Anti inflammatory agents used in asthma and cough suppressants

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.