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ANTI-INFLAMMATORY AGENTS USED IN ASTHMA AND COUGH SUPPRESSANTS
ANKIT GILANIDEPT OF PHARMACOLOGY AND TOXICOLOGYNIPERA1113PC03 (sem-1)SUBJECT – PC-620
ASTHMA
An inflammatory condition in which there is recurrent reversible airways obstruction in response to irritant stimuli that are too weak to affect non-asthmatic subjects.
symptoms
wheezing
shortness of breath
( especially in breathing out)
cough.
PATHOGENESIS
characterised by:
inflammation of the airways bronchial hyper-reactivity reversible airways obstruction
TREATMENT
BRONCHODILATORS
β-Adrenoceptor agonists,
Xanthine drugs ,Muscarinic receptor
antagonists,Cysteinyl
leukotriene receptor antagonists,
Histamine H1-receptor
antagonists.
ANTI-INFLAMMATORY
AGENTS Glucocorticoids ,Cromoglicate and
nedocromil ,Anti-IgE treatment .
ANTI-INFLAMMATORY AGENTS
Mainly glucocorticoids Cromoglicate and nedocromil (weak
anti-inflammatory and short duration , now hardly used for asthma)
Omalizumab (humanised monoclonal anti-IgE
antibody)
Mechanism of glucocorticoids
decrease formation of cytokines, in particular the Th2 cytokines that recruit and activate eosinophils and are responsible for promoting the production of IgE and the expression of IgE receptors.
Glucocorticoids also inhibit the generation of the vasodilators PGE2 and PGI2, by inhibiting induction of COX-2
By inducing annexin 1, they could inhibit production of leukotrienes and platelet- activating factor.
Corticosteroids inhibit the allergen-induced influx of eosinophils into the lung.
Glucocorticoids up-regulate β2 adrenoceptors, decrease microvascular permeability, and indirectly reduce mediator release from eosinophils by inhibiting the production of cytokines (e.g. IL-5 and granulocyte-macrophage colony-stimulating factor) that activate eosinophils.
EXAMPLES :
1) Systemic ( given orally) : Prednisone Prednisolone Methylprednisolone
2) Inhaled : Beclometasone Budenoside Fluticasone Mometasone Ciclesonide
Unwanted effects
Systemic : Thinning of the skin, Tendency to bruise, Osteoporosis, Muscle Weakness, Infections ,Hypertension, etc.
inhaled :Oropharyngeal candidiasis (thrush)sore throat and croaky voice [ use of 'spacing' devices, reduces these problems ]
DRUGS FOR COUGH
COUGH : a protective reflex that removes foreign material and secretions from the bronchi and bronchioles.
It can be triggered by inflammation in the respiratory tract, for example by undiagnosed asthma or chronic reflux with aspiration, or by neoplasia.
In these cases, cough suppressant (antitussant) drugs are useful.
DRUGS FOR COUGH
Pharyngeal demulcents
Expectorants (mucokinetics)
Antitussives (cough centre suppressants)
Adjuvant antitussives (bronchodilators)
MECHANISM OF COUGH SUPPRESSION
Antitussive drugs act by an ill-defined effect in the brain stem, depressing the 'cough centre'.
All opioid narcotic analgesics have antitussive actions in doses below those required for pain relief.
Those used as cough suppressants are members of the group with minimal analgesic actions and addictive properties.
New opioid analogues that suppress cough by inhibiting release of excitatory neuropeptides through an action on μ receptors on sensory nerves in the bronchi are being assessed.
EXAMPLES
Codeine (methylmorphine) is a weak opioid with considerably less addiction liability than the main opioids, and is a mild cough suppressant.
It decreases secretions in the bronchioles, which thickens sputum, and inhibits ciliary activity. Constipation is common.
Dextromethorphan and pholcodine are believed to have fewer adverse effects.