Cystic fibrosis pharmacology

Question 1

What is the action and indication of Ivacaftor ?

Answer 1

*It is a CFTR potentiator. It increases the time the activated CFTR channel remains open, enhancing chloride ion transport in those with class III gene mutations (about 5% of those with cystic fibrosis).
* It also improves lung function, reduces exacerbations of lung disease and promotes weight gain.

Question 2

How does the combination of Tezacator and Ivacaftor work and when they are indicated?

Answer 2

Tezacator is a CFTR correcter, it acts by increasing the translocation of CFTR protein to the cell surface. When it is combined with Ivacaftor in people with Class II mutation( the most common F508del mutation) they together improves lung function, reduce exacerbations and improves QL in patients with homozygous F505del mutation and moderate effect in heterozygous F508del mutations.

Question 3

What is the pharmacokinetics of Tezacator and Ivacafactor ?

Answer 3

They are activated by the CYP450- 3A4/5 and the metabolites are excreted in faeces. They have a 1/2 life of 15 to 30 Hrs.

Question 4

why to manage infection and cross infection in cystic fibrosis rapidly ?

Answer 4

Rapid and intensive treatment of clinical infection slows the decline in lung function and is the main reason for the prolongation of life expectancy in recent years.

Question 5

What are the most common lung pathogens in very young cystic fibrosis patients?

Answer 5

Staphylococcus aureus (50%), Haemophilus influenzae (30%) and Pseudomonas aeruginosa (20%)

Question 6

How to treat Stap aureus in the first three years of the life of an infant with CF?

Answer 6

Prophylactic antistaphylococcal therapy with flucloxacillin is usually given to reduce exacerbations of lung disease.

Question 7

How to treat P. aeruginosa which is the common pathogen in adolescent CF patients ?

Answer 7

Regular treatment with inhaled nebulised tobramycin or nebulised colistimethate sodium combined with oral ciprofloxacin. exacerbations require oral therapy.

Question 8

How to treat malabsorption in CF ?

Answer 8

• Nutritional supplementation.
• Pancreatic enzyme supplements (Pancreatin) should be done either as enteric-coated formulations or 1 hr after H2 inhibitor such as Ranitidine.