Leukotriene inhibitor. 

Leukotriene Modifiers

Leukotriene modifiers, also called leukotriene receptor antagonists, are a group of medications. They can help prevent breathing problems associated with allergies, asthma and chronic obstructive pulmonary disease. Examples include montelukast, zafirlukast and zileuton..

Mechanism of action 

How do leukotriene receptor antagonists work?

Leukotriene receptor antagonists are medications used to treat inflammatory respiratory conditions such as asthma and allergic rhinitis. Leukotriene receptor antagonists relieve the symptoms of asthma and allergic rhinitis by preventing leukotriene-induced inflammation, swelling of airways, excess mucus secretion and airway constriction.

Asthma and rhinitis episodes are triggered by allergens or exercise when the immune system releases inflammatory substances to attack what it perceives as foreign to the body. Cysteinyl leukotrienes are a group of inflammatory molecules released by immune cells such as mast cells, eosinophils, basophils and macrophages in the airway.

Cysteinyl leukotrienes trigger bronchial constriction and inflammation by activating protein molecules known as CysLT1 receptors on the surface of bronchial smooth muscle cells and immune cells in the airway. Cysteinyl leukotrienes promote inflammatory processes which include:

Migration and aggregation of other immune cells in the airway which further promote inflammation.

Greater permeability of small blood vessels (capillaries), which allows inflammatory proteins and immune cells to leak out.

Contraction of the airway smooth muscles.

Leukotriene receptor antagonists prevent inflammation by binding to the CysLT1 receptors and blocking cysteinyl leukotrienes from stimulating them. Leukotriene receptor antagonists block the activity of three types of cysteinyl leukotrienes, LTC4, LTD4 and LTE4..

Brand name

What are names of leukotrienes receptor antagonists?

Generic name and brand name of leukotrienes  receptor antagonist include:

--Accolate

----montlukast

----singulair

----zafirukast

Uses

How are leukotriene receptor antagonists use?

Leukotrienes receptor antagonists oral tablet or granules used in treatment of the following conditions 

-prevent and maintaince treatment of chronic asthma 

-exercise induced bronchospasm

- perennial allergic rhinitis 

- seasonal allergic rhinitis 

What  are side effect of leukotrienes receptor antagonist?

Since effect of leukotrienes receptor antagonists may include  the following:

-headache 

- abdominal pain

--laryngitis

- pharyngitis 

- wheezing

- viral infection 

--Nausea

- Diarrhea 

- vomiting 

- dyspepsia 

- back pain

- Depression 

- fever

- Eczema

- insomnia 

-myalgia

- upper respiratory infection 

- liver injury 

- ear infection 

Drug drug interaction 

What interaction should I watch out for?

Leukotriene modifiers may interact with other medications, so it,s important to tell your health care provider about everything you take. 

The drug might interact with;

_Alpelisib,dabrafenib or enzalutamide (treatment for cancer)

- Erthromycin and rifapentine ( antibiotics that treat bacterial infection)

- loxapine( drug to treat  mental health conditions such as schizophrenia)

  -  lumacaftor( a treatment for cystic fibrosis).

- Terfenadine( an anti histamine to prevent or treat symptoms)

- warfarin ( blood thinner that can help prevent blood clots, strokes and heart attacks).

How are leukotriene modifiers administrated?

Leukotriene modifiers are available in granules, tablets, and chewable tablets.  Allow about three days to two weeks for leukotrienes inhibitor to offer  full benefits for management of allergies and asthma. 

Drug food  interaction 

Food interaction with leukotrienes inhibitor can affect their absorption and efficacy. Here's how food can food interact with some leukotrienes inhibitor:

-*  montelukast * : this medication can be taken with or without food, as food does not significantly affect its absorption. However, taking it on an empty stomach may result in faster absorption 

-* zafrirlukast*: this medication should be taken at least one hour before or two hours after meals,as food can decrease its absorption by about 40%. High _fat meals in particular can significantly reduce its bioavailability. 

-* zileuton *: fofood can decrease the absorption of zizileuton by about 40%, so it,a recommended to take it at least one hour after meals. However, taking it with food  may help gastrointestinal side effects. 

Overall, while food interaction may vary depending on the specific  leukotriene inhibitor, it's important to follow the prescribing health care  provider instructions regarding whether to take the medication with or without food to ensure optimal absorption and effectiveness. 

Pharmacokinetics of leukotrienes inhibitor 

-*Absorbtion*leukotrienes inhibitor are generally well absorbed after oral administration, with peak plasma concentrations reached within a few hours. However, their absorption can be affected by factors such as food, with some inhibitor needing to be taken on an empty stomach to optimize absorption. For example, montelukast can be taken with or without food, while zafirlukast should be taken at least one hour before or two hours after meals 

* Distribution * leukotrienes inhibitor distribute throughout the body via the blood stream after absorption. 

They can penetrate various tissues, including lung tissue, where they exert their pharmacological effects by blocking the action of leukotrienes these inhibitor may also cross the blood brain barrier to some extent, influencing their potential effects on CNS. Additionally, they can bind to plasma proteins, such as albumin, which can affect their distribution and availability for action

-* metabolism *: leukotrienes inhibitor undergo hepatic metabolism, primarily through the cytochrome p450(CYP) enzyme system in the  liver..for example, montelukas  is metabolized by CYP2C8 and CYP2C9.CYP2C9.zileuton is unique in that it inhibit the enzyme 5- lipoxygenase,thereby preventing the formation of leukotrienes rather than being metabolized itself. Metabolism of leukotrienes inhibitor ultimately lead to the formation of inactive metabolites which are then eliminated from the body ,mainly through the urine

-*excreation * leukotrienes inhibitor undergo hepatic metabolism and are excreted mainly via the kidneykidneys

After metabolism,the metabolites are eliminated primarily through urine .they exact excretion pathways may vary depending on the specific inhibitor. 

Contraindications and precautions 

Leukotriene inhibitor are generally well tolerated, but there are some contraindications and precautions to consider:

1.* allergic reaction * patients with a known hypersensitivity to leukotrienes inhibitor should avoid them

2.* liver dysfunction *: caution is divided in patient  with pre- existing liver condition, as leukotrienes inhibitor may affect liver function 

3.*pregnancy and breastfeeding *:the saftey of leukotrienes inhibitor during pregnancy and breastfeeding is not well established, so they should be used with caution in these populations 

4.* children *while leukotrienes inhibitor are commoncommonly used in children, dosages may need  adjustments based on age and weight 

5.* interaction *: they may interact with other medications, so it,s essential to consult health care professionals before starting any new medication regimen. 

As with any medication, it,s crucial to discuss potential risks and benefits with health care provider before starting treatment of leukotrienes inhibitor. 

References 

https://my.clevelandclinic.org/health/drugs/14278-leukotriene-modifiers

https://www.rxlist.com/leukotriene_receptor_antagonists/drug-class.htm