + leads to relaxation of the bronchial smooth muscles and inhibition of mast cell degranulation.
10
Q
Sympathomimetics used as antiasthmatics have different affinities for adrenergic receptors.
Sympathomimetics with α and β adrenergic actions
A
such as adrenaline - with beta actions (both
β1 and β2) are used, but without alpha actions - for example isoprenaline - or
selective β2 agonists
- for example salbutamol, phenoterol, etc.
- the latter have the advantage of a reduced risk of side effects.
11
Q
Adrenaline ( Epinephrine )
A
Catecholamine adrenergic agent; non-specific alpha + beta
12
Q
SABA
A
Adrenaline
Isoprenaline
curative treatment
13
Q
MABA
A
Salbutamol
terbutaline
phenoterol
treatment + prophylaxis
14
Q
LABA
A
Salmeterol
is used exclusively prophylactically.
15
Q
Catecholamine effects
A
increased HR, BP, smooth muscle relaxation. Rapid onset, short acting, quickly inactivated by COMT & MAO. Heat, light and air sensitive. Inhalation or injection (cannot be taken orally).
16
Q
Non-catecholamine effects
A
synthetically produced modifications of catecholamines. Longer duration of action, not inactivated by COMT or MAO. Minimal Beta 1 response (^HR). Usually only acute therapy/maintenance.
17
Q
Internal administration
A
may be useful in the case of long-term prophylactic treatment for asthma attacks, especially when aerosols cannot be used. In this case the effect is installed more slowly but is longer lasting.
The main disadvantage is the higher risk of side effects compared to aerosols (achieved plasma concentrations are much higher which can lead to loss of β2 selectivity).
18
Q
Sympathomimetics can cause
A
vasoconstriction and hypertension (α adrenergic effects),
cardiac stimulation with tachyarrhythmias,
palpitations and
angina attacks (β1 adrenergic effects),
vasodilation,
relaxation of the uterus,
stimulation of striated muscles, increase in blood glucose (β2 effects).
Sympathomimetics can also produce psychomotor stimulation with β adrenergic anxiety and nervousness.
Headache, dizziness or fine trembling of the fingers are other side effects that can be caused by sympathomimetics.
19
Q
A problem of chronic treatment with β2 stimulants is the
A
decrease in the duration of the bronchodilator effect over time, less the decrease in its intensity.
Tolerance is mainly due to the
decrease in the number of adrenergic receptors by inhibiting their synthesis (down regulation).
Cortisones quickly restore (in 6-8 hours) this reactivity.
20
Q
In some asthma patients, the administration of selective β2 sympathomimetics may initially lead
to a decrease in arterial blood oxygen saturation.
A
This undesirable effect is the consequence of
the imbalance between ventilation and perfusion - the arterioles, dilated by beta2-adrenergic
action, provide an increased amount of blood to the alveoli, still insufficiently ventilated, if the
bronchodilation is not sufficiently operative. The adrenaline that produces vasoconstriction does
not cause an imbalance between ventilation and infusion.
21
Q
The antiasthmatic sympathomimetics currently used belong to three structural groups:
A
catecholamines, resorcinols and saligenins
22
Q
The differences between the three structural categories are due to
A
substituents on the phenolic nucleus.
23
Q
the size of the substituents on the amino group is important for the action on different
adrenergic receptors.
A
Increasing the size of the substituent increases the selectivity for β or β2 adrenergic receptors.
24
Q
Catecholamines
A
- adrenaline, isoprenaline, isoetarine -
due to the polar character of the
substituents, pass hard through the membranes (intestinal absorption is poor, the blood-brain
barrier passes a little). Internally administered catecholamines are largely inactivated by sulfation
in the intestine, and the small amount absorbed is practically completely degraded by methylation
to the oxidril group at position 3. This explains the ineffectiveness of the oral route. The duration
of action is short for both injected adrenaline and for preparations introduced by inhalation, due
to inactivation in the body by tissue uptake and metabolism by COMT and MAO.
25
Resorcinols
orciprenaline, terbutaline, phenoterol; have 2 oxidril groups substituted at positions
3 and 5 of the benzene nucleus - have higher selectivity for β2 receptors. The molecule is more
stable which makes the availability after oral administration better and prolongs the duration of
the effect.
26
Saligenins
- salbutamol, have a -CH2OH substituent in position 3 and a -OH group in position 4.
They have intense β2 adrenergic actions. The molecule is stable, which gives the possibility of
oral administration and prolongs the effect.
27
Adrenaline (epinephrine)
is used for the asthma attack treatment by subcutaneous administration. It can also be administered in aerosols. In both cases the effect settles quickly and is short-lived.
28
Isoprenaline -
synthetic catecholamine with predominantly beta-adrenergic action – administered
by inhalation can be used as a symptomatic treatment of asthma attack or other bronchospasm
(in bronchitis, bronchiectasis with emphysema). The effect occurs quickly and lasts 1 / 2-2 hours
29
Orciprenaline
(the resorcinol analog of isoprenaline) has a more lasting effect. It is used for crisis
prophylaxis administered by inhalation. The therapeutic benefit occurs quickly and lasts 3-4 hours.
It can also be administered internally (the effect appears after 15-30 minutes and lasts about 4
hours).
30
Terbutaline (tertiary analogue of orciprenaline)
has a higher beta2 selectivity and a slightly more
lasting effect. It can be inhalatory administered, the effect is installed after 5-30 minutes and lasts
3-6 hours. In the case of oral administration the effect occurs after 1/2 hour and lasts 4-8 hours.
Administered by injection subcutaneously the effect is evident after 6-15 minutes and is maintained for 1.5-4 hours.
- Administered by inhalation is indicated for the treatment and prophylaxis of moderate asthma attacks.
- Oral administration is appropriate when crisis are
frequent or dyspnea is continuous.
- Injectable administration is recommended for the emergency treatment of asthma attacks.
31
Clenbuterol
a terbutaline analogue that has two Cl- substituents instead of phenolic oxidils
has a partial agonist effect on β2 adrenergic receptors.
Clenbuterol has high potency and medium
duration effect. It is given orally or by inhalation
32
Phenoterol
(a resorcinol derivative) has a more lasting bronchodilator effect. It is administered
inhaler for crisis prophylaxis or internally.
33
Salbutamol
(a saligenin derivative) has a selective β2 action and a relatively long-lasting effect.
It can be administered inhaler or internally.
In the case of inhalation administration,
bronchodilation is evident after 15 minutes and is maintained for 3-4 hours; after internal
administration the effect begins in 30 minutes and lasts 3-4 hours.
Aerosols are useful in asthma of medium intensity.
In asthma with continuous dyspnea, internal administration is recommended.
34
Salmeterol
(a salbutamol-like compound) has a relatively slow and long-lasting effect.
The effect occurs 10-20 minutes after inhalation and lasts about 12 hours.
It is advantageous for the long - term prophylaxis of asthma attacks, but not stop crisis once produced.
The long duration of the effect is explained by the stable fixation of the side chain at a site on the β2 adrenergic receptor close to its active site.
Inhalatory administration.
35
Parasympatholytics bronchodilators
Parasympatholytics inhibit direct the reflex vagal mediated bronchoconstriction, with important
effect on large bronchia. It also inhibits the mast cell degranulation produced by acetylcholine.
The effects are produced by blocking of muscarinic cholinergic receptors and altering the balance
of intracellular cyclic nucleotides in favor of cGMP.
36
Atropine
is not used as antiasthma drug because, in clinical conditions, the bronchodilator effect
occurs at high doses, difficult to tolerate
37
Ipratropium
(a synthetic anticholinergic substance) administered in aerosols has a bronchodilator effect of moderate intensity, which installs slightly slower than for
sympathomimetics and is relatively durable;
mucociliary clearance,
volume and viscosity of tracheobronchial secretions are not significantly altered.
The effects are due to blockage of respiratory muscarinic receptors.
38
Ipratropium
The therapeutic benefit is important in asthmatics in whom bronchospasm has an important vagal
reflex component, the compound being indicated mainly in
reflex asthma. Patients with a weak
response to β2 adrenergic stimulants and those with contraindications to them as well as chronic
bronchitis (due to the important vagal reflex component) are other indications of the compound.
39
Ipratropium has a ___ and is slightly absorbed through the ____
1) polar molecule
2) tracheobronchial mucosa.
It is taken up by the mucociliary escalator and swallowed at the level of the pharynx. It is not
absorbed from the digestive tract and is eliminated by feces.
Reduced absorption explains the limitation of the effect on the bronchial system and lack of atropine-type systemic side effects.
40
Administration + side effects of ipratropium
It is administered inhalatory in the form of dosed pressurized aerosols. Ipratropium is generally
well tolerated. Side effects:
dry mouth,
bitter taste,
constipation caused by direct action on the
digestive tract.
In patients with narrow-angle glaucoma or prostate adenoma, however, caution is required due to the theoretical risk of uncontrolled digestive absorption due to possible mucosal damage.
41
The phenoterol-ipratropium combination is
advantageous due to the synergistic
bronchodilator action of the two components.
In this situation, the bronchodilator effect affects
both the small bronchia (through the β2 adrenergic agonist) and the large bronchia (through ipratropium). There are commercial preparations (berodural, ipratropium / salbutamol) containing the same combination that are administered in aerosols and are indicated especially for the elimination of dyspnea attacks during periods of asthma exacerbation.
42
Oxytropium
has properties similar to those of ipratropium. It is administered inhaler
43
Musculotropic bronchodilators
(caffeine-like xanthine alkaloid)
1. relaxes the smooth muscles of the bronchia and other smooth muscles,
2. stimulates the myocardium,
3. stimulates HCl gastric secretion,
4. increases diuresis and
5. excites the central nervous system.
44
Theophylline
It can be used in the treatment of asthma as such or in the form of an aminophylline that is more
soluble and has a higher bioavailability after oral administration.
45
Theophylline
| effects (I)
has a bronchodilator effect (less intense than for sympathomimetics) and may be
effective in patients in whom sympathomimetics have become inactive.
The relaxation of the bronchia is due to a direct action on the smooth muscles. In addition to bronchodilation, the stimulation of mucociliary clearance is favorable.
46
Theophylline effects (I)
In addition to these effects, theophylline is effective in 1.bronchial asthma and
2.has an anti-inflammatory and
3.immunomodulatory effect (attributed to reducing the action of LTD4 on specific receptors and blocking the release of proinflammatory substances from mast cells by adenosine)
4.and a central stimulant effect that may have favorable consequences in nocturnal asthma
(increasing respiratory volume and reactivity of respiratory centers to carbon dioxide).
5.Removing fatigue and increasing diaphragm contractility can also be beneficial.
6.Hemodynamic effects of the compound (increases myocardial contractile force, decreases preload and decreases venous filling pressure, dilates pulmonary arteries) may also be favorable in asthmatic patients.
47
Theophylline
| Side effects
anorexia,
nausea,
gastric irritation,
palpitations,
headache,
nervousness,
insomnia.
Excessive doses can cause tachycardia, arrhythmias, convulsions.
Rapid intravenous injection may cause skin congestion, hypotension, severe arrhythmias, precordial pain, nausea and
vomiting, marked restlessness, seizures. Cases of sudden death have been reported during i.v.
injection
48
Theophylline
| Contraindications
in patients with epilepsy, acute myocardial infarction and theophylline allergy.
Gastroduodenal ulcer is a relative contraindication. Use in cardiac, hypertensive, hyperthyroid, hepatic disease, elderly and newborns requires caution.
Do not administer concomitantly with other xanthine preparations. The combination with
ephedrine or other sympathomimetics increases the risk of toxic reactions.
49
Mast cell degranulation inhibitors
This therapeutic group includes substances able to prevent the release and / or production of
chemical mediators of the inflammatory process by mast cells and other cells involved in inflammation of the bronchial mucosa and which are prophylactically effective in asthma, especially allergic.
Mast cell degranulation inhibitors are not useful as a curative treatment for asthma attacks once triggered
50
Chromoglycic acid
1. is used as a medicine in the form of sodium cromoglycate (disodium salt).
2. It acts as an antiasthmatic due to its anti-allergic and anti-inflammatory properties
3. Administered before antigenic contact, it prevents the onset of an allergic asthma attack.
It also prevents seizures caused by effort, cold and irritants.
4.Chronic administration in patients with mild
or moderate asthma improves lung function and avoids dyspnea attacks caused by antigen exposure and effort.
5.The frequency and intensity of crisis decreases, the need for sympathomimetic bronchodilators or glucocorticoids may be reduced.
6.Therapeutic benefits are obtained in most patients with allergic asthma, especially in children.
7.Full effectiveness is manifested after 3-4 weeks of treatment. In patients with intrinsic asthma or asthmatic bronchitis, the effectiveness is lower.
51
Chromoglycic acid is also useful in
allergic rhinitis and topical allergic conjunctivitis.
- Administered internally, it can be useful in various food allergies, as well as in patients with systemic
mastocytosis and gastrointestinal disorders.
- Chromoglycate stabilizes the membrane of lung
mast cells and inhibits the release of histamine from them as well as the excessive formation of
leukotrienes by leukocytes, mast cells and tracheal epithelium, triggered by IgE in allergic asthma.
- These effects are attributed to a decrease in the availability of calcium ions in sensitized mast
cells, phosphorylation of a specific protein, and inhibition of phosphodiesterase by increasing the
amount of cyclic adenylate.
- Some actions of platelet aggregation factor - PAF - (accumulation of eosinophils in the lungs and bronchospasm) are also prevented under the action of
chromoglycate.
- The chromoglycate passes little through the biological membranes.
- After internal administration it is absorbed insignificantly.
- It is also slightly absorbed after inhalation.
- The absorbed drug is excreted unchanged in bile and urine.
- The half-life is short.
52
Chromoglycic acid
| Adverse reactions
nausea,
unpleasant taste,
arthralgia,
urticaria,
eosinophilic lung infiltration,
dysuria.
Administered inhaler may cause: transient bronchospasm, cough, wheezing (due to local
irritation) which can be prevented or treated by administration of a parasympatholytic or
sympathomimetic bronchodilator.
Very rarely, severe anaphylactic or anaphylactoid reactions may occur.
53
Nedocromil
(a derivative of chromoglic acid) has similar properties to chromoglic acid but a higher potency.
It is indicated, in combination, in mild and moderate forms of asthma, also as an alternative to beta-adrenergic stimulants or orally administered theophylline.
It is also used in rhinitis and allergic conjunctivitis, administered locally.
Side effects have been reported:
headache, bitter taste, nausea, abdominal discomfort, usually minor and transient.
54
Ketotifen
has antianaphylactic and antihistamine properties. At the respiratory level it has properties similar to the chromoglic acid to which is added the prolonged blockade of H1-type histaminergic receptors which may contribute to the antiasthmatic effect
55
Ketotifen
| Absorption + side effects
almost completely absorbed from the intestine. About half of the amount absorbed is inactivated at the first hepatic passage.
It is mostly metabolized.
The drug has not been shown to be effective in intrinsic asthma and exercise asthma.
Side effects:
sedation and drowsiness,
dry mouth, nausea, anorexia, epigastralgia, constipation,
rarely dizziness, weight gain.
56
Combination of Ketotifen with sedatives and hypnotics
The combination with sedatives and hypnotics is not recommended (potentiation of central depression).
Co-administration of ketotifen and oral antidiabetics may cause thrombocytopenia.
57
Glucocorticoids in asthma
Glucocorticoids are very effective in asthma, but are an alternative therapeutic, considering the high risk of side effects.
It causes a spectacular improvement in clinical and lung function, restores reactivity to sympathomimetics. The effect is obvious in patients who do not respond to bronchodilators and in severe cases of asthma
58
The therapeutic benefit of glucocorticoids
is mainly due to the anti-inflammatory action as well as the ability of these compounds to inhibit the formation of many important chemicals in the pathogenesis of asthma.
Oral preparations are appropriate in chronic asthma refractory to bronchodilators
59
Prednisone
is usually used.
Side effects and contraindications are common to cortisone. The main problem of long-term treatment is the depression of adrenal cortex function, which causes many patients, who are recommended glucocorticoids with the intention of a limited cure, to become corticosteroid-dependent.
Therefore, the use of this medication in chronic asthma requires discernment and medical supervision.
Intravenous injections, with relatively rapid action, are indicated in severe asthma attacks.
Respiratory tests begin to improve after 2 hours after injection and the effect is clinically evident
after 6-12 hours.
High doses are recommended, given early and for a short time.
Water-soluble preparations such as hydrocortisone hemisuccinate are used.
60
Prednisone
| Intramuscular injections
with slow and prolonged action, are advantageous for cures for several weeks, when the disease worsens or in patients who require oral treatment but do not cooperate
61
Methylprednisolone acetate or triamcinolone acetonide
may be used.
These glucocorticoids cause the usual side effects of cortisone medication.
Because it achieves active blood
concentrations for a long time, the risk of depression of adrenal pituitary function is high, so such
cures should be occasional (except for patients already corticosteroid-dependent).
62
Cortisone inhalation preparations, in the form of aerosols, such as beclomethasone
dipropionate,
have a limited action on the bronchi.
They are useful for the prophylaxis of asthma
attacks and the avoidance of exacerbations in chronic asthma, allowing the avoidance of cortisone systemically.
They are much better tolerated compared to systemic preparations with a minimal risk of corticosteroid dependence or other glucocorticoid-specific side effects.
However, they can cause some side effects such as promoting the development of oropharyngeal
candidiasis and can cause dysphonia.
In addition, exacerbation of asthma may sometimes occur upon discontinuation of inhaled glucocorticoids, necessitating resumption of treatment and gradual dose reduction.
63
Leukotriene antagonists and lipoxygenase inhibitors
Leukotrienes, especially LTD4 and LTE4 (peptidyloleukotrienes known as SRS-A, the slowreactive substance of anaphylaxis) are important autacoids in the pathogenesis of asthma, having
proinflammatory and bronchoconstrictor effects. Impairment of the synthesis or action of such
substances appears to be an important possibility in the drug control of asthma
64
Montelukast and Zafirlukast
are competitive antagonists of peptidyloleukotrienes, blocking their receptors.
They are administered internally for the prolonged prophylaxis of mild or moderate asthma attacks.
The effectiveness and risk of side effects are not fully evaluated.
65
Zileutone
inhibits 5-lipoxygenase, an enzyme involved in the synthesis of leukotrienes.
The substance inhibits the production of leukotrienes involved in bronchospasm (LTC4 and LTD4) as
well as LTB4, an autacoid with chemotaxic action and leukocyte activation in the bronchial
mucosa. It is indicated as a long-term prophylactic treatment in mild-to-moderate asthma. It is
administered internally. Leukotriene antagonists and lipoxygenase inhibitors are especially
indicated as a prophylactic treatment for asthma induced by acetylsalicylic acid or other non- steroidal anti-inflammatory drugs.
66
Anti-IGE monoclonal antibodies
| Omalizumab,
is useful in patients with severe chronic asthma who do not respond to beta-stimulant treatment with high-dose inhaled glucocorticoids.
Omalizumab reduces bronchial
inflammation and reduces the frequency and severity of seizures. The indication of choice is for
patients with demonstrated IgE-mediated hypersensitivity. The drug is given subcutaneously
twice a week.
67
Drugs used to treat cough
Are medicines that can reduce/calm the cough. Their effect is mainly due to the depression of the
cough reflex (cough center). Some antitussives also have a peripheral action, at the airway
mucosa.
Antitussives are a symptomatic medication useful in all situations when the cough is harmful (unproductive cough that tires the patient).
The antitussive treatment must take into account that the cough reflex also has a defensive character, representing an important mechanism for cleaning and draining the tracheobronchial tree, especially in the case of subjects with lung infections.
68
Opium and morphine
are active antitussives, depressing the cough center.
They are used sparingly because they have important side effects: risk of addiction, respiratory depression,
favored bronchospasm, thickening of tracheobronchial secretion, paralysis of vibrating cilia.
They may be useful in special situations, where it is desirable to combine antitussive action with intense
analgesic and sedative effect (patients with lung cancer, rib fractures, pneumothorax, heart attack,
hemoptysis).
69
Codeine
the methylated derivative of morphine, has a marked antitussive effect.
Like morphine,
1.it depresses breathing,
2.dries bronchial secretions,
3.promotes bronchospasm,
4.causes constipation,
but has the great advantage that the potential for developing addiction is much lower.
- It is administered orally, being the most widely used antitussive.
- It has an analgesic action of moderate intensity, for which it is sometimes associated with antipyretic analgesics, especially acetylsalicylic acid.
```
Codeine should be avoided in patients with marked respiratory failure. Use in young children
requires caution (high doses may cause seizures)
```
70
Noscapine,
an isoquinoline alkaloid from opium (related to papaverine), has an antitussive action,
is weakly bronchodilator, stimulates breathing.
It has no analgesic properties, does not cause
addiction.
71
Dextromethorphan
is commonly used in antitussive associations but its effectiveness as an antitussive is considered to be poor. It acts as an opioid receptor antagonist and by antagonizing NMDA receptors centrally.
Administered in high doses it has an increased risk of tolerance and dependence. It can also cause hallucinations when given in high doses.
72
Benzonate
is a local anesthetic that works by inhibiting peripheral receptors involved in producing the cough reflex.
As side effects may cause: dysphagia, dizziness, severe allergic reactions in patients allergic to paraaminobenzoic acid (a metabolite of benzonate). Administered in large doses may cause seizures and cardiac arrest
73
Clofedanol
a synthetic compound, is a relatively weak antitussive, but slightly more durable than codeine.
74
Moguistein
1) theobromine,
2) guaifenesin
3) baclofen
a peripheral-acting compound that opens K + ATP-dependent channels,
1) a methylxanthine derivative that inhibits phosphodiesterases,
2) a compound indicated primarily as an expectorant, baclofen,
3) a selective GABAB receptor antagonist,
are compounds that have been shown to be effective. Significant antitussives compared to placebo and which may be indicated in particular circumstances in patients with upper respiratory infections.
75
Studies have recently begun for new antitussives such as compounds that antagonize TRPV1
(Transient Receptor Potential V1) and TRPA1 (Transient Potential Receptor A1) receptors that
are activated by
compounds such as capsaicin, bradykinin or H +, substances known as cough agents.
76
Expectorants
The expectorant action is due either to the stimulation of the secretory activity of the glands of the
tracheobronchial mucosa, or to the direct fluidification of the mucous secretions.
77
Secretostimulating expectorants
are stimulating the activity of the serous glands in the
bronchial mucosa and increasing plasma transudation at this level. Some, administered orally,
have a weak irritating action on the gastric mucosa, triggering a reflex tracheobronchial
hypersecretion. Others are absorbed, then partially eliminated through the mucosa of the airways,
acting directly on the secretory cells.
The therapeutic efficacy of these classical expectorants is relatively poor.
78
Ammonium chloride and other ammonium salts
reflexively stimulate bronchial secretion. It
also has weak acidifying and diuretic properties. Ammonium chloride can cause nausea and
vomiting. It is contraindicated in patients with ammonia intoxication - in uremia and severe hepatic
impairment - in conditions of acidosis and severe respiratory failure.
79
Potassium iodide and sodium iodide
stimulate reflex and direct bronchial secretion.
They are used especially in chronic bronchitis.
The spectrum of pharmacological actions of iodine also
includes:
1. influencing thyroid function,
2. promoting the healing of chronic inflammatory processes,
3. antiseptic properties.
80
iodine
| side effects
can cause stomach irritation with nausea and
vomiting.
Prolonged administration or the first doses of idiosyncrasies can cause minor toxic phenomena, known as iodism: oculonasal catarrh, headache, acneiform eruptions.
Iodine interferes with thyroid tests for a long time (several months) and rarely promotes goiter
development.
It should be avoided in patients with pulmonary tuberculosis, because, due to its irritating and congestive action, they can promote the activation of the disease.
81
Gaiacol, potassium gaiacolsulfonate and guaifenesin
have poor expectorant action
82
Secretolytic expectorants
act directly on bronchial secretions, fluidizing them. This group comprises mucolytic substances, surfactants and moisturizers.
83
Mucolytics
act on mucous secretion, loosening various types of bonds responsible for the aggregation of proteoglycemic macromolecules that form the skeleton of mucus, with consecutive fluidization and relief of sputum
84
N-acetylcysteine
is a mucolytic with a thiol structure. The expectorant effect is due to the -SH group, which disrupt the inter- and intracaternary disulfide bridges of the mucosal aggregate,
forming new -S-S- bonds between the drug and the mucoprotein fragments. It is administered
internally, injected intramuscularly or slowly intravenously, in aerosols or in direct instillations,
being indicated in hypersecretory syndromes with respiratory tree loading: bronchopulmonary
infections, chronic obstructive pulmonary disease, cystic fibrosis.
85
In particular, acetylcysteine is also used in the treatment of
acute paracetamol intoxication. In this
case it is administered as an intravenous infusion, at a total dose of 300 mg / kg, over 20 hours.
It acts as a hepatoprotector by increasing glutathione levels and preventing the formation of hepatotoxic metabolites of paracetamol.
Brutal fluidization of secretions can cause bronchial flooding in patients unable to expectorate
(which requires bronchoaspiration). Acetylcysteine should be used with caution in asthmatics as
it may promote bronchospasm.
86
Carbocysteine, methylcysteine, erdosteine
are N-acetylcysteine-like derivatives but
| considered to have lower expectorant efficacy.
87
Bromhexine
a synthetic compound with a quaternary ammonium structure, has mucolytic properties.
The effect is probably exerted by means of lysosomal enzymes, whose activity increases at the mucosal surface.
Bromhexine is administered orally, by injection subcutaneously, intramuscularly or intravenously or by inhalation, and is indicated in bronchitis and bronchiectasis.
```
Administered internally it can cause nausea. The solution for injection should not be mixed with
alkaline preparations (glucocorticoids, ampicillin, etc.).
```
In all cases, hydration of the patient is essential.
