Tiotropium

BRAND NAMES

• The most common brand name for tiotropium is Spiriva, which is available in different inhaler forms like the Spiriva HandiHaler and Spiriva Respimat.

• Other brand names, though less common or region-specific, may include Inspiolto Respimat, Stiolto, Bontiair, and various generic or regional formulations found on platforms like IndiaMART

MECHANISM OF ACTION

• Tiotropium is a long-acting muscarinic antagonist (LAMA). 

• It blocks muscarinic receptors in the airway smooth muscle, preventing the action of acetylcholine. 

• This leads to relaxation of the airway muscles and bronchodilation, which helps to alleviate bronchospasm. 

 PHARMAKONETICS

Absorption: 

Tiotropium exhibits low systemic absorption when administered either through the gastrointestinal tract or via inhalation. When inhaled, its systemic bioavailability ranges between approximately 19.5% and 33%, whereas oral administration results in much lower bioavailability, around 2-3%. This limited absorption into the bloodstream means that most of the drug remains localized within the lungs, where it exerts its therapeutic effects by blocking muscarinic receptors, leading to bronchodilation.

Distribution: 

Tiotropium has a volume of distribution of 32 L/kg, which suggests it extensively distributes and binds to tissues throughout the body. Additionally, about 72% of the drug binds to plasma proteins.

Metabolism: 

Tiotropium undergoes minimal metabolism in the body. Approximately 74% of an intravenous dose is eliminated unchanged through the urine. The drug is primarily broken down nonenzymatically into inactive metabolites, including N-methylscopine and dithienylglycolic acid.

Excretion:

Excretion of tiotropium occurs primarily through the kidneys, with the remainder of the dose being eliminated in the feces. The pathway for elimination differs depending on whether the drug is absorbed into the body (systemic circulation) or remains unabsorbed.

PHARMACODYNAMICS

Tiotropium is a long-acting antimuscarinic agent that promotes bronchodilation. Its effects persist for more than 24 hours, and it has a wide therapeutic window, with overdoses being rare even at doses significantly higher than the recommended maximum.

ADMINISTRATION

Tiotropium is available as either an inhalation spray or powder, both administered through an inhaler. Before using a tiotropium inhaler, the device must be assembled and the medication capsule loaded, followed by priming the inhaler. Proper priming ensures the medication is delivered effectively for inhalation. The inhaler device includes several components such as a cap, mouthpiece, air vent, dose indicator, and a button to release the dose. The dose indicator shows how many doses remain in the medication capsule.

DOSAGE AND STRENGTH

Tiotropium is typically administered once daily for the maintenance treatment of respiratory conditions such as Chronic Obstructive Pulmonary Disease (COPD) and asthma. When delivered via the HandiHaler dry powder inhaler, the standard dose is 18 micrograms taken once a day by inhaling one capsule. For the Respimat soft mist inhaler, the usual dosage is 2.5 micrograms per inhalation, with two inhalations once daily, totaling 5 micrograms per day. 

DRUG INTERACTIONS 

Tiotropium, an anticholinergic medication for conditions like Chronic Obstructive Pulmonary Disease (COPD) and asthma, interacts significantly with other anticholinergics. Other interactions vary in severity and depend on the specific medications taken concurrently. Patients should always inform their doctor and pharmacist about all medications, supplements, and herbal products they are taking.

FOOD INTERACTIONS 

No known food or beverage interactions with tiotropium have been identified. It is unclear whether alcohol consumption affects tiotropium, but drinking alcohol while using the medication may increase the risk of dizziness.

CONTRAINDICATIONS

Tiotropium bromide should not be used in patients who are allergic to tiotropium, ipratropium, or atropine because of the risk of anaphylaxis, as well as in those with narrow-angle glaucoma. Additionally, tiotropium powder capsules contain milk protein and are therefore contraindicated for individuals with a milk allergy.

SIDE EFFECTS: 

• Respiratory: Sore throat, cough, sinus inflammation (sinusitis), or cold-like symptoms.

• Oral: Dry mouth is the most frequently reported side effect and can be managed by staying hydrated and using sugar-free candy or gum. Oral yeast infections (oral candidiasis) are also possible; gargling with warm water after use can help prevent this.

• Gastrointestinal: Upset stomach, constipation, and indigestion.

• Neurological: Headaches and dizziness. 

Serious side effects

• Urinary retention: This can make it difficult to empty the bladder. Symptoms include trouble urinating, painful urination, or a weak stream. It is more common in those with an enlarged prostate or bladder obstruction.

• Eye problems (glaucoma): Tiotropium can increase pressure inside the eye, which may cause or worsen narrow-angle glaucoma. Symptoms include eye pain or redness, blurred vision, seeing halos around lights, and severe headache.

• Heart problems: A fast, irregular, or pounding heartbeat (palpitations) has been reported. Studies on the cardiac risks of tiotropium have had mixed results, though some report a potential link to an increased risk of heart attack or stroke.

OVER DOSE 

overdose or accidental ingestion can lead to anticholinergic effects, such as a fast or irregular heartbeat, dry mouth, blurred vision, and urinary retention. Tiotropium should be used cautiously in patients with glaucoma, prostatic hyperplasia, or heart rhythm disorders due to potential risks. The most common adverse effect with regular use is dry mouth, which is often mild and can resolve with continued treatment.

TOXICITY

Tiotropium has a wide therapeutic index, and its systemic toxicity is generally low due to poor absorption from the lungs and gut. The primary toxic effects associated with tiotropium are extensions of its anticholinergic properties and can occur with overdose or in susceptible patients, particularly those with kidney impairment.