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Pharmacology of respiratory system
Dr. Jawad Al-Musawi (THI-QAR MEDCAL COLLEGE-IRAQ-)
The main symptoms of respiratory diseases are:-
A-Cough
B-Dyspnea
C-Nasal congestion
A.treatment of cough
1-We must exclude any drugs used by the patients which causing cough
like ACE INHIBITORS.
2- Cough reflex is via both the afferent and efferent nerves (i.e. involving
the central and peripheral nervous systems), as well as the smooth muscles
of the bronchial tree .
3- A useful physiological mechanism that serves to clear the respiratory
tract of foreign materials and excess secretion .
It should not be suppressed indiscriminately. However, cough at times may
not serve any useful/ physiological purpose and could therefore be
pathologic
* Productive cough should not be suppressed as sputum needs to be
cleared .
Drugs
:
I. Antitussives :
Centrally-acting Antitussives
a. Narcotics :
Opiates: Codeine, Pholcodeine, Hydrocodone, Morphine .
Opioid derivatives: Dextromethorphan, Levopropozyphene, Noscapine.
b. Non-Narcotics: Benzonatate, first generation Antihistamines e.g.
Diphenhydramine, having sedative, anticholinergic actions, crossing the
BBB.
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II. Expectorants (Mucokinetics)
Make cough more productive by loosening and liquefying bronchial
secretions .
Reflexly-acting:
a. Ipecacuanha
b. Ammonium chloride
c. Potassium iodide
Directly-acting: Guaiphenesin
III. Mucolytics
Break down thick mucus, making it thinner and easier to cough out. Split
disulphide bonds in mucoprotein present in sputum and reduces its
viscosity .
Acetylcysteine
Carbocysteine
Methylcysteine
IV. Demulcents
E.g. Liquorice, Glycerin, Lozenges .
They provide relief to throat.
Promote salivation and inhibit impulses from inflamed mucosa.
B.Treatment of dyspnia
Dyspnia is the non-desire sign bronchoconstriction as in ASTHMA and
COPDs
Causes: Lower respiratory tract disorders include infections, restrictive
pulmonary disorders, obstructive pulmonary disorders, and lung cancer
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Lower Respiratory Tract Infections
1- Acute Bronchitis: An infection that is located in the bronchi is called
bronchitis. Most of the time, it is preceded by a viral URI that led to a
secondary bacterial infection. Usually, a nonproductive cough turns into a
deep cough that will expectorate mucus and sometimes pus.
2- Asthma
3- (COPD)
3- Chronic Obstructive Pulmonary Disease
Cough - this is the most common symptom and is usually dry and
persistent. Coughing can occur any time, but it is often worsened at night
and after exercise .
Wheezing - a high-pitched wind blowing noise, usually heard on breathing
out .
Shortness of breath - breathing is fast and shallow. Unable to get enough
air into the lungs.
Chest Tightness - The chest feels ‘tight’ and unable to expand freely when
breathing .
Asthma may be acute or chronic .
- Chronic asthma: individual has intermittent attacks of dyspnoea,
wheezing and cough .*
- acute severe asthma (status asthmaticus): not easily reversed. Often
fatal and requires prompt and aggressive treatment. Hospitalization is
necessary.
Asthma may be intrinsic or extrinsic .
- Intrinsic (Type II, Non-allergic reaction): no obvious allergic basis.
Cold, respiratory tract infection, changes in weather, exercise, stress, etc.
are precipitating factors and may induce inflammatory reactions.
It predominates in small children particularly below 5 years and in adults
over the age of 45 years
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The treatment aims to reverse airflow obstruction and reduces asthma
exacerbations thus improving quality of life. However, long-term use of
high dose inhaled corticosteroids therapy may lead to detrimental effects,
such as cataracts, osteoporosis in elderly patients, and stunting of growth in
children .
Moreover, the combination therapy may not modify the disease
progression and are not curative
*Medications include quick-relief therapies to treat acute symptoms of
an attack and long-term control medications to prevent further
exacerbation:
1-Bronchodilators-sympathomimetics, methylxanthines, anticholinergics
2-Corticosteroids-systemic, inhalation Leukotriene antagonists
3-Mediator-antagonists: Antihistamine
4-Mast cell stabilizers
5-Anti-IgE antibody
The treatment aims to reverse airflow obstruction and reduces asthma
exacerbations thus improving quality of life. However, long-term use of
high dose inhaled corticosteroids therapy may lead to detrimental effects,
such as cataracts, osteoporosis in elderly patients, and stunting of growth in
children .
Moreover, the combination therapy may not modify the disease
progression and are not curative
1.Bronchodilators
Are medications that relax the bronchial muscles, making the airway
larger, and allowing air to pass through easily Thus relieving
breathlessness, chest tightness, and other acute symptoms of asthma
1-Sympathomimetics-β2-receptor agonists
i.
Short-acting: salbutamol, pirbuterol, terbutaline
ii.
Long-acting: salmeterol, formoterol
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Salbutamol
Mechanism
Beta adrenoceptors are coupled to a stimulatory G protein, which activates
adenylyl cyclase to produce the second messenger cAMP.
In the lung, cAMP decreases Ca++ concentrations within the cells and
activate myosin light chain phosphatase .
In addition, there is increased membrane potassium conductance.
All these culminate into muscle relaxation.
Side effects: Nervousness, restlessness, tremor, headache, insomnia, chest
pain, palpitations, angina, hypertension, tachycardia.
Xanthine derivatives :
Theophylline :Water insoluble
Theophylline + Ethylene Di-Amine = Aminophylline
Mechanism: Theophylline is a competitive nonselective phosphodiesterase
inhibitor, which raises intracellular cAMP, activates Protein kinase
A, inhibits TNF- alpha and inhibits leukotriene synthesis, and reduces
inflammation and innate immunity .
Nonselective adenosine receptor antagonist. (Adenosine is a
bronchoconstriction)
Pharmacological effects:
• Bronchial muscle: Bronchodilatation
• CNS: cortical stimulation, excitement, insomnia, stimulation of
medullary respiratory and vomiting centre, reduced mental exhaustion
and fatigue .
Side effects of theophylline: Nausea, vomiting, convulsion, arrhythmias,
anorexia, palpitations
Therapeutic index is very low
Indications: Bronchial asthma, COPD, and Apnea .
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Anticholinergic drugs
Short-acting: ipratropium
Long-acting: tiotropium
Anticholinergics prevent the increases in intracellular concentration of
cyclic guanosine monophosphate (cyclic GMP), most likely, due to actions
of cGMP on intracellular calcium, this results in decreased contractility of
smooth muscle in the lung, inhibiting bronchoconstriction and mucous
secretion .
2.Corticosteroids
I. Topical inhalation:
- betamethasone
- beclomethasone
II. Systemic :
- oral prednisolone
- i.v: hydrocortisone
- Methyl prednisolone (Depomedrol) as injection
Mechanisms of Action :
1- Inhibit the formation of cytokines.
2- Inhibit the generation of vasodilators PGE2 and PGI2 by inhibiting the
induction of cyclooxygenase.
3- Induce lipocortin (a phospholipase A2 inhibitor) therefore, inhibiting
LTC4 and LTD4 production .
4- Decrease the synthesis of leucocyte chemotaxins LTB4 and PAF, thus
reducing recruitment and activation of inflammatory cells .
5- Inhibition of synthesis of bronchoconstrictor substances e.g. histamine.
6- Suppression of enzymatic processes that are triggered by the union of
antigen with antibody.
7- Reduces antibody formation
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Side effects of corticosteroids:
1- Adrenal suppression.
2- Impairment of wound healing.
3- Peptic ulcer.
4- Immunosuppression.
5- Osteoporosis.
6- Hyperglycemia.
7- Menstrual irregularities.
8- Fluid retention.
9- Muscle weakness .
3.Prophylactic agents in BA:
1 -Mast-cell stabilizers:
i. Cromones: Na+ cromoglycate, Nedocromil Na
ii. Ketotifen
Mechanism of Action
- Inhibit release of mediators from mast cells by stabilizing the mast cells .
- Inhibit several inflammatory cells e.g. neutrophils, macrophages,
eosinophils. Cromoglycate is poorly absorbed from the gut, so it is only
effective through inhalation.
Ketotifen: is both a 5HT and histamine antagonist. Orally active but with a
slow onset of action. Must be administered regularly for 6-12 weeks before
any beneficial effect is noticeable .
2 -Mediator Antagonists:
i. Antihistamines: azelastine, cetirizine
ii. Leukotriene pathway inhibitors :
• lipoxygenase enzyme inhibitor: zileuton
• leukotriene-receptor antagonists: zafirlukast, montelukast,
pranlukast
The End…… (thank you)