Anticholinergics in COPDpresented by:Soha Ragab Moselhy group 2

Role of anticholinergics in COPD:

-Anticholinergics are used in the management of COPD for their

bronchodilatory effects .-These agents are antagonists of muscarinic

receptors (i.e., M1, M2 , and M3 subtypes). Blockade of these receptors in the smooth muscle of the airways inhibits the activity of acetylcholine thereby relaxing the muscle tissue and keeping the airways open.

-In addition to helping COPD patients take fuller breaths, They may protect the airways from spasms that can suddenly cause the airway to become narrower (bronchospasm). They also may reduce the amount of mucus produced by

the airways .

-maintenance use of anticholinergic medication may also help lower the incidence of acute

exacerbations in COPD patients.

How Well It Works

A number of studies indicate that inhaled anticholinergics improve lung function as measured by tests (spirometry). They also reduce the number of COPD exacerbations. There is no evidence of their effect on the progression of the disease

Studies have shown that:

-In short-term treatment, ipratropium and tiotropium both improved lung function

compared to a placebo. -After one year of treatment, tiotropium

improved lung function and reduced the number of COPD exacerbations and hospital admissions, compared to a

placebo .

-Combining an anticholinergic with a beta2-agonist may help your lung function more than using either medicine alone. Doing so usually increases your cost but, compared to increasing the dose of one medicine, may also reduce the risk of side effects.

-Compared to tiotropium alone, combining tiotropium with a beta2-agonist (salmeterol) and corticosteroid (fluticasone) improved lung function and quality of life and lowered the number of hospital visits

Types of anticholinergics

-There are 2 types of anticholinergics: short-acting and long-acting .

-The short-acting type relieves symptoms and the long-acting type helps prevent breathing problems. Short-acting anticholinergics are used for treating stable COPD in a person whose symptoms come and go (intermittent symptoms) .

-Long-acting anticholinergics are effective and convenient for preventing and treating COPD in a person whose symptoms do not go away (persistent symptoms ).

Long acting anticholinergics

Tiotropium bromide

(Spiriva HandiHaler)

Mechanism of action:

Tiotropium is a long-acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle

leading to bronchodilation .

-Tiotropium's differences in receptor association and dissociation rates distinguish its pharmacology from that of

ipratropium .

-Tiotropium dissociates most rapidly from the M2 receptors. Stimulation of the M2 receptors reduces acetylcholine release; blockade may result in further

bronchoconstriction .

-Tiotropium's long duration of action is likely a result of its slower dissociation from the M1 and M3 receptors.

-Tiotropium demonstrates competitive and reversible receptor antagonism, as shown in human, animal, and isolated organ preparation studies.

Dosage and Administration-Tiotropium powder is supplied in capsules

containing tiotropium 18 µg (as tiotropium bromide monohydrate) and lactose monohydrate (as the carrier).

- The recommended dosage is the inhalation of one capsule's contents once

daily. -The capsules are designed to only be used

with the HandiHaler breath-activated inhalation device

Adverse Effects

-The most frequently reported adverse effect was dry mouth

-Other adverse effects, such as constipation, tachycardia, and blurred vision, were also

reported . -cautious use of tiotropium in patients with

conditions that could be exacerbated by the addition of an anticholinergic agent, such as

benign prostatic hyperplasia and glaucoma.

FDA has requested further postmarketing studies to evaluate the effect of tiotropium on the QT interval bec changes in QT interval reported in some patients.