Resp: LTRA, Theophylline Flashcards
What is LTRA (Leukotriene Receptor Antagonists)?
Asthma:
Adults:
- Add-on therapy for asthma, where symptoms are not adequately controlled by ICS and LABA
Children ages 5-12years:
- Alternative to LABAs as an add-on therapy where ICS are insufficient to control asthma symptoms
Children <5years:
- 1ST LINE preventative therapy for asthma who are unable to take an ICS
MOA of LTRA (Leukotriene Receptor Antagonists)?
In asthma, leukotrienes are produced by mast cells and eosinophils.
Leukotrienes activate G protein-coupled leukotriene receptor CysLT1.
→ this leads to inflammation and bronchoconstriction.
So LTRA (antagonists) reduce this inflammation and bronchoconstriction in asthma by blocking the CysLT1 receptor and damping down the inflammatory cascade.
Adverse effects of LTRA (Leukotriene Receptor Antagonists)?
Common, mild SEs:
- Headache
- Abdominal pain
Increased rate of URTI
Uncommon:
- Hyperactivity
- Reduced ability to concentrate
- Churg-Strauss syndrome (eosinophilic autoimmune disorder)
Warnings of LTRA (Leukotriene Receptor Antagonists)?
Should NOT be prescribed in asthma unless if is UNCONTROLLED WITH ICS and LABA.
May use in pregnancy if LTRA has lead to improvements in asthma symptoms compared to other tx.
Interactions of LTRA (Leukotriene Receptor Antagonists)?
None significant.
Monitoring of LTRA (Leukotriene Receptor Antagonists)?
Efficacy monitored by:
- symptom diary
- serial measurement of PEFR
Pt education of LTRA (Leukotriene Receptor Antagonists)?
Aim to make their airways relax and improve breathing and control their disease.
LTRA does not help in an acute attack of breathlessness.
→ so seek medical advice in an event of exacerbation.
Ensure they take the LTRA tablet with the inhalers because they work in different ways to help control asthma.
Report any worsening of symptoms, e.g. rash, numbness or weakness -uncommon SEs but serious adverse effect.
Examples of LTRA (Leukotriene Receptor Antagonists)?
montelukast
Indications of theophylline?
Reversible airway obstruction
Severe acute asthma
Chronic asthma
COPD
MOA of theophylline?
Competitively inhibits type III and type IV phosphodiesterase (PDE).
→ this is unable to breakdown cAMP in smooth muscle cells.
→ results in bronchodilation.
Also binds to adenosine A2B receptors and BLOCKS adenosine mediated bronchoconstriction.
In inflammatory states, theophylline activates histone deacetylease.
→ prevents transcription of inflammatory genes that require histone acetylation.
Adverse effects of theophylline?
- Anxiety
- Arrhythmias
- Diarrhoea
- Dizziness
- GI discomfort
- GORD
- Headache
- Palpitations
- Seizure
- Skin reactions
- Sleep disorders
- Tremor
- Urinary disorders
Warnings of theophylline?
Avoid in pts with:
- porphyria
- hypersensitivity to xanthines
- infants <6months of age
- children receiving ephedrine
Caution in pts with:
- CVB, including cardiac arrhythmias
- Hepatic impairment
- Hypokalaemia risk
- HTN
- Hyperthyroidism
- Peptic ulcers
- Epilepsy
Interactions of theophylline?
Avoid OTC cough and decongestant that contain theophylline.
Hypokalaemia caused by interaction with:
- β2-agonists
- corticosteroids
- diuretics
Fluvoxamine can raise plasma level of theophylline.
Plasma levels of theophylline can be altered by concomitant use with liver enzyme-inhibiting drugs:
- verapamil
- clarithromycin
- fluconazole
- allopurinol
Can affect excretion of lithium.
Smoking can increase theophylline clearance, so give higher dose. If stop smoking, adjust dose.
Monitoring of theophylline?
Before starting tx, check for:
- U&Es (potassium levels)
- LFTs
Check drug plasma levels:
- 5days after starting tx
- routinely every 6-12months
- at least 3 days after any dose adjustments
