Cystic Fibrosis 2- MJ

Question 1

What are the 10 ADEs of inhaled Aztreonam? (3 were in red)

Answer 1

1. *Fever (MC in children)

2. *Cough

3. *Rash

4. Nasal congestion
5. Pharyngeal pain
6. Wheezing
7. Bronchospasm
8. Chest discomfort
9. Abd pain
10. Vomiting

Question 2

Do not repeat aztreonam ______ days after completion

Answer 2

28 days

(to provide continuous coverage: could do 28d Aztreonam then 28d Tobramycin then 28d Aztreonam….)

Question 3

The following is the mechanism of which drug?

–Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes

–decreased formation of prostaglandin precursors

Answer 3

Ibuprofen

Question 4

Which drug?

–antipyretic

–analgesic

–anti-inflammatory properties

Answer 4

Ibuprofen

Question 5

What is the minimum age that you can give ibuprofen?

Answer 5

must be > 6 months

Question 6

Which patients is high-dose ibuprofen indicated for?

Answer 6

Patients under 18y/o w/ FEV >60%

(insufficient evidence for ppl under 18y/o)

Question 7

Which med?

• Less decline in pulmonary function
• Able to maintain weight and had less hospital admissions
• Benefits exceed the risks of GI complications and nephrotoxicity
• < 5% of CF patients on this regimen

Answer 7

High-dose Ibprofen

Question 8

What are requirements to obtain a specific therapeutic level of ibuprofen?

Answer 8

Frequent blood draws for pharmacokinetic monitoring

• Target peak plasma concentration between 50-100 μg/ml

Question 9

What are the 6 main ADEs of Ibuprofen?

Answer 9

1. *Edema

2. *Headache

3. *Fluid retention

4. *Epigastric pain

5. *GI bleed

6. *Tinnitus

(also dyspepsia and flatulance can occur)

Question 10

Interactions of which CFTR modulator?

–Substrate of CYP3A4 (major);

–Inhibits CYP2C8 (weak), CYP2C9 (weak), CYP3A4 (weak), P-glycoprotein

Answer 10

Ivacaftor

Question 11

The following are the main ADEs of which med?

• *Headache
• *Abdominal pain
• *Nasopharyngitis
• *Hyperglycemia
• _*Transaminases increased_
• *Arthralgia

“HAN HAT”

Answer 11

Ivacaftor

(a CFTR modulator)

Question 12

MOA of which med?

–Potentiates epithelial cell chloride ion transport of defective (G551D mutant) cell-surface CFTR protein

–improves regulation of salt and water absorption and secretion in various tissues (eg, lung, gastrointestinal tract).

Answer 12

Ivacaftor

(a CFTR modulator)

Question 13

What is the con of Ivacaftor?

Answer 13

Very expensive (~300,000/year)

Question 14

MOA of the combination of which 2 drugs?

1. ________=
   
   • F508del mutation interferes with CFTR protein folding and channel gating activity
   • partially corrects the CFTR misfolding
2. ________=
   
   • Improves the gating abnormality

Answer 14

1. Lumacaftor

2. Ivacaftor

Question 15

People w/ 2 copies of the ______ mutation represent the largest group of people w/ CF

Answer 15

F508del

Question 16

Data from 2 phase III studies on people w/ 2 copies of the F508del mutation showed statistically significant improvements in lung function when pts were treated with what?

Answer 16

Lumacaftor/Ivacaftor

Question 17

Data from 2 phase III studies on people w/ 2 copies of the F508del mutation showed that patients who took Lumacaftor/ivacaftor also experienced reductions in _____ and improvements in _______*

(in addition to i_mprovements in lung function)_

Answer 17

_*reductions in pulmonary exacerbations*_

*Improvements in _BMI*_

Question 18

>10% of people taking Lumacaftor/Ivacaftor experience what main ADE? (the only red one)

Answer 18

Nasopharyngitis

(Also nausea, diarrhea, chest discomfort and dyspnea)

Question 19

What are the 6 main ADEs of Lumacaftor/Ivacaftor? (the ones in red)

Answer 19

1. Nasopharyngitis

2. Fatigue

3. Menstrual disease (amenorrhea, dysmennorhea, etc)

4. Increased creatinine phosphokinase

5. URI

6. Rhinorrhea

“FIN RUM”

Question 20

Tezacaftor/Ivacaftor is combination therapy used to tx CF…. What is Tezacaftor designed to do?

Answer 20

Tezacaftor is designed to move the defective CFTR protein to the proper place in the airway cell surface (similar to Lumacaftor)

Question 21

Tezacaftor/Ivacaftor is combination therapy used to tx CF…. What is Ivacaftor designed to do?

Answer 21

Ivacaftor helps facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell

Question 22

Who is Tezacaftor/Ivacaftor combination therapy approved for? (2 different types of individuals)

Answer 22

1. individuals >12y/o with 2 copies of 508del (MC CF mutation)
2. individuals who have a single copy of one of 26 specified mutations – regardless of their other mutation

Question 23

Tezacaftor/Ivacaftor (Symdeko) should be taken with what type of food?

Answer 23

fat-containing food

Question 24

The dose of Tezacaftor/Ivacaftor should be reduced in patients with moderate and severe _______

Answer 24

hepatic impairment

Question 25

The dose of Tezacaftor/Ivacaftor should be reduced when it is co-administered with drugs that are moderate or strong _______ inhibitors

Answer 25

_CYP3A_

Question 26

Concomitant use of Tezacaftor/Ivacaftor with strong CYP3A inducers (e.g., rifampin, St. John’s wort) may substantially **decrease the therapeutic effectiveness** of \_\_\_\_\_\_\_\_\_\_thus co-administration is not recommended

Answer 26

Tezacaftor

Question 27

Avoid food containing grapefruit or Seville oranges when giving what med?

Answer 27

Tezacaftor/Ivacaftor

Question 28

What are the 4 common adverse drug rxns of Tezacaftor/Ivacaftor?

Answer 28

1. HA 2. Nausea 3. Sinus Congestion 4. Dizziness "Some Headaches Never Die"

Question 29

How should you monitor a patient on Tezacaftor/Ivacaftor?

Answer 29

**ALT and AST prior** to initiating treatment and **every 3 months** during the first year of treatment, annually thereafter

Question 30

Monitoring parameters for Tezacaftor/Ivacaftor: When should you discontinue treatment?

Answer 30

**If significant elevations of transaminases** (ALT or AST \>5 x upper limit of normal (ULN), or ALT or AST \>3 x ULN with bilirubin \>2 x ULN)

Question 31

Why is baseline and follow-up examinations recommended in pediatric patients prior to initiating treatment with Tezacaftor/Ivacaftor?

Answer 31

Cataracts: Non-congenital lens opacities/cataracts have been reported in pediatric patients

Question 32

Which 2 vaccines should be given to patients with CF?

Answer 32

_**1. influenza vaccine (anyone older than 6mo)\*\***_ _**2. Pneumococcal vaccine\*\***_ 3. Palivizumab

Question 33

The following describes which recommended vaccine for patients w/ CF? 1. Monoclonal antibody against respiratory syncytial virus 1. Children younger than 24 months of age 2. Not a firm recommendation

Answer 33

Palivizumab

Question 34

When should a CF patient be given oxygen and BiPAP?

Answer 34

Oxygen: progressive CF accompanied by worsening hypoxemia BiPAP: advanced CF and hypercapnia

Question 35

According to the International Society for Heart and Lung Transplantation, when should a pt be referred to a transplant center? (4 things)

Answer 35

1. **FEV \<30% predicted** or a r**apid decline in FEV1,** particularly in young female patients 2. Increasing freq. of **exacerbations requiring abx** 3. Refractory/recurrent **pneumothorax** 4. Recurrent **hemoptysis** not controlled by emobilization

Question 36

What 4 GI treatments are used in CF?

Answer 36

1. **GERD** tx 2. **Pancreatic enzyme** supplementation 3. **Vitamin** supplementation 4. Prevention and tx of **cirrhosis**

Question 37

What disease is 6-8x more common in CF children than those w/o CF? How do you tx this?

Answer 37

* GERD * Proton Pump Inhibitors

Question 38

Which group of meds? ## Footnote –act by irreversibly **blocking the hydrogen/potassium adenosine triphosphatase enzyme system** (the H+/K+ ATPase, or more commonly, the gastric proton pump) of the gastric parietal cells. –The **proton pump** is the terminal stage in gastric acid secretion, being directly responsible for **secreting H+ ions into the gastric lumen.**

Answer 38

Proton Pump Inhibitors

Question 39

The following are apart of which group of meds and what do they treat? ("-prazole") 1. Omeprazole 2. Lansoprazole 3. Dexlansoprazole 4. Esomeprazole 5. Pantoprazole 6. Rabeprazole

Answer 39

Proton Pump Inhibitors Used to tx GERD

Question 40

What are the 5 main ADEs of Omeprazole? (the ones in red)

Answer 40

**1. Acid regurgitation** **2. Constipation** **3. Back pain** **4. Weakness\*\*** **5. Cough** "AW CBC"

Question 41

What is the "backbone of GI therapy" in patients w/ CF?

Answer 41

pancreatic enzyme supplementation

Question 42

**Dosage of Pancreatic enzyme supplementation is calculated using ______ units**

Answer 42

_**\*\*Lipase** units_

Question 43

ADEs of pancreatic enzyme supplementation: Prolonged contact of the enzyme supplements with **oral mucosa may cause \_\_\_\_\_\_,** especially with the powdered form

Answer 43

_**\*ulcers\***_

Question 44

Which med? _**–Administer with food (eg, applesauce), even in infants\***_ _**–Mouth should be rinsed after administration, particularly in infants\***_

Answer 44

Pancreatic Enzyme Supplementation

Question 45

**\*Excessive doses of pancreatic enzymes can cause what?\***

Answer 45

_**\*\*Fibrosing colonopathy**_ _**(characterized by inflammation and strictures)\*\***_ (risk reduced by limiting dose to \< 2500 lipase units/kg)

Question 46

* Pancreatic insufficiency and CF related liver dz lead to ____ \_\_\_\_\_\_\_ * This predisposes to what?

Answer 46

* **_Fat malabsorption_** * predisposes to deficiencies **_(Vitamins A, D, E, K)_**

Question 47

Decreased calcium absorption and intake in CF can lead to what?

Answer 47

Bone loss

Question 48

Dosing of Vitamin A, D, E, and K supplementation is based on what?

Answer 48

age

Question 49

The following describes what med, which is used to tx CF- related liver disease: ## Footnote –Decreases the cholesterol content of bile and bile stones –Mechanism is reduction of the secretion of cholesterol from the liver and the fractional reabsorption of cholesterol by the intestines

Answer 49

Ursodeoxycholic acid: _Gallstone dissolution agent_

Question 50

What are the 4 main ADEs of Ursodeoxycholic acid (Gallstone dissolution agent) (the ones that are blue on the slide)

Answer 50

**1. Alopecia** **2. Leukopenia** **3. Thrombocytopenia** **4. Serum creatinine increased** "LAST"