Pharmacotherapy III: Exam 5

How is CF diagnosed?

-Newborn screening/ Immunoreactive Trypsinogen (IRT) NOT diagnostic—only identifies infants at risk for CF High value necessitates genetic testing -Meconium Ileus (MI) ~ 20% of CF cases present with MI 80-90% of patients with MI have CF -*Sweat Chloride test is diagnostic gold standard* 2nd confirmatory test required ≥ 60 mmol/L: CF diagnosis Borderline sweat chloride ranges vary between infants and older children/adults- •Patients with borderline values may still have CF

When is Lung Transplantation used?

-Option for severe lung disease ~150-200 CF patients transplanted per year -New lungs, not a complete cure for CF -Sinuses, pancreas, intestines, sweat glands, reproductive tract still affected by CFTR mutation -Immune suppressants increase risk of infection -Survival: 80% at 1 year post-transplant; >50% at 5 years -Most transplant centers will not accept B. cepacia patients -Lung allocation score determines position on transplant list -Adherence to treatment prior to transplant is a huge factor in determining qualification for transplant

What is the treatment overview for an acute exacerbation?

-Oxygen & ventilatory support -Bronchodilators -Corticosteroids -Antibiotics -Additional Measures

What are the Airway Clearance Techniques?

-Percussion Vest -Manual chest percussion therapy (CPT) -Positive Expiratory Pressure >FlutterTM device >AcapellaTM -Postural drainage -Aerobic exercise

What vitamins need to be supplemented in CF?

-Poor absorption of fat-soluble vitamins in CF AquADEK •Contains A,D,E,K and other minerals •Dosed Qday - BID •Hydrophilic microsphere structure aids absorption •3 formulations: liquid, gelcap, and chewtab •OTC; often not covered by insurance, cost ~$30/60 doses -Additional supplementation of A, D, E, K may be necessary •Vitamin K (Mephyton): 5 or 10mg PO Qday to BID

How should you counsel Smoking Cessation?

-Smoking cessation has the greatest capacity to influence the natural history of COPD. -If effective resources and time are dedicated to smoking cessation, long-term quit success rates of up to 25% can be achieved.

What are the cultures to take for CF?

-Sputum or throat -Usually done quarterly -Commonly isolated organisms >MSSA (methicillin-sensitive staph aureus) >MRSA >Pseudomonas aeruginosa >Stenotrophomonas maltophilia >Achromobacter >Burkholderia cepacia -Often multiple organisms on culture -Full eradication is rare; methods being studied -Antibiotic resistance is common

How is the GI tract affected in CF?

-Thick secretions in bile ducts => scarring => gallstones, decreased bicarbonate production, liver dysfunction -Thick secretions in pancreas => plugged pancreatic ducts & scarring => decreased pancreatic enzyme secretion => poor digestion => poor nutrient absorption => decreased weight gain, malnutrition => worsened lung disease, osteoporosis => decreased or sporadic insulin secretion, impaired insulin sensitivity => hyperglycemia => microvascular complications (nephrotoxicity, neurotoxicity, retinopathy)

What is Ursodiol used for in CF?

-Treats & prevents CF liver disease -Children: 20-30mg/kg/day, divided BID -Adults: 600mg BID -Give with food -Side effects: constipation, N/V, diarrhea, backache, dizziness, rash, cough, pharyngitis/bronchitis -MOA: decreased biliary cholesterol concentration => breakdown of gallstones; increases bile flow, protects liver by decreasing toxicity of bile acids -Monitoring: LFTs; dose titration dependent upon LFTs

What are the causes of respiratory alkalosis?

(CO2 is blown off) Anything that increases ventilation and increases respiratory drive Hypoxia (decreased O2), altitude, severe anemia Increased ventilation: CHF, sepsis, PE, pulmonary fibrosis Ventilator setting is too high (hyperventilation) CNS stimulation: anxiety, pain (increased respirations) Rx: salicylate intoxication

What are the causes of Respiratory Acidosis?

(CO2 retention) Things that keep you from breathing effectively or that can cause hypoventilation: Asthma, COPD, severe pneumonia, ARDS, sleep apnea Ventilator setting is too low (hypoventilation) CNS depression: stroke, brain/spinal injury, oversedation Pulmonary embolism, myocardial infarction Rx: anesthesia, opioids, sedatives Neuromuscular disorders affecting diaphragm and/or chest wall function -Myasthenia gravis, Guillain-Barre, etc

Case: •KM is a 5 yo female with CF (deltaF508/deltaF508) •Medications •Albuterol inhaler 1-2 puffs BID before nebulized medications •Hypertonic saline 7% via neb BID •Dornase alfa via neb BID •Ranitidine BID •Enzymes per weight/meal calculation (4-5 capsules per meal, 2-3 per snack) •Orkambi 2 tabs PO BID with high fat meal Clinic Visit •9 weeks ago KM had her quarterly clinic visit. Her throat swab came back positive for pseudomonas aeruginosa. She was prescribed 28 days of TOBI via nebulizer. She came back in 4 days ago to retest to see if it cleared, however it has not. Her parents also mention that she has mentioned it feels like someone is pushing on her chest. 1.What will you prescribe? Include sig and any special instructions 2.How will this medication fit into the schedule of her other medications? 3.What DME is required? 4.Given KM may be having a negative reaction to Orkambi, what options does KM and her family have? 5.What other medication do you want to start discussing with the family that KM will be eligible for in a few years? Why should you start this conversation early with the family?

(deltaF508/deltaF508) most common 1. Inhaled preferred Cayston (aztreonam) 75 mg inhaled TID pre-treat with albuterol -Has to be mixed with sterile diluent before nebulizing it 2. Albuterol (MDI or neb), Hypertonic saline, then Pulmozyme with vest simultaneously, Inhaled antibiotic, Steroid nebulizer or inhaler 3. Altera nebulizer 4. Talk to pt's parents about whether the ADE is worth taking her off Orkambi. She is too young for anything else right now, prepare pt for Symdeko in a year 5. Trikafta at age 12 is way better *Know orders of meds, gene modifiers, which mutations, which ages they work for*

What are the complications of acute kidney injury?

*1. Metabolic acidosis* •↓ Ammonium (NH4+) excretion •↓ bicarbonate (HCO3-) production and reabsorption •Blood becomes acidic => hyperkalemia *2. Hyperkalemia* •H + and K+ intracellular shift from acidosis •Potassium (K+) is excreted by the kidneys •Inability to excrete potassium causes accumulation => cardiac arrhythmias 3. Fluid overload/edema 4. Hyperphosphatemia and hypermagnesemia

What is Hypertonic Saline?

-7% NaCl via nebulizer (some pts use 3% or 10%) -Increases hydration of airway surface liquid -Qday-BID -Can cause airway irritation and bronchospasm lUse bronchodilator pre-treatment -Studies show improved lung function and reduced frequency of exacerbations, to lesser extent than dornase alfa -Not FDA approved for CF, but used by >50% of pts -CF Foundation recommends chronic therapy with hypertonic saline Cost: ~$35/60 (generic)

What is COPD?

-A common, preventable, treatable disease -Persistent respiratory symptoms and airflow limitation -Due to airway and/or alveolar abnormalities -Usually caused by significant exposure to noxious particles or gases -Irreversible

What are the clinical pearls of acid-base disorders?

-Acid-base disorders are common -Disorders may be simple or mixed -Respiratory cause = Metabolic compensation -Metabolic cause = Respiratory compensation -Respiratory compensation occurs quickly (hours) but metabolic compensation takes up to 48 hours (days) -Correction of underlying disorder is most important aspect of treatment Acid-base disorders are common. They can sometimes be simple but they get a lot more complicated if they're mixed. If the primary cause is respiratory, meaning the primary disorder is due to changes in pCO2, you may see a metabolic compensation through regulation of bicarb. The opposite is true with a metabolic cause. If the primary disorder is metabolic, meaning the bicarb level explains the abnormal pH, *respiratory compensation can occur very quickly because the lungs respond very quickly*. *Metabolic compensation may take days, weeks, or even months*. Correction of the underlying disorder is the most important aspect of treatment.

What is Pancreatic Enzyme Replacement Therapy (PERT)?

-Administered with all meals and snacks -Capsules contain microtablets or microspheres -Enteric-coated -Role of H2 blockers & PPIs Dose usually based on units of lipase/kg ~1500 lipase units/kg/meal -Usual max dosage = 2,500 units of lipase/kg/meal, 10,000 units of lipase/kg/day -Colonic strictures associated with lipase >6000 units/kg/meal Several brands FDA approved -Cotazyme, Zenpep, Creon, Pancreaze, Pertzye, Ultresa, Viokace *DO NOT SUBSTITUTE* Options for tube feed patients -New options may be coming out soon -Jejunally-placed tube: Dissolve capsule contents in Sodium Bicarbonate -Gastrically placed tube: distribute contents in acidic juice such as nectar-thick (don't crush)

How common is CF?

-Affects ~1 in 2000-3000 Caucasian infants -1 in 11,500 Hispanic Americans, 1 in 10,900 Native Americans, 1 in 17,000 African Americans, 1 in 31,000 Asians -Median survival age is currently ~47 years (was 39 just a couple years ago) -CF genetic carrier frequency is 1 in 20 for Caucasian Americans, 1 in 29 Ashkenazi Jews, and 1 in 60 African Americans

What are the Group A agents?

-All Group A patients should be offered bronchodilator treatment based on its effect on breathlessness. This can be either a short- or a long-acting bronchodilator. -This should be continued if benefit is documented. SEE CHART

What is Periactin (cyproheptadine) used for in CF?

-Appetite stimulant -Children: 0.25mg/kg/day in 2-3 divided doses OR •2-6 years old: 2mg q8-12 hours (NTE 12mg/day) •7-14 years old: 4mg q8-12 hours (NTE 16mg/day) -Adults: 4-20mg/day divided q8 hours (NTE 0.5mg/kg/day) -Side effects: drowsiness, diarrhea, N/V -MOA: histamine, serotonin, and acetylcholine antagonist; likely alters serotonin activity in the appetite center of the hypothalamus -May require gradual dose titration

What is the assessment of COPD?

-Assess degree of airflow limitation using spirometry -Assess symptoms -Assess risk of exacerbations -Assess comorbidities

What is Kalydeco (ivacaftor)?

-CFTR potentiator; facilitates opening of chloride channel -Initially indicated for CF patients >2 years old with G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, and R117H mutations -2017: increased mutations from 10 above to 38, but all rare so increase only impacted ~3% of CF population, or roughly 900 patients -Studies show improved PFTs, increased weight gain, decreased frequency of exacerbation -Dosing: 150mg tablet, 1 PO BID, with high-fat meal -Side effects: URI, stomach ache, HA, rash, diarrhea, dizziness, elevated LFTs, cataracts (must have eye exam before starting) Drug interactions: Contraindicated with strong CYP3A4 inducers Moderate CYP3A4 inhibitors: may require dose adjustment Strong CYP3A4 inhibitors: dose adjustment required -Monitoring: LFTs at baseline, throughout treatment Cost $25,000/month ($300k/year)

What is Orkambi (lumacaftor/ivacaftor)?

-CFTR potentiator; increases processing and trafficking of CFTR (lumacaftor), and improves gating function of CFTR at cell surface -Indicated for CF patients >2 years old with homozygous f508del mutation -Studies show slight improvement in PFTs (~3% average) Dosing: lumacaftor 400mg/ivacaftor 250mg PO every 12h -Comes as 200mg/150mg tablet, so 2 tablets po bid -Take with high fat meal (~20g fat) -Adjustment for mod-severe hepatic impairment -Side effects, warnings, precautions: SOB, chest tightness, chest discomfort, fatigue, menstrual irregularities, elevated LFTs, cataracts -Complicated drug interactions with CYP450 enzymes -Hormonal birth control rendered ineffective -Monitoring: LFTs, eye exam at baseline Cost: $25,000/month ($300k/year)

What is Trikafta (elexacaftor/tezacaftor/ivacaftor)?

-CFTR potentiator; increases processing and trafficking of CFTR (tezacaftor), and improves gating function of CFTR at cell surface -Indicated for CF patients >12 years old with homozygous f508del mutation or if at least 1 of any other mutation - Because the 2nd mutation doesn't have to be a specific one, this medication works for ~90% of people with CF who have one copy of f508del and any other mutatation -Studies show improvement in PFTs (~13.8% average) compared to placebo and improvement in PFTs (~10% average) compared to Symdeko -Dosing: elexacaftor/tezacaftor/ivacaftor 100mg/50mg/75mg 2 tabs PO every am and 150mg ivacaftor every pm (12 hours apart) -Take with high fat meal (~20g fat) -Adjustment for mod-severe hepatic impairment -Side effects, warnings, precautions: headache, common cold, stomach pain, diarrhea, elevated LFTs, cataracts -No chest tightness like with Orkambi -Drug interactions with CYP3A enzymes (rifampin, St. Johns Wart lower efficacy of Trikafta) -Monitoring: LFTs, eye exam at baseline Cost: $25,000/month ($300k/year)

What is Symdeko (tezacaftor/ivacaftor)?

-CFTR potentiator; increases processing and trafficking of CFTR (tezacaftor), and improves gating function of CFTR at cell surface -Indicated for CF patients >6 years old with homozygous f508del mutation or if at least 1 mutation of 26 to show response -Homozygous f08del is the MOST COMMON mutation(s), affecting over 50% of CF patients -The other 26 listed are very rare and account for less than 5% of patients with CF -Studies show slight improvement in PFTs (~5% average) Dosing: tezacaftor/ivacaftor 100mg/150mg PO every am and 150mg ivacaftor every pm (12 hours apart) -Take with high fat meal (~20g fat) -Adjustment for mod-severe hepatic impairment -Side effects, warnings, precautions: headache, nausea, sinus congestion, dizziness, elevated LFTs, cataracts -No chest tightness like with Orkambi -Drug interactions with CYP3A enzymes (rifampin, St. Johns Wart lower efficacy of Symdeko) -Monitoring: LFTs, eye exam at baseline -Cost: $25,000/month ($300k/year)

What is the Economic burden of COPD?

-COPD is associated with significant economic burden. -COPD exacerbations account for the greatest proportion of the total COPD burden. European Union: -Direct costs of respiratory disease ~6% of the total healthcare budget -COPD accounting for 56% (38.6 billion Euros) of the cost of respiratory disease. USA: -Direct costs of COPD are $32 billion -Indirect costs $20.4 billion.

How common is COPD?

-COPD is currently the fourth leading cause of death in the world -COPD is projected to be the 3rd leading cause of death by 2020 -More than 3 million people died of COPD in 2012 accounting for 6% of all deaths globally. -Globally, the COPD burden is projected to increase in coming decades because of continued exposure to COPD risk factors and aging of the population

What are the Social Issues in CF?

-Cost of treatment -Amount of time required for treatment -Missed school/work -Medication administration at school/work -Denial -Death & dying -Social worker is required on CF team

What is Cayston (aztreonam lysine)?

-Dose is 75mg inhaled TID via *Altera nebulizer* -Usually 28 days on, 28 days off -Binds to PBP-3 on gram(-) aerobes, inhibits cell wall synthesis; bactericidal -Side effects: cough, bronchospasm, hoarseness -Always pre-treat with albuterol or other beta agonist -Supplied by only a few specialty pharmacies in the US

What is Colistin (colistimethate)?

-Dosing is 150mg inhaled BID via nebulizer -Usually a 28 day course -May alternate with tobramycin or aztreonam inhalation for 28d on, 28d off -Use injectable colistin in the nebulizer -Cationic detergent; damages bacterial cytoplasmic membrane causing leaking of intracellular substances and cell death -Pre-treat with bronchodilator

What is the non-pharm treatment for COPD?

-Education and self-management -Physical activity -Pulmonary rehabilitation programs -Exercise training -Self-management education -End of life and palliative care -Nutritional support -Vaccination -Oxygen therapy

What are the complications of CKD?

-Electrolyte abnormalities -Anemia -Metabolic acidosis -Secondary hyperparathyroidism -Hypertension -Cardiovascular disease

What is the prevalence of COPD?

-Estimated 384 million COPD cases in 2010. -Estimated global prevalence of 11.7% (95% CI 8.4%-15.0%). -Three million deaths annually. -With increasing prevalence of smoking in developing countries, and aging populations in high-income countries, the prevalence of COPD is expected to rise over the next 30 years. -By 2030 predicted 4.5 million COPD related deaths annually.

What is CF-Related Diabetes (CFRD)?

-Features most similar to T1 Diabetes -2h oral glucose tolerance test is gold standard -Pancreatic duct blockage and scarring, loss of beta cells prevents insulin secretion -Insulin resistance may develop over time -Study of 448 patients showed survival at age 30 was 25% for CFRD patients vs 60% for non-CFRD patients

What is the Treatment of stable COPD?

-Following implementation of therapy, patients should be reassessed for attainment of treatment goals and identification of any barriers for successful treatment (Figure 4.2). Following review of the patient response to treatment initiation, adjustments in pharmacological treatment may be needed

What are the risk factors for COPD?

-Genes -Infections -Socioeconomic status -Cigarette smoke -Occupational dust and chemicals -Environmental tobacco smoke -Indoor and outdoor air pollution -Aging problems

What is the pathophysiology of CF?

-Genetic mutations cause defect in the CFTR >1700 different genetic mutations identified -CFTR normally regulates Na+ and Cl- transport across the cell membrane -Defective CFTR => impaired chloride transport => dehydrated cell surface liquid => mucus plugging => organ dysfunction

What is the CF diet?

-High-calorie, high-protein, unrestricted fat diet -Balance -Nutritional supplements •Scandishakes •Boost, Kids Essentials, Ensure, etc. -Good nutrition means better lung health, outcomes •Goal BMI ≥ 50 percentile -Hyperlipidemia is rare in CF

What is Inhaled Tobramycin?

-Indication: treatment of CF patients with pseudomonas -Aminoglycoside; inhibits protein synthesis; bactericidal; concentration-dependent -Little-to-no systemic absorption -Generic tobramycin neb solution now available (do not sub without authorization from MD) -Tobi: 300mg (5mL ampule) BID via neb -Bethkis: 300mg (4mL ampule) BID via neb -Tobi Podhaler: 4 caps (2 inhalations per cap; 112mg total), inhaled BID via device -Usually 28 days on, 28 days off; Some patients alternate with Cayston or Colistimethate -Do not mix Tobi in nebulizer with any other meds -May cause coughing, wheeze, sore throat, hoarseness

What should you counsel about Vaccination?

-Influenza vaccination can reduce serious illness (such as lower respiratory tract infections requiring hospitalization) and death in COPD patients. -Pneumococcal vaccinations, PCV13 and PPSV23, are recommended for all patients ≥ 65 years of age.

What are the Group B agents?

-Initial therapy should consist of a long acting bronchodilator (LABA or LAMA). -Long-acting inhaled bronchodilators are superior to short-acting bronchodilators taken as needed i.e., pro re nata (prn) and are therefore recommended. SEE CHART

What are the Group C agents?

-Initial therapy should consist of a single long acting bronchodilator. -In two head-to-head comparisons the tested LAMA was superior to the LABA regarding exacerbation prevention therefore we recommend starting therapy with a LAMA in this group.

What is Cystic Fibrosis?

-Initiation of treatment early in life is critical to prevent disease progression -Multiple organ-system disease: pulmonary, digestive, reproductive organs are affected -Mortality usually due to lung disease

What is the electrolyte composition in the body?

looking at a chem 7 and so we know that sodium and chloride have large numbers on our chem 7 and that's what we're measuring is the amount of those electrolytes in the blood and so that's why they are high and are going towards the top of the graph. we know potassium calcium and magnesium are intercellular components and that's why their graph is going toward the bottom the change in intercellular osmolality is a reflection of a change of intercellular fluid water content

1. CH is a 75 yo M admitted to your service for COPD exacerbation and possible community acquired pneumonia (CAP). He is currently being managed with albuterol-ipratropium nebs, IV solu-medrol and an antibiotic regimen of ceftriaxone + azithromycin. In reviewing his chart, you notice the following labs. ABG: (7.38/62/90/32) (pH/pCO2/pO2/HCO3) · What type of acid-base disorder does CH have? 141 104 25 139 4.7 31 1.1

pCO2 high HCO3 high Respiratory acidosis with compensation Classic COPD presentation

What is the Henderson-Hasselbalch equation?

pH = pKa + log (Base/acid) pH is maintained by keeping the ratio between your acid and base constant. The Henderson-Hasselbalch equation correlates pH with the pKa and the log of the base over the acid. The point I want to make here is it's the ratio of the base and the acid that's responsible for any change in the pH. So as long as any changes in the base or acid concentrations are kept proportional to each other - if that ratio stays the same - then the pH will remain constant despite any changes to the base or acid concentration.

What happens when we plug bicarb and carbonic acid into the Henderson-Hasselbalch?

pH = pKa + log(HCO3/H2CO3) pH = 6.1 + log(HCO3/pCO2 x 0.03*) Ratio of 20:1 Notice on the right-hand side, even though carbonic acid is the acid component of the HendersonHasselbalch equation, what we actually measure in clinical practice is the partial pressure of CO2. But remember from a previous slide, carbonic acid and CO2 exist in equilibrium so we can use the pCO2 to give us an accurate measurement of carbonic acid in the body. With bicarb as the base and pCO2 being the acid, this would be the complete HendersonHasselbalch equation used to assess the pH of the body in terms of the bicarb/carbonic acid buffer system. Again, it's the ratio of bicarb to CO2 that ultimately determines pH. If you see a change in one, as long as you see an appropriate change in the other, normal pH can be maintained. The buffer system is the body's first defense that occurs rapidly against sudden changes in hydrogen ion concentration. But it's not always enough and that's why we have 2 other mechanisms for maintaining acid-base homeostasis.

1. What are normal ranges for the following components of the arterial blood gas? pH ________________ pCO2 ________________ HCO3- ________________

pH: 7.35-7.45 pCO2: 35-45 HCO3-: 22-28

What is the Hyponatremia: Hypotonic/hypovolemic treatment?

signs and symptoms related to loss of volume so you'll have a low blood pressure and elevated heart rate, orthostasis said we want to give a solution that's going to correct intervascular volume •Correct hypovolemia - infuse 0.9% saline •Discontinue causative agent - diuretic •Correct underlying cause

How does CF affect the bones?

~50-75% of CF patients Risk factors -Poor Calcium, Vit D & K absorption -Glucocorticoid, PPI, H2 blocker therapy -Low activity levels -Chronic inflammation Bone density scans and vitamin levels recommended for monitoring Consider bisphosphonates if T/Z score ≤ -2.0 -IV better than oral?? No data, but worry about absorption -Calcium, Vitamin D & K supplementation -Exercise

What is Dextrose?

•5% dextrose in water (D5W) •Distribution - Rapid dextrose metabolism/clearance - "free water" - Equal distribution throughout body •Rehydrate plain water cannot be infused safely because of tonicity and then the adverse effects like we saw with the hypotonic crystal to give patients water we infused 5% dextrose or D5W dextrose makes the solution isotonic and prevents hemolysis and also is a source of calories dextrose is rapidly cleared and metabolized leaving free water which distributes evenly throughout the body compartments. D5W is prescribed to treat hypernatremia and reduce total body water it is not appropriate to support circulating blood volume so rehydration not intervascular volume depletion

What do ACEs/ARBs do to cause prerenal injury?

•ACE inhibitors and ARBs block angiotensin II's effects •Unable to vasoconstrict the efferent arteriole

How is fluid replacement used to treat acute kidney injury?

•AKI can be "volume unresponsive" sometimes •ATN, AIN, other non-prerenal kidney injury causes •Administering fluids in these cases may cause fluid overload and worsen AKI •Crystalloids vs. colloids •Colloids (apart from albumin) have proven to increase mortality and worsen AKI •Limit albumin use to patients with third spacing •Crystalloids are therefore preferred over colloids •Fluid balance •Goal of fluid resuscitation is to replace any lost fluid without overloading patient •Need to balance maintenance fluids and diuretics

What is Acute tubular necrosis (ATN) in intrinsic damage?

•Accounts for ~85% of intrinsic AKI •~60% of cases due to ischemia -Hypotension -Vasoconstrictive drugs •~40% from direct tubule toxins -Endogenous vs. exogenous toxins •Tubule in medulla are very sensitive -Metabolically active => require a lot of oxygen -Don't get much oxygen distribution compared to cortex of kidney

What is the Assessment of Exacerbation Risk?

•COPD exacerbations are defined as an acute worsening of respiratory symptoms that result in additional therapy. •Classified as: •Mild (treated with SABDs only) •Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids) or •Severe (patient requires hospitalization or visits the emergency room). Severe exacerbations may also be associated with acute respiratory failure. •Blood eosinophil count may also predict exacerbation rates (in patients treated with LABA without ICS).

How does CARDIOVASCULAR DISEASE contribute to CKD?

•Cardiovascular disease is the leading cause of death among patients with CKD

What are the Symptoms of COPD?

•Chronic and progressive dyspnea •Cough •Sputum production •Wheezing and chest tightness •Others - including fatigue, weight loss, anorexia, syncope, rib fractures, ankle swelling, depression, anxiety.

What are CALCIMIMETICS?

•Cinacalcet hydrochloride (Sensipar) •Mechanism of action •Acts on the calcium-sensing receptor on the surface of the chief cell on the parathyroid gland •Mimics the effect of extracellular ionized calcium •Increases sensitivity of calcium-sensing receptor to calcium •Reduces PTH secretion •Administration •Take with food or shortly after a meal •Adverse effects •Nausea, vomiting, hypocalcemia •Elimination •Extensively metabolized by multiple CYP450 enzymes (CYP3A4, 2D6, and 1A2) and glucuronidation

What are the Hypovolemia: signs & symptoms?

•Consistent history: and just kind of seeing what caused it diarrhea blood loss are they having a GI bleed and a need to transfuse blood or are they having vomiting due to a stomach virus and then just fluids would be appropriate •Continuum of severity - Variable dependant on age (remember children and elderly and more sensitive to volume change), rapidity (sudden or acute or is this chronic and on-going so the acute losses tend to be more symptomatic and less well tolerated and whereas chronic and on-going is really less symptomatic), diseases, meds - Mild thirst to shock, simple to thirst all the way to circulatory collapse and shock •Signs: ↑pulse/resp rate, ↓BP, ∆mental status, agitation, ↓capillary refill, ↓urine output •Symptoms: thirst, nausea, anxiety, weakness, dizzy/light headed

What are the goals of therapy for CKD?

•Delay the progression of CKD •Manage and minimize the development of complications associated with CKD •Decrease proteinuria •Maintain sodium, water, potassium, and acid-base homeostasis •Achieve glycemic control in patients with DM •Control hypertension through achieving blood pressure goals •Smoking cessation

What is Acute interstitial nephritis (AIN) in intrinsic injury?

•Delayed hypersensitivity immune reaction. Usually manifests 2 weeks after exposure Causes: •*Drugs* •Infections •Autoimmune disease -Idiopathic -Characterized by inflammation and edema -Lesions of WBCs in affected area -Can progress to interstitial fibrosis and tubular atrophy

What are the parts of dialysis?

•Dialysate: Fluid of solutes that passes through the dialyzer •Dialyzer: Tube holding a semipermeable membrane in which blood flows in one direction and the dialysate flows in the opposite direction •Passive diffusion: Movement of substances down a concentration gradient •Ultrafiltration: Movement of water and small molecules across the dialyzer membrane as a consequence of hydrostatic pressure •Convection: Substances being dragged across the membrane along with other fluid passing through

What are Colloid solutions: Hetastarch?

•Fluids that contain high molecular weight substances - Do not readily migrate across capillary walls - Oncotic activity "pulls" fluid intravascularly • Preparations - Hetastarch 6%: Iso-oncotic •Uses - Third-spacing - Resuscitate •ADR - Bleeding/anaphylaxis - Kidney injury osmotically active fluids that are prescribed to increase circulating volume they work in really two ways expand volume due to volume actually infused and they also pull fluids into the vascular space due to their oncotic activity we have two available hetastarch and albumin and hetastarch is generally avoided due to adverse reactions including clotting and acute kidney injury but we do use albumin in certain instances in clinical practice

What are the four phases of ATN?

•Four phases of ATN 1.Initiation •Renal tubular epithelial cell injury resulting from vasoconstriction and ischemia •Epithelial cells no longer able to regulate fluid and electrolyte balance •Filtrate leaks back into interstitium and is reabsorbed back into systemic circulation •Dead epithelial cells slough and form casts => post renal obstruction/injury 2.Extension •Continued hypoxia •Inflammatory response 3.Maintenance •GFR reaches nadir •Cellular repair processes initiated to maintain current renal function 4.Recovery •New tubule cells are regenerated •Kidney function improves •Sometimes damage is too severe for recovery

What are the causes of hypovolemia?

•GI Losses - Vomiting, diarrhea, fistula, bleeding, drainage •Renal Losses - Diuretics, osmotic agents, etc. •Skin Losses - Sweat, burns, etc. •Third Spacing - Bowel obstruction, crush, fractures, pancreatitis - leaking of fluids due to inflammation or sepsis •Bleeding

What happens in glomerular damage in intrinsic damage?

•Glomerular damage •Nephrotic/nephritic glomerulopathies •Autoimmune disease

What is hypernatremia?

•Hyperosmolar - *always* going to be additional salt - Potent thirst stimulus (access to water?) - Often associated with severe underlying disease •HYPERvolemic - Iatrogenic, Cushing's Syndrome, hyperaldosteronism •ISOvolemic - Nephrogenic or central diabetes insipidis •HYPOvolemic - Diuretics, osmotic diuresis (DKA), GI losses

What are the hypotonic crystalloids?

•Hypotonic crystalloids - 0.45% normal saline, "half-normal saline" •Distribution - ½ H2O : ½ NS - Routine maintenance fluid - Inadequate for fluid resuscitation •Dextrose added for isotonicity, calories to prevent ketosis if you consider .45% Saline or half normal think of this as half plain water and then half normal Saline. D5NS is the standard fluid prescribed to adults for maintenance of hydration and volume when fluids can't be taken orally Hypotonic crystalloids should not be infused by themselves because of adverse effects on the red blood cell structure and function. Typically dextrose is added or additional electrolytes like potassium chloride or sodium bicarb to make them isotonic

What is the role of a pharmacist?

•IV preparations - Safely prepare, label, and dispense solutions - Recognize iatrogenic causes of abnormalities - Participate in managing shortages - ex. normal saline •Assist with treatment and monitoring of imbalances •Recognize and communicate the potential for other medications to cause or worsen imbalances

What is the Hypovolemia: laboratory evaluation?

•Increased BUN:creatinine ratio is fairly universal for dehydration •Hyper or Hypo-natremia doesn't always clearly link to either a hypo or hyper volemia they can have a varying degree and change depending on the amount of water versus solute retained •Hyper or Hypo-kalemia if we think about hyperkalemia we can develop this secondary to decrease perfusion of the kidneys leading to acute kidney injury or hypo due to losses through the GI tract •Acidosis or Alkalosis develop depending on the cause of the volume loss •Elevated hematocrit - unless acute blood loss is usually due to decrease or hemoconcentration so a decreased water in the blood leads to increased numbers of red cells per volume leading to an increased hematocrit or hemoglobin and thus the cause of hypovolemia is secondary to blood loss

What is the Hyponatremia: Hypotonic/HYPERvolemic causes?

•Increased ECF due to decreased renal sodium and water excretion •Decreased Effective Arterial Blood Volume (EABV) => Renal sodium retention/ADH => ECF expansion with resultant increase in hydrostatic pressure => edematous state •Retention of Water >> Na •CHF, cirrhosis, nephrotic syndrome •Present with symptoms from the underlying disease

What are the Isotonic Crystalloids?

•Isotonic crystalloids - Lactated Ringer's (LR) - 0.9% "normal" saline - 300 mOsm/L •Distribution - 100 % ECF - Osmolality approximates that of the ECF - No osmotic pull •Resuscitate Increasing circulating volume so increasing blood pressure these are used to resuscitate or in patients that have low blood pressure or decrease intervascular volume

How are diuretics used to treat acute kidney injury?

•Loop diuretics used most often •Diuretic resistance is common in AKI •The part of the nephron where diuretic works may be damaged or inflamed •Loop diuretics are protein bound, and proteinurea can prevent them from reaching site of action •Gut edema can affect oral absorption of furosemide •Recommend switching to torsemide and bumetanide, which have increased oral bioavailability •Continuous vs bolus dosing approaches •Combination of a loop diuretic and metolazone may be warranted once GFR < 20

What are phosphate binders?

•Mechanism of action •Binds to dietary phosphorous in the GI tract •Provides cations → binds with dietary phosphate (H₂PO₄- and HPO₄²⁻) → insoluble cation + phosphate salt complex → excreted in the feces •Binding affinity varies depending on binding agent •Administration •Take with meals to maximize potential of binding to dietary phosphorous •Adverse effects •Nausea, vomiting, abdominal pain, bloating, diarrhea, constipation •Drug interactions •Phosphate binders with multivalent cations (calcium, aluminum, and iron) chelate with and decrease the absorption of some medications •Separate administration of medications known to chelate with multivalent cations by 2 hours

What are VITAMIN D & VITAMIN D ANALOGS for CKD?

•Mechanism of action •PTH secretion suppression •Indirectly through stimulating absorption of serum calcium •Direct activity on parathyroid land decreases PTH synthesis •Adverse effects •Hypercalcemia, hyperphosphatemia •Elimination •Calcitriol, paricalcitol, doxercalciferol, and califediol are extensively metabolized in the liver by CYP3A4, CYP24, and UGT1A4 •Ergocalciferol and cholecalciferol are metabolized through similar routes

What are the iron supplements?

•Mechanism of action •Provides elemental iron to produce Hgb •Administration •Either oral or IV administration is recommended in non-HD patients •IV iron preferred in patients with CKD 5D •Food may decrease oral absorption •Adverse effects •Oral - GI (constipation, nausea, abdominal cramping), dark colored stools •IV - Hypotension, dizziness, dyspnea, headaches, lower back pain, anaphylaxis

What is ERYTHROPOIESIS-STIMULATING AGENT THERAPY?

•Mechanism of action •Same biologic activity as endogenous erythropoietin •Binds to and activates erythropoietin receptor to stimulate erythropoiesis •Takes ~10 days for erythrocyte progenitor cells to mature and release into circulation •Administration •IV or SC •Less bioavailability but prolonged absorption phase with SC administration •Adverse effects •Hypertension/hypertensive encephalopathy •Seizures •Thrombosis

What are Vasopressin receptor antagonists?

•Mechanism: block vasopressin action in renal collecting ducts to promote water excretion •Agents available •Conivaptan (Vaprisol) - parenteral only •Tolvaptan (Samsca) 15-60 mg orally daily - Associated with hepatic injury - Prescription limited to 30 days in US •Overcorrection is a risk - Monitor every 6 hours in hospital, during initiation - Discontinue fluid restriction when initiating therapy •NO Place in therapy -toxicity as well as cost isn't allowing us to use these for long term and as well as not correcting the underlying cause so as soon as the drug courses stopped then the sodium readjust back to the original level

What is the EFFECT OF CKD ON DRUG ELIMINATION?

•Medications should be reviewed in patients with stages 3, 4, and 5 CKD •As a general rule, medications should be reviewed for renal dosing in patients with a CrCl <60 mL/min •Medication dosing in dialysis •Supplemental dosing •Considerations for renal dose adjustments: •Elimination profile •Elimination half-life •Nephrotoxicity •AUC

What is the Maintenance - monitoring & adjustment?

•Monitoring - reevaluate IVF "prescription" at least daily, this is a common source of error - Physical assessment - looking for signs/symptoms of volume deficits or overload - Ins & outs, weight- daily - Laboratory assessment- daily •Adjustments: serum sodium - a measure of water balance - Serum sodium dropping - decrease "free water", D5NS - Serum sodium increasing - increase "free water", D5 ¼ NS, which provides more water per volume - Add or remove potassium as needed

What is hyponatremia?

•Most common electrolyte abnormality in the hospital •Associated with poor patient outcomes •Primarily a Water abnormality -with abnormal ADH •Defined - serum Na < 135 mEq/L acute is going to have developed over the first 48 hours and then chronic they've been hyponatremic greater than 48 hours - severe is considered a sodium less than 120 - moderate is 120 to 129 - then mild is 130 to 134 so again this is going to be primarily of water abnormality

What do NSAIDs do to cause prerenal injury?

•NSAIDs block prostaglandin's effects • Unable to vasodilate the afferent arteriole

What are Colloid solutions: Albumin?

•NaCl content iso-osmotic •Iso-oncotic 5% albumin: hypovolemia •Hyperoncotic 25% albumin: Pull fluid for diuresis - treat problems associated with fluid accumulation in the extravascular spaces and to provoke diuresis •$$$ - Pooled Blood Product •Leakage to interstitial space - Hours to days •Shortages have been common - Restricted use - generally crystalloids are preferred due to cost and also due to potential problems that may develop as a result of the albumin infusion - we do use albumin in some clinical situations particularly in liver disease for treatment of hepato-renal syndrome as well as spontaneous bacterial peritonitis you also see it used in patients that need additional diuresis is sometimes given at the same time as a dose of a loop diuretic

What is the Ongoing monitoring required?

•Physical Exam - Vital signs - Neurologic status, lung exam, cardiac exam, extremities, skin •Clinical Documentation - Volume of fluid received, current rates and composition - Urinary output - hourly, totals •Laboratory Assessment - Electrolytes, acid/base, renal function, lactate - Other medications •Determine need for continued therapy: if they're taking orals we give orals and DC IV •Alter prescription as needed if patients will be seeing fluid overload they'll start using a loop diuretic to get off fluid when we could simply just turn off the maintenance fluids making sure you look at these monitoring just like we had already talked about do we need to alter the prescription do we need to continue that fluid therapy

What are the Causes of Hypotonic Hyponatremia?

•Plasma osmolality < 280 mOsm/kg 1. Hypovolemic - ADH secretion is normal •GI losses - vomiting/diarrhea •Renal losses - thiazide diuretics 2. Hypervolemic •Cirrhosis, heart failure, renal failure 3. Isovolemic •Normal ADH - beer potomania, psychogenic polydipsia •Syndrome of inappropriate ADH secretion (SIADH)

What is the Hyponatremia Hypotonic/HYPERvolemic treatment?

•Prevention - Iatrogenic: HF, ARF/CRF - Control of associated disease - Very careful fluid therapy with intense monitoring •Fluid restriction - salt and water anywhere from 1000 to 1500 mils, even within ESRD and dialysis we may be even lower than that •Diuretics - Multimodal (loop + aldosterone antagonist), or thiazide type diuretics in combination •Optimize treatment of underlying disease - Dialysis if chronic kidney disease: it's reassessing their volume status are we removing enough fluids with our dialysis

What is the Treatment of Hypovolemia & Shock?

•Rate of repletion - as fast as possible •Choice of fluid - Give blood if bleeding - Isotonic crystalloid solutions - 0.9% saline preferred - 250-500 mL NS over 15 min, reassess, repeat as needed - Effective, inexpensive, and we usually do small volumes first to make sure the patient responds as well as don't get overloaded - Avoid hetastarch - increased kidney injury & mortality - Avoid colloid - does not improve outcomes - Exception may be use of albumin in severe sepsis •Monitoring - Continuous assessment of vital signs, urine output, perfusion, and decreased in the compensatory mechanism - Others: physical exam, serum lactate, arterial pH

What happens in vascular damage with intrinsic injury?

•Renal artery/vein thrombosis -Can develop during vascular procedures like angioplasty -Left ventricle thrombus •Vasculitis -Inflammatory processes -Neutrophils cause damage => ischemic ATN •Accelerated HTN -Renal microvascular flow compromised •Hemolytic uremic syndrome (HUS) -Hemolytic anemia and thrombocytopenia -Complement mediated vs bacteria

How can we prevent AKI in the future?

•Renal dose adjustments •Since SCr generally lags actual kidney function by 1-2 days, providers must be proactive with renally adjusting medications •Watch for trends in SCr •Volume of distribution of drugs changes during AKI •Water soluble drugs •Utilize loading doses for certain drugs in order to achieve steady state •Discontinue the offending agent and any drug that can potentially exacerbate the AKI

What is blood?

•Replace blood with blood (PRBCs) it will expand circulating volume and this is really indicated for a patient that has lost blood so give blood when the patient lost volume due to losing blood - Hemorrhage - Anemia - O2 carrying - Goal hemoglobin? we're going to transfuse if the patient's hemoglobin is less than Seven or in cardiac disease maybe less than eight when we think about giving one unit of packed red blood cells they will raise the hemoglobin by approximately 1 so if your hemoglobin was 7 and you gave one unit of blood then you would raise it to 8 •Blood products - FFP is fresh frozen plasma and this is generally given for patients that have a coagulation disorder or need to reverse someone that is hypo-coaguable or needs more clotting factors due to an urgent surgery or procedure - Platelets: not used for volume expansion but to correct an underlying deficit

What is Prevention and Treatment of Overcorrection?

•Risk factors for overcorrection - Due to volume depletion - Due to adrenal insufficiency - SIADH •Risk Factors for ODS - Serum sodium < 105 - Concurrent hypokalemia - Chronic Excess alcohol intake - Acute or chronic hepatic disease - Malnourishment Treatment: •Desmopressin 1-2 mcg IV or SQ every 6-8 hours in conjunction with our 3% Saline •Free Water as we continue treatment we want to maintain that 4-6 mEq every 24 hours until our serum sodium is normal even after the first day of correction we want to maintain that same amount of correction every 24 hours

What is the epidemiology of acute kidney injury?

•Risk factors include: •CKD •Diabetes •Heart or liver disease •Albuminuria •Major surgery (especially cardiac surgery) •Sepsis •Hypotension/volume depletion •Certain medications •Demographics (age, male gender, AA race) AKI is associated with increased length of stay, higher costs, readmission, and ventilator days

What are the Kidney Disease: Improving Global Outcomes (KDIGO) criteria?

•SCr increase of ≥ 0.3 within 48 hours •SCr increase of ≥ 1.5 times baseline within the prior 7 days •Urine output < 0.5 mL/kg/hr for ≥6 hours

Calculate the patient's serum osmolality. 140 109 32 4.0 25 1.3 245

•Serum osm = (2 x [Na]) + ([Glucose]/18) + ([BUN]/2.8) = (2x140) + (245/18) + (32/2.8) =305

What is Osmotic Demyelination Syndrome (ODS)?

•Symptoms •Flaccid paralysis, mutism, pseudopalsy •5-7 days after sodium replacement treatment •25% mortality rate •Prevention: Avoid overcorrection - ODS occur in patients who's sodium is risen at 10 to 12 mEq in 24 hours and sometimes of in patients with 18 mEq per liter in the first 48 hours and this has also had reported cases ODS in 9 mEq per liter in 24 hours this is really in patients that have chronic hyponatremia. there is some data that says acute hyponatremia or less than 48 hours can be corrected quicker than this

What should be considered for hypovolemia in the elderly?

•Thirst •Communication - Impaired sensation - Disabled, comatose •Decreased TBW •Kidney has decreased concentrating ability - decreased response to ADH - decreased # of nephrons

What should be considered for hypovolemia in children?

•Thirst •Communication • Increased mL/kg water requirement • Increased TBW relative to weight • Increased metabolism (heat) •Kidney has decreased concentrating ability - Immature

What is Blood volume & Plasma osmolality?

•Tightly regulated •Essential for normal function •Frequently cause or contribute to hospitalization •Blood volume - saline balance •Assessed by physical exam •Regulated by RAA, ANP, sympathetic nervous system Blood volume is also described as effective circulating volume and is related to saline balance or intervascular volume and this is assessed clinically on physical exam by things like blood pressure, pulse, and organ perfusion and is regulated by the RAS system, the sympathetic nervous system in ANP (atrial naturetic peptides •Plasma osmolality - water balance •Assessed by serum sodium and osmolality •Regulated by osmoreceptors, vasopressin, thirst Plasma osmolality is a measure of water balance and water balance is assessed by looking at serum sodium first and then osmolality, osmolality is regulated by osmoreceptors in the CNS and circulatory system in then by secretion of ADH and vasopressin and finally by the stimulation of thirst

What is the Hyponatremia: Hypotonic/Isovolemic treatment?

•Treat underlying condition as indicated - Hypothyroidism - check TSH - Adrenal insufficiency - ACTH stim test - Primary or psychogenic polydipsia > Compulsive water consumption > Phenothiazines (dry mouth) - Low solute and protein diets > Tea & toast diet so they're not taking in enough solute you but still taking in fluid > Sodium-free vegetarian - Beer potomania •TREATMENT: Fluid restrict

What is intrinsic injury?

•Vascular Damage •Glomerular damage •Acute tubular necrosis (ATN) -Ischemic -Endogenous toxins -Exogenous toxins •Acute interstitial nephritis (AIN) -Drugs -Infection

What is prerenal injury?

•Volume depletion •Decreased effective circulatory blood volume •Functional (Drugs) •Afferent arteriole: brings blood to glomerulus •Efferent arteriole: carries blood away from glomerulus •When renal blood flow is compromised or blood volume is decreased, the body will compensate 1. Angiotensin II vasoconstricts •Primarily efferent arteriole 2. Prostaglandins vasodilate •Primarily afferent arteriole •Reduced blood flow/volume caused by: •Diuretics •Dehydration •Heart failure

What is the clinical presentation of acute kidney injury?

•Weight gain •Flank pain -Unilateral vs. bilateral •Fever/rash/arthralgias •Fluid overload vs. volume depletion -Overload: edema, ascites, dyspnea, increased JVP -Volume depletion: dehydration, hypotension, decreased JVP

How can we Assess Acid-Base Status?

1) Assess pH value 2) Evaluate ABG data to see which primary parameter abnormality is consistent with pH 3) Evaluate whether compensation has occurred

What are the mechanisms for Acid-Base Homeostasis?

1) Buffering System Bicarbonate/carbonic acid buffer system The first line of defense against any sort of acid or base disorders in the body. A buffer system is the presence of a weak acid or weak base with its conjugate base or conjugate acid, respectively. And together they help maintain pH at a constant level by neutralizing the effects of additional acids or bases that are added to the system. Bicarb and carbonic acid make up the most common buffer system present in the body 2) Respiratory Regulation (Lungs) pCO2 By increasing or decreasing ventilation, the lungs can regulate the amount of carbon dioxide that is present in the bloodstream and this can help with acid-base regulation 3) Metabolic Regulation (Kidneys) HCO3 − Kidneys are a site where excess protons are excreted and bicarb is either excreted or reabsorbed as needed by the body based on acid-base status. This is another mechanism for helping to regulate any sort of acid-base disorders in the body

What is the body weight: daily fluid requirement?

1-10kg 4 mL/kg/hour >10-20kg + 2 mL/kg/hour >20kg + 1 mL/kg/hour Alternate for Adults: 25-35 mL/kg/day water

Case example Calculations: 1.EH is a 49-year-old male. He is 6'7" and weighs 225 lbs. His SCr today was 0.9mg/dL. what is his CrCl? 2.While on your clinical shift, you notice that patient AS wasn't ordered a BMP the day before. Fortunately, the nurses have been keeping track of urine output. What can you determine from the last few shifts? Weight = 70 kg 290 mL 300 mL 240 mL 190 mL 100 mL 80 mL 3. While working in the core, you come across a fluid bolus order for patient JH. Before verifying the order, you want to evaluate if this is appropriate. You quickly check the patient's most recent labs. What assessment can you make? 142 100 25 108 4.1 28 0.8

1. 136 mL/min 2. Decreased 3. Na- normal Cl- normal BUN-elevated K-normal CO2- normal SCr- normal Glucose- high BUN:SCr= 31.25 VERY HIGH Prerenal probably

How many liters of plasma are in a 70 kg adult male? What is his blood volume? Step 1 - plasma is water so what % total body water (TBW) is an adult male? Step 2 - what spaces does TBW distribute into, in what fractions and what volumes? Step 3 - what spaces is the ECF further divided into and what are their volumes? Step 4 - what is blood volume?

1. 70 kg x 0.6= 42 L 2. ICF 2/3 (28 L) and ECF 1/3 (14 L) of that 3. Intravasular 3.5 L 24% and Interstitial 75% 10.5 L 4. *Blood= 45% 3.5 x 1.45= 5 L*

Case: CP is an 80-year-old female who was admitted on 3/11 with community acquired pneumonia leading to respiratory failure. She had a respiratory panel and blood cultures drawn. Her respiratory panel was unremarkable, but blood cultures grew enterococcus. A transesophageal echocardiogram confirmed the presence of endocarditis. She was started on antibiotics on 3/12. •PMH: aortic stenosis s/p TAVR valve, AFib, HTN, CAD, COPD •FH: unremarkable •SH: smokes 2 packs per day •Allergies: NKDA Labs: K 3.2 HCO3: 15 SCr: 0.42=>7.2 Urine output: 1750=>1800=>1600=>980=>710 RBC: Many •Hospital Medications •Albuterol-ipratropium 2.5-0.5 mg/3mL nebulizer solution four times daily as needed •Ampicillin 2 g IV every 4 hours •Bisacodyl suppository 10 mg as needed •Bupropion ER tablet 150 mg PO daily •Gabapentin capsules 600 mg by PO 3 times daily •Gentamicin 55mg IV every 8 hours •Polyethylene glycol powder 17g PO daily •Senna tablet 17.2 mg PO twice daily •Warfarin 5 mg PO daily 1. What risk factors does CP have for AKI? 2. Does CP meet criteria for an AKI? Why or why not? 3. Which medication likely caused her AKI? 4. What kind of AKI does this medication cause? 5. What is the mechanism of injury? 6. What is CP's CrCl? 7. What medications should be renally dose adjusted? (ok to use Lexicomp/Micromedex/etc. for this question) 8. What AKI complication is present in CP? 9. How can the complication be managed? 10. If her condition got worse and her AKI became severe, what treatment option may be necessary?

1. Age, hypertension, antibiotics, heart disease, surgery 2. AKI 3. SCr increase of ≥ 0.3 within 48 hours SCr increase of ≥ 1.5 times baseline within the prior 7 days Urine output < 0.5 mL/kg/hr for ≥6 hours Her: 710 mL/60 kg/24 hours SCr: 0.42=>7.2 4. Ampicillin and Gentamicin 5. Intrinsic- RBCs, AIN 6. 54 mL/min 7. Renally dosed meds- Gabapentin 600 TID 8. Low Bicarb- metabolic acidosis 9. Aminoglycosides- switch him Extended interval to less nephrotoxic, fluid resuscitation 10. Dialysis

What is the Bronchodilator Therapy?

1. Albuterol 2.5-10 mg every 20 min x 3 then every 1-4 hours as needed by nebulizer 2. Ipratropium 0.5 mg every 6 hours by nebulizer Inhaled vs nebulizer -Initiate or continue maintenance inhalers when stable

What is the Correct Order of Respiratory Meds?

1. Albuterol (MDI or neb) 2. Hypertonic saline, then Pulmozyme - vest simultaneously 4. Inhaled antibiotic 5. Steroid nebulizer or inhaler Goal is open, clear airways for better drug distribution and absorption into lung tissue

How is the balance of fluid volume maintained?

1. Antidiuretic Hormone (ADH) •Increases water permeability of renal collecting duct •Increases peripheral vascular resistance secreted by the posterior pituitary and stimulated by both hyper osmolality an hypovolemia it can be overridden by volume deficits 2. Renin - Angiotensin - Aldosterone System •Vasoconstriction => increased renal perfusion • Increased reabsorption of sodium, chloride, and water maintaining a circulating volume including renal perfusion through vasoconstriction and increases in salt and water reabsorption in the kidneys 3. Sympathetic nervous system - Vasoconstriction activated by a decrease in circulating volume and leads to vasoconstriction as well as increased heart rate 4. Thirst- can be triggered by both hyperosmolar and hypovolemia Osmoreceptors in the hypothalamus •Baroreceptors - L Atrium, Carotid arteries, Macula Densa 5. Normal responses to hypovolemia/hyperosmolality An inability to respond appropriately to thirst can lead to serious complications of dehydration and volume depletion, the two groups that we worry most about this is really the elderly and the children

What are the important drugs associated with AIN?

1. Antimicrobials -Beta-lactams -Fluoroquinolones -Bactrim 2. Diuretics 3. Neuropsychiatric -Lithium 4. NSAIDs 5. Miscellaneous -Cyclosporine -Radiocontrast media

1. Given an arterial blood gas, describe the 3 step process for determining what type of acid-base disorder is present.

1. Assess pH value 2. Evaluate ABG data to see which primary parameter abnormality is consistent with pH 3. Evaluate whether compensation has occurred

What are the Pharmacologic Therapies?

1. Bronchodilators -Anticholinergics -Beta 2 Agonists -Theophylline 2. Corticosteroids -Inhaled vs Systemic 3. Additional drug therapy -Antibiotics -Roflumilast

COPD vs Asthma?

1. COPD Age of Onset: Usually > 40 yrs Smoking History: Usually > 10 pack-yrs Sputum Production: Often Allergies: Infrequent Spirometry: May improve but never normalize Disease Course: Progressive worsening (with exacerbations) Clinical Symptoms: Persistent and progressive Response to Beta-Agonists: Moderate Response to Anticholinergics: Normal Response to Corticosteroids: Diminished 2. Asthma Age of Onset: Usually < 40 yrs Smoking History: Not causal Sputum Production: Infrequent Allergies: Often Spirometry: Often normalizes Disease Course: Stable (with exacerbations) Clinical Symptoms: Intermittent and variable Response to Beta-Agonists: Dramatic Response to Anticholinergics: Becomes blunted with repeated use Response to Corticosteroids: Robust

How can you assess the symptoms of COPD?

1. COPD Assessment Test (CAT): An 8-item measure of health status impairment in COPD 2. Modified Medical Research Council (mMRC) Questionnaire: relates well to other measures of health status and predicts future mortality risk.

What are the VITAMIN D & VITAMIN D ANALOGS agents?

1. Calcitriol •Activated form of vitamin D •Calcijex, Rocaltrol •1,25-dihydroxyvitamin D3 2. Paricalcitol •Synthetic analogs of calcitriol •May reduce proteinuria •Zemplar 3. Doxercalciferol •Synthetic analogs of calcitriol •Hectorol 4. Ergocalciferol •Must be hydroxylated to 1,25-dihydroxyergocalciferol •Calcidol, Calciferol, Drisdol •Vitamin D2 5. Cholecalciferol •Must be hydroxylated to calcidiol •Dialyvite Vitamin D •Vitamin D3 6. Calcifediol •Treatment of secondary hyperthyroidism in adult patients with stage 3 or 4 CKD •Rayaldee •25-hydroxyvitamin D3

What are the phosphate binders agents?

1. Calcium-Based •First line •Calcium citrate and calcium chloride not recommended •AE: Hypercalcemia, calcium-phosphate crystal formation/vascular occlusion •Calcium carbonate (Tums, Oscal-500, Caltrate-600, Neprho-Calci, LiquiCal, CalciChew) •Calcium acetate (Phoslo, Phoslyra) 2. Sevelamer •Anion-exchange resin •Sevelamer carbonate •Does not contain calcium •Less GI adverse effects •Sevelamer carbonate (Renvela) •Sevelamer hydrochloride (Renagel) 3. Lanthanum-Based •AE: Peripheral edema, myalgias •Interactions: •Cationic antacids •Quinolone antibiotics •Lanthanum carbonate (Fosrenol) 4. Iron-Based •Ferric citrate •210mg ferric iron in 1 g ferric citrate •Sucroferric oxyhydroxide •Minimal systemic absorption •AE: Increased serum iron, ferritin, and Tsat, discolored (dark) stools •Ferric citrate (Auryxia) •Sucroferric oxyhydroxide (Velphoro) 5. Aluminum-Based •Not first line •Reserve for short-term use (4 weeks) •AE: Aluminum toxicity (CNS toxicity, encephalopathy), worsening anemia •Do not use with citrate-containing products •Aluminum carbonate (Basaljel) •Aluminum hydroxide (Alterna GEL, Amphojel, Alu-cap)

What are the Goals of Respiratory Treatments?

1. Clear mucus from lungs -Improve respiratory function -Prevent further colonization -Prevent further lung damage 2. Reduce bacterial concentration in sputum -Reduce inflammation in the lungs -Prevent exacerbations 3. Improve quality of life & survival

What are the types of Parenteral Fluid Therapy?

1. Dextrose solutions (water) •Electrolytes can be added as needed - administered to patients to replace water so water not intervascular volume- total body water dextrose is added to maintain appropriate tonicity but is rapidly taken up into cells leaving water behind 2. Crystalloids (Salt containing) •Additional electrolytes can be added •Isotonic vs. Hypotonic - crystalloids are salt solutions or saline sodium chloride solutions are commonly prescribed in general terms and they're used to correct volume deficit or intervascular volume 3. Colloids •Hetastarch, Dextran, Albumin - used to increased circulating volume or intervascular volume 4. Blood and blood products - used to increased circulating volume or intervascular volume

What is the non-pharm for CKD?

1. Dietary •Protein •Restriction to slow progression of CKD: 0.8 g/kg/day •Increase during dialysis: 1.2 - 1.3 g/kg/day •Phosphorus •Restriction if serum phosphorous high and/or if iPTH high: 800 - 1,000 mg/day •Sodium •Restriction in CKD: <2 g/day •Restriction in ESRD: <2-3 g/day 2. Modifiable risk factors •Smoking cessation •Weight loss 3. Avoid nephrotoxic agents •NSAIDs, radiocontrast dyes, aminoglycosides

What are the ERYTHROPOIESIS-STIMULATING AGENT THERAPY agents?

1. Epoetin alfa •Glycoprotein •Recombinant DNA with the same amino acid sequence as endogenous erythropoietin •Epogen •Procrit 2. Darbepoetin alfa •Two additional N-linked carbohydrate chains •Decreased affinity for erythropoietin receptor •Longer duration of activity •Aranesp 3. Methoxy PEG-epoetin beta •Additional amide bond between the N-terminal or ε-amino group of epoetin beta and methoxy polyethylene glycol butanoic acid •Continuous erythropoietin receptor activator (CERA) •Longest half-life •Mircera

What are the body fluid compartments?

1. Extracellular Fluid 1/3 of the total body water •Intravascular Space -25% of the extracellular compartment - in order to increase circulating volume you must get fluid into the intervascular space and keep it there •Interstitial Space a space between the cells veins and arteries separate the inner vascular and interstitial spaces and this can have some mixing particularly when it gets to the capillary -75% of the extracellular compartment 2. Intracellular Fluid 2/3 of the body's total water

Case: JV is a 65 year old female admitted with COPD Exacerbation 3 days ago who is now much improved and being prepared for discharge. PMH: COPD x 8 yrs, 2 prev hospital admissions SH: 1ppd x 30 yrs, quit x 1 year Home Medications: Ipratropium MDI 2 puffs QID Albuterol MDI prn Physical Assessment: BP 134/82, P 84, RR 12, T 37 C Lungs: clear with mild insp/exp wheeze still evident Lab: Hgb 14.5, Hct 43.5%, WBC 9, pulse oximeter - 91% oxygen saturation, SrCr 1.2 Spirometry: FEV1 48% predicted COPD Assessment Test (CAT) Score: 9 1. What patient information will you use to assess this patient's risk for COPD morbidity and to determine maintenance therapy needs? Using the GOLD guideline, how would you categorize this patient based on her history and most recent spirometry and symptom scores? 2. Evaluate this patient's prior maintenance regimen in terms of current evidence-based treatment guidelines and make a recommendation for additions/deletions/changes, if needed, to optimize care. Justify your drug selections based on efficacy, safety, adherence, and cost. 3. Describe how you would educate a new prescriber on the benefits versus risks of inhaled corticosteroid therapy in COPD. Consider specifically the risk for development of pneumonia. 4. What additional interventions drug and non-drug would you recommend for this patient after discharge? 5. What will you assess and monitor the patient for at a 4 week post-discharge follow up visit?

1. FEV=Severe 2. LAMA or LABA+LAMA combo, consider pt specific factors, cost, formulary 3. ICS= Decrease symptoms, exacerbations bone fractures, thrush, pneumonia but LABA+LAMA preferred 4. NO ANTITUSSIVES- no efficacy, more ADEs, treat co morbidities, Oxygen 5. Non-pharm interventions IRREVERSIBLE CONDITION

What are the iron supplementation agents?

1. Ferric carboxymaltose •Injectafer •Adult patients with CKD not on dialysis •IV push or diluted 2. Ferumoxytol •Adult patients with iron-deficiency anemia associated with CKD •Dilute in NS or D5 •Feraheme 3. Iron dextran •Patients with iron deficiency in whom oral iron is unsatisfactory or impossible •Test dose required •InFeD •Dexferrum 4. Iron sucrose •Adult and pediatric CKD and CKD 5D patients aged ≥2 years •IV push or diluted •Venofer 5. Sodium ferric gluconate •Adult and pediatric CKD 5D patients aged ≥6 years receiving ESA therapy •Slow IV push or diluted •Ferrlecit

Case: RG is an 87-year-old Caucasian female who presents at the Kidney Disease and Blood Pressure Clinic for follow up of stage 3 chronic kidney disease (CKD). She says she is doing well and denies chest pain, shortness of breath, weight gain, or edema. RG repots excessive sleeping over the past couple of weeks due to feeling tired and weak but denies dizziness. She has had a gradual weight loss of 20 pounds over the last 4 years. She denies alcohol use and is a never smoker. Past Medical History: CKD stage 3, Solitary kidney on right, Hypertension, Hyperlipidemia, Vitamin D deficiency, Hypothyroidism Gastroesophageal reflux disease, Depression, Osteoarthritis, Urinary incontinence Meds: Acetaminophen (Tylenol® Arthritis) 650 mg controlled-release tablet Aspirin 81 mg enteric-coated tablet Cholecalciferol (vitamin D3) 400 unit tablet Levothyroxine (Synthroid®) 100 mcg tablet Lisinopril 5 mg tablet Naproxen (Aleve ®) 500 mg capsule Oxybutynin (Ditropan®) 5 mg tablet Famotidine (Pepcid®) 20 mg tablet Rosuvastatin (Crestor®) 10 mg tablet Tramadol 50 mg tablet Venlafaxine (Effexor®-XR) 37.5 mg XR capsule Vitamin C/vitamin E (cranberry concentrate) capsule Labs: BP 160/88 Sodium: 133 (L) CO2: 20 (L) BUN: 35 (H) Creatinine: 1.8 (H) GFR: 27 (L) Hb: 9.6 (L) Ht: 33 (L) Calcium: 8.4 (L) PTH: 104.1 (H) Urine protein:creatinine ratio: 0.3 (H) Iron serum, TIBC, UIBC, Iron saturation: Hemolyzed (A) 1. Classify RG's stage of CKD based on today's calculated GFR. 2. What susceptibility and initiation factors did the patient have for developing CKD? 3. What CKD progression factors does the patient have? 4. List and provide explanations for at least 3 therapies that can be either added or optimized to manage RG's progression factors/complications from CKD.

1. GFR is 27 so Stage 4 2. Susceptibility factors: Age, dyslipidemia Initiation factors: hypertension 3. Progression: Dyslipidemia, hypertension 4. She has hyperparathyroidism=low calcium -Vitamin D: she is deficient so increase her dose -Oral Iron supplement: Anemia -Increase lisinopril -D/C Naproxen -Increase statin dose

What are the complications of PD?

1. Glucose load /weight gain •Management - Intraperitoneal insulin, dietary caloric restriction 2. Thrombosis •Management - Intraperitoneal heparin 3. Infections •Management - Antibiotics

Case: AS is a 55-year-old female who visits your pharmacy complaining about lower back pain that started a few days ago. After asking her about any recent changes she's had she commented that she has been volunteering to set up the Pig Out at the Park event. She says she has been "putting up the booths and canopies." She asks you for your expertise in choosing a medication. •PMH: HTN •FH: father had acute MI •SH: 1 mixed drink nightly •Allergies: lisinopril (cough) •Home medications: •Losartan 100 mg PO daily •Chlorthalidone 25 mg PO daily 1. What risk factors does AS have for AKI? 2. Which kind of AKI? 3. Which medications can contribute to AKI? 4. Which medication(s) would you recommend against? Why? 5. Which medication(s) would you recommend him for his pain? 6. What non-pharmacological recommendations would you give EH for preventing kidney injury?

1. HTN, dehydration 2. Prerenal AKI 3. Chlorthalidone, Losartan, Don't want her to take NSAID 4. Don't take NSAID 5. Take Acetaminophen 6. Stretches, drink water

What are the Anti-inflammatory/Other Therapies?

1. Ibuprofen -Traditional dosing 200-400mg q 4-6 hours -High dose 20-30mg/kg/day, divided twice daily •Requires PK monitoring of Ibuprofen levels; goal peak 50-100mcg/mL 2. Azithromycin -250mg (<40kg) or 500mg (>/=40kg) three times weekly -Studies show benefit for nutritional status and fewer pulmonary infections -Monitor yearly for atypical mycobacterium

How is the reproductive system impacted by CF?

1. In utero blockage of vas deferens leads to male infertility in CF -Do not assume infertility -Sperm may still be produced and may be retrieved for In-Vitro Fertilization (IVF) 2. Females may be infertile due to thickened cervical mucus or malnutrition -Medication counseling by the pharmacist -Recommend genetic counseling

What is Respiratory Regulation (Lungs)Alveolar Ventilation?

1. Increased respiratory rate ↑ CO2 excretion, ↓ pCO2 For example, if you see an increased respiratory rate in the lungs, this means that the lungs are increasing the amount of CO2 that's being excreted or blown out of the body. This decreases the pCO2 in the body 2. Decreased respiratory rate ↓ CO2 excretion, ↑ pCO2 Decreased respiratory rate achieves the opposite, meaning you're blowing off less CO2 so you have less CO2 excretion which means you keep more CO2 in the body, resulting in an increased pCO2 in the body. These adjustments would be made based on the acid-base status of the body. pCO2 or CO2 is the acidic component. If you are acidic= hyperventilate to decrease CO2 If you are basic= hypoventilate to increase CO2 Respiratory regulation of acid-base status is achieved through the lungs with alveolar ventilation. CO2 is something that comes from cellular metabolism. The CO2 that's produced can either bind with water to form carbonic acid or combine with hemoglobin. In either form, CO2 eventually travels to the lungs where it passively diffuses into the alveoli and can be exhaled through breathing. As you can see with the double arrows, all of these systems exist in equilibrium. Depending on the needs of the body, you might have more or less CO2 exhaled by the lungs.

What are the COMPLICATIONS OF HD?

1. Interdialytic •Hypotension •Management - Trendelenburg position, decreasing ultrafiltration rate, replacement fluids, midodrine (ProAmatine) •Muscle cramps •Management - Massage, decreasing HD rate, vitamin C, vitamin E, quinine 2. Thrombosis •Dialysis port thrombosis •Management - Saline flush, alteplase (Cathflo) 3. Infections •Catheter-related infections or bacteremia •Management - antibiotics, access replacement

How should anemia be treated?

1. Iron Initiation •CKD - TSat ≤30% and ferritin ≤500 ng/mL •CKD 5HD - TSat ≤30% and ferritin ≤500 ng/mL 2. Erythropoiesis-Stimulating Agent (ESA) initiation •CKD - Hgb <10 g/dL •Consider rate of fall of Hgb, prior response to iron, risk of needing transfusion •Do not initiate if Hgb ≥10 g/dL •CKD 5HD - Hgb 9 - 10 g/dL, use to avoid drop in Hgb to <9 *Do not use ESAs to intentionally increase Hgb to >13 g/dL or to maintain Hgb >11.5 g/dL

How do you treat the other complications?

1. Metabolic acidosis •Sodium bicarbonate solution •Treat underlying cause 2. Fluid overload/edema •Loop diuretics +/- metolazone •Dialysis 3. Hyperphosphatemia •Diet restriction •Phosphate binders 4. Hypermagnesemia •Discontinue magnesium supplements or antacids

Case: EH is a 80-year-old male presenting to the ER with altered mental status. HIs granddaughter reports that he has been acting "unusual and confused" lately. She decided to bring her grandfather in after he was unable to get of his bed this morning. A urine culture was drawn upon admission. •PMH: Alzheimer's disease, BPH, seasonal allergies •FH: mother had breast cancer •SH: not pertinent •Allergies: penicillin (rash) •Home Medications: •Donepezil 10 mg PO nightly •Tamsulosin 0.4 mg PO daily •Diphenhydramine 25 mg PO daily •UA obtained through strait cath. •Ultrasound of bladder showed 2000 mLs of urine. •Pt states he has been having difficulty urinating for the last few days. Urinalysis Volume 1000 mL Color Clear Cellular debris Present Bacteria Present RBC None WBC Present EH was diagnosed with a UTI. The provider elected to start ceftriaxone 1g IV daily. 1. Does ceftriaxone require any renal dose adjustments? 2. What risk factors did EH have for AKI? 3. What kind of AKI is EH presenting with? 4. What is contributing to his AKI? Medications? Conditions? 5. What changes can be made to his home medication list to potentially reduce his future risk of developing an AKI?

1. No 2. Age, male, BPH, catheter use 3. Postrenal oDonepezil and diphenhydramine oTrouble ruining past couple of days oUltrasound: 2000 mL of urine in bladder scan 4. Diphenhydramine anticholinergic causes bladder obstruction, Ceftriaxone 5. D/C Diphenhydramine, switch to intranasal ICS like fluticasone

What are the antibiotics for MRSA?

1. Oral -High-dose Septra •20mg/kg divided BID for children •Septra DS: 2 tabs BID for adults -clindamycin -minocycline, doxycycline (CI <8 years old) -linezolid (Zyvox) 2. IV -vancomycin, linezolid -daptomycin not appropriate (poor lung penetration)

What are the Antipseudomonal Antibiotics?

1. Oral *recent studies have shown that eradication of pseudomonas infections is better with inhaled antibiotics, so the oral treatment(s) are rarely used.* Ciprofloxacin •Children: 40mg/kg/day PO divided q12 hours -lower bioavailability <13 compared to >13 years old •Adults: 750mg PO BID, typically x 14 days, could be more •Cipro suspension cannot be given per tube •Benefit outweighs risk of joint/connective tissue toxicity •Counsel to separate from dairy, enteral feeds, Ca, Fe, Zn 2. Inhaled -Tobi (tobramycin) & Tobi Podhaler -Cayston (aztreonam) -Off-label: colistimethate, ceftazidime, meropenem

What is the Movement of solutions in the Body?

1. Osmotic Pressure •Ability of solutes to cause osmotic driving forces •Osmolarity (mOsm/L) takes into account all the solute concentrations, not just the ones that can't cross the semipermeable membrane •Osmolality (mOsm/kg)- not used in practice because water changes its volume according to the temperature but mass remains the same. Osmolality is the same in the intercellular fluids and the extracellular fluids or both inside and outside •Serum osm @ (2 x [Na]) + ([Glucose]/18) + ([BUN]/2.8) •Na-mEq/L; Glucose and BUN mg/dL •Tonicity = effective osmolality •Osmotic solutes that CANNOT freely move across membranes •Serum tonicity = 2 x (Na) + (Glucose/18) Tonicity is the measure of osmotic pressure gradient between the two solutions. unlike osmolarity. tonicity is only influenced by solutes that cannot cross the semipermeable membrane. Because these are the solutes influencing the osmotic pressure gradient. The osmotic pressure gradient is 25 to 30 millimeters of Mercury or about .5% of total osmotic pressure this is not much but it's enough to keep the water in the vascular circulation so based on this you can have a fluid that is iso-osmolar but not isotonic so when we look at the calculation serum osmolality why is it 2 times sodium this is really to account for chloride and other anions and then glucose and BUN are divided by things that correct for the fact that they are in milligrams per deciliter and as the endpoint in milliosmoles. when we get into tena city we notice that the BUN falls off because it's freely permeable to cellular membranes and it goes back and forth. imbalances of water flow from the intercellular to the extracellular fluid result from solutes that may change in inter and external osmolality 2. Oncotic Pressure •Plasma proteins

What is the Pathology, pathogenesis & pathophysiology of COPD?

1. Pathology •Chronic inflammation •Structural changes 2. Pathogenesis •Oxidative stress •Protease-antiprotease imbalance •Inflammatory cells •Inflammatory mediators •Peribronchiolar and interstitial fibrosis 3. Pathophysiology •Airflow limitation and gas trapping •Gas exchange abnormalities •Mucus hypersecretion •Pulmonary hypertension

What are the IV Antipseudomonal Antibiotics?

1. Penicillins: Piperacillin-Tazobactam (Zosyn) 2. Cephalosporins: Ceftazidime (Fortaz) and Cefepime 3. Carbapenems -Meropenem (Merem)- first choice among carbapenems -Doripenem (Doribax) or Imipenem-cilastatin (Primaxin) •Resistance may develop more quickly to Primaxin 4. Tobramycin 5. Ciprofloxacin -30mg/kg/day IV required for CF children due to increased clearance 6. Aztreonam

What is the presentation for each of the types of acute kidney injury?

1. Prerenal Urine sediment: Hyaline casts- Normal Hematuria (RBCs): None Urinary WBC: None *Urine Na: Low* *FENa (%): <1* *BUN/SCr: >20* 2. Instrinsic *Urine sediment: Granular casts/Cellular debris* *Hematuria (RBCs): Yes* Urinary WBC: Moderate-High *Urine Na: High* FENa (%): >2 BUN/SCr: about 15 3. Postrenal Urine sediment Hematuria (RBCs): Sometimes Urinary WBC: Low *Urine Na: High* FENa (%): Variable BUN/SCr: about 15

How do you treat the three types of acute kidney injury?

1. Prerenal AKI •Hemodynamic support and volume replacement 2. Intrinsic AKI •Discontinue the offending agent •Can give IV fluids before some drugs to reduce risk of nephrotoxicity -Radiocontrast media -High dose methotrexate -IV acyclovir -Many others 3. Postrenal AKI •Remove obstruction •Discontinue offending agent

How do you manage hyperkalemia?

1. Protect the heart from arrhythmias -IV Calcium chloride or calcium gluconate 2. Shift potassium into cell •Beta agonists -Albuterol •Insulin + dextrose •Sodium bicarbonate 3. Eliminate excess potassium •Cation exchangers •Sodium polystyrene sulfonate (Kayexelate) •Patiromer (Veltassa) •Loop diuretics •Dialysis

1. Fill in the expected changes/values for the following parameters for each acid/base disorder. RESPIRATORY ACIDOSIS RESPIRATORY ALKALOSIS METABOLIC ACIDOSIS METABOLIC ALKALOSIS With/without compensation: pH pCO2 HCO3-

1. RESPIRATORY ACIDOSIS pH: low pCO2: high HCO3- No Compensation: normal HCO3- With compensation (kidneys): slowly increases 2. RESPIRATORY ALKALOSIS pH: high pCO2 : low HCO3- No Compensation: normal HCO3- With compensation (kidneys): slowly decreases 3. METABOLIC ACIDOSIS pH: low HCO3-: low pCO2 No Compensation: normal pCO2 With compensation (lungs): rapid decrease 4. METABOLIC ALKALOSIS pH: high HCO3-: high pCO2 No Compensation: normal pCO2 With compensation (lungs): rapidly increase

What is postrenal injury?

1. Renal pelvis/tubular obstruction Direct obstruction • Drugs that precipitate •*Acyclovir* •Triamterene •*Methotrexate* •*Ciprofloxacin* •Sulfonamides Indirect obstruction •Drug induced rhabdomyolysis •Statins •Tumor lysis syndrome •Chemotherapeutic drugs 2. Ureteral obstruction •Nephrolithiasis •Calcium + excess vitamin C •Triamterene •Protease inhibitors •Ciprofloxacin •Nitrofurantoin •Blood clots 3. Bladder outlet obstruction •Urinary catheters •Anticholinergic drugs •Anatomy •BPH •Cancer

What is the Acid-Base Disorders Summary?

1. Respiratory Acidosis pH: Decreased Primary Disturbance: Increased pCO2 Compensation: Increased HCO3− 2. Respiratory Alkalosis pH: Increased Primary Disturbance: Decreased pCO2 Compensation: Decreased HCO3− 3. Metabolic Acidosis pH: Decreased Primary Disturbance: Decreased HCO3 Compensation: Decreased pCO2 4. Metabolic Alkalosis pH: Increased Primary Disturbance: Increased HCO3 Compensation: Increased pCO2

What do we do when patients are HYPERnatremia: Hypovolemic?

1. Resuscitate First! •NS until hemodynamically stable •Correct potassium depletion as needed 2. Estimate the "free water" deficit Deficit = current TBW x [(serum Na/140)-1] then we're going to use that deficit to know how much free water or D5W we need to give back to our patient do a net positive balance of 3 Mills of electrolyte freewater or D5W per kilogram of lean body weight will lower the serum sodium by approximately 1 mEq/L 3. Determine safe rate of correction •Consider Acute vs Chronic and ongoing losses - acute you can usually correct much quicker versus chronic you would want to go a little slower •*Na correction NTE 10-12 mEq/L in 24 hours* •Give half deficit over first 24 hours, rest over next 48 hours, you want to use continuous monitoring to prevent from going too slow or too quickly

What are the Daily Fluid Requirements: Sensible vs Insensible losses?

1. Sensible Losses •GI output, urinary output •Readily measurable 2. Insensible Losses - mostly water loss •From skin, lung, some GI losses •Difficult to measure •Variable - Respiratory Rate - Mechanical Ventilation - Ambient Temperature - Febrile illness •Add 10% for each degree over 37 C°

What are the important labs with acute kidney injury?

1. Serum Creatinine (SCr), GFR, and CrCl •Difficult to use at the time of AKI. •CrCl and GFR overestimates patient's true renal function at the beginning of AKI •SCr lags the time of AKI by 1-2 days •Once AKI resolves, CrCl and GFR underestimates patient's true renal function •Be sure to account for a patient's baseline SCr when assessing renal function 2. BUN/SCr ratio •Normal ratio is 15:1 •The ratio for pre-renal AKI and dehydrated patients is usually ≥ 20:1 3. Electrolytes •K, Phos, and Mg are renally excreted, and will be elevated during AKI •Significant increases in K and Mg can lead to cardiac arrhythmias •Elevated phosphorus can form precipitates with calcium and cause further damage 4. Urine output •Can be used for short-term kidney function assessment •A significant decrease indicates kidney injury •Normal values between 1-1.5 mL/kg/hr 5. Fractional Excretion of Sodium (FENa) •Measures ability of kidneys to retain sodium. •Useful for determining the type of renal impairment •A low FENa (<1%) is consistent with prerenal injury •An elevated FENa (>1%) is consistent with tubular necrosis

What are the Mechanisms Underlying Airflow Limitation in COPD?

1. Small Airways Disease •Airway inflammation •Airway fibrosis, luminal plugs •Increased airway resistance 2. Parenchymal Destruction •Loss of alveolar attachments •Decrease of elastic recoil

Case: JV is a 65 year old female CC: "I can't catch my breath" HPI: SOB x 3 days, sputum production that is yellow/thick PMH: COPD x 8 yrs, 2 prev hospital admissions SH: 1ppd x 30 yrs, quit x 1 year Home Medications: Ipratropium MDI 2 puffs QID Albuterol MDI prn Physical Assessment: BP 134/82, P 106, RR 24, T 36.4C Lungs: - breath sounds, insp/exp wheeze Lab: Hgb 17.5, Hct 51.2%, WBC 11, 67% segs, 4% bands, 19% lymphs ABG: 7.42/46/61, 93% saturation CXR: no infiltrate or effusion 1. What are this patient's risk factors for developing COPD? Give an example of at least two additional risk factors for the development of COPD in general. 2. What are the signs and symptoms that suggest a diagnosis of COPD exacerbation in this patient? Include those that help to rule out alternative diagnoses. 3. What are the indications for initiating antibiotic therapy in the treatment of acute exacerbation of COPD according to the most current guidelines? Are antibiotics indicated in this case? What regimen do you recommend based on likely pathogens? 4. What other interventions (drug and non-drug) should be administered in the initial treatment of this patient's COPD exacerbation? Consider bronchodilators, anti-iflammatory agents, prophylactic agents, and others. Make complete dosing recommendations for the drug therapies you include. 5. List the monitoring parameters that you will follow to ensure that this patient is responding appropriately (safety and efficacy) to your recommendations.

1. Smoking, age, genetics, socioeconomic status 2. Shortness of breath, sputum production (quantity, color), she is having an *exacerbation*, Elevated hematocrit-hypoxia, dehydration, No pneumonia (no left shift) 3. Bacterial infection, clinical signs- sputum production that is yellow/thick, Azithromycin, doxycycline, augmentin all for 5-7 days 4. Albuterol nebulizer, Ipratropium, prednisone, oxygen, heparin for DVT prophylaxis 5. Monitor for fever, lab abnormalities, HR for beta2 agonist tachycardia, Blood glucose for steroid

What is Steno & Cepacia?

1. Stenotrophomonas maltophilia -Bactrim is drug of choice (DOC) -levofloxacin, minocycline are alternatives -Often resistant to aminoglycosides & carbapenems 2. Burkholderia cepacia -Bactrim is drug of choice -levofloxacin, minocycline are alternatives -May be resistant to aminoglycosides, piperacillin, ceftazidime

What is the ETIOLOGY of CKD?

1. Susceptibility factors: •Advanced age •Reduced kidney mass and low birth weight •Racial/ethnic minority status (especially African Americans) •Family history of CKD •Low income/education •Autoimmune diseases •Dyslipidemia 2. Initiation Factors: •Diabetes mellitus •Hypertension •Glomerulonephritis 3. Progression factors: •Proteinuria •Hyperglycemia •Hypertension •Smoking •Dyslipidemia •Obesity

Case: JB is a 50-year-old male who was admitted complaining of severe lower right quadrant pain. Upon admission to the hospital on 3/14, he stated that he has been unable to eat or drink anything due to the pain. A CT of JB's abdomen revealed an appendicitis. He underwent an appendectomy on 3/15. •PMH: T2DM, HTN, hyperlipidemia •FH: unremarkable •SH: unremarkable •PE: eyes sunken, dry skin, slow capillary refill •Allergies: NKDA Vitals: Urine output: 0000-0400: 220 0400-0800: 150 0800-1200: 120 BUN: 41 SCr: 1.8 •Hospital medications •Acetaminophen 500 mg every 4 hours as needed •Ceftriaxone 1 g daily •Ketorolac 30 mg every 6 hours •Metronidazole 500 mg every 8 hours The last nursing note states "JB has been unable to tolerate food and drink. No bowel movements. Little urine output. Urine is dark colored. Patient lethargic this shift." 1. What risk factors does JB have for AKI? 2. Does JB meet criteria for an AKI? 3. If so, what type of AKI is likely present? 4. Which medications can contribute to AKI? 5. What labs should be ordered to monitor JB? 6. How should JB be managed?

1. T2DM, male, HTN, medications, recent surgery 2. Yes 3. Prerenal, decreased urine output, NSAID 4. ceftriaxone, metronidazole, Ketorolac 5. Electrolytes, BUN/SCr ratio= 22 (Over 20 is prerenal), FEna, urine output 6. Hemodynamic support and volume replacement, stop antibiotics Urine output calculation: 220 mL/100 kg/ 4 hours 150 mL/100 kg/4 hours 120 mL/100 kg/4 hours <0.5 mL/kg/hr >6 hours means AKI

If 1000 mL of 5% dextrose in water (D5W) was administered, what volume would stay in the intravascular space? Is D5W an appropriate fluid to use for resuscitation? Why or why not? ___%ICF = _________mL ___%ECF=_________mL %_____ interstitial = ___________mL %_____ intravascular = _________mL

67% ICF = 670 mL 33% ECF= 330 mL 75% interstitial = 248 mL 25% intravascular = 82 mL No because so little goes to intravascular

What are the INDICATIONS FOR DIALYSIS?

A: Acidosis (metabolic) E: Electrolyte abnormalities I: Ingestion O: Overload (hypertension, heart failure) U: Uremia (anorexia, N/V, confusion)

Adequately circulating blood volume is: A: Assessed by physical exam (BP, HR, etc.) B: Assessed by measurement of serum sodium C: Depleted with free water D: Is part of ICF

A: Assessed by physical exam (BP, HR, etc.)

Although a bronchodilator is recommended before all lung therapies, it is required at least four hours before? A: Cayston B: Pulmozyme C: TOBI D: Hypertonic saline

A: Cayston

Which of the following is true? A: Euvolemic hyponatremia- treat with free water restriction B: Hypovolemia hyponatremia- treat with conivaptan C: Hypervolemic hyponatremia- treat with normal saline

A: Euvolemic hyponatremia- treat with free water restriction

Which of the following vaccines is proven to decrease mortality in pts with COPD? A: Influenza B: Herpes Zoster C: Rubella D: PCV-13

A: Influenza

An evidence-based maintenance regimen for a pt with COPD group C may include? A: Tiotropium B: Prednisone C: Roflumilast D: Amoxicillin

A: Tiotropium roflumilast is for Group D pts with history of bronchitis and exacerbations amoxicillin is for Group D pts with frequent exacerbations

What are the indications for dialysis?

AEIOU *A*cid-base abnormalities -Metabolic acidosis resulting from accumulation of organic and inorganic acids *E*lectrolyte imbalance -Hyperkalemia, hypermagnesemia *I*ntoxications -Salicylates, lithium, methanol, ethylene glycol, theophylline, phenobarbital Fluid *O*verload -CHF, pulmonary edema, diuretic resistance *U*remia -Accumulation of uremic toxins

1. ACEis and ARBs are recommended as first line therapy in most patients with CKD and hypertension based on data showing significant benefits in cardiovascular and renal outcomes in this patient population. However, in the setting of acute kidney injury (AKI), ACEi/ARB therapy is held or discontinued until the AKI is resolved. Using your knowledge on the pathophysiology of CKD, explain how ACEis/ARBs can be both beneficial and harmful to the kidneys. Please draw a diagram of a nephron to supplement your explanation.

AKI= body does compensatory mechanisms to maintain GFR, ACE-i exacerbates AKI with NSAIDs CKD= ACE inhibitors and ARBs lower intraglomerular pressure by decreasing efferent arteriolar pressure Angiotensin II increases glomerular pressure which can cause damage When AKI patients are given an ACE inhibitor or ARB, the protective mechanism is blocked, and renal function can deteriorate rapidly, producing acute renal failure. In contrast, patients with hypertensive renal disease can improve their renal status after being treated with such drugs because they will lower AFFERENT pressure, which helps to protect the kidney

What are Acids vs Bases?

Acid - donates protons Example - hydrochloric acid HCl => H+ + Cl− Base - accepts protons Example - ammonia NH3 + H+=> NH4+

1. DF is a 57 yo F with history of lupus, admitted with a 2 day history of severe acute diarrhea and decreased urinary output. She is seen by the nephrology service and diagnosed with renal tubular acidosis (RTA) type 1. Due to long history of malnutrition and inability to tolerate tube feeds, she is also on TPN. ABG: (7.31/29/95/15.3) (pH/pCO2/pO2/HCO3) · What type of acid-base disorder does DF have? · What specific factors are contributing to DF's acid-base disorder? 139 113 45 116 3.9 15 3.5

Acidosis Low pCO2, Low HCO3= Metabolic acidosis Compensated Renal tubular acidosis Anion Gap = Na+ - (Cl− + HCO3−) = 139 - (113+15) =11 Not anion gap TPN= lower amount of acetate:Chloride ratio

What is hemodialysis?

Advantages: •Higher solute clearance, intermittent treatment •Parameters of adequacy of dialysis •Low rate of technique failure •Close monitoring •Hemostasis parameters Disadvantages: •Multiple visits to HD center each week •Side effects (headache, hypotension, infection) •Risk for infection and thrombosis •Faster decline in residual renal function Access: 1. Arteriovenous (AV) fistula 2. Arteriovenous (AV) graft 3. Central venous catheter

What is PERITONEAL DIALYSIS?

Advantages: •No HD machine •Slow ultrafiltration rate •Better preservation of residual renal function •Convenient route for medications Disadvantages: •Patient burnout (high rate of technique failure) •Increased absorption of dextrose •Loss of protein and amino acids •Risk of peritonitis/infections •Catheter malfunction

What are the Albuminuria stages?

Albuminuria •At least 2 positive tests measured during a 3-6 month period A1 Normal to mildly increased <30 mg/g <3 mg/mmol A2 Moderately increased 30-299 mg/g 3-29 mg/mmol A3 Severely increased ≥300 mg/g ≥30 mg/mmol

1. JS is a 39 yo male in the ICU with a long history of alcohol abuse who was recently admitted with an 8-day history of nausea, vomiting, and diarrhea and severe alcohol withdrawal. ABG: (7.60/52/92/50.8) (pH/pCO2/pO2/HCO3) · What type of acid-base disorder does JS have? · What specific factors are contributing to JS's acid-base disorder? 145 94 28 153 3.5 49 0.9

Alkalosis high HCO3= metabolic alkalosis Compensation has occurred NaCl responsive N/V/D

1. OB is a 79 yo WM in the ICU at your hospital during your 4th year of PharmD school. He has been diagnosed with metabolic acidosis (pH: 7.31), and the medical interns want to know if they are dealing with an anion gap acidosis. Please use the following labs - Does OB have a gap or non-gap acidosis? 125 99 21 134 4.0 5 0.9 In general, what are possible causes of OB's acid-base disorder?

Anion Gap = Na+ - (Cl− + HCO3−) = 125- (99+5) = 21 YES Normal anion gap <15 mEq/L Elevated anion gap >15 mEq/L Diabetic ketoacidosis Lactic acidosis Alcoholic and starvation ketoacidosis Renal failure (acute or chronic) Ingestions: methanol or ethylene glycol, salicylates

What is Metabolic Acidosis - Anion Gap?

Anion Gap = Na+ - (Cl− + HCO3−) Normal anion gap <15 mEq/L Elevated anion gap >15 mEq/L The anion gap is calculated using your sodium, chloride, and bicarb values from your BMP. This can help determine what the cause of your metabolic acidosis is. An anion gap in the body is typically less than 15 mEq/L and an elevated anion gap is greater than 15 mEq/L. This number 15 might vary depending on your institution; The anion gap is just a calculation of the excess anions that are present in the body. In order to maintain a neutral status, all ions are balanced equally between positives and negatives in the human body. But labs only measure sodium, chloride, bicarb, and a handful of others. There are some anions that we just never measure in a lab, so all of us have an anion gap (less than 15) because we always have a discrepancy between the amount of positive and negative anions we can measure in the lab. So again, an anion gap less than 15 mEq/L is normal and we can use the anion gap to help diagnose metabolic acidosis disorders.

What is the memory tool for the causes of metabolic acidosis anion gap?

Anion Gap Metabolic Acidosis Methanol Uremia Diabetic ketoacidosis (DKA) Poisoning Isoniazid Lactic acid Ethylene glycol Salicylate overdose

What are the Other Drug Therapies?

Antibiotics -Chronic azithromycin reduces exacerbations -Increases resistance and hearing loss Mucolytics - N-acetylcysteine Cough suppressants - avoid Beta-blockers OK if indicated for CV disease Others: statins, leukotriene modifiers, vasodilators

What is an Acid-Base Status Assessment?

Arterial Blood Gas (ABG) *pH/pCO2/*pO2/*HCO3* pCO2 - acidic (normal *40*, *range 35-45 mmHg*) HCO3 - basic (normal *24*, *range 22-28 mmol/L*) pO2 - oxygenation (normal 95, range 80-100 mmHg) Basic Metabolic Panel (BMP) Na Cl BUN Glucose K *CO2* SCr Chloride - acidic (normal 100, range 95-105 mmol/L) CO2 - basic (normal *24*, range 22-28 mmol/L)

What are some Other Interventions?

Assess risk for DVT - consider prophylaxis -Heparin 5000 units SQ every 8 hours -Enoxaparin 40 mg SQ daily -Fondaparinux 2.5 mg SQ daily Maximize therapy for comorbid conditions IV fluids, diuretics, nutrition support Know patients' end of life wishes

How do genetics play a role in CF?

Autosomal recessive disease -1 mutation on each allele of cystic fibrosis transmembrane conductance regulator (CFTR) gene leads to CF -Presentation on only 1 allele prevents full expression of CF -2 mutations identified on genetic testing of CF patient -Most common genetic mutation is F508del Disease severity depends on genetic mutation -Mutations fall into 1 of 6 classes •Class 1 is the most severe form •F508del is a class 2 mutation Class 4-6 usually pancreatic sufficient

What are the Short-acting Beta-agonists?

Available agents -Most common is albuterol -No benefit of levalbuterol Place in therapy -"Rescue" inhaler for acute symptoms -Alternative to LABA for maintenance -Treatment of acute exacerbation Maintenance Dose - 2 puffs every 4-5 hrs

Secondary evaluation of pts with hyponatremia includes: A: Measurement of ADH levels B: Assessment of volume status C: Work up for malignancy D: Assessment of plasma osmolality

B: Assessment of volume status

Total body water content (TBW not to be confused with total body weight): A: Can fluctuate widely depending on intake B: Distributes to the ICF and ECF compartments C: Is analogous to effective circulating volume D: Is higher in the elderly compared with infants

B: Distributes to the ICF and ECF compartments

All of the following are correct regarding maintenance IV fluids for "normal" adults EXCEPT: A: May be associated with serious side effects B: Estimated at 150 mL/kg/day C: Daily monitoring is recommended D: Provided with DS 1/2 NS with 20 mEq/L KCl

B: Estimated at 150 mL/kg/day

Which therapy is first line in acute exacerbation management? A: Inhaled fluticasone B: Inhaled albuterol C: Oral doxycycline D: IV Lorazepam

B: Inhaled albuterol

This medication is a cure for CF for over 50% of those with the disease with homozygous delta F508? A: Pulmozyme B: Orkambi C: Kalydeco D: Ursodiol

B: Orkambi Symdeko and Trifkafta work too Kalydeco for other mutations

Which item below best describes the hallmark finding in COPD? A: Chronic cough and sputum production B: Persistent, progressive airflow limitation C: Reactive, reversible airway obstruction D: Infiltrates present on chest radiograph

B: Persistent, progressive airflow limitation A-Chronic bronchitis C-Asthma D-Pneumonia/HF

Mortality in CF is most typically from what? A: Liver failure B: Respiratory failure C: CF related diabetes D: Malnutrition

B: Respiratory failure Multiple infections, lung damage, repiratory failure

What are the Combination Bronchodilators?

Better response compared to monotherapy Short Acting: Ipratropium + albuterol New Long Acting Options -Umeclidinium + vilanterol -Tiotropium + oladaterol -Glycopyrrolate + indacaterol -Glycopyrrolate + formoterol

Which fluid is optimal for resuscitation of an adult pt with GI related volume losses? A: Albumin B: D5W 1/2 NS with 20 mEq/KCl C: 0.9% saline solution D: Blood

C: 0.9% saline solution B for maintenance D only use blood to replace blood loss

Treatment of SIADH includes all of the following EXCEPT: A: Fluid restriction B: Work up to find underlying cause C: Conivaptan (Vaprisol) as first line intervention D: Hypertonic saline (3%) if severe symptoms

C: Conivaptan (Vaprisol) as first line intervention

Which of the following are proven outcomes of inhaled steroid therapy in COPD? A: Increased exacerbations B: Halted disease progression C: Improve quality of life D: Reversal of emphysematous changes

C: Improve quality of life

TOBI and Cayston are the two most common inhaled CF antibiotics for this infection? A: MRSA B: Burkholderia cepacia C: Pseudomonas aeruginosa D: Aspergillus

C: Pseudomonas aeruginosa

Which of the following tests are needed to confirm the diagnosis of COPD? A: Oxygen saturation B: Chest x ray C: Spirometry D: ECG

C: Spirometry

What are COPD exacerbations?

COPD exacerbations are defined as an acute worsening of respiratory symptoms that result in additional therapy. They are classified as: 1. Mild (treated with short acting bronchodilators only, SABDs) 2. Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids) or 3. Severe (patient requires hospitalization or visits the emergency room). Severe exacerbations may also be associated with acute respiratory failure

What are the common acid/base pairs?

Carbonic acid/Bicarbonate H2CO3 HCO3− Monobasic/Dibasic phosphate H2PO4 HPO4− Ammonium/Ammonia NH4+ NH3 Lactic acid/Lactate H6C3O2 H5C3O2−

What is anemia and CKD?

Causes •Decreased erythropoietin synthesis •Decreased GI absorption of iron •Iron and vitamin B12 deficiency •Blood loss Diagnosis •Signs and symptoms •Fatigue, shortness of breath, cold intolerance, tingling in the extremities, general malaise •Hemoglobin <13 g/dL in males, <12 g/dL in females •Annually in CKD 3 •Biannually in CKD 4-5 Every 3 months in CKD 5 D

What is CKD and ESRD?

Chronic kidney disease (CKD): •Abnormalities in kidney structure or function, present for ≥3 months, with implications for health •Progressive and irreversible loss of kidney function characterized by a significant reduction in glomerular filtration rate (GFR) End stage renal disease (ESRD): •GFR <15 mL/min/1.73 m² •Chronic dialysis or kidney transplantation

What is the Pathogenesis of COPD?

Cigarette smoke and Host factors Amplifying mechanisms -Biomass particles -Particulates Cause Lung Inflammation 1. Oxidative Stress 2. Proteases, Repair mechanisms =COPD

A patient comes in with Diabetic Ketoacidosis. The provider is considering starting hypertonic saline in addition to the insulin. Glucose is 645, Na is 118. Calculate the corrected sodium level.

Corrected Na= Measured Na+ 0.024 (Glucose-100) =118 +0.024 (645-100) = 131 mEq/L 1. Assess patient's osmolality 2. Assess volume status

Hyponatremia is: A: The most common disorder of fluid/electrolyte balance B: Is frequently associated with inappropriate ADH secretion C: Is first evaluated by considering plasma osmolality D: All of the above

D: All of the above

Plasma osmolality control is: A: Is calculated using Na, Gluc, BUN B: Equal in ECF and ICF C: Tightly regulated to maintain normal function D: All of the above

D: All of the above

Which is an example of how CF can affect the GI system? A: Decreased pancreatic enzyme secretion from obstructed duct B: Reduced insulin production resulting in CF related diabetes C: Decreased absorption of nutrients leading to weight loss D: All of the above

D: All of the above

Which of the following are evaluated when determining COPD severity? A: FEV1 B: Symptoms C: Exacerbation history D: All of the above

D: All of the above

Factors to consider when initiating inhaled steroid therapy in COPD include? A: History of frequent exacerbations B: Elevated blood eosinophil count C: History of asthma D: All of these should be considered

D: All of these should be considered

Which factors should be considered when selecting a bronchodilator for a specific pt? A: Patient preference B: Symptom severity C: Exacerbation risk D: All should be considered

D: All should be considered

When comparing asthma and COPD management which of the following is false? A: Adherence and inhaler technique are taught in both B: Bronchodilators are maximized in acute exacerbations of both C: Oral steroids are indicated for acute exacerbations of both D: Inhaled steroids are first line maintenance therapy for both

D: Inhaled steroids are first line maintenance therapy for both

Chronic hypernatremia: A: Must be corrected rapidly to prevent brain damage B: Is treated with careful infusion of 3% saline C: Is treated before correction of volume deficits D: Is treated after correction of volume deficits

D: Is treated after correction of volume deficits

Which organ system is not directly affected by the CFTR defect in CF? A: GI B: Respiratory C: Hepatic D: Renal

D: Renal ***This one is important! Know which organ systems are affected

Which of the following therapies can slow or halt the progression of COPD? A: Oxygen B: Inhaled corticosteroids C: Systemic steroids D: Smoking cessation

D: Smoking cessation

The pharmacist should monitor all of the following at every visit EXCEPT? A: Smoking status B: Inhaler technique C: COPD symptoms D: Spirometry

D: Spirometry

What are the Inhaled Corticosteroids?

Demonstrated Benefits -Decrease symptoms, exacerbations -Do not alter progression Indications -Combined with a LABA for patients with exacerbations despite appropriate bronchodilator therapy Adverse Effects -Pneumonia, increased fracture risk, others -Increased exacerbation with withdrawal

What are the primary causes of Anion Gap Metabolic Acidosis?

Diabetic ketoacidosis Lactic acidosis Alcoholic and starvation ketoacidosis Renal failure (acute or chronic) Ingestions: methanol or ethylene glycol, salicylates Treatment: Treatment of an anion gap metabolic acidosis is really focused on correcting the underlying disorder: treat the DKA, treat the renal failure, eliminate or reverse the effects of the ingested toxic agent Primary: correct underlying disorder DKA: fluids and insulin, etc Renal failure: dialysis

What is Tiotropium (Spiriva)?

Dry powder inhaler & soft mist inhaler Duration 24 hours - once daily dosing DPI - 2 puffs (1 cap) daily Soft mist inhaler - 2 puffs (5 mcg) daily Several newer options -Aclidinium bromide (Tudorza Pressair) -Glycopyrrolate (Seebri Neohaler) -Umeclidinium (Incruse Ellipta)

What are the PPIs & H2 blockers in CF?

Dual mechanism of action in CF -GERD -Improved enzyme efficacy •Decreased bicarb production by the pancreas may inhibit release of enzymes from microspheres Risk vs. Benefit -Infection risk? -Bone health?

What are the Symptoms of Hyponatremia?

Due to alterations in cell volume Acute vs. Chronic changes - Acute changes again are more likely to cause symptoms compared to chronic changes most patients can be asymptomatic if they're in the mild category however if sodium drops very quickly neurologic changes can occur •Moderate: Nausea, confusion, headache •Severe: Vomiting, somnolence, seizures, coma, brain herniation, cardiorespiratory distress - the goal is to prevent brain herniation if we have severely low sodium •Other - chronic hyponatremia - Gait disturbance, falls, congitive deficits, osteoporosis/fractures - Increased risk of death

What is E-Rapid®?

E-Rapid® nebulizer handset now available for use with Altera® compressor A substitute for the Pari-LC Plus® nebulizer that allows for rapid administration of meds

What is the Osmolarity of the solutions?

ECF 285-295 Lactated Ringer's* 273 0.9% NaCl* 308 - NS is considered isotonic 0.45% NaCl* 154 - half normal saline which is considered hypotonic D5W 252 transient 6% Hetastarch 310

How do we evaluate Low (<280) hypotonic hyponatremia?

ECF volume 1. HYPOvolemic UOsm: >450 - UNa <20= Extra renal losses - UNa >20= Renal losses, Diuretics, Adrenal insufficiency 2. HYPERvolemic UOsm: >100, UNa <20 - CHF, Cirrhosis, CKD 3. ISOvolemic - UOsm: >100, UNa >20= SIADH - UOsm: <100, UNa <20= Primary polydipsia Low solute intake

What two disease states underly COPD?

Emphysema Chronic Obstructive Bronchitis

What is renal replacement therapy for ESRD?

End -stage renal disease •GFR <15 mL/min/1.73m2 •Build-up of renally eliminated substances Management •Renal replacement therapy (RRT) •Kidney transplant Renal Replacement Therapy •Intermittent dialysis •Hemodialysis (HD), peritoneal dialysis (PD) •Continuous dialysis •Continuous venovenous hemofiltration (CVVH)

How do we Evaluate the ABG Data?

Evaluate ABG data to see which primary parameter abnormality is consistent with pH pCO2 is acidic (lungs = respiratory component) HCO3 is basic (kidneys = metabolic component) Example: pH 7.32 (acidemia) If pCO2 is high => respiratory If HCO3 is low => metabolic In a patient that has a pH of 7.32, you would conclude this patient has acidemia. Something is making their blood more acidic. There are two ways to make your blood more acidic: either 1) you have too much of the acidic component (CO2) and the pCO2 is high or 2) you don't have enough of the basic component (bicarb) and the bicarb is low. Example: pH 7.5 (alkalemia) If HCO3 is high => metabolic If pCO2 is low => respiratory Here we have a pH of 7.5, which means you have alkalemia. And there would be two ways to make your blood basic: 1) you might have too much of the basic component (bicarb) and your bicarb is high or 2) you don't have enough acidic component (CO2) and your pCO2 is low

How do we Determine If Compensation Occurred?

Evaluate whether compensation has occurred pCO2 is acidic (lungs = respiratory component) HCO3 is basic (kidneys = metabolic component) 1. Primary Respiratory Acidosis Compensate with kidneys by retaining HCO3 2. Primary Metabolic Acidosis Compensate with lungs by hyperventilation ("blowing off CO2) 3. Primary Respiratory Alkalosis Compensate with kidneys by excreting HCO3 4. Primary Metabolic Alkalosis Compensate with lungs by retaining CO2 Basically, if you've determined from the second step that the primary disorder is due to pCO2, which is the respiratory component, then compensation could occur by making changes through the metabolic component bicarb. The opposite is true. If you've determined that the primary disorder is metabolic because the changes in bicarb explain the abnormal pH, then the body could compensate with the lungs blowing off or retaining CO2

Gold treatment Class A

Exacerbations < 1/year, No hospitalizations Symptom Score: CAT score <10 First Line Therapy: A bronchodilator - can be short or long acting, continue if symptomatic benefit is documented Albuterol, salmeterol, ipratropium, tiotropium, others Step Up Therapy Options: Theophylline, long acting

Gold treatment Class B

Exacerbations: < 1/year, No hospitalizations Symptom Score: CAT score > 10 First Line Therapy: A long acting bronchodilator (LABA or LAMA) Step Up Therapy Options: LABA or LAMA, combination LABA+LAMA

Gold treatment Class C

Exacerbations: > 2/year or >1 with hospitalization Symptom Score: CAT score <10 First Line Therapy: LAMA - tiotropium Step Up Therapy Options: LAMA+LABA, ICS+LABA

Gold treatment Class D

Exacerbations: > 2/year or >1 with hospitalization Symptom Score: CAT score > 10 First Line Therapy: LAMA (more effective than LABA for exacerbation prevention) or LAMA+LABA (if highly symptomatic) or ICS+LABA (not as effective as LAMA+LABA for exacerbation prevention, risk of pneumonia, only use for continued exacerbations) *Combination therapy is preferred* Step Up Therapy Options: Add/switch agents, Triple therapy (LABA+LAMA+ICS), Add systemic corticosteroid, Add Roflumilast if you still have exacerbations chronic bronchitis FEV1<50,

Metformin is first line therapy for CFRD (CF related diabetes)? T/F

False For type 2 only

Hypertonic saline is recommended to help with hemoptysis in a CF pt? T/F

False Hemoptysis is when there is blood in the lungs from tears due to coughing Hypertonic saline should be D/C in this case immediately

Male patients with CF are infertile and do not produce sperm? T/F

False Likely going to be infertile- still produce sperm but the semen is extra thick so the sperm can't swim through it as well Women- thick uterine fluid may result in ectopic pregnancy

In CF, PPIs help with GERD and increases stomach acid which reduces enzyme action? T/F

False They decrease stomach acid

Pulmozyme is only recommended for CF patients with moderate to severe respiratory symptoms? T/F

False Thin up the mucus for everyone

What are the GFR Stages?

G1 Normal or high GFR≥90 G2 Mildly decreased GFR 60-90 G3a Mild to moderately decreased GFR 45-59 G3b Moderately to severely decreased GFR 30-44 G4 Severely decreased GFR 15-29 G5 Kidney failure GFR<15

What is the Classification of severity of airflow limitation?

GOLD 1: Mild FEV1 > 80% GOLD 2: Moderate FEV1 50-80% GOLD 3: Severe FEV1 30-50% GOLD 4: Very Severe FEV1 <30%

What is hypovolemia?

Goal: Maintain/restore BP and tissue perfusion -to correct it as quickly as possible, restoring effective circulating volume and good tissue perfusion in order to prevent an organ damage •Physiologic compensation occurs - Thirst, ADH, Renin, Aldosterone - Sympathetic nervous system: to provoke vasoconstriction and reabsorption of salt and water •Oral or Intravenous intervention administration of fluids •Electrolyte correction is often also needed this is often needed depending on the cause of the volume depletion for example if a patient is having diarrhea or vomiting you may see a lot of potassium as well

What is the relationship between plasma osmolality and ADH levels?

Graph: the sensitivity of ADH secretion to plasma osmolality as the plasma osmolality reaches the upper level of normal ADH secretion begins and continues to increase linearly. The normal serum osmolality Is 285 to 295 milli osmoles per kilogram •Calculated serum Osm = 2(Na) + (glucose)/18 + (BUN)/2.8

If 1000 mL of D5W ½ NS is administered, what volume is available in the intravascular space?

Half normal water half saline average of normal water and D5W (82.5+250)/2 =166.25 mL

What is Metabolic Alkalosis?

High pH with high HCO3 Compensation - pCO2 rapidly increase Example ABG: pH 7.54 pCO2 50 mmHg HCO3 33 mEq/L Metabolic alkalosis is when the pH is high because your bicarb is high since bicarb is the basic metabolic component. If you do see compensation, you would see an increase in pCO2 in order to offset the increased pH. An example ABG for metabolic alkalosis would include a pH of 7.54 which is high and a bicarb that is high. The bicarb here is 33 which is above normal range. If you have compensation, you'd see a high pCO2. In this example, because pCO2 is above the normal range, we have respiratory compensation. There are 2 types of metabolic alkalosis: NaCl responsive and NaCl nonresponsive metabolic alkalosis

What is Respiratory Alkalosis?

High pH with low pCO2 Compensation - HCO3 slowly decrease Alkalosis is when the pH is higher than 7.45. Since it's respiratory, it means you don't have enough acidic component and the pCO2 is low. If there is compensation, then you would see a decrease in bicarb to help reduce the pH. An example of an ABG for respiratory alkalosis is a high pH and a pCO2 that's low because the primary reason for the alkalosis is you don't have enough pCO2. If you were to see compensation, you would see a bicarb that's lower than the typical range. In this example, the bicarb is within normal range so we would call this uncompensated respiratory alkalosis. Example ABG: pH 7.5 pCO2 25 mmHg HCO3 26 mEq/L

How does hypertension contribute to CKD?

Hypertension leading to CKD •Uncontrolled hypertension → high intraglomerular pressure → impaired glomerular filtration •Increased heart workload, causing left ventricular hypertrophy CKD leading to hypertension •Electrolyte abnormalities → volume overload → increased vascular resistance Goals •BP ≤140/90 mmHg in patients with category A1 albuminuria •BP ≤130/80 mmHg in patients with category A2 or A3 albuminuria

What are the Group D agents?

In general, therapy can be started with a LAMA as it has effects on both breathlessness and exacerbations.

What is the Monitoring and Follow-up for pharmacological treatment?

In order to adjust therapy appropriately as the disease progresses, each follow-up visit should include a discussion of the current therapeutic regimen. Monitoring should focus on: -Dosages of prescribed medications. -Adherence to the regimen. -Inhaler technique. -Effectiveness of the current regime. -Side effects. Treatment modifications should be recommended.

What is the Antibiotic Therapy for exacerbations?

Indications - still evolving, limited evidence Dyspnea, sputum volume, sputum purulence Appropriate agents for uncomplicated patient: -Macrolide -azithromycin, clarithromycin -2nd or 3rd generation cephalosporin -Doxycycline -May need to consider resistant organisms Duration - 5-7 days

What are the Systemic Corticosteroids?

Indications in maintenance therapy -Avoid if possible -No evidence of long-term benefit Adverse Effects - serious toxicities Dosing & Administration -Lowest effective dose -AM, once daily administration

What are the Daily Fluid Requirements: Maintenance I's = O's?

Intake: total 2500 mL - Water 1500 mL - Food 700 mL - Metabolic generated intercellularly during carbohydrate metabolism 300 mL Output: total 2500 mL - Urine 1500 mL - GI insensible losses 100 mL - Lung/Skin insensible losses 900 mL through sweat respiration and normal conditions this can increase significantly with heat fever exercise

How do we Assess pH value?

Is pH abnormal? Acidemia: pH <7.35 (7.4) Alkalemia: pH >7.45 (7.4) Note - pH may not always be abnormal in acid/base disorders (i.e., compensated or mixed disorders) acidemia and alkalemia describe what the pH of the blood is. Acidosis and alkalosis describe the disorders that cause pH disturbance In a mixed disorder, a patient might have acidosis and alkalosis at the same time and their pH can present as normal if these two different disorders balance each other out. So in patients with mixed disorders, just because the pH is normal does not necessarily mean there is no acid-base disorder present

What is the ROLE OF VITAMIN D IN SECONDARY HYPERPARATHYROIDISM?

Kidneys contain 1 α-hydroxylase •Converts 25-hydroxyvitmin D [25(OH)D] (vitamin D precursor) to 1,25-dihydroxyvitamin D₃ [1,25 (OH)₂D] (active from), also known as calcitriol Vitamin D₃ promotes calcium absorption from the GI tract •Suppresses PTH production •Parathyroid gland hyperplasia becomes resistant to calcium and vitamin D supplementation Reduced kidney function results in impaired vitamin D production, reduced intestinal calcium absorption and increased mobilization of calcium from the bone

What is respiratory acidosis?

Low pH with high pCO2 Compensation - HCO3 slowly increase Example ABG: pH 7.33 pCO2 60 mmHg HCO3 32 mEq/L 1. The first step is to assess the pH value. The pH is 7.33 and that is less than 7.35 so we have acidemia, so our disorder is going to be an acidosis 2. The second step is to evaluate the ABG to try and figure out which parameter is consistent with that pH. We have a pCO2 of 60 and that's abnormal because it's higher than 45 and we have a bicarb of 32 which is also abnormal because it's higher than 28. Which of these explains the acidic pH level. Having a high pCO2 or a high bicarb? CO2 is the acidic component and bicarb is your basic component so having more of the acidic component pCO2 explains the low pH. Since pCO2 is associated with the lungs, we've confirmed that this is respiratory acidosis 3. The third step is to evaluate whether compensation has occurred. Since we know pCO2 explains the pH and it is respiratory acidosis, we'll look at bicarb and see if it is within normal range or not. Since bicarb is high at 32 (normal is 22 to 28), you can say that the kidneys have started to retain more bicarb in order to offset that the low pH (i.e., partial metabolic compensation).

What is Metabolic Acidosis?

Low pH with low HCO3 Compensation - pCO2 rapidly decrease Example ABG: pH 7.25 pCO2 30 mmHg HCO3 17 mEq/L Metabolic acidosis is a decrease in pH and this is because there is a decrease in bicarb. If there is compensation, you would see a decrease in pCO2 in order to help balance out the low pH. An example ABG includes a pH of 7.25 which is lower than 7.35 and a low bicarb of 17. Bicarb is the basic component and it's low so that explains the low pH. If we were to see compensation, pCO2 would be lower than normal because the lungs would blow off CO2 in order to offset the low pH. Since pCO2 here is lower than the normal range, this would be called metabolic acidosis with respiratory compensation. There are two types of metabolic acidosis: anion gap metabolic acidosis and non-anion gap metabolic acidosis

How are the lungs affected in CF?

Lungs: thickened mucus => decreased mucus clearance => bacterial overgrowth and colonization => plugging, increased cough, SOB=> decreased O2 sats, lung scarring => eventual mortality Other complications -Pneumothorax -Pleurisy

What are the Beta 2 Agonists?

MOA -Stimulation of beta-2 adrenergic receptors -Resulting in airway smooth muscle relaxation -Safe and well tolerated -May use without ICS in COPD -Alternative to anticholinergic agents

What are the Anticholinergic Agents?

MOA: airway smooth muscle relaxation Safe & well tolerated Considered first line therapy in COPD

How to manage hypertension and CKD?

Management •First line therapy with ACEi or ARB •Decrease intrafiltration pressure •Second line therapy includes CCBs or thiazide diuretics Holding therapy •Hyperkalemia •Adverse effects •AKI

What is Roflumilast (Daliresp)?

Mechanism of Action - PD4 inhibitor Clinical effects -Small decrease in rate of exacerbation Adverse effects -Nausea, vomiting, weight loss -CNS, psychiatric

2. The 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease does not provide recommendations for patients with ESRD on dialysis. With ACEis/ARBs recommended as first line antihypertensive therapy in patients with non-dialysis CKD, what are differences to consider between CKD and ESRD when selecting an antihypertensive agent? (Hint: think about the mechanism of action of ACEis/ARBs and why they might be less effective in anuric patients requiring HD)

Mechanisms of the RAS system will be compromised so ACE/ARB will not work as well and won't benefit ESRD as much

What is Metabolic Alkalosis - NaCl Responsive?

Metabolic alkalosis is primarily caused by disorders that either promote the loss of protons/chloride or increase the amount of bicarb. NaCl responsive metabolic alkalosis is caused by increased GI losses -vomiting, increased NG suctioning, and laxative abuse can all cause a loss of protons which can cause metabolic alkalosis Primary causes (H+ or Cl− loss or high HCO3) Sodium chloride responsive (urine NaCl <10 mEq/L) Increased GI losses: vomiting, increased NG suctioning, lax abuse Diuretics: loop diuretics and thiazides can increase bicarb reabsorption Patients with cystic fibrosis have dysfunctional chloride channels which can lead to metabolic alkalosis Treatment Correct underlying cause (antiemetics, d/c NG suction) Volume resuscitation with fluids containing NaCl and KCl Switch to K-sparing diuretics

What is Steroid Therapy in Exacerbation?

Moderate Benefit Improve patient outcomes: recovery time, lung function, relapse -Monitor for adverse effects -Hyperglycemia, worsening HF Dosing & Administration 40 mg prednisone daily for 5 days Emerging role for inhaled steroids

What is the Monitoring and Follow-up for COPD?

Monitoring disease progression and development of complications and/or comorbidities -Measurements. Decline in FEV1 can be tracked by spirometry performed at least once a year. -Symptoms. At each visit, information on symptoms since the last visit should be collected, including cough and sputum, breathlessness, fatigue, activity limitation, and sleep disturbances. -Exacerbations. The frequency, severity, type and likely causes of all exacerbations should be monitored. -Imaging. If there is a clear worsening of symptoms, imaging may be indicated. -Smoking status. At each visit, the current smoking status and smoke exposure should be determined followed by appropriate action.

What is Pulmozyme (dornase alfa)?

Mucolytic; breaks up long DNA strands, decreases mucus viscosity -Nebulized liquid -Dosed 2.5mg Qday - BID -Studies show improved PFTs, decreased risk of infections requiring IV antibiotics -May cause increased cough, wheeze, hoarseness, skin rash, fever, HA, malaise -*CF Foundation recommends using dornase alfa even in asymptomatic patients with mild lung disease* Cost: ~$2300/30 doses

What are the Long-acting Beta-agonists?

Multiple available agents Salmeterol (Serevent Diskus) •1 puff inhaled every 12 hours Several other new options •Arformoterol (Brovana) •Formoterol (Perforomist) •Indacaterol (Arcapta Neohaler) •Olodaterol (Striverdi Respimat) Alternative to long-acting anticholinergic

Which Nebulizer for Which Drug?

NEBULIZERS 1. t-piece -as recommended by your physician 2. Sidestream® -Pulmozyme® (dornase alpha) -Albuterol (salbutamol) BREATH-ENHANCED NEBULIZERS 1. PARI LC PLUS® Use with 25 psi compressor -TOBI® -Colymycin (sterile -colistimethate sodium, USP) -Albuterol -Pulmozyme® -Pulmicort® (budesonide) 2. PARI LC STAR® -Colymycin -Albuterol -Pulmozyme® -Pulmicort® 3. Altera® with eFlow® technology -Cayston ®

What are the Consequences Of COPD Exacerbations?

Negative impact on quality of life Impact on symptoms and lung function Accelerated lung function decline Increased Mortality Increased economic costs

What are the Symptoms of Hypernatremia?

Neurologic - Lethargy, confusion, seizures, myoclonus - Due to alterations in cell volume Other - Hypotension, tachycardia, oliguria, etc. - Due to volume depletion most patients are asymptomatic if it's a chronic change however the sodium drops quickly when we're adjusting this neurologic symptoms can occur

What are the causes of Non-Anion Gap Metabolic Acidosis?

Non-anion gap metabolic acidosis is when your anion gap is less than 15 Primary causes (low HCO3, bicarb wasting) Diarrhea Pancreatic or small bowel fistula Carbonic anhydrase inhibition (acetazolamide) (acetazolamide is a drug that can inhibit carbonic anhydrase, which is responsible for converting carbonic acid to water and CO2 - if we were to inhibit carbonic anhydrase, we can potentially decrease the amount of bicarb that's reabsorbed at the kidney) Renal tubular acidosis - decreased HCO3 reabsorption Treatment Primary: correct underlying cause GI loss - fluid/electrolyte replacement

What is the MANAGEMNET OF SECONDARY HYPERPARATHYROIDISM?

Non-pharmacologic •Dietary phosphorous restriction - first line •800 - 1000 mg/day •Organic: Poultry, fish, nuts, beans, dairy •Inorganic: Canned and bottled drinks, enhanced meats, processed foods •Dialysis •Parathyroidectomy Pharmacologic •Phosphate binding agents •Calcimimetic therapy •Vitamin D

What is blood pH?

Normal pH = 7.40 (range, 7.35 to 7.45) pH < 7.35 = acidemia pH > 7.45 = alkalemia pH <6.7 or >7.7 = incompatible with life The body maintains extremely tight pH control. There's a narrow window of pH that is appropriate for the human body. A normal pH is usually around 7.4 with a range of 7.35 to 7.45. Anything less than 7.35 is referred to as acidemia, or acidic blood, and anything higher than 7.45 is referred to as alkalemia, or basic blood. A pH of less than 6.7 or higher than 7.7 are not compatible with life. It is abnormal pH that's used to diagnose acid-base disorders

What is the treatment of CFRD?

Oral anti-diabetic agents not appropriate in CF -Metformin: CI in hypoxia due to risk of lactic acidosis; GI SE -Thiazolidinediones: risk of hepatotoxicity -Sulfonylureas: may bind and inhibit the CFTR BMC Endocr Disord. 2006; 6:4. *Primary treatment is insulin therapy* -Results in increased BMI, improved FEV1, improved survival -NO calorie or fat restrictions; emphasis on balanced diet -Exercise to improve peripheral insulin sensitivity, pulmonary function, overall health

What are Theophylline?

Place in therapy - controversial -Less effective than inhaled therapy -Risks may outweigh benefits -2nd or 3rd line Mechanism of action- unknown Dosing and Administration -Use long acting forms - 300-900 mg daily

What is Ipratropium (Atrovent HFA)?

Quaternary amine Decreased systemic absorption MDI or nebulizer Onset 1-2 hours, Duration 4-6 hours Dosing: -MDI 2 puffs inhaled 4 times daily -Neb 0.5 mg (2.5mL) inhaled every 6-8 hours

What are the goals of therapy?

Reduce symptoms: -Relieve symptoms -Improve exercise tolerance -Improve health status Reduce risk: -Prevent disease progression -Prevent and treat exacerbations -Reduce mortality

What is SECONDARY HYPERPARATHYROIDISM and CKD?

Referred to as CKD-mineral and bone disorders (CKD-MBD) Parathyroid hormone •Regulates serum calcium and potassium homeostasis •Released in response to hypocalcemia •Indirectly stimulates osteoclast activity •Can be released in response to hyperphosphatemia •Inhibits proximal and distal tubular reabsorption of phosphorous Renal osteodystrophy can occur as a result of persistent hypocalcemia and hyperphosphatemia Decreased phosphate excretion=>Hypocalcemia=>Secondary hyperparathyroidism=>Renal osteodystrophy

What is spirometry?

Required for diagnosis decreased FEV1 decreased FEV1/FVC ratio Impaired gas exchange Not fully reversible

What is the Hyponatremia:Hypotonic/Isovolemic SIADH treatment?

SIADH Treatment - Asymptomatic •Water restriction - 800-1000 liter/day •Insensible losses, obligate urine/feces > intake •Correct underlying cause (drugs) Medications for Hyponatremia - not recommended •Vasopressin receptor antagonists >Conivaptan - IV infusion, short course >Tolvaptan - Hepatotoxicity, NTE 30 days •Demeclocycline 600-1200mg/day (3-4 doses) - Blocks ADH action - Nephrotoxicity seen especially in cirrhosis patients

What is the Hyponatremia:Hypotonic/Isovolemic SIADH Causes?

SIADH is a syndrome of inappropriate anti diuretic hormone (ADH) so here total body sodium content is normal or slightly decreased and total body water is increased but not enough to cause peripheral or pulmonary edema so they appear euvolemic intakes exceed outputs because the kidneys can't excrete H2O or water •Drugs •Enhanced Renal Sensitivity to ADH - Chlorpropamide, carbamazepine, cyclophosphamide, NSAIDs •Enhanced Release of ADH - SSRIs, TCAs, Ecstasy, opioids •Tumors •CNS injury: Trauma, stoke, meningitis •Others: lung disease, post-op, pain, nausea, stress •Elderly

What is the Hyponatremia Classification?

Serum Osmolality 1. Normal (~280)= Isotonic hyponatremia > Cause: pseudohyponatremia (ex: hyperlipidemia), usually correcting the underlying cause 2. Elevated (>280)= hypertonic hyponatremia > Cause: Excess effective osmoles - hyperglycemia, mannitol, alcohols - Diffusion of water from cells Correction factor - For every 100 mg/dL in glucose the measured serum Na falsely decreases by 2.4 meq/L - *Corrected Na=Measured Na + 0.024 * (Serum Glucose-100)* 3. Low (<280) hypotonic hyponatremia

What are the recommendations for bronchodilators?

Short-acting bronchodilators (short-acting muscarinic antagonist [SAMA] or short-acting inhaled beta2 agonist [SABA]) should be prescribed to all patients for immediate symptom relief, regardless of their GOLD classification Inhalers- technique

What are the Available Options?

Single agent - not approved for COPD -Beclomethasone, fluticasone, others Combination Products -Budesonide + formoterol (Symbicort) -Fluticasone + salmeterol (Advair) -Fluticasone + vilanterol (Breo Elipta) New Triple Therapy - Trelegy Elipta -Fluticasone + umeclidinium + vilanterol

What are ELECTROLYTE ABNORMALITIES and CKD?

Sodium and water •High serum sodium level - dysfunctional sodium excretion •Low serum sodium level - dysfunctional sodium conservation •Decreased sodium excretion → water retention/volume overload → systemic hypertension/pulmonary edema Potassium and phosphate •Hyperkalemia, hyperphosphatemia •Reduced potassium and phosphate secretion by the collecting ducts

What is Metabolic Alkalosis - NaCl Non-Responsive?

Sodium chloride non-responsive metabolic alkalosis is caused by increased mineralocorticoids and TPNs compounded with too much acetate can potentially contribute to metabolic alkalosis Primary causes (H+ or Cl− loss or high HCO3) Sodium chloride non-responsive (urine NaCl >20 mEq/L) Increased mineralocorticoid: hyperaldosteronism, Cushing's, Bartter Syndrome TPN with too much acetate Treatment Remove source of excess mineralocorticoids Modify the ratio of chloride:acetate in TPN Acetazolamide for patients unable to tolerate fluid loads to reduce the amount of bicarb that's being absorbed (a temporary fix)

What is the role of water?

Solvent Delivery/removal of nutrients/wastes Medium for electrolyte/chemical Rxn water takes up about half or a little over half Body water- TBW - Pediatrics > Adults > Geriatrics - Children and men <70 years: 0.6L/kg x wt - Men >70 and women <70 years: 0.5 L/kg x wt women has less and that's really because she has an increased amount of adipose tissue - Women > 70 years: 0.45 L/kg x wt - Dehydrated older patients: 0.4 L/kg x wt - Muscle > Fat

What electrolytes are lost via fluids?

Sources: Urine Nasogastric Pancreas/ Small bowel Diarrhea Sweat Electrolytes: Sodium, Potassium, Chloride, HCO3-

What are the sympathetic NS signs/symptoms in hypovolemia?

Sympathetic Activation •Tachycardia •Increased Systemic Vascular Resistance (SVR) shunts blood to *heart and brain* •Brain - the altered mental status, lightheadedness or potentially even progress to coma •Heart - strain can cause demand infarct: get a tachycardia with decreased perfusion you can also lead to decrease oxygen supply versus its demand which can cause ischemia or chest pain and infarction •Skin - cyanosis with cold clammy skin •Kidneys: the activation of the RAS and the ADH - Decreased urine output (<500ml/day) - normal: 0.5~1ml/kg/h - Dark-yellow urine w/ increased specific gravity meaning it's very concentrated and you can see some changes in lab values - BUN : Creatinine > 20-40 : 1 Muscle, GI tract, Liver: see poor perfusion leading to tissue injury

How are airway and sweat ducts involved?

The chloride channels in the airway and many other organs move chloride out of the cell, allowing sodium and water to follow, making mucus in the airways watery and thin enough to cough out. In a CF patient, the chloride channel doesn't work properly, so the movement of water does not occur, leaving the mucus too thick to clear easily and a growing area for bacteria. People with CF are known to have salty skin. This is because in the sweat gland, the CF gene moves chloride back into the interstitium, allowing sodium and water to follow, resulting in less sweat and preventing dehydration. In a CF patient, this does not occur so more salt and sweat are lost. CF patients have salty skin as a result and are at higher risk of dehydration. This is why when they exercise or it is hot out they are instructed to drink extra water and to eat extra salt to replace what is lost.

What is METABOLIC ACIDOSIS and CKD?

The kidneys play a vital role in maintaining acid-base balance •Splits carbonic acid (H₂CO₃) into H+ and bicarbonate (HCO₃-) •HCO₃- is reabsorbed •Neutralize non-volatile acids in the blood •H+ is secreted •Facilitates HCO₃- reabsorption •Reacts with non-HCO₃- buffers (phosphate, ammonia) → forms dihydrogen phosphate ion and ammonium ion In renal failure, improper buffering of non-volatile acids and reduced excretion results in severe acidosis •Decreased ammonia synthesis •Decreased bicarbonate reabsorption

What is Metabolic Regulation (Kidneys)?

The third mechanism for acid-base homeostasis is done through the kidneys by maintaining serum bicarb levels, which remember is the basic component of the HendersonHasselbalch equation. The majority of bicarb reabsorption occurs in the proximal tubule. Once bicarb is in the tubular lumen, it combines with hydrogen ion to form carbonic acid and then the carbonic acid is quickly converted into water and CO2 by carbonic anhydrase. Once in the CO2 form, it moves into the tubular cell where then it is converted back to carbonic acid by carbonic anhydrase. The carbonic acid quickly dissociates to form hydrogen ions that are secreted back into the tubular lumen and the bicarb is absorbed into the peritubular capillary to enter the bloodstream. So through this process, the kidneys can help with maintaining acid-base status by controlling how much bicarb is reabsorbed into the capillary and how much is excreted in the urine.

What is the Pharmacologic treatment of COPD exacerbations?

The three classes of medications most commonly used for COPD exacerbations are: 1. Bronchodilators •Although there is no high-quality evidence from RCTs, it is recommended that short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are the initial bronchodilators for acute treatment of a COPD exacerbation. 2. Corticosteroids •Data from studies indicate that systemic glucocorticoids in COPD exacerbations shorten recovery time and improve lung function (FEV1). They also improve oxygenation, the risk of early relapse, treatment failure, and the length of hospitalization. 3. Antibiotics

What is the IV Tobramycin Dosing?

Traditional vs. extended interval dosing (EID) EID is preferred at the Sacred Heart CF Clinic (q24h dosing) -Provides higher peak:MIC ratio -Maximizes concentration-dependent post-antibiotic effect -2.5-fold higher sputum Cmax vs TID dosing -Lengthens drug-free interval •Theoretically decreasing risk of nephro- & ototoxicity •Increased resistance? -Improved quality of life? -Initial starting dose ~10mg/kg -Vd & clearance rates are higher in CF -Tobramycin levels after 1st or 2nd dose -2 & 6 hours post-dose for patients <18 •Goal AUC: 80-120 -2 & 8 hours post-dose for ≥ 18 •Goal True peak (Cmax): 25-30, Goal Cmin: <1mg/L -Difficult to obtain consistent levels; much adjustment required

What is the treatment for Hyponatremia: SEVERE?

Treatment <120mEq/L & Severe symptoms •Correct sodium with 3% saline - 100 mL 3% saline over 10 min - May repeat x 3 to reach goal •Goals to prevent ODS - Goal correction 4-6 mEq/L in 24 hours and each day, appears to be sufficient to reverse the most severe manifestations of hyponatremia specifically brain herniation - Maximum correction 8 mEq/L in 24 hrs actual correction often exceeds what it's intended to, and therefore if we increase it greater than four to six we may lead to cases of ODS •Lasix 20-40 IV every 6 hours as needed - Prevent volume overload - Promote water elimination Monitoring: our 24 hour goal is usually achieved within the first few hours so we want to do frequent lab monitoring and look for a daily change rather than an hourly change in serum sodium patients that required this correction can correct rapidly so frequent monitoring is important

Cystic fibrosis related diabetes closely resembles Type 1 diabetes? T/F

True

People with CF excrete high amounts of salt through their skin? T/F

True

Trikafta is the first CFTR potentiator approved for those with one copy of deltaF508 and ANY other mutations? T/F

True ***Important Age and which mutations for each CFTR

What are the causes of COPD exacerbations?

Viral or bacterial infections Air pollution No identifiable cause Rule out other co-morbid conditions •Pneumonia •Heart failure exacerbation •Acute coronary syndrome

What is Bicarbonate/Carbonic Acid Buffer System?

[HCO3 −] + [H+] <=> H2CO3 <=> H2O + pCO2 Carbonic acid (H2CO3), which is in the middle of the equation, is a weak acid and bicarb (HCO3-) is the conjugate base. Bicarb can combine with a proton to form carbonic acid. And these compounds exist in equilibrium in the body. The way the buffer system works is, for example, if we saw an excess of protons in the bloodstream, this would normally create an acidic environment. But bicarb can bind with those extra protons to form carbonic acid, which is a much weaker acid, and will decrease the effect on pH (bicarb soaks up extra hydrogen ions). The right side of the equation shows that carbonic acid also exists in equilibrium with water and carbon dioxide. This will be important to remember when we start talking about lung regulation of acid-base status

4. 72 year old female NM is brought in to the emergency department by her caregiver with complaints of falling frequently and now an inability to walk or speak. She had the "flu" for 2 weeks with abdominal pain, decreased oral intake, and vomiting for the past 4 days. PMH: Lung cancer with recent chemotherapy. On initial laboratory assessment you find: serum Na = 112 mEq/L, calculated serum osmolality 265 mOsm/kg, weight 63 kg. Her blood pressure is 96/65, pulse is 118, and her urine output is reduced. Urine studies show Urine osm 650 mOsm and urine sodium < 20mEq. The ED physician consults you for assistance with fluids. a. Is this patient's hyponatremia considered acute or chronic, mild or severe? b. What type of hyponatremia is this based on serum osmolality and her volume status? c. Is hypertonic saline appropriate at this time? If yes, proceed to next question. If no, what fluid do you recommend and why? d. Assume the patient was euvolemic and make a recommendation for Hypertonic saline. Include dosing, treatment goals and monitoring

a) Chronic >48 hours normal 135-145 b) Hypovolemic low sodium and serum osmolality Extra renal losses c) NS, 3% saline, Desmopressin high risk of ODS d) Correct with sodium with 3% saline 100 mL over 10 mins, repeat to reach goal Goals to prevent ODS: Goal correction 4-6 mEq/L in 24 hours, max 8 mEq/L in 24 hours Lasix 20-40 IV every 6 hours as needed to prevent volume overload

3. JM is a 62yoF with a history of stage 3 CKD presenting to the clinic for her routine check-up. She states that she has been following the lifestyle modification recommendations provided to her from her last clinic visit and has been adherent with her dietary protein, and phosphorus restrictions although she admits to adding more salt to her veggies to make them taste better. She takes atorvastatin 40 mg daily for dyslipidemia and lisinopril 40 mg daily for hypertension. Her vital signs today are HR 65bpm and BP 128/80 mmHg. Her physical exam was grossly normal except for some mild pitting edema in her ankles. Her laboratory results are as follows: Sodium today: 149 Ref 135-145 mEq/L Phosphorus: 5.5 Ref 2.7-4.5 mg/dL a) Based on the physical exam and labs, how would you describe JM's fluid status? Explain how CKD can affect her ability to maintain electrolyte and fluid homeostasis. b) The PA at the clinic would like to start a phosphate binder to manage JM's hyperphosphatemia and asks you, the pharmacist, for a recommendation. Which phosphate binder would you recommend and why? c) What patient counseling information would you provide to the patient for the phosphate binder you recommended?

a) High sodium, edema= hypervolemic b) Sevelamer for this pt. We want to avoid calcium based binders due to age, lanthanum-based not recommended but they need to be chewed c) Must be taken with meals

CD is a 80 year-old male and has been admitted after being found down at home. He is confused. Upon further review, you discover that CD's serum sodium is elevated at 160 mEq/L, his serum creatinine is at 1.9, and BUN is elevated at 54. Vitals are normal. Wt 82kg. Ht 5'11" a. What is the first step in correcting CD's hypovolemic hypernatremia? b. Calculate CD's estimated free water deficit. c. Make a recommendation for an IV fluid and rate for the safe correction of CD's water deficits (after his volume has been corrected)

a) Resuscitate with NS (Fluid replacement) then correct sodium b) Deficit = current TBW x [(serum Na/140)-1] TBW= 0.5 L/kg x 82= 41 = 41 L x [(160/140)-1] =5.8 c) NTE 10-12 mEq/L in 24 hours give 3 L over 24 hours (*half the deficit*)

2. JB is a 54 year old male who returned from a vacation cruise with traveler's diarrhea. He weighs 70 kg. He has been ill for the last seven days with nausea, vomiting, and diarrhea. His wife brought him to the ED, for evaluation because he is weak, dizzy, and unable to stand. At this time he is also unable to answer any questions. His BP is 80/60 with a HR of 115 BPM. He has not been able to keep down food or water for several days and has been having multiple diarrheal episodes daily. a. What subjective and objective findings indicate that this patient is hypovolemic? b. Make a recommendation for an initial IV fluid therapy that include the appropriate solution, volume/rate, and other dosing parameters. c. How will this fluid distribute throughout JB's body compartments? d. How will you monitor for a response?

a) S: diarrhea, N/V, dehydrated O: BP, HR Acute <48hrs so he is chronic b) NS or LR 250-500 mL over 15 mins to get to intravascular space (D5W IS WRONG), reassess in a few mins c) Monitor BP, HR

4. SB is a 78yoM with ESRD on HD (M/W/F) returning to clinic to discuss initiation of an erythropoiesis stimulating agent (ESA). During his last office visit with his nephrologist, SB was found to have a significant drop in his hemoglobin from a baseline of 15.1 g/dL to 9.2 g/dL and was subsequently recommended to start epoetin alfa (Epogen®) for anemia of CKD. a) What additional iron studies would you like to see to guide your decision on selecting an appropriate iron product for treatment? Why? b) SB's iron studies resulted with a ferritin of 387 ng/mL and TSat 24%. Explain what considerations you would account for when choosing between oral versus intravenous iron replacement. Additionally, explain the difference between when you would initiate iron replacement therapy and when you would initiate ESA therapy. c) Compare and contrast the advantages and disadvantages between the different medications used for ESA therapy and their administration routes. d) Before initiating Epogen®, SB requests for medication counseling to better understand the risks and benefits of treating anemia with ESA therapy. If you were counseling the patient, how would you describe the goal of ESA therapy? What are the major risks of ESA therapy? e) How would you evaluate and monitor SB's response to therapy?

a) Tsat and ferritin, TSat ≤30% and ferritin ≤500 ng/mL b) Erythropoiesis-Stimulating Agent (ESA) initiation Hgb <10 g/dLESA to avoid hb drops below 9, Iron initiation when TSat ≤30% and ferritin ≤500 ng/mL, Iron: IV preferred in Stage 5 c) Iron comes first to saturate and collect Hb, ESA Takes ~10 days, ESA: IV or SC Less bioavailability but prolonged absorption phase with SC administration d) Goal: stimulate erythropoiesis Risks: Hypertension/hypertensive encephalopathy, Seizures, Thrombosis, Antibody-associated pure red cell aplasia (PRCA), Epogen has to be administrated the most frequently e) Monitor Hemoglobin we want (10-11) not too high because too much ESA can cause increased risk of mortality, Tsat, ferritin Life span of RBC is 3 months If increase Hgb in short time, decrease dose Hgb takes too long to increase, increase dose Iron is building block of RBC production

1. DB is a 63 year-old male admitted for elective open cholecystectomy (removal of gall bladder). He is 6 feet tall and weighs 70 kg. After the procedure he is NPO (nothing by mouth) with intermittent naso-gastric suction applied with minimal volume being lost. His serum electrolytes and renal function are within normal limits. Order for: 5% Dextrose in Water and 0.45% NaCl with 20 mEq/L Potassium Chloride at 125 ml/hour (D51/2 NS w/20KCl) a. Is this an appropriate IV fluid? b. Is this an appropriate IV Fluid rate? Calculate this patients maintenance fluid volume needs.

a) Yes b) Yes 25-35 mL/kg/day and he is 70 kg... 1750-2450 mL/day =72-102 mL/hr so it is a little fast But apparently its fine?

Case: RL is a 49yoM w/ PMH significant for insulin dependent type II DM, HTN, HLD, anxiety and CKD which has now progressed to ESRD (not anuric). He presents to the kidney transplant clinic today to be evaluated for his eligibility for kidney transplantation. During his transplant evaluation he states that he is a lawyer who owns his own law firm, he has been adherent with taking his diabetes and blood pressure medications, and he has a wife and two kids which he attributes to as his main motivation for seeking a kidney transplant. His home medications are as follows: Aspirin 81 mg tablet Atorvastatin 40 mg tablet Fexofenadine 60 mg tablet Hydroxyzine 50 mg tablet Insulin glargine 100 units/mL vial Regular insulin 100 units/mL vial Lisinopril 40 mg tablet Verapamil 120 mg tablet a. Transplant centers across the country have different factors that contribute to the ranking of patients on the kidney transplant list. One commonly considered factor is how long a patient has been on dialysis. If RL's nephrologist were to recommend starting renal replacement therapy for his ESRD, would you recommend hemodialysis or peritoneal dialysis for him? Why? b. If the decision was made to start peritoneal dialysis on RL, which (if any) medications would need to be renally adjusted? c. If the decision was made to start peritoneal dialysis on RL, what are potential complications you would counsel him on?

a) Young, peritoneal would be more convenient, better preservation of renal function b) Allegra, hydroxyzine c) Glucose load /weight gain, thrombosis, infections