Leukotriene receptor antagonists Flashcards
What is the general action of leukotriene receptor antagonists (LTRA)?
Prevent leukotriene synthesis or activity by blocking it from binding to its receptors
What are leukotrienes?
Released by mast cells during an asthma attack
Cause bronchoconstriction
In chronic, more severe asthma case general bronchial hyperractivity is largely caused by eosinophils which are attracted to bronchioles by leukotrienes and also release leukotrienes
Which molecules is leukotriene derived from?
Arachnoid acid
A precursor of prostaglandins
Name the two main LTRA that you should know?
Montelukast
Zafirlukast
What is the typical dose of montelukast in adults and children aged 15 years and older?
10mg OD PO
What is the typical dose of montelukast in children aged 6-14 years?
5mg OD PO
What is the typical dose of montelukast in children aged 6 months to 5 years?
4mg OD PO
What is the typical dose of zafirlukast in adults and children aged 12 years and older?
20mg BD PO
Can zafirlukast be used in children younger than 12?
Not licensed for use in younger children
What are the contraindications for montelukast?
No contraindications or cautions
What are the contraindications for zafirlukast?
Hepatic impairment or cirrhosis
Children under 12 until safety information is available
What are the cautions for zafirlukast?
People with mild renal impairment
What are the adverse effects of montelukast?
Arthralgia
Bruising
Dyspepsia
Excessive thirst
GI upset
Headache
Hyperkinesia (in young children)
Infections
Malaise
Myalgia
Nose bleeds
Nervous system disorders (e.g., dizziness, drowsiness, paraesthesia/hypoesthesia, seizure)
Oedema
Psychiatric disorders
Rash
Thrombocytopenia
Tic
Enuresis in children
What are the psychiatric disorders that can be adverse effects of montelukast?
Dream abnormalities inc. nightmares
Insomnia
Somnambulism
Anxiety
Agitation inc. aggressive behaviour or hostility
Depression
Psychomotor hyperactivity inc. irritability, restlessness and tremor
What are the adverse effects of zafirlukast?
Arthralgia
Bruising
GI upset
Hepatic disorder - person or their parent/carer should be advised to alert for signs and symptoms of this e.g., persistent nausea, vomiting, malaise or jaundice and to seek medical attention if they develop
Hyperbilirubinaemia
Infections
Insomnia
Malaise
Muscle cramps
Myalgia
Rash
What are the very rare adverse effects from LTRA? What should done if a person develops them?
Systemic eosinophilia
Eosinophilic pneumonia
Clinical features of systemic vasculitis consistent with Churg-Strauss syndrome
LTRA should be stopped if patient develops any of this
What are the important drug interactions for montelukast?
Phenytoin, phenobarbital and rifampicin - CYP 3A4, 2C8, 2C9 inducers = reduced levels of montelukast
What are the important drug interactions for zafirlukast?
Aspirin 650 mg QDS + zafirlukast = ~ 45% increased zafirlukast levels
Warfarin + zafirlukast = 35% increase in max prothrombin time
Theophylline + zafirlukast = increased theophylline levels (rare) - monitor theophylline levels in patients on both drugs
Erythromycin + zafirlukast = 40% decreased plasma level of zarfirlukast
What are the pharmacokinetics of montelukast?
Oral bioavailability = 64%
Protein binding = > 99%
Half-life = 2.7 - 5.5 hours
Metabolism = hepatic via CYP 3A4, 2C8, 2C9
Excretion = exclusively bile and faeces
What are the pharmacokinetics of zafirlukast?
Oral bioavailability = ?
Protein binding = 99%
Half-life = 10 hours
Metabolism = hepatic
Excretion = Faeces
Sources
https://cks.nice.org.uk/topics/asthma/prescribing-information/leukotriene-receptor-antagonists/
https://go.drugbank.com/categories/DBCAT000910 (LTRA)
https://www.bmj.com/content/319/7202/90.1
https://go.drugbank.com/drugs/DB00549 (Zafirlukast)
https://go.drugbank.com/drugs/DB00471 (Montelukast)
