CF - Rever

What is Cystic Fibrosis? (CF) What are some misconceptions?

mutation of the CFTR gene, which is an autosomal recessive gene inherited by both parents. It is a progressive disease that fx the exocrine gland. Onset is varied.

• misconceptions: contagious, always diagnosed at birth, only a pediatric disease

What are the 5 different types of CF? (I-V)

1. no CFTR gene

2. misfolding → does not reach cell surface

3. channel doesn’t open properly

4. function is faulty

5. not enough quantity

What is the general clinical presentation of CF?

1. thick and sticky mucus

2. most common in Europeans > hispanics, blacks

3. salty tasting skin

4. persistent cough w phlegm

5. frequent lung function

6. wheeze/SOB

7. poor growth/wt gain

8. greasy/bulky stools

9. nasal polyps + infections

10. fingers/toes clubbing

Describe the absorption of CF

1. Increased GI acidity due to low duodenal pH and ovorectal transit time

2. bile acid dysfunction

describe the distribution of CF?

1. hypoalbuminemia decreases protein binding

2. less adipose tissue and lower body mass

describe the metabolism and execretion of CF

M: increased CYP2C8 and CYP1A2 clearance

E: increased renal clearance

Newborn Screening (NBS) is a mandatory test done within the first few days after birth. What does it check for?

heel prick blood draw and placed on Guthrie car to check immunoreactive trypsinogen (IRT)

• high IRT = CF or bc baby is preterm

When is the sweat test indicated? What indicates CF?

positive NBS; measure chloride in sweat by using pilocarpine + elecrical stimulation

• ≤ 29mmol/L = unlikely

• 30-59 = need more testing

• ≥ 60mmol/L = CF

patient presents with cough w/wo sputum/phlegm, wheezing, repeat infections, SOB, and has difficulty exercising. In their lower respiratory tract they have an infection, inflammation, and damage. And in upper respiratory tract they may have sinusitis and nasal polyps. What tests can you do to diagnose the patient?

chest xray, PFTs, sputum culture, blood work

What are complications in the respiratory system for a CF patient?

bronchiectasis, pneumothorax, hemptysis, allergic bronchopium aspergillus (ABPA), infection (pseudomonas aeruginosa), pulmonary execerbations, lung transplant

If a patient with CF has a lung infection, which pathogens should you cover in ABX?

pseudomonas aeruginosa

If patient has a pulmonary exacerbations, what should you give the patient?

continue chronic therapies and ACT

When is a patient indicated for a lung transplant?

Advanced lung disease, early referral INC survival

What is the MOA for CF on the respiratory system?

thick mucus prevents cilia from cleaning dust/bacteria from lungs and blocks the airways

What is the MOA of CF in the GI system?

1. weak esophageal sphincter

2. slow motility in stomach, intestine, colon

3. thick secretions prevent nutrient absorption

CF pt presents with N/V/C, bloating/gas, ab pain, distention, heart burn, acid reflux, and bacterial overgrowth. What are the the potential complications if this isn’t treated?

1. poor nutrition

2. GERD

3. meconium ileus

4. distal intestinal obstruction syndrome (DIOS)

5. rectal prolapse

6. fibrosing colonopathy

7. intussusception

8. appendicitis

9. small intestine bacterial overgrwoth (SIBO)

10. c.diff colitis

11. colorectal cancer

What is the MOA of CF on the pancreatic system?

thick mucus blocks pancreatic ducts which prevents enzymes from secreting to breakdown foods. Leading to pancreas scarring.

pt presents with ab distention, frequent bulky, foul/smelling oily stools, and stools that float to stick to the bowl. What test should you give them and what does this indicate?

1. fecal elastase <200mcg = pancreatic insufficiency

2. may be pancreatic insufficiency or pancreatitis (if sufficient)

what are the complications of pancreatic insufficiency/pancreatitis in an untreated CF pt?

1. poor growth

2. malnutrition

3. fat soluble vitamin def (ADEK)

4. bone disease

5. CF related diabetes (B cell dysfunction)

If patient has CF-related diabetes (CFRD), what is used for screening and what is the treatment?

OGTT (not HbA1c); insulin

What is the MOA of CF on the hepatobiliary system?

CFTR is on the apical membrane of biliary epithelium instead of the hepatocyte which creates a thick bile. This leads to biliary obstruction, inflammation, and biliary fibrosis

pt presents with INC AST, ALT, ALP, GGT, bilirubin; DEC platelets and albumin. Has liver stiffness, an abnormal ultrasound/MRI, fibrosis, steatosis, cholestasis. What might the patient have?

CF hepatobiliary involvement (CFHBI) or advanced CF liver disease (ACFLD) like cirrhosis, non-cirrotic portal HTN

What are some complications of a CF patient with a compromised hepatobiliary system?

1. portal HTN

2. variceal bleeding,

3. hepato pulmonary syndrome

4. porto pulmonary HTN

5. cirrhosis

6. HF

What tests should you use to screen for CFHBI? What is the treatment?

1. Liver function tests and abdominal US

2. treatment: CFTR modulators (?), liver transplant

3. DONT GIVE URSODIAL

What is the MOA for CF on the reproductive system (m/f)

1. male: congenital bilateral absence of vas deferens (CBAVD) → sperm can’t reach semen

2. female: thick cervical mucus → sperm cant penetrate

pt has infertility, delayed puberty, irregular ovulation due to CF. What is the treatment?

IVF and CFTR modulator to increase pregnancy

What is the MOA for CF on the skeletal system?

DEC osteoblast, INC osteoclast activity

pt presents with low bone mineral density (BMD), frequent fractures, and kyphosis. What are some contributing factors to this?

1. malabsorption, DEC bone mass, low BMI

2. physically inactive

3. sex steroid deficiency, delayed puberty

4. corticosteroids

5. INC inflammatory cytokines

6. chronic infections

7. pancreatic insufficiency, diabetes

pt presents with low bone mineral density (BMD), frequent fractures, and kyphosis. What should you test them to diagnose?

DEXA scan; T/Z = 2.0

What impact does CF have on the skeletal system on adults vs children?

1. adults: femoral neck, total hip, lumbar spine, forearm

2. children: body less head, lumbar spine, femur, forearm

If patient has low BMD and frequent fractures they are likely to have CF related bone disease (CFBD). What is the screening technique and what is the method of treatment?

1. DEXA

2. bisphosphonates

What is a nonpharmacological treatment for CF?

Airway Clearance Therapy (ACT) and physical activity (atleast 150min/wk, indiv therapy, fluids + electrolytes)

What are the different types of ACT?

1. coughing, huffing

2. chest physical therapy

3. high frequency chest wall oscillation

4. autogenic drainage

5. positive expiratory pressure

6. active cycle breathing technique

What are the different mechanisms of CFTR modulators?

1. correctors: make mature CFTR protein and move to cell surface

2. potentiators: open channel to increase Cl- and bicarb mvt across cell

3. triply therapy combo: do both

Which medication is indicated for CF in children ≥ 6years old and taking 2 tablets in the morning

alyftrek (vanzacaftor/tezacaftor/deutrivacaftor)

Which medication is indicated for CF in children ≥ 2 years old and taking 2 tablets in the morning and 1 tablet in the evening?

trikafta (elexacaftor/tezacaftor/ivacaftor)

Which two CFTR modulators are highly effective modulator therapies? (HEMT)

Alyftrek and Trikafta

Which medication is indicated for CF in children ≥ 6 years old and taking 1 tablet in the morning and 1 tablet in the evening?

Symdeko (tezacaftor/ivacaftor)

Which medication is indicated for CF in children ≥ 1 year old and taking 2 tablets Q12H?

orkambi (lumacaftor/ivacaftor)

Which medication is indicated for CF in children ≥ 1 month old and taking 1 tablet Q12H

Kayldeco (ivacaftor)

What are the ADE of CFTR modulators?

1. neuropsychiatric effects

2. GI upset

3. cough/upper respiratory symptoms

4. BP increase

What should you take CFTR modulators with?

take with fat-containing food to improve absorption (INC AUC 2-4) DO NOT EAT GRAPEFRUIT/GF JUICE

What is the BBW for CFTR modulators?

drug induced liver injury and liver failure

What is the LFT monitoring schedule?

monitor at baseline

• every month x 6 mo

• every 3 months x 12 months

• annually

What decreases HEMT exposure? Should you continue to use them?

CYP3A4 inducers: rifampin, carbamazepine, phenytoin

• avoid use

What increases HEMT exposure? Should you continue to use them?

CYP3A4 inhibitors: ketoconazole, clarithromycin

• reduce HEMT dose

What substrates have increases exposure with both Alfytrek and Trikafta? This will require more frequent monitoring.

1. CYP2C9 substrates: warfarin, glipizide, glimepiride

2. P-gp substrates: digoxin, tacrolimus, cyclosporine

What substrates have increases exposure with alfytrek only?

BCRP substrates: rosuvastatin, sulfasalazine

What substrates have increases exposure with trikafta only?

OATP substrates: statins, glyburide, nateglinide, repaglinide

HEMT and warfarin interactions requires what?

more INR monitoring

What is the MOA of Pancreative Enzyme Replacement Therapy? (PERT)

combo of protease, amylase, lipase to digest fats, proteins, carbs, vitamins, and nutrients. It is to improve pancreatic insufficiency sympoms, fecal fat absorpiton, and maintain healthy weight.

PERT formulations are NOT interchangeable and they are enteric coated to prevent stomach degradation. How would you counsel a patient on PERT?

1. take before meals and snack with fat, protein, and/or complex carbs.

2. do not crush/chew

3. side effects of constipation and perianal ulcers

4. keep in cool/dry place

5. open capsule and put in applesauce

6. controversial may give PPI or H2RA

What is the dosing for PERT?

oInitial = 500 lipase units/kg/meal

oMaintenance = 500-2500 lipase units/kg/meal

oMax dose per meal = 2500 lipase units/kg

oMax dose per day = 10,000 lipase units/kg

• Larger doses (> 6,000 lipase units/kg) associated with fibrosing colonopathy or colonic strictures

Bronchodilators relaxes and opens airways. You would usually give a CF pt a MDI w spacer or nebulizer soln:

• albuterol (proair, ventolin), levalbuterol (xopenex)

How would you counsel a patient on this medication?

1. ADE: tremor, N/V, tachcardia

2. use 15-30 min before ACT, mucolytics, ABX, and perhaps exercise

Which bronchidilators will you give a CF patient?

MDI w spacer or nebulizer soln: albuterol (proair, ventolin), levalbuterol (xopenex)

mucolytics can thin mucus in the lungs to clear out with coughing. When are they used?

After using a bronchodilator and before ACT

indicated for children > 6 years old

What are the formulations of mucolytics?

1. hypertonic saline (3% or 7%) 4ml nebulized BID

2. Dornase Alfa (Pulmozyme) 2.5mg nebulized BID

3. Mannitol (Bronchitol) DPI BID

What are the ADE of mucolytics?

1. hypertonic saline: cough/sore throat, chest tightness

2. dornase alfa: change in voice dizziness

To suppress bacteria in mucus and prevent chronic lung infection what medication should you give?

inhaled ABX after bronchodilator+muclytic+ACT

1. aerol neb (DPI/MDI) 28 days on and 28 days off

A pt has a mild pulmonary exacerbation. What should you give them?

oral ABX

• if its mod-severe or oral doesn’t work then give IV ABX.

What is reserved for chronic pseudomonal infection/frequent exacerbations and can be given to suppress inflammation in the bronchial tubes?

azithromycin 250mg QD or 500mg 3x weekly

REVIEW ABX COVERAGE

a pt is on IV tobramycin. How should you monitor this patient?

high dose extended interval (QD, preferred)

• peak 20-35mcg/ml

• trough <1mcg/ml

patient has impaired absorption of fat soluble vitamins (ADEK). What medications are indicated and what should you monitor for?

1. AquaADEKs, DEKAs, MVW complete formulation

2. maintain 25-hydroxyvita D lvls ≥30ng/mL (take cholecalciferol D3 > ergocalc D2)

pt has iron deficiency. What should you give them?

1. ferrous sulfae, ferrous gluconate, ferrous fumarate

2. take every other day wiht vitamin C to increase absorption

What are additional medications to take for CF?

1. asthma inhalers

2. nasal rinse

3. oral antihistamine

4. steroid nasal sprays

5. osmotic laxatives

6. antiemetics

7. appetite stimulant

What is the order of inhaled therapy?

1. bronchodilator: open airway

2. hypertonic saline: pull water into thin mucus

3. dornase alfa: breaks DNA to further thin mucus

4. ACT: physically shakes and clears mucus from lungs

5. ABX: cleans airways wo mucus blocking

6. corticosteroids: reduce inflammation

REVIEW CF TREATMENT OVERVIEW

pulmonary function tests (PFTs) are done with spirometry where it is performed 3x and record best results. This is done in pts > 5-6 years old. What indicates infection and how should you counsel the patient?

1. reductions in FEV1 indicate infection/obstruction

2. counsel:

• avoid smoking 1hr, heavy exercise 30 min, large meal 2hr before

• monitor at each clinic visit to compare to pt baseline

What are common complications of pregnancy in CF pts?

1. premature delivery

2. more frequent pulmonary exacerbations

3. gestational diabetes

4. constipation

5. vitamin A toxicity

6. HTN

REVIEW LABS AND IMAGING

What screenings should you do?

1. routine clinic visit: Q3M, Q4-6M if ≥6yrs and stable

2. BP: annual

3. mental health: annual @12yrs old

4. colonoscopy: every 5 years @40 yrs old

5. immunizations: influenza, RSV, pneumococcal, COVID19

What is the role of the pharmacist?

1. counsel + educate

2. med rec

3. ID DDIs

4. mitigate access barriers

5. cost effective strats

6. liaison

7. med management services

8. prevent and screen

9. write/med prescription

10. order/review labs

11. manage home IV ABX

12. non-CF therapy

Summary