Respiratory: Leukotriene Modifiers Flashcards
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Basic Understanding:
What theory were Leukotriene Modifiers developed under?
What are medications that modify leukotrienes referred to as?
What does LTRAs stand for?
What type of substance are Leukotrienes?
Where are Leukotrienes produced?
What do Leukotrienes do?
What are some effects that Leukotrienes contribute to the inflammatory process?
What are LTRAs used to treat?
That cysteinyl leukotrienes play a significant role in the chronic inflammation associated with asthma and allergy.
- LTRAs OR
- 5-lipoxygenase pathway inhibitor
Leukotriene-receptor agonists
Inflammatory mediators
In leukocytes
Induce numerous effects that contribute to the inflammatory process
- Smooth muscle contractility
- Neutrophil aggregation, degranulation and chemotaxis
- Vascular permeability
- On lymphocytes?
Asthma
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Examples:
DO NOT NEED TO KNOW FOR QUIZ
What are the LTRAs that are available?
DO NOT NEED TO KNOW FOR QUIZ
What is the 5-lipoxygenase pathway inhibitor that is available?
Which Leukotriene Modifiers do we need to know for the quiz?
INN/Generic Names:
zafirlukast
montelukast
Brand Names:
Accolate
Singulair
INN/Generic Name:
zileuton
Brand Name:
Zyflo
INN/Generic Names:
montelukast
Brand Names:
Singulair
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers:
Pharmacodynamics:
Is Montelukast selective or non selective?
What is the mechanism of action of Montelukast?
What does CysLT1 stand for?
How does Montelukast inhibit the CysLT1 receptor?
Is Montelukast selective or non selective?
What does Montelukast selectively bind to?
Does Montelukast bind to CysLT1 receptors with high or low affinity?
What is being blocked from reaching the CysLT1 receptor site when Montelukast binds to them?
What is an LTD4?
What family does LTD4 belong to?
How does blocking LTD4 help in treating asthma and allergy?
How do Cysteinyl leukotrienes contribute to the pathophysiology of asthma and allergy?
In addition to many other sites what is one area of the body that leukotrienes are released from?
When are leukotrienes are released from the nasal cavity?
What does the release of leukotrienes from the nasal cavity during allergen exposure indicate?
What is rhinitis?
Selective
It inhibits the CysLT1 receptor
Cysteinyl leukotriene receptor 1
It binds to the CysLT1 receptor
Selective
CysLT1 receptors
High affinity
LTD4
A leukotrine
Cysteinyl leukotrienes
Cysteinyl leukotrienes contribute to the pathophysiology of asthma and allergy
The contribute to:
- Airway edema
- Smooth muscle constriction
- Cell changes in the inflammatory process
Nasal mucosa
During allergen exposure
That Montelukast may inhibit symptoms of allergic rhinitis
Stuffy nose
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacokinetics: Absorption and Distribution:
How is Montelukast administered?
What different forms of oral medication is Montelukast available in?
Is Montelukast absorbed slowly or rapidly?
How long after administration do the film coated tablets of Montelukast take to achieve their peak plasma concentration?
How long after administration do the chewable tablets of Montelukast take to achieve their peak plasma concentration?
What percentage of Montelukast is protein bound?
Is there distribution of Montelukast across the blood–brain barrier?
Is there distribution of Montelukast across the placenta?
Is there excretion of Montelukast in breast milk?
Why is it unknown if Montelukast is excreted in breast milk or distributed across the blood–brain barrier and placenta?
Has there been any studies done on animals to determine if there is distribution of Montelukast across their the blood–brain barrier, the placenta, or excretion in breastmilk when taking the medication?
If so what animal?
In the study done on rats was it determined if there was distribution of Montelukast across their blood–brain barrier?
If so, how much?
In the study done on rats was it determined if there was distribution of Montelukast across their placenta?
In the study done on rats was it determined if there was excretion of Montelukast into their breast milk?
Orally
- Film coated tablet
- Chewable tablet
Rapidly
3 to 4 hrs
2 to 2.5 hrs
> 99%
It is unknown
It is unknown
It is unknown
There are no human studies available
- Yes
- Rats
- Yes
- Minimal Distribution
Yes
Yes
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacokinetics: Metabolism and Excretion:
What is the bioavailability of Montelukast?
How long after administration does it take for Montelukast to achieve it’s half-life?
Where is Montelukast metabolized?
Is it metabolized well or poorly?
What percentage of metabolites are detected in plasma after Montelukast is metabolized by the Liver?
What substances are involved in the metabolism of Montelukast?
Which liver enzymes are involved in the metabolism of Montelukast?
How is Montelukast excreted?
How are Montelukast’s metabolites excreted?
What percentage of Montelukast and it’s metabolites are excreted in bile?
What percentage of Montelukast and it’s metabolites are excreted in urine?
64%
2.7 to 5.5 hrs
In the Liver
Very well
None
Liver enzymes
- CYP3A4
- CYP2C9
Bile and urine
Bile and urine
> 99.8%
< 0.2% excreted in the urine
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacotherapeutics: Precautions and Contraindications:
Are leukotriene modifiers used for primary treatment of an acute asthma attack?
What patients is Montelukast contraindicated in?
In which patients are the chewable tablets of Montelukast contraindicated?
What is phenylketonuria?
In patients with phenylketonuria; what does the inability to breakdown phenylalanine cause to happen?
In patients with phenylketonuria; what could a buildup of phenylalanine lead to?
Why are the chewable tablets of Montelukast contraindicated in patients with phenylketonuria?
Should Montelukast be avoided in patients with hepatic insufficiency?
Why is Montelukast safe to use in patients with mild to moderate hepatic insufficiency?
Montelukast should not be abruptly substituted for which medications?
Caution is advised when administering Montelukast in patients who are being treated with steroids in which manner?
If systemic corticosteroids are being reduced
What type of event has been reported to occur in patients taking Montelukast?
What are the neuropsychiatric events that have been reported to occur in patients taking Montelukast?
Which disorder found more frequently in Montelukast than in placebo in the original clinical trials?
What does the FDA recommend practitioners do regarding the reports of neuropsychiatric events occurring with use of Montelukast?
What pregnancy category is Montelukast?
Can Montelukast be prescribed for children?
What would Montelukast be prescribed to a child to treat?
Caution should be used in prescribing Montelukast to which population of patients?
Why should caution be used when prescribing Montelukast to lactating women?
PARAGRAPH 1
No
Hypersensitivity to any of the components of Montelukast
Patients with phenylketonuria
A disorder which causes the patient to be unable to breakdown phenylalanine.
Phenylalanine builds up in the body
- Damage to the CNS
- Brain damage
The tables contain phenylalanine
- Mild to moderate insufficiency: no
- Severe insufficiency: yes
The elimination is only slightly prolonged in these patients
When systemic corticosteroids are reduced being reduced
Neuropsychiatric events
- Agitation
- Aggression
- Anxiousness
- Dream abnormalities
- Hallucinations
- Depression
- Insomnia
- Irritability
- Restlessness
- Suicidal thinking/behavior
- Suicide
- Tremor
Sleep disorders
- Inform Patients of events
- Discontinue if patient develops neuropsychiatric symptoms or problems
Pregnancy Category B
Children 12 months +
Chronic asthma
Lactating women
The effects on infants are unknown
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacotherapeutics: Adverse Drug Reactions:
What are the adverse reactions of Montelukast?
None
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacotherapeutics: Drug Interactions:
Patients should be monitored closely if they are taking medications that are metabolized by what substances?
What medications are metabolized by CYP450 isoenzymes and therefore should be monitored closely?
What is a possible effect when Montelukast is taken with Phenobarbital?
What is a possible effect when Montelukast is taken with Rifampin?
- CYP450 isoenzymes
- Phenobarbital
- Rifampin
Decreases area under curve (AUC) of
dose by about 40%
Decreased metabolism of Montelukast
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacotherapeutics: Rational Drug Selection:
What is drug selection for Montelukast based on?
When choosing a Leukotriene Modifier to prescribe it is important to remember that a which age group can only be prescribed Montelukast?
How many times a day is Montelukast dosed?
Should Montelukast be taken with food or at meals?
Do other Leukotriene Modifiers offer once a day dosing that without need to administer with meals?
Does once a day dosing without the need to administer with meals make Montelukast more convenient than other Leukotriene Modifiers?
How much does a a 30-day supply (30 tablets) of Singulair cost?
How much does a 30-day supply of generic Montelukast cost?
How does the cost of a 30-day supply of Singulair compare to the cost of a 30-day supply of Accolate?
How does the cost of a 30-day supply of generic Montelukast compare to a a 30-day supply of generic zafirlukast?
How does the cost of a 30-day supply of Singulair compare to the cost of a a 30-day supply of zileuton (Zyflo)?
- Age
- Convenience in dosing
Under 5 yrs
1 time
No, it does not matter
No
Yes
$170
$40
Singulair costs 35 dollars MORE than Accolate
Generic Montelukast costs 23 dollars MORE than generic zafirlukast
Singulair costs 390 dollars LESS than Zyflo
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacotherapeutics: Monitoring
What type of changes should the practitioner monitor for in
patients taking Montelukast?
What respiratory related changes should the practitioner monitor for in patients taking Montelukast?
Why do practitioners need to monitor their patients on Montelukast for: changes in asthmatic symptoms, bronchodilator use, and pulmonary function?
What neuropsychiatric related changes should the practitioner monitor for in patients taking Montelukast?
- Respiratory
- Neuropsychiatric
- Improvement or worsening of asthmatic symptoms
- Bronchodilator use
- Pulmonary function
To determine the efficacy of the medication
Symptoms of:
- Depression
- Behavior Change
Types of Respiratory Drugs:
Bronchodilators: Leukotriene Modifiers
Pharmacotherapeutics: Patient Education:
Table 17-6 presents the available dosage forms.
PARAGRAPH 1
Patient education focuses on proper dosing of the medication, adverse reactions, and the general asthma management plan. The incorporation of the leukotriene medications into the asthma treatment plan is covered in Chapter 31.
PARAGRAPH 2
Administration
The patient must take the medication as prescribed, even if symptom-free. These medications are not for acute episodes of asthma. Patients must continue to use the bronchodilator inhaler for acute episodes of bronchospasm. They are not to decrease or discontinue any of their other asthma medications unless instructed to do so by their health-care provider.
PARAGRAPH 3
Zafirlukast must be taken on an empty stomach, whereas montelukast may be taken without regard to meals.
PARAGRAPH 4
Pregnant or nursing women should not take these
medications.
PARAGRAPH 5
Patients should be aware of significant drug interactions with leukotriene modifiers because of the way these drugs are metabolized by the liver. Patients should be advised to discuss with their health-care provider any new medications that are prescribed or discontinued.
PARAGRAPH 6
Adverse Reactions
Patients and parents of pediatric patients should be informed of the potential for neuropsychiatric events, including agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor. Any new neuropsychiatric symptoms should be reported to the provider.
PARAGRAPH 7
Lifestyle Management
Lifestyle management issues related to the disease process should be discussed. They often include the following:
- The patient needs to self-monitor respiratory status
with a peak flowmeter to determine the effectiveness of the medication prescribed. - The patient should avoid or quit smoking.
- The patient should avoid environmental triggers for
asthma at home, work, and school.
Table 17-6 presents the available dosage forms.
