MD. HAMZA ALBEE ASHANIA AKHTER TASNOVA NOWRIN KANZIL MAULA MOU RUBAIYAT ISLAM MONA AFRIN A RAHMAN AIRIN NAHER SHAGUFTA JASMIN SUBI

ANTIMUSCARINIC AGENTS Ipratropium and tiotropium

Mechanism of action Ipratropium Ipratropium blocks the effect of acetylcholine on airways (bronchi) and nasal passages. Acetylcholine is a chemical that nerves use to communicate with muscle cells. In asthma and chronic obstructive pulmonary disease, cholinergic nerves going to the lungs cause narrowing of the airways by stimulating muscles surrounding the airways to contract. The "anti-cholinergic" effect of ipratropium blocks the effect of cholinergic nerves, causing the muscles to relax and airways to dilate. Mucus glands in the nose also are controlled by nerves that use acetylcholine to communicate. By blocking acetylcholine, ipratropium helps relieve symptoms of allergies and the common cold by preventing secretion of mucus by mucus glands in the nose. When inhaled, ipratropium travels directly to airways, and very little is absorbed into the body. The FDA approved ipratropium in October 1995.

Pharmacokinetics Absorption Mean bioavailability is 7% (inhalation). Ipratropium is not readily absorbed. Distribution 0 to 9% is protein bound. Metabolism Partially metabolized. Elimination The t ½ is approximately 2 h (inhalation or IV). Following IV administration, approximately half of the dose is excreted unchanged in the urine. Pharmacology Antagonizes action of acetylcholine on bronchial smooth muscle in lungs, causing bronchodilation. Pharmacology and Pharmacokinetics of Ipratropium

Therapeutic uses: Ipratropium is used to control and prevent symptoms (wheezing and shortness of breath) caused by ongoing lung disease (chronic obstructive pulmonary disease-COPD which includes bronchitis and emphysema). It works by relaxing the muscles around the airways so that they open up and you can breathe more easily. Controlling symptoms of breathing problems can decrease time lost from work or school. For preventing symptoms of lung disease, this medication must be used regularly to be effective. Use your quick-relief inhaler or nebulized solution for wheezing or sudden shortness of breath unless otherwise directed by your doctor. Ipratropium does not work as fast as your quick-relief medication, but may sometimes be used together with your quick-relief medication to

Ipratropium may cause side effects: Dizziness Nausea Heartburn Constipation Dry mouth Difficulty urinating Pain when urinating Frequent need to urinate Back pain rash Swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs Chest pain

Mechanism of Action Tiotropium Tiotropium is a long-acting, antimuscarinic agent, which is often referred to as an anticholenergic. 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. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site-specific effect.

Pharmacology and Pharmacokinetics of Tiotropium Pharmacology Inhibits smooth muscle receptors, leading to bronchodilation. Pharmacokinetics Absorption Bioavailability is approximately 19.5%. T max is 5 min. At steady state, peak and trough plasma levels are 17 to 19 pg/mL and 3 to 4 pg/mL, respectively. Distribution Vd is 32 L/kg. Protein binding is 72%. Metabolism CYP2D6 and CYP3A4 are involved. Elimination Approximately 14% is eliminated unchanged in the urine; the remainder is not absorbed in the gut and is eliminated in the feces. Terminal elimination half-life is 5 to 6 days.

Therapeutic use of Tiotropium Tiotropium is used for maintenance treatment of chronic obstructive pulmonary disease (COPD) which includes chronic bronchitis and emphysema. It is not however used for acute exacerbations.

Adverse effects Adverse effects are mainly related to its antimuscarinic effects. Common adverse drug reactions associated with tiotropium therapy include: dry mouth and/or throat irritation. Rarely treatment is associated with:urinary retention, constipation, acute angle closure glaucoma,and/or allergy (rash, angioedema anaphylaxis). Tiotropium and another member of its class ipratropium were linked to increased risk of heart attacks, stroke and cardiovascular death.