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210 Cards in this Set

  • Front
  • Back
risk factors for acute respiratory distress in infants
- Occurs in more than ½ of infants born at 30 weeks’ gestation or earlier
- Extremely common in low-birth weight infants born prematurely
- Surfactant deficiency is a more common cause of ARDS in infants than in adults
risk factors for acute respiratory distress in adults
- Patients are at risk for aspiration in the hospital
- Other complications: severe trauma with shock, acute pancreatitis, overdose
- Most will get ARDS due to some kind of other cause (ex. asthma)
role of surfactant tx in infants and adults
• Surfactant replacement and medications may be useful in battling and preserving lung function
- Surfactant can reduce surface tension, keep alveoli open, and increase oxygenation
* Pre-term infants are at higher risk and would benefit more from surfactant because they do not have well-developed lungs to produce surfactants
* In adults, we hesitate in giving surfactant therapy because there may be an underlying cause for the patient’s symptoms
- Surfactant therapy is very expensive for adults
pathophysiology of ARDS in infants
- Type II pneumocyte formation and differentiation dysfunction
-- Regulating surface tension and surfactant production
- The pneumocytes work to release and produce surfactant
- Surfactant prevents the alveoli from collapsing by using their phospholipid content to decrease surface tension
- Atelectasis results when hypoxia arises
- Immature maturation of the ENaC (sodium channels) that usually helps regulate the presence of fluid in the lungs…
- ENaC is stimulated enough so that fluid doesn’t accumulate in places that they don’t belong
- Increased mucus buildup and ENaC dysfunction causes a decrease in pulmonary volume control and can increase the risk of pulmonary edema, mucus, and infection.
pathophysiology of ARDS in adults
- Damage to alveolar-epithelium can occur: decrease surfactant production
- The damage erodes the alveolar-capillary membrane/barrier
- The damage increases permeability and allows protein rich fluid to enter the lung spaces
- Surfactant production also suffers and this increases the risk of increasing surface tension and alveolar collapse
- Increased permeability leads to systemic infection risk increase
- Increased damage begets increased risk of fibrosis and further remodeling
role of glucocorticoid therapy in the treatment of ARDS
• Glucocorticoids are used to induce maturation of preterm fetal lungs by stimulation of the pulmonary surfactant system
• They affect the antioxidant enzyme production, lung fluid absorption, and alveolar development
• They induce genes associated with the synthesis of surfactant proteins, FA synthase, ENaC, and the membrane protein Na+/K+ ATPase
- They help development of EnaC by stimulating growth factors, leading to more surfactant production
• They increase the expression of vascular endothelial growth factor, which may inhibit alveolarization and lead to abnormally large alveoli
• For prevention of ARDS, glucocorticoids can increase the rate of cellular maturation of the lungs
short-term adverse reactions to glucocorticoids
- Na+ retention
- Edema
- Hyperglycemia
- Agitation/psychosis
- Weight gain
long-term (>2 weeks) adverse rxns to glucocorticoids
- Diabetes
- Straie
- Osteoporosis
- Glaucoma/cataracts
- Cushingoid
- Immune suppression
- Skin atrophy
specific risk factors for development of ARDS in adults
- Adults develop ARDS in the presence of other disorders (precursors in developing ARDS)
-- Asthma
-- Pulmonary arterial HTN
- ARDS is categorized in adults who have lots of chronic medications
- Proinflammatory mediators increase with chronic damage
-- Interleukins, cytokines, neutrophils, leukotrienes
-- Increased risk of thrombotic elements – PAF
tocolytic tx in infants
- Start this in the mother
- This prevents birth from occurring early
-- It can prolog labor up to 1 week
- This will increase chance for the infant to produce pneumocytes and decrease use of corticosteroids
- Tocolytic agents are widely used today to treat premature labor and permit pregnancy to proceed and so let the fetus gain in size and maturity before being born
- Tocolytic eligibility: measurements of fibronectin have been proposed as useful to identify the patients eligible for tocolytic therapy
Examples of tocolytic agents
o MgS04
o Nifedipine
o Salbutamol
o Indomethacin
o Terbutaline
o Ritodrine
o Fenoterol
o Atosiban
- Systemic inflammatory response system
- Without a proven source of infection
-- SIRS + proven infection = sepsis
- Multiple organ dysfunction syndrome
- the presence of altered organ function in acutely ill patients such that homeostasis cannot be maintained without intervention
- It usually involves two or more organ systems
- Kidneys are highly susceptible to damage due to chronic conditions and ICU
- Results from the immune response to a severe infection
- SIRS and MODS can progress into sepsis
subjective/objective signs of ARDS
• Subjective/Objective
- Difficulty breathing
 Get ABG, chem panel, AG, FEV/FEV1, D-dimer, etc
 Want to prevent acidosis, coagulation issues, electrolyte disorders, etc.
- Chest x-ray showing infiltrates
 Infiltrates can be caused by almost anything (infection, fluid, TB, HF, etc.)
• Most common presentations:
- Pneumonia
- Severe lung damage
oxygen therapy for a severely-ill/disabled patient vs. for a less severe and more capable patient
• Less severe and more capable patient
o Will receive O2 via nasal cannula or mask
 This is less invasive than ventilation machines
o The patient will undergo ABG testing within 15-30 minutes
 Can expect to see at least mild respiratory acidosis
• More severely ill/disabled pt.
- The patient will be intubated
- Ventilation will be started with the most appropriate ventilator
- 02 sat >90%
- A catheter, such as a Swan-Ganz, will be inserted to monitor pulmonary pressure
what is PWCP monitoring?
- Objective: the pulmonary capillary wedge pressure provides an indirect measure of the left atrial pressure which is helpful in diagnosis of left ventricular failure and mitral valve disease
- Monitoring PCWP will determine to see if there are any cardiac collapsing symptoms
- Normally used to determine to see if there is decompensated acute heart failure
What do PWCP values mean?
• If PCWP < 18mmHg:
- The patient assessment will exclude cardiogenic sources of the presentation
- If the pressure is very LOW, then this is mainly a pulmonary pathology
• If PCWP < 18 mmHg:
- The patient must be considered for cardiogenic collapse and failure
- So not just respiratory therapy, but also cardiogenic therapy
 Need pressor agents and IV fluids
 PCWP, HR, and BP are used to determine if dobutamine or dopamine needs to be administered
- If the pressure is very HIGH, then cardiac causes are suspected
What is the significance of decreases in hemoglobin and hematocrit
• Decreases in hemoglobin and hematocrit will result in a decrease in EABV because not enough RBC are available to distribute oxygen to other organs of the body
What kinds of medications can help patients remain comfortable when having to be tested for ABG values?
• BZD (Midazolam drip)
+/- (Morphine/Dilaudid drip)
+/- (Propofol drip)
• NMJ blocker
- Given until the patient is less responsive to pain / discomfort
- Given so that patient will not feel discomfort when ABG is drawn
- These meds can decrease respiratory drive
- Have to watch O2 saturation continuously while receiving these agents
14. What is the treatment for severe drops in hemoglobin and hematocrit? Why is the treatment followed by furosemide therapy?
• Hemoglobin < 10mg/dl
- RBC/plasma transfusion is needed
 Erythropoietin
- Plasma transfusions can be given with furosemide to prevent the accumulation of volume
 This will help stabilize the patient’s volume
What signs can point to renal or liver damage (like common labs SCr elevations, LFT’s, urine output, etc…) – how does organ damage affect perfusion?
• Considerations for perfusion:
- Vitals, urine output (+), rise in SCr <0.5mg/dl from admission baseline, liver tests WNL
- This along with PCWP helps determine if patient will benefit from pressor therapy
- If have low oxygenation, then will not have good perfusion (low EABV)
• If the patient is exhibiting appropriate organ perfusion, then the patient will have nosocomial infections ruled out
• If the patient is NOT exhibiting appropriate organ perfusion, then addition of vasopresor agents and diuretics are needed for edema relief
• Appropriate tissue perfusion is necessary to optimize oxygen dissociation at the tissue level
• Adequate perfusion supplies glucose and electrolytes to tissues while also eliminating metabolic by-products
• Improving oxygen supply should improve oxygen delivery to tissues
16. What medicines can help with perfusion? Which medications are known as pressors? How does dopamine compare to dobutamine?
• Pressors offer theoretical benefits because catecholamines like isoproterenol and dopamine can upregulate ENaC and thus help reduce pulmonary edema
• Dopamine might have better affect on renal flow than dobutamine
• DA1 acts on the kidney
• DA2 acts on the brain
• Dobutamine acts on the sympathetic drive regardless of dose
- It lacks theoretical impact on D1 and renal flow
What is the role of empiric tx in treating infection?
• Empiric therapy is the initiation of treatment prior to determination of a firm diagnosis
• These antibiotics are typically broad spectrum in that they treat a wide variety of possible microorganisms
• Once the organism is identified, a different antibiotic can be given that is specifically used to fight against that particular organism
What is an antibiogram?
An antibiogram is the result of a laboratory testing for the sensitivity of an isolated bacterial strain to different antibiotics
What happens when O2 tx is too aggressive?
• When 02 therapy is too aggressive, it pops the collapsed alveoli to open up, causing pneumothorax
- Will cause respiratory depression and respiratory failure
- It will send 02 to areas where that will not show any benefit for the patient
- That is why you will not see patients on 100% saturation therapy
Know the names and the role in therapy of the surfactant agents. Focus on the agents: Infasurf, Curosurf and Survanta. How do they compare in their onset of action? Does a more rapid onset of action make them more effective?
• Surfactant prevents the alveoli from collapsing by using their phospholipid content to decrease surface tension
• Efficacy and prevention of death in animals did not increase with administration of the rapid-acting agents
• Infasurf and Curasurf proved to be equally safe and effective, but more effective than Survanta (fast-acting) in the acute setting for neonatal and pediatric ICU
Can agents in the surfactant class be switched in equivalent doses from one to the other? Can agents in this class be given as early as in the delivery room to an infant?
• The agents are NOT directly interchangeable and are not recommended to be changes without monitoring the patient’s O2 saturation
- Onset of action and potency are NOT identical among the agents
- All the dosing is individualized for that specific medication
- Must look at the packet insert before dosing these medications for the patient
• Onset of initial therapy:
- Early use in the delivery room has been safely compared to initiating surfactants in the NICU later post-delivery
- However, some feel it is better to give ASAP because they feel that the patient may respond better if exposed early
4. How does surfactant therapy affect the aggressiveness of O2 therapy? What does this do to reduce the risk of pneumothorax?
• Surfactant therapy prevents unnecessary excessive ventilation pressures with oxygen therapy
- If you give the surfactant early, their saturation levels will be okay
- Patients will still need oxygen therapy, but they will need less aggressive amounts
- Waiting to administer after ARDS is confirmed results in unnecessary exposure to increased ventilator pressures and oxygen supplementation
 This is associated with greater pulmonary damage
• Surfactant therapy helps decrease the risk of pneumothorax development by preventing the lung from collapsing
Which types of patients benefit most from surfactant with regard to patient characteristics, use of the agent and concurrent use of CS? When is stopping surfactant OK?
• Infants of 4-5 lbs
- The more you weigh as an infant, the more chance the infants has to thrive
• Patients with a recent trial course of corticosteroids
- Having healthy and well-developed lungs may increase the efficacy of the surfactant
- CS + surfactants = stimulating growth factors that allow pneumocyte type II cells to grow and make more surfactants
• Surfactant therapy may be discontinued when the oxygen status improves and stabilizes
patients who do not respond well to surfactant tx
* Patients with other health-complications
- Sepsis
- Pneumonia
- Congenital cardiac disease
- Pulmonary hypertension
- Meconium aspiration
- Pulmonary underdevelopment
toxicities of surfactants
• Theoretical allergy
- The ICU is equipped with emergency medications that can mitigate an allergic reaction to non-synthetic products
• Tissue Damage effects
- Can be attributed to the ET (endotracheal) tube as well
 Bacteria can be present for those who are on ET for a long time
 This can increase risk for infection
- Airway obstruction (if hyper-mucus secretion) and aspiration
- Hemorrhage and drops in oxygenation
• Cardiac effects
- Bradycardia
 Possible link to sepsis or poorly perfused organs
 Remember: sepsis causes lowered EABV
dosing of surfactants, and specific dosing of survanta
- dosing of these agents may vary, may be weight-based, may result in non-effectiveness
- may be continued as long as the oxygen status is poor
• Survanta
- 4 ml/kg/dose x up to 4 doses usually 6-12 hours apart with ventilation assessment for improvement in oxygen saturation
- Stop therapy when the patient is able to breathe comfortably again
- Might need more than 4 doses, so monitor saturation to ensure no more doses need to be given
• Reassessment of pulmonary function and ventilation is routine and important
• Using multiple doses improves efficacy because the majority of the first dose is inhibited by soluble proteins and other factors in the small airways and alveoli
how are sedating/analgesic agents used in ARDS?
• All of these agents are used as supportive therapy to:
- Alleviate pain and discomfort
- Minimize ventilator complications
- Correct any metabolic and/or fluid imbalance
• Sedation/induction of retrograde amnesia
- Sedation has affect on cardiac (decrease RR and BP) and on brain function
- MONA = morphine, oxygen, nitroglycerin, and aspirin
- Morphine = must watch respiratory work and reduced cardiac work (hypotension)
 Can flat line due to too much exposure of these medications
 must monitor carefully
sedatives, anticonvulsants, and NMJ blockers in ARDS tx
• Sedative agents
- BDZP: lorazepam and midazolam drips
 Lorazepam is the preferred sedative agent in the absence of pain
 Midalozam is more costly and requires more fluid
- Anticonvulsants: Phenobarbital or dilantin
 Available in liquid form that can be forced down a NG tube
- Must assess for “feeling” using the sedation scores based on the patient’s level of response
• Neuromuscular junction blockers
- Can help calm down nerves
- Can be bad because if the patient begins to have pain, then the physician would not be able to detect where it is located because the patient won’t be able to move
propofol vs. midazolam
• Midalozam
- Has greater amnesic effects than propofol
- It is cheaper than propofol
• Propofol
- It is an anesthetic induction agent
 It allows the body to rest and relax by sedation
- Has a rapid onset of action
 Patients tend to get better faster than midalozam (faster extubation)
 It tends to accumulate in the peripheral tissue leading to a longer sedative effect
- Has a short t1/2
- Very expensive
- Renal clearance does NOT play a role in dosing adjustments (just like heparin)
- It can undergo tachyphylaxis/tolerance (like calcitonin and β2-agonists) around 7 days or sooner
- Renal or hepatic dysfunction does NOT significantly affect clearance of propofol
• Adverse effects
- Heodynamic and respiratory depression
- Pain with peripheral administration
- Green discoloration of the urine
- Hypotension: dose and rate-dependent
- Propofol is dissolved in a lipid emulsion and prolonged infusion (>72 hrs) requires frequent monitoring of TG levels to avoid pancreatitis
- Microbial contamination of the lipid emulsion is a significant risk, and the infusion setup must be changed every 12 hours
• Propofol consensus
- The SCCM TF recommends propofol or midalozam for short-term sedation (<48 hrs)
- They both provide equally effective sedation
- With propofol, the time to extubation is shorter once the drug is d/c, but the degree of hypotension and cost are higher than with midalozam
 The cost may be offset by a longer ICU stay with midalozam
What is the role of sodium bicarbonate and the indication for use of tromethamine over sodium bicarbonate? What are the dangers of alkali therapy?
• Sodium Bicarbonate
- Less preference for sodium lactate or other alkali solutions
- It is used concurrently with attempts to find the underlying cause
- Always watch for pH and watch for rebound alkalosis
- Might have excess of Na+, so may see a drop in K+ levels
-- This is because the K+ will start migrate inside the cells
- With Na+ overload will lead to volume overload, problematic in CHF patients
• Patients in ICU have very low perfusion, so will get delayed response when use other forms of sodium (citrate, lactate, etc.)
• Tromethamine
- This is preferred in the setting of CHF or in cases where adding the excess sodium of NaHCO3 may be detrimental
- It acts as an osmotic diuretic
- It combines with H+ to form bicarbonate
- It is given as a rapid infusion, which increases alkalosis risk
• Dangers of alkali therapy
- Will start to see hypokalemia
 Replacement of Mg2+ should be a considerable part of therapy if needed
 Or, it can be due to hypoaldosteronism
What is the function of the upper GI tract?
- H+ ions play a central role in the digestion of proteins, both by a direct action and by facilitating the role of Pepsin
- H+ ions are secreted by parietal cells in the gastric mucosa as a result of stimulation of acetylcholine, gastrin and histamine receptors
What are the defense mechanisms that prevent auto-digestion?
- The production of a mucous gel layer by mucous-secreting cells in the gastric mucosa, secretion of bicarbonate ions into the gel and maintenance of a pH neutral layer of protection for gastric mucosal cells.
- The body has a natural ability to allow bicarbonate to infiltrate in the GI and help keep acids and bases in check
- Globet cells secrete mucus and PG to help form a protective layer on the GI
- Mucosal cells are rapidly replaced in the crypts by proliferation and migrate to damaged surfaces by the process of restitution.
- Prostaglandins play an important role in maintaining these defenses.
- Good regional blood supply and perfusion is needed to support the intense metabolic activity required to maintain these processes.
Prevention and tx of stress ulcers?
• PPI and H2 blockers are effective
• Carafate won’t be helpful at all if the patient has an active bleed (only good for active bleed)
• ZES will need double doses of PPIs and H2 blockers
• Treatment
- Intravenous PPI therapy
 Example: IV Prevacid
- Intravenous H2B therapy
 Example: IV cimetidine
• Prevention
- Intravenous H2B therapy is more cost effective than intravenous (or oral) PPI therapy for patients needing prevention
- PPI is used for both active bleeds and for prevention
• Conversions
o Patients on PPI and H2B therapy can be changed to oral therapy as soon as the patient is able to tolerate food and other oral medications
Toxicity risks of certain antibiotics
 AMPHOTERACIN B: renal danage
 CUBICIN: increased CPK
 FOSCARNET: electrolyte disorders
 AMINOGLYCOSIDES: renal failure (ATN = acute tubular necrosis)
 BACTRIM: hyperkalmeia
lepirudin & agatroban
- These are DTIs that are used for acute anticoagulation needs in patients who have developed a HIT reaction
- These bind directly to thrombin and neutralize it
- Lepirudin
 given when the patient has a good kidney
 Monitor aPTT in 4 hours then every 12 hours when stable
 Monitor PT, CBC, SCr, INR (if also on warfarin)
- Agatroban
 Given when the patient has a good liver
• No renal issues
 Monitor aPTT in 2 hours
 Can also monitor PT and INR (if also on warfarin
types of protein C deficiency
* protein C is the body's natural anticoagulant
- Type I protein C deficits
 Result in decreased amounts of protein C
- Type II protein C deficits
 Results in decreased function of protein C
 This is referred to as natural protein C resistance
• Patients with defects in both protein C genes (homozygous) can develop a severe form of thrombosis called purpura fluminans
- This results in severe clotting that causes death to tissues and can be life-threatening
what does Xigris do?
• When patients have infections in the blood this condition is called sepsis
- During this time of fighting off the infection, there are a lot of chemicals that start the clotting cascade which can cause clots to form
• By using Xigris, a exogenous source of Protein C, this can help prevent the clotting cascade by naturally anticoagulating the blood through mechanism of Protein C
• Protein C (with it’s cofactor protein S) inactivates factor 5A and 8a and promotes fibrinolysis by reducing the concentration of plasminogen activator inhibitor 1
- The Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study was initiated in July 1998. Enrollment was suspended at the second interim analysis in June 2000 because Xigris demonstrated a significant survival benefit that exceeded the prospectively set stopping rules.
- Analysis indicated a statistically significant 29% relative reduction in risk of death among high-risk (APACHE II score ≥ 25) patients. In these patients, survival rates were 69% for Xigris patients, compared to 56% for standard therapy patients at 28 days. The difference in survival was sustained through 2.5 years of follow-up.
APACHE score
- APACHE II was designed to measure the severity of disease for adult patients admitted to Intensive care units.
- The point score is calculated from 12 routine physiological measurements (such as blood pressure, body temperature, heart rate etc.) during the first 24 hours after admission, information about previous health status and some information obtained at admission (such as age)
How does genetics play a role in CF?
• CF is a preventable disease
• CF is an inherited disease that affects the normal movement of salt (sodium chloride) into and out of certain cells, including those that line the lungs and pancreas.
- Depends on the carrier status of both parents
• CF is inherited through an autosomal (Mendelian) recessive mode
- Of a couple with each parent being a carrier (heterozygous) a child has:
 1 in 4 chance of having the disease
 1 in 2 chance of being a carrier
 1 in 4 chance of being normal (having neither the disease or the trait)
CF mutation types
• Not all patients with CF mutations can/will manifest the disease
• Mutation types:
1. Class I – defective protein production
2. Class II – defective protein processing
3. Class III – defective channel regulation
4. Class IV – defective channel conductance
• Symptoms may be either pulmonary or GI or both
• Can have more respiratory problems versus GI (or vice versa) depending on what class they are in
• Class II diagnoses are most commonly “spotted” early because patients will have MOST severe pancreatic insufficiency… may need therapy at early phase
CF pathway from mutation to syndrome
1. CFTR dna
2. CFTR protein
3. ION transport
4. Altered secretions
5. Blocked ducts, impaired mucosal defense
6. infection, inflammation
7. CF
symptoms of CF
- salty sweat
- intestinal block
- fibrotic pancreas
- failure to thrive
- recurrent bacterial lung infections
- filled sinuses
- gallbladder, liver
CF hematology
- abnormal presentation in whichever blood line is affected most
- Usually link to anemia – fatigue, malaise…
CF in liver
- Cirrhosis or fatty liver
- Portal HTN / esophageal varices
CF in intestines
- Viscous secretions
- GI obstruction and bloating
CF in pancreas
- Digestive and insulin
- Dietary supplementation and glucose control via insulin
CF in GI system
- Meconium ileus – small bowel obstruction
 The baby’s first stool
 In CF patients, they lack trypsin (pancreatic enzymes to digest stool properly) and will get sticky substance
 Lipase and amylase are pancreatic enzymes
- Complications – chronic bloating and constipation
 Meds like Zelnorm will not be useful for those with CF
 May need Colace and lactulose
- Pancreatic deficits in up to 85-90% of patients with CF – with deficits in amylase and lipase function
- Vitamin supplementation is necessary
 If patients do not absorb vitamins
- Avoidance of EtOH is best recommended due to the impact on the liver health
 Alcohol is a fatty substance that be responsible for forming fatty infiltrates in the liver
• Gall stones, pancreatitis
- Other supplements – B vitamin complex, folic acid, zinc and vitamin E may be indicated
 If lack B viatmins, that may not be good with regard to mood, anemia, and preventing other issues such as encephaopathy
- Insulin may be useful if glucose intolerance surfaces
 If patients do not have a good pancreas, then would need insulin therapy
- Insulin pathology is distinct from DM 1
 In CF, patients have insulin receptors – but response to insulin is decreased…
- Development of hepatic, pancreatic and diabetogenic type effects increases with AGE
CF in respiratory system
- Increased infection risk: viral, bacterial and fungal sources
- Chronic inflammation and immune suppressive component
 O2 sat and FEV values will decrease
- Remodeling component with hyperinflation of lungs
- Increased sensitivity to irritants
- Pathogens involved:
 Pseudomonas sp.; staphylococcus aureus; H. influenzae
 Others: Klebsiella and Stenotrophomonas maltophilia
 Fungal: aspergillus fumigatus
- Effects alpha-1 antitrypsin vs. neutrophil elastase balance – causing more inflammation
- Chronic bronchial damage: inflammation and reduced O2 use with a progression to hemoptysis
- Relationship to increased sinusitis
CF in sweat glands (detail)
- Problems with epithelia can cause changes in Na+ and Cl- channel function
- This begets disorders of electrolytes – higher conc. of Na+ and Cl- may be found in sweat
- The amount of Cl- in the sweat is a diagnostic indicator helpful in identifying CF
- These disorders do not cause a serious impact on electrolytes UNLESS there is an underlying risk factor or condition that causes dehydration or in severely salt deficient diets
 Will not have clinical hyponatremia from CF alone!!
• Ex. CF + dehydration will lead to clinical hypnotremia
- A salt deficient diet is difficult to achieve in the U.S.
CF in reproductive system (detail)
- Sterility / Reduced Fertility
 Men: vas deferens obstruction and aspermia from seminal vesicle damage
 Women: menstrual irregularities, thickened cervical secretions and oligomenorrhea
- Sexual development delay
 Relationship of dietary deficits and physical failure to thrive (other organ systems) – delayed secondary sex characteristics
- Complications with pregnancy, if achieved
 Nutrition
 Physical complications
 Oxygenation is poor to mother and fetus
CF in bones and joints (detail)
- CF complications are thought to be related to abnormalities in bones and joints / arthritis
- Osteopenia and osteoporosis
 Occur more in adults with CF
- Linked to the deficit in dietary consumption of vitamin D and the impact of diet and CF on development
 Vitamin D malabsorption
 Decreased vitamin D conversion
 Delayed puberty and endocrine development
 Poor nutrition
 Limited physical activity
 Chronic acidosis
subjective s/sx of CF
- GI upset and discomfort, pain and nausea
- Fatty / Oily stools (steatorrhea)
- Respiratory Sx
- Clubbing of fingers
 Patient has fingers signs of low oxygen (hypoxia)
 Fat fingers that are blue and round at the tips
 Oxygen trying to get to extremities
- Infection Sx
- Sinusitis
- Fatigue and general malaise
 Due to not absorbing vitamins adequately
 Or can be due to hemotologic issues
objective s/sx of CF
- Low levels of lipase and amylase
- Lower than normal weight
 If patient cannot absorb vitamins/food the right way, they will have delay growth, and delay secondary sexual traits (ex. delayed menses)
- Fever
- White cell elevations
 Increase risk for infections
- Red Blood count decreases (anemia)
- Spirometry values reduced (FEV1)
sweat testing in CF
- measures of sweat with Cl- >60meq/L can help screening PRIOR to testing for CFTR (CF transmembrane regulator) mutations
mucus thinners for CF
- Drugs such as Pulmozyme (Dnase) help thin the mucus so that the child can cough up it up more easily.
 Dnase will lyse all the enzymes secreted by neutrophils
antibiotics for CF
- An inhaled antibiotic called TOBI (tobramycin) is commonly used
 Acts directly on lungs
 The patient may develop resistance when used chronically
- Levofloxacin for pneumonia or infection of the lung
- Aminoglycosides given directly into the lungs will have quick onset and will have fewer systemic side effects
anti-inflammatories for CF
- Medications, such as inhaled steroids and ibuprofen, help prevent lung inflammation (redness and swelling) that can make breathing difficult.
 NSAIDs block inflammatory mediators such as PG and help slow progression of the disease
 Afferent arteriole route in kidneys is blocked by NSAIDs, causing decreased renal perfusion
 Inhaled steroids have failed to demonstrate efficacy (risks > benefits)
pulmonary medication interventions
- Bronchodilating medications
- Medications used to prevent inflammation
- Vaccination for infection prevention
o Antibiotic therapy
 If patients have chronic infections, there will not be year-round therapy with antibiotics
• Have to worry about resistance when used chronically
• Tobramycin: given for 1-3 months then off for 1-3 months
pancreatic enzymes in CF
• The pancreatic enzymes are useful when patient have problems with the digestion and storage of nutrients
- Without these, patients may form gallstones
- These pancreatic enzymes will break up the gall stones from forming
• Age, weight, and diet has to be considered when figuring out dosing in patient who need pancreatic enzymes (dosing is variable with each patient)
• They are highly degraded by GI acid, so need to give PPI or H2 blockers to prevent degradation of these pancreatic enzymes
• Most common agents (Trade name)
- Pancrease
- Pancrelipase
- Ultrase
• Key Ingredients
- Lipase: 4,000 – 20,000 U
- Protease: 12,000 – 78,000 U
- Amylase: 12,000- 78,000 U
• Microencapsulated Forms
- Dose forms are protected from high degradation from GI acids
 Enteric coated microspheres or beads
- Lesser doses of the agents may be needed
- Other dose forms: caps, tabs, powder
• Use of lipase in patients:
- Lipase is the most important ingredient
 It digests fat in the system
- The amount of lipase is dependent on the amount of lipid (fat grams) consumed
 Sometimes, it is based on weight, or how much intake there is, or based on standard therapy
 Infants: 2,000 – 4,000 Lipase Units / 120 mL formula
 Dose Range: 500 – 4,000 Lipase Units / gm fat
 Starting Dose: 1,000 Lipase units / kg at each meal (50% for snacks)
ADRs of pancreatic enzymes in CF
• Elderly and children: irritation (diaper-rash like) – possibly d/t the enzyme byproducts eliminated in the feces (dose-dependent effect)
o They are at higher risk because these meds are acidic when they leave the body
o Will leave a rash, especially when they wear diapers
o These populations are difficult to get them to swallow meds
• Uric acid levels – uric acid levels may rise in decreased renal function (elevations in uric acid may not always equate to clinical gout and patients should be treated based on Sx)
• High doses of lipase have been linked to proximal colonic stricture
fat-soluble vitamins in CF
• Patients who do not have a balanced diet may need vitamin supplements EVEN WHILE on pancreatic enzymes
• Medications / supplements used in this situation include the fat soluble vitamins:
- A, D, E & K of fat
- Patients who lack these vitamins or those who are on CF meds
- Gastric bypass patients also lack these vitamins and minerals
• Objective Information:
 Serum carotene = Vitamin A
 Vitamin E Serum levels = Vitamin E and alpha-tocopherol
 Cholecalciferol levels = Vitamin D
 INR / protime values = Vitamin K
• Ursodiol is used in the treatment of gallstone disease
• It is taken PO to dissolve the galltones
• It is used in patients with gallstones who do not need to have their gallbladders removed or in those in whom surgery should be avoided because of other medical problems
- Surgery performed to avoid subsequent gallstone formation
• Ursodiol works only in those whose gallstones are made of cholesterol and works best when the stones are small
• This medication is also beneficial to prevent gallstones in patients who are on rapid weight-loss programs
• This is NOT effective for kidney stones
• Dosing for gallstone disease:
- Adults and children 12 years of age and older
 The dose is based on body weight
• Different dosing used for different populations based on weight
 The usual dose is 8 to 10 mg/kg of body weight a day, divided into two or three doses.
 Each dose is usually taken with a meal or 30 min – 1 hr before
• Dosing for prevention of gallstones during rapid weight loss:
- Adults-Oral, 300 mg two times a day
• In CF, thick mucus in the lungs obstructs airways and allows bacterial infection and inflammation to occur.
- Neutrophils are sent to fight these infections.
- When the neutrophils die, they release DNA and elastase, which further thicken the mucus and cause additional airway obstruction, infection, and inflammation.
• Pulmozyme is a man-made form of a naturally occurring DNase.
- Pulmozyme works by "cutting up" the DNA left by neutrophils.
- Dosing: 2.5 mg daily – BID via inhalation
What is the biofilm?
• The biofilm protects the bacteria from the host defenses as well as antibiotics
- Eventually CF patients develop chronic airway infections that cannot be eradicated fully even with prolonged use of systemic antibiotics
• When the bacterial colony (biofilm community) becomes too large and begins to expand to other sites, the acute exacerbations begin to surface – at this stage patients may have severe symptoms and the treatment will be a long process
- Biofilm is a protective layer that the bacteria uses to thrive and grow
- It protects them from the body’s own immune system
- When it explodes, you get organisms at places where they should not belong
 Will lead to SOB symptoms
early and late phase anaphylactic reactions
• Early phase
- On exposure or re-exposure to irritants
- Strongest reactions can be sudden after initial exposure (this allows the immune system to create a response)
• Late Phase
- Can occur up to 8 hrs following the initial reaction
- Remember the presentation on Xolair therapy
- Symptoms may peak even at 24 hrs after initial exposure
- Release of inflammatory cytokines contributes to the chronic inflammation and damage
- A state of hyperresponsiveness occurs
antihistamines for SAR
Symptom targets: Sneezing, rhinorrhea, itch, conjunctivitis
Issues: Intranasal – may still cause drowsiness
intranasal corticosteriods for SAR
Symptom targets: same as antihistamines, little effect on conjunctiva
Issues: Use before Sx are severe – can help prevent Sx
mast cell stabilizers for SAR
Target: Sx prevention
Issues: Use before Sx – full benefits may not be seen until up to 1 month
intranasal anticholinergics
target: rhinorrhea
issues: many side effects, used as last resort
epinephrine for SAR
- First line for anaphylaxis
- It causes vasoconstriction and squeezes the blood vessel to make them less leaky
- It is an SNS stimulant that will reduce vessel inflammation and permeability
- Since it is a SNS stimulant, it will help with breathing
Corticosteriods for SAR
- Adjunct agents
- Nasal steroids relieve sneezing, rhinorrhea, pruritis, and nasal congestion
- They have minimal SE
- Block inflammation by:
 Blocking mediator release
 Suppressing neutrophil chemotaxis
 Causing mild vasoconstriction
 Inhibiting mast cell-mediated late-phase reactions
- Blocked nasal passages should be cleared with a decongestant before administration of glucocorticoids to ensure a adequate penetration of the spray
Glucagon for SAR
Only use if needed to control severe symptoms when patient is not responsive to all other measures (Epi)
brand names: clemastine, Cyproheptadine
Clemastine: Tavist, Contac, Allerhist
Cyproheptadine: Periactin
cautions with decongestants
• SNS-mimetic agents
• Cause vasoconstriction via alpha / beta agonism
• Can caution in HTN and/or insomnia
• Caution in long-term use
- Rebound congestion (rhinitis medicamentosa)
- Prolonged use or abrupt discontinuation
• Topical agents: burning and stinging of the eyes
• Duration of agents
- Many need to be dosed repeatedly (Q4H, Q6H, Q12H)
• Avoid therapy lasting more than 1 week.
• Dose dependent effects of pseudoephedrine
• Pseudoepinephrine and HTN
- AVOID IN SEVERE HTN and uncontrolled (labile) HTN, above stage II
- Stroke complications can occur even at low doses
- Higher doses of Sudafed (210-240mg) can raise both BP and HR
- The risk of CV and stroke complications when combined with:
 MAOIs: Tranylcypramine (Parnate), Isocarboxazid, Phenelzine (Nardil)
 Anorexic agents/illicit stimulants
 Other stimulants/herbals
• MAOIs relieve depression by preventing the enzyme monoamine oxidase from metabolizing the neurotransmitters norepinephrine serotonin and dopamine in the brain
o As a result, these levels remain high in the brain, boosting mood.
• Some common MAOIs
o Phenelzine (Nardil)
o Tranylcypromine (Parnate)
o Isocarboxazid (Marplan)
o Selegiline (Emsam)
- Tyramine is an amino acid normally found in your body that helps regulate blood pressure
- In combo with MAOI can cause dangerously high increase in BP which can lead to a stroke
- Seen a lot in cheese, pickled foods, chocolates, certain meats, beer, wine
• Tyramine-like reaction
- You see the increase in BP
- Tyramine can cause blood vessels to dilate, and this may be what starts the migraine chain-reaction in some people
brand-generic names of nasal corticosteroids
Beclomethasone: Beconase
Betamethasone: Betamethacot, betastat, maxivate
Fluticasone: Flonase
Mometasone: Nasonex
Triamcinolone: Nasacort
singular dosing
Age dependent dosing:
2-5 y/o:4 mg CHEW tab daily, 2-5 y/o: 4 mg oral granule packet
6-14 y/o: 5 mg CHEW tab daily
> 15 y/o: 10 mg tab daily
drugs that put pts. at high risk for drug-induced apnea
• Ventilation
o If too aggressive, can cause respiratory disorders
• Psychiatric patients (BZD agents, sedatives and various neuroleptic agents)
o Controls CNS, which controls respiratory drive
o Common: overdose of BDZ due to suicidal ideation
• Chronic pain patients (outpatient) and opioid overuse or rapid titrations
o Can cause respiratory distress at too high doses
o Can cause respiratory drive if given too fast via IV
• Medications that can alter the metabolism of these agents (CYP 3A4 and 2D6 inhibitors can alter the way these meds work)
o Must watch direct and indirect affects (metabolism) of medications
risk factors for drug-induced apnea
• Patients who are at high risk for drug-induced apnea:
- The elderly (>65 y/o)
- Patients on multiple sedating medications
 Can cause respiratory drive, leading to SOB symptoms
- Remember: CNS controls ventilation
• Must take caution when using CS and aminoglycosides together
• Medications associated with frequent drug-induced apnea:
- Narcotics (high, acute doses)
 And in chronic overuse
- Benzodiazepines > barbiturates
 These are sedative classes
- Corticosteroids
 Not sure how it causes respiratory distress, but know that it occurs at high doses
 Possible reason: May cause insomnia agitation
NMJ blockers and drug-induced apnea
• This can occur within 24-48 hours and is dose-dependent
• The drug most pronounced to cause drug-induced apnea is vecuronium and pancuronium
• If used concurrently with high doses of CS, then can get worsening of respiratory symptoms
• These kind of medications are only administered in a setting where monitoring is intense and there is a mechanism to ventilate the patient quickly if needed
• These meds can cause paralysis in the involuntary muscles of the lungs
allergenic medications that can cause bronchospasm
• Patients with infections
- Sulfa and beta-lactam antibiotics (bactrim)
- More of an anaphylactic reaction
• Irritants
- Smokers
• Patients on pain medications
- Salicylates
- Any med that affect inflammatory mediators
• Patients undergoing invasive visualization procedures
- Radiocontrast dyes
- Metformin is a biguanide is held/stopped until the radiocontrast dye procedure is over or when SCr level is normalized
• Patients with HTN, CHF and other cardiac conditions
- Beta-blockers
 Block beta cell function, then the muscles will squeeze
- ACE (-) > ARB’s
 Cause bradykinin function to increase
- When have cough, then give ARB
 Have little cross reactivity
- Bradykinin cough will not produce angioedema reaction
allergic risk of beta-lactams
• Penicillins have a high chance of anaphylactic reactions
• Cephalosporins are less in risk than penicillins, but the risk is still there due to cross-allergy
- 1st generation: most cross reaction with PCN
- 2nd generation: less than 1st generation
- 3rd generation: Less than 1st and 2nd generations
- 4th generation: Least cross reaction than all others
• So, if the patient Is allergic to PCN, then can get a cephalosporin
- There is some cross sensitivity with SOB and drug-induced reactions
SDRI for smoking cessation
- Wellbutrin formulation and Zyban formulations
- They are DA/serotonin reuptake inhibitors
- Start is gradual 150mg QD and increase in 3-7 days to 150mg BID
- It is started 1-2 weeks before the quit date
Acomplia for smoking cessation
- It is a selective antagonist of the cannabinoid type 1 receptor (CB1) to reduce tobacco dependency
- Still under review by FDA for smoking cessation
 It is approved for weight loss indications
- Dosing is uncertain at this point
Chantix for smoking cessation
- Chantix is a partial nicotine receptor agonist
 However, CHANTIX does not contain nicotine
- Should not use with other cessation products
- Administration
 Should start one week before the quit date
 Maintain on therapy for 12 weeks
 Days 1-3: 0.5mg QD
 Days 4-7: 0.5mg BID
 Day 8-end of treatment: 1mg BID
SOB caused by NSAIDs
• Blocking the COX and PGD pathways makes the body shift efforts to the LT pathway
- LT are inflammatory mediators responsible for the genesis of Sx of allergies and shortness of breath – medications that block LT effects are used for asthma and seasonal / continuous allergic rhinitis
• Blocking COX will block PGs, so your body will make more LT and produce the SOB response
role of radio-contrast dye in bronchospasm
• Bronchospasm from radiocontrast dye is just an “allergic reaction”
- It causes the stimulation of mast cell degranulation
• When patients will receive radiocontrast dye, the metformin should he held/stopped until the procedure is over or when the SCr level is normalized
- Remember: radiocontrast dye and metformin causes an increase in SCr
cardioselective beta-blockers
Metoprolol tartrate
Metoprolol succinate
risks for developing ACE/ARB bradykinin cough
- Females > males
- Cough on exposure (1/4 patients) – some develop tolerance
 Is not an emergency, but it does bother the patient
- CHF patients > HTN patients
 component of hypoxia and SOB in CHF patients may be a reason
- A history of reaction to ACE-I/ARB will increase the risk when re-exposed to EITHER of the two
 This is not a contraindication but the patient should be warned about the possibility (initiate in a controlled environment) – bradykinin-induced
Treatment of the bradykinin cough if intolerable
- Stop the ACE-I/ARB
 Can give Epi if absolutely needed
- Recommend an agent for treatment of symptoms
 Theophylline or cromolyn have been around and are known to be effective
- Cromoyn is preferred due to its side effect profile
medications causing pulmonary edema
- Hydralazine (Apresoline)
- Nitrofurantoin for UTI (Macrobid or Macrodantin)
- Corticosteroids- these are Na+ retaining agents)
- Opiates- have histamine-like release
- Illicit drugs such as heroin
 Used to treat HTN and CHF
- MOA unclear
 It is a peripheral vasodilator that acts predominantly on the arterial smooth muscle to reduce SVR and increase stroke volume and cardiac output
 Helps increase blood and 02 to the heart and decrease workload on the heart
- Side effects
 Flushing, diarrhea, tachycardia- due to baroreceptor reflex, heachache, loss of appetite, N/V, pounding heartbeat, drug-induce SLE
- Use with BB and diuretics
 Hydralazine can cause tachycardia and fluid retention so a BB (or a rate-controlling CCB) and a diuretic will help prevent with this
• Naloxone (Narcan)
- Dose: 0.4-2 mg IV
 May repeat until SOB is stopped
 Max: 10mg
• If no effect, then may use Naltrexone
• Post-op and chronic opiate users should receive smaller doses to prevent sudden CV changes
- Dose: 0.2mg
MTX pulmonary toxicity
- It is an anti-metabolite that have been known to cause pulmonary toxicity
- Pulmonary symptoms, especially a dry, non-productive cough, may require interruption of treatment and careful investigation
- Patient will present with fever, cough, dyspnea, hypoxemia, and an infiltrate on chest X-ray
 Infection needs to be excluded
 This lesion can occur at all dosages. (pulmonary fibrosis)
amiodarone pulmonary toxicity
Onset: Slow
 Can be weeks to onset of pulmonary fibrosis symptoms
- Routine CXR to monitor
 Spirometry does not predict progression
 Can detect pulmonary fibrosis
- Pulomary fibrosis development is dose dependent (> 2 months)
- Pulmonart fibrosis development is duration dependent (> 2 years)
- Mechanism: thought to destroy protective phospholipids in the lung
nitrofurantoin pulmonary toxicity
- Possibly related to long-term use as a prophylactic agent against UTI infections in chronically debilitated patients
- Mechanism: involve the inhibition of antioxidants and the increased formation of super-oxide free radicals
• Patients who are on both amiodarone and nitrofurantoin would benefit from a monthly CXR to watch for pulmonary fibrosis
• Eosinophilia is inflammation of the lungs associated with an increase in eosinophils
- Eopsinophil is a type of WBC
• Eosinophilia may be due to an allergic reaction of some sort, either from a drug, such as sulfonamide, or parasitic infection, such as that caused by the worm (Hookworm)
- Other parasites may also cause the syndrome
• Common agents known to raise eosinophils and contribute to the inflammation of the lungs (SOB)
- Nitrofurantoin (Macrobid), Sulfonamides, Imipramine (Doxepin), PCN agents
• The onset occurs in about 1 month after the start of therapy
- There is no relationship to duration of therapy or doses for these agents and are onted to contribute to the diagnostic picture
• Usually, it improves without treatment (within a few months)
- If needed, can give CS
- If it the reaction is due to a medication, then d/c the culprit
nitrofurantoin pulmonary toxicity
- Possibly related to long-term use as a prophylactic agent against UTI infections in chronically debilitated patients
- Mechanism: involve the inhibition of antioxidants and the increased formation of super-oxide free radicals
• Patients who are on both amiodarone and nitrofurantoin would benefit from a monthly CXR to watch for pulmonary fibrosis
• Eosinophilia is inflammation of the lungs associated with an increase in eosinophils
- Eopsinophil is a type of WBC
• Eosinophilia may be due to an allergic reaction of some sort, either from a drug, such as sulfonamide, or parasitic infection, such as that caused by the worm (Hookworm)
- Other parasites may also cause the syndrome
• Common agents known to raise eosinophils and contribute to the inflammation of the lungs (SOB)
- Nitrofurantoin (Macrobid), Sulfonamides, Imipramine (Doxepin), PCN agents
• The onset occurs in about 1 month after the start of therapy
- There is no relationship to duration of therapy or doses for these agents and are onted to contribute to the diagnostic picture
• Usually, it improves without treatment (within a few months)
- If needed, can give CS
- If it the reaction is due to a medication, then d/c the culprit
management goals of ARF
• Objective: Management and prevention of re-occurrence
- Stop the medications that may have caused it
- ARF can happen from slow to quick onsets
- When come in the hospital, the patients will receive every medication to help them relieve the symptoms
 IV fluids, diuretics, etc
- If have other conditions such as DM, HTN, then they will also receive those meds
• Supportive care is the gold standard for treatment of ARF
prevention of progression of ARF
- BP and BG control
 Keep perfusion good to help continue good renal function
 Any hospitalized patient can get renal failure. higher risk in the ICU
- Pre-medications / pre-hydration when using potentially toxic chemotherapy or antiviral meds given IV
 Ex. if patient receives amphotericin or cisplatin (cancer med), they need pre-hydration bag that have lots of electrolytes because this drug depletes a lot of its electrolytes
 Want to prevent ARF
- Ensuring good baseline electrolytes, vitamins and supplements is important
 In treating hypercalcemia, want to use IV bisphosphantes such as aredia and zometa
risk factors for development of "hospital-acquired renal failure"
- ICU patients have high risk for getting renal failure
- CHF population are common patients
- They are given lots of diuretics
- As they get better, the doses must be decreased or else will get pre-renal failure
protein intake recommendations
- predialysis pts: 0.8 g/kg/day
- stable maintenance hemodialysis patients: 0.9–1.0 g/kg/day
- peritoneal dialysis pts: 1.0–1.1 g/kg/day
why is protein intake control important in renal failure?
• Want to reduce amount of protein in your diet when you start to have renal failure
• Must watch in the elderly if they get too much or too little
- They are at higher risk for malnutrition resulting from lack of proteins in the diet or lack of appetite (dementia)
• Too much can spill out in your urine as your kidney becomes worse
• Might need to increase protein intake after HD
• Too much or too little protein intake is not good
• Want to keep mesangeal matrix integrity to keep GFR functioning
• Keep protein in system to keep amino acid build-up adequate
presentation of ARF
• Various causes and presentations of ARF exist
- Harbinger signs:
 Elevations in SCr
 Decreased urine output
• SCr elevations
- Increases > 0.5 mg/dl from baseline in patients with PRIOR normal renal function
- Increases > 1.0 mg/dl from baseline in patients with PRIOR renal insufficiency (SCr > 2 – 2.5 mg/dl at baseline)
- SCr levels can change due to dehydration
 Never make dose changes based solely on SCr levels
 Have to look at the entire patient
• If the patient was dehydrated but is now given fluids to rehydrate them, the SCr levels would change again
anuria vs. oliguria
• Anuria
- No sufficient urine output – not enough to clear wastes
- Volume < 50 mL per day
- Can make certain electrolytes accumulate and cause problems with your heart
• Oliguria
- Just enough urine output to eliminate wastes
- Volume 50 – 450 ml per day (sources vary)
key populations at risk for ARF
• Hospitalized patients (especially in the ICU)
- Variable definition and presentation makes the discovery and diagnosis elusive
- Need oxygen to prevent renal artery stenosis and have decreased urine production
- Need oxygen to have good perfusion
• Patients on NSAID medications (both in the inpatient and outpatient setting)
- These medications are directly damaging to the renal system in the face of ARF
- They can cause a constriction of the afferent renal arteriole via prostaglandin blockade – leading to pre-renal azotemia and reducing renal flow
- If cannot dilate the afferent, then it will decrease the GFR
role of efferent and afferent arterioles in intraglomerular flow
• The blood enters the glomerulus by the afferent arteriole and leaves via an efferent arteriole
- Changes in glomerular afferent arteriole circumference
 GOOD: vasodilation – lets flow in
 BAD: vasoconstriction – does not let flow in
- Changes in glomerular efferent arteriole circumference
 GOOD: vasoconstriction – good in normal non-ARF kidney d/t promoting good perfusion in the glomerulus and allowing production of urine
 BAD: vasodilation – bad in impaired ARF kidney d/t loss of renal perfusion and lack of urine production – increased risk of anuria
• The resistance of the arterioles results in high pressure in the glomerulus which aids the process of ultrafiltration where fluids and soluble materials in the blood are forced out of the capillaries
why are the kidneys described as the "high pressure system"?
• the kidneys take up ¼ of the body’s cardiac output
• But kidneys only make up <1% of the body’s total weight
- Because they receive so much of the body’s CO relative to their size, they are classified as a high pressure system
• The renal afferent and efferent arterioles are the terminal resistance vessels of the kidney
• The afferent controls the glomerular inflow resistance and the efferent controls the glomerular outflow resistance
• The vessels exert opposing effects on the pressure within the glomerular capillaries
pharmacological measures to prevent renal toxicity
• No nephrotoxins
- Aminoglycosides, amphotericin B, NSAIDS and ACE (-) and ARB agents, diuretics and lowest dose of immune suppressants effective
 Can continue to use amphotericin because it has a lot of data and support behind it
• Using radiocontrast dyes with care and avoid high osmolarity / high glucose immune globulins
- Metformin is not nephrotoxic, but dyes can increase renal damage leading to high risks of lactic acidosis related to metformin
• Pharmacist-run renal dosing protocols
- Make sure the patient will not get toxicity or progress disease
• Managing chronic disease states
• Careful use of sedating medications
- Sedating meds can cause the brain to trigger lungs to reduce ventilation
- Can reduce perfusion and facilitate renal failure from occurring
• Monitoring high doses of statins with fibric acids
- Prevent falls and rhabdomyolysis
- Watch for cross reactions for rhabdomyolysis
 Myoglobin leaves through the kidney
amphoteracin forms
- Liposomal forms: Ablecet, Amphotec, Ambisone
- Non-liposomal forms: Fungizone
immune globulins on tubular damage
- Have high concentration, high sucrose/dextrose products
- All these extra solutes/sugar can further damage the kidneys
 Elecrolyte imbalances and ARF
- Used for those who have hypoglobulinemia
specific chemo med that causes tubular damage
- Cisplatin therapy
 more renal toxic than the analogue carboplatin
Intrinsic renal failure
- At the glomerulus and/or tubule
- There is structural kidney damage
- Has the most diverse list of treatment pathway and list of causes
- SLE can cause damage to the tubules
- AIN: acute interstitial nephritis
- ATN: acute tubular necrosis
- Tubules need more oxygen than any where else in the kidney
- That is why tubule damage has such a high mortality rate
post-obstructive renal failure
- at the ureters and/or bladder
 There is obstructive flow of the urine out of the body
 Underlying cause may be a medication that can cause urine retention (BPH meds)
chemo drugs that cause tissue damage in the bladder
Cytoxin and Ifex - directly neurotoxic
functional renal failure
glomerular changes without loss of flow or direct structural damage
HELLP syndrome
- seen a lot of pregnancies which may be a variant of pre-eclampsia
- HELLP = Hemolytic anemia, Elevated Liver enzymes, Low Platelet count
pre-renal causes of ARF
- Decreased EABV, CHF, obstruction of renal blood flow.
- Causes of dec. EABV: hemorrhage, shock, trauma, excessive sweating, anaphylaxis, ascites, vomiting, diarrhea, polyuria (diuretics, DI, DM)
what types of medications can cause renal dysfunction?
1. Vasoconstrictors of the afferent arteriole
 Want to keep afferent open as possible
 No NSAIDS should be given in acute setting
2. Vasodilators of the efferent arteriole
 Want to keep it closed
 No ACE-Is or ARBs in acute setting
3. Meds that cause severe electrolyte disorders
4. Meds that promote complex formation and calcification
how can bactrim cause renal dysfunction?
o Bactrim (trimethoprim/sulfamethoxazole – hypoaldosterone reaction, hyperkalemia)
 Cause electrolyte problems
 Heparin can also cause hypercalemia
 Aldactone, inspra, droperinone can all block aldosterone
medication causes of acute intrinsic renal failure (ATN)
• Sudden hypotension
- Meds for BP control should be slowly introduced and titrated slowly
• Radiocontrast dyes
- May cause tubular constriction and damage from a very sudden prevention of flow
- Can cause ATN AND vasoconstrict the afferent
• Amphotericin B
- Patients on liposomal formulations compared to non-liposomal have a decreased risk
• Aminoglycosides
• Rhabdomyolysis
- Statins with fibric acids at high doses
• Penicillins (ampicillin), Quinolones (levofloxacin) and Sulfonamides (trimethoprim)
- Renal tubule effects of allergy-type reactions from the above medications
- Post-streptococcal conditions can increase the risk of AIN allergic reaction via formation of antibodies to the meds used to treat the strep infection
 Antibodies formed during strep therapy can attack the glomerulus
- Post-strep conditions can affect the glomerulus as well as the interstitium/tubule and can cause a condition called GLOMERULONEPHRITIS (GN)
drug causes of post-renal damage
- Indinavir (saquinavir) – can form crystals and patients should be advised to drink water
- Sulfonamides (ex. Bactrim) – same as saquinavir with regard to water intake
- Acyclovir – may precipitate and the agent is renally adjusted in patients with lowered CrCl
-- Med itself is not toxic to most patients
-- Only if they are forming precipitates if when you need to make renal dose adjustments
- Chemotherapy – Tumor Lysis syndrome
- K+, phosphates, uric acid can all be released, leading to electrolyte imbalances
- Uric acid release can lead to gout
- So need pre-meds to prevent complications (i.e. colchicine for pain)
- Urinary retention – medications that have anticholinergic effects are risks
effects of ACE-I on the kidneys
• GOOD effects of ACE-I on the kidneys
- Ace inhibitors attenuate expansion of the mesangial matrix
- They help reduce proteinuria possibly by selectively decreasing the permeability of the glomerular membrane
 This effect stabilizes the glomerular basement membrane
• BAD effects of ACE-I on the kidneys
- ACE inhibitors prevent the conversion of AT-I to AT-II, thus releasing the vasoconstriction of the efferent glomerular arterioles with a subsequent decrease in the glomerular hydrostatic pressure
- With less glomerular hydrostatic pressure, there is less glomerular filtration
- If block rennin, then may get hyperkalemia and elevation is SCr
 But, high SCr level is not a diagnostic tool by itself
- Ace inhibitors induce renal failure in conditions in which angiotension plays a crucial role in maintaining the GFR
 Bilateral renal artery stenosis
 Severe volume depletion
 Hyponatremia
lupus nephritis
- Two major populations can develop this autoimmune response: post-strep and Lupus
- Symptoms: HTN, proteinuria, and renal failure
- Deposition of the immune deposits initiates an inflammatory response by activating the complement cascade and recruiting inflammatory cells
- Will see abnormal lab readings such as:
 Elevated SCr
 Low albumin
 Proteinuria
• Treatment
- corticosteriods, immune suppressants
MTX in acidic renal environment
- Can precipitate in the presence of renal tubular acidosis
 Can cause chronic problems and in-hospital ATN
- Acidic environments can cause an agent like methotrexate to precipitate
- Methotrexate is a medication that may be renal adjusted for renal impairment
 Can also result in long-term damage and pulmonary fibrosis
 Adjusting the dose can lead to a decrease in the risk of toxicity and precipitation
effects of aminoglycosides on the kidney
- Since reabsorption of most of the water occurs in the PCT, there is greater contact between the tubule lumen and AG medication
- The PCT can be at risk more due to the recycling nature of water reaborption
- The kidney gets re-exposed to these nephrotoxic medications which can lead to damaging the PCT more than any other areas of the kidney
- Increased exposure allows the drugs to bind to tubular epithelial cells and cause real damage
- The damage of the PCT section in the tubule stops normal water reabsorption and the result is VOLUME DEPLETION
cyclophosphamide and iphosfamide
- These are metabolized by the aldehyde dehydrogenase enzymes
- Ifosfamide is metabolized to chloro-acetyl-dehyde which is harmful to the kidney because of this active metabolite
- This is a urotoxic metabolite causing hemorrhagic cystitis
- When given with MESNA, hemorrhagic cystitis is thwarted
• Cyclophosphamide can cause hemorrhagic cystitis via the formation of acrolein, a toxic metabolite
- Higher doses may be teamed with MESNA to prevent toxicity
nitrofurantoin pulmonary toxicity
- Possibly related to long-term use as a prophylactic agent against UTI infections in chronically debilitated patients
- Mechanism: involve the inhibition of antioxidants and the increased formation of super-oxide free radicals
• Patients who are on both amiodarone and nitrofurantoin would benefit from a monthly CXR to watch for pulmonary fibrosis
• Eosinophilia is inflammation of the lungs associated with an increase in eosinophils
- Eopsinophil is a type of WBC
• Eosinophilia may be due to an allergic reaction of some sort, either from a drug, such as sulfonamide, or parasitic infection, such as that caused by the worm (Hookworm)
- Other parasites may also cause the syndrome
• Common agents known to raise eosinophils and contribute to the inflammation of the lungs (SOB)
- Nitrofurantoin (Macrobid), Sulfonamides, Imipramine (Doxepin), PCN agents
• The onset occurs in about 1 month after the start of therapy
- There is no relationship to duration of therapy or doses for these agents and are onted to contribute to the diagnostic picture
• Usually, it improves without treatment (within a few months)
- If needed, can give CS
- If it the reaction is due to a medication, then d/c the culprit
tx of methanol poisoning
- Gut decontamination – syrup of ipecac (not recommended)
- Epogen and Aranesp do not work fast enough
- Activated charcoal – 1 gm/kg is best for gut decontamination
- To reverse SOB, give naltrexone or naloxone
- Vitamins and supplements:
 Folinic acid at 1-2 mg/kg IV then folic acid 50 mg IV q4h x 2 days – change to oral folate 1mg daily may be an option
 Vitamin B6 and B1 to prevent Wernicke’s encephalopathy (blindness)
 Prevent anemias that patients have
 MCV elevation (megaloblastic anemia), need folic acid or vitamin B12 to bring back to normal level
- Ethanol therapy
 Diverts the metabolism of methanol
- Fomepizole Therapy
- Hemodialysis
-- Dialysis will increase the clearance of ethanol and fomepizole
• Doses of both may need to be supplemented or rates of infusion increased during emergency HD
ethanol for methanol poisoning
 Diverts the metabolism of methanol
 Ethanol 10% in D5W @ 10 ml/kg over 1 hr followed by
 Ethanol 10% 1-2 ml/kg/hr
 Do not exceed levels of ethanol > 150 mg/dl
 Tx stops when the methanol level = 0
• Dialysis clears out both ethanol and methanol
• Just watch out for CNS side effects from ethanol
fomepizole for methanol poisoning
- Dose 15 mg/kg slow IV over 30 minutes, then 10 mg/kg q12h x 4 doses
- Works to compete against methanol for alcohol metabolism via inhibiting aldehyde DH
• Slows metabolism of methanol
• Works directly on the enzyme and stops it from doing what it is suppose to do
- NO CNS SX compared to ethanol
- Reabsorbs up to 70% of the ultrafiltrate created
- Site of amino acid, glucose and bicarbonate reabsorption
- Regulates acid-base
-- Site of carbonic anhydrase enzyme
ascending loop of henle
- Reabsorption of Mg++ and Ca++ and K+ under normal bodily function
- loop diuretics may cause hypomagnesemia, hypocalcemia and hypokalemia
- Important with Ca2+ and ADH/SIADH
- If have SIADH may be due to a med condition (i.e. lung cancer) or due to a medication
- Hydrogen ion (acid) secretion
- Secretion of K+
- Water reabsorption – mostly CT (during ADH and SIADH)
- Ca++ elimination – mostly DCT
- AMPHO-terrible B (amphotericin)
-- Thought to cause injury to the tubule that forms pores
-- The pores allow K+ to be wasted from the tubule and hypokalemia is commonly seen in ARF associated with Amphotericin B
-- Causes pores and damages the way tubule works, leads to volume depletion
- Patient may be given hydration pre-treatment of amphotericin
- The distal tubule lacks the ability to eliminate H+ effectively
- Patient presents with hypokalemia
- amphoteracin
- Proximal tubule cannot reabsorb bicarbonate
- Patient presents with hypokalemia
- diamox, topamax
- The distal section of the tubule has low renin activation and low aldosterone activity
- This causes a buildup of K+, and the patient presents with hyperkalemia
- Medications that worsen hyperkalemia:
• ARBs
• Aldactone and Inspra
• Bactrim (the trimethoprim component)
• Heparin
- Medications that further worsen renal function
• Antiviral agents
• Immune globulins
• Immunosuppressants
• Radiocontrast dye
renoprotective measures
• Hydration
- Use sodium chloride/sodium loading
- Saline was better than glucose
• Theophylline
- meds might be good at stimulating whole part of renal flow
• Acetylcysteine
- Used with varying success at a dosage of 600 mg PO q12h. This is administered to high-risk patients the day before a contrast study is performed and is continued the day of the procedure
• ICU diabetes control with narrow window of 80 – 110 mg/dl
- The distal tubule lacks the ability to eliminate H+ effectively
- Patient presents with hypokalemia
- amphoteracin
- Proximal tubule cannot reabsorb bicarbonate
- Patient presents with hypokalemia
- diamox, topamax
- The distal section of the tubule has low renin activation and low aldosterone activity
- This causes a buildup of K+, and the patient presents with hyperkalemia
- Medications that worsen hyperkalemia:
• ARBs
• Aldactone and Inspra
• Bactrim (the trimethoprim component)
• Heparin
- Medications that further worsen renal function
• Antiviral agents
• Immune globulins
• Immunosuppressants
• Radiocontrast dye
renoprotective measures
• Hydration
- Use sodium chloride/sodium loading
- Saline was better than glucose
• Theophylline
- meds might be good at stimulating whole part of renal flow
• Acetylcysteine
- Used with varying success at a dosage of 600 mg PO q12h. This is administered to high-risk patients the day before a contrast study is performed and is continued the day of the procedure
• ICU diabetes control with narrow window of 80 – 110 mg/dl
CKD staging
- At increased risk for CKD: GFR >60 with CKD risk factors
- Stage 1: GFR >90, kidney damage with normal or increased GFR. Action – diagnosis and tx, tx of comorbid conditions, slowing progression, CVD risk reduction.
- Stage 2: GFR 60 – 89, kidney damage with mild decreased GFR. Estimate progression.
- Stage 3: GFR 30 – 59, moderate decrease in GFR. Evaluate and tx complications.
- Stage 4: GFR 15 – 29, severe decrease in GFR. Preparation for kidney replacement tx.
- Stage 5: GFR <15 (or dialysis), kidney failure. Replacement if uremia is present.
cholesterol level guidelines
- Total cholesterol: desirable < 200, borderline 200-239, high >240
- LDL: optimal < 100, near optimal 100-129, borderline 130-159, high 160-189, very high >190
- Triglycerides: normal <150, borderline 150-199, high 200-499, very high >500
- HDL: low <40
cholesterol meds for pts. with CKD
- stages 1-4 CKD: statin. Any lipid profile or increased LDL.
- stages 1-4 CKD: fibrate. Increased triglycerides with elevated non-HDL cholesterol.
- hemodialysis: statin or sevelamer hcl. Any lipid profile
- hemodialysis: statin, or fibrate, or sevelamer hcl. Increased triglycerides with elevated non-HDL cholesterol.
- peritoneal dialysis: statin. Any lipid profile, or increased LDL.
- transplant: statin. Any lipid profile, or increased LDL.
inulin and sinistrin
- These substances are used to measure GFR
- They are NOT protein-bound, absorbed, altered or metabolized
 They are completely filtered at the glomerulus but neither secreted nor reabsorbed by the tubules
 So, whatever you put in, you should see it come out
- They look at how long it took to produce the urine, how often they went, what was in the urine, etc.
- The only difference between the two substances is the cost and water solubility of sinistrin
mediators and hormones that affect renal fxn
• Catecholamines: help with BP, vision, control bowel
• Prostaglandins
- Are inflammatory mediators
- Have effect on arterioles in the kidney (afferent)
• Renin
- This is what catalyzes the reaction of the RAAS
- May see hyperkalemia, increase in SCr with renin inhibitors
- Not good to use renin inhibitors in those with bilateral renal stenosis
• Angiotensin / aldosterone
- Improtant in the distal and collecting tubule
- Affect on both afferent and efferent (mostly efferent)
- Damage to mesangial cells can be bad for maintaining the integrity of the kidneys
- Can increase the intracranial pressure
• Antidiuretic hormone
• Natriuretic hormone: Ridding excess Na+ gets rid of excess water
- Not a pressor
 Pressors are DA or Dobutamine
endocrine effects of the renal system
• Renin secretion and the RAAS
- Origin from SNS stimulation and the cells of the juxtaglomerular apparatus
• Inflammatory / vasoconstricting mediators
- Prostaglandins: keep the renal afferent arteriole open
- Angiotensin II: closes the renal afferent arteriole
- BOTH of the above function promote good perfusion at the glomerulus and promote flow to the tubule
 Patients with HTN benefit from ACE inhibitors to prevent renal damage because the agents reduce glomerular pressure
 In the acute RF setting, ACE inhibitors reduce the glomerular pressure so much that perfusion of the kidneys will suffer
hematological effects of the renal system
• EPO production in the peritubular fibroblast cells
- Produce EPO in response to low O2 in the blood
- Renal mass decreases in CKD/CRI, resulting in low H/H is seen
- Result:
 Decreased EPO production and this results in anemia S/Sx
early CKD s/sx
- No apparent S/Sx
- May see HA, but everyone gets HA
- Labs
 Micro-albuminuria
 If not detected soon enough, can lead to kidney damage
 Problem is, can only get these labs in a hospital setting
 Elevated SCr and BUN
• BUN for kidney, for liver, and nutrition
late CKD sx
- Edema
 Patient with CHF can have edema
 Patients with bad kidneys can have edema (stages 3, 4, or 5)
- S/Sx of fatigue
- Itching (histamine retention)
- Nausea and dyspnea
- Anemia
 Can only be detected with CBC
 Ferritin levels or transferrin levels can also be used
 These symptoms are not easily diagnosed
labs for late CKD
- Proteinuria
• Progressed from micro-albuminuria
- Decreased CrCl / GFR --> might see glucose and blood in urine
- UA changes
• Might see more infections, more nitrites
- Reduced H/H
- Electrolyte imbalances – high k+ can cause cardiac problems
- Phosphorous tends to linger
- CNS Symptoms
• Patient has urea bulit up might damage other organs later on
• Usually it doesn’t do anything, but built-up of this waste can cause change in CNS
- Reduced renal mass / via ultrasound
• As patients get older, their kidneys do shrivel up
• Histological changes are hard to pick up early on
nitrites in urine
- Bacteria can change nitrates to nitrites
- The formation of nitrites and their detection gives us clues that gram negative bacteria known to cause UTI’s may be present
- Can benefit from abx that covers gram negative bacteria
- Bactrim (+ bacteria) and nitrofurantoin (- bacteria)
 The problem is that they can cause electrolyte and lung disorders
 Bactrim can cause hyperkalemia (trimethoprim component)
 To prevent post-obstructive renal failure, drink lots of water
 Macrobid needs chest x-ray to detect pulmonary fibrosis or lung disorders
- WBC presence in the urine leukoesterases may be indicating that the patient is fighting infection (UTI)
heme tests in urine
- Indicate either hemoglobin or myoglobin
- Suggest either RBC hemolysis or rhabdomyolysis
- CK elevations can increase risk of developing rhabdomyolysis (if up to 10x normal level)
- Urine might have a different color
• High albumin can be classed as proteinuria
- Proteinuria is an indicator that renal damage is progressing
- Large proteins are normally kept out of the urine due to proper renal function
- The PCT reabsorbs smaller proteins and prevents them from crossing into the urine
- ARB and ACE-Is can help reduce albuminuria and protein in someone’s urine
• Protein in the urine can begin to be detected at the following measures:
- 30 – 150 mg/day with at least 30 mg of the amount being albumin in 1 day
- Look at changes in UA
• The excretion of specific types of protein, such as albumin or low molecular weight globulins, depends on the type of kidney disease that is present.
• Increased excretion of albumin is a sensitive marker for chronic kidney disease due to diabetes, glomerular disease, and hypertension.
• Increased excretion of low molecular weight globulins is a sensitive marker for some types of tubulointerstitial disease.
- Proteinuria refers to increased urinary excretion of albumin, other specific proteins, or total protein;
- Albuminuria refers specifically to increased urinary excretion of albumin.
micro- vs. macroalbuminuria
• Microalbuminuria refers to albumin excretion above the normal range but below the value described as albuminuria
- This is a small amount of protein in the urine which is the first sign of kidney damage
- This is the measurement of small amounts of albumin in the urine that cannot be detected by urine dipstick methods
• Macroalbuminuria occurs as damage to the kidneys progresses
- Will see larger amounts of protein spill into the urine and blood pressure rises
unstable renal fxn definitions
- In previously NORMAL renal fxn: SCr 1.0 – 1.5 mg/dl
-- Change of more than 50% over the period of 1 day to the next
-- Increase in SCr of more than 0.5 mg/dl from the baseline
- In previous CRI / ESRD: SCr > 2.0 mg/dl
-- Increase in SCr of more than 1 mg/dl from the baseline
JNCVII HTN guidelines
• Following the JNCVII Guidelines
- BP for patients ON medications: < 140/90 mmHg
- BP for patients in Stage II HTN: decrease to below 160/100 mmHg using 2 antihypertensive agents at lower doses
• Medications
- ACE – I Agents
- Angiotensin receptor blockers
 Help with reducing the prevalence of surrogate markers of micro and macro-albuminuria
- Calcium channel blockers to a lesser extent
glycemic index
• This is a ranking system for carbs based on their effect on blood glucose levels in the first two hours
• High glycemic carbs can increase glucose dramatically
• Carbs that break down rapidly during digestion have the highest glycemic index
- A lower glycemic index suggests slower rates of digestion and absorption of the sugars and starches in the foods and may also indicate greater extraction from the liver and periphery of the products of carbohydrate digestion
- A lower glycemic response is often thought to equate to a lower insulin demand, better long-term blood glucose control and a reduction in blood lipids
 But in fact, some foods having a low glycemic index or having very little carbohydrate cause a high insulin response or raise blood lipids
protein intake considerations in SCr
• High protein diets may be associated with greater progression to proteinuria and CRI progress
- Remember: with patients on HD, they need additional nutritional supplements
• Moderate protein intake is recommended to reduced the risk of complications related to ESKD/ ESRD
• In HD, the patient’s protein dietary intake can be increased to prevent the risk of malnutrition since HD is being used to eliminate excess protein
- Vegetarians and elderly with little mass are more likely to have a lower SCr – in those patients, the best maneuver is to round the SCr up to 1.0 mg/dl, if less than 1.0 mg/dl
activation of the RAAS system
• The system is activated when there is a loss of blood volume or a drop in BP
• The juxtaglomerular apparatus will detect this low perfusion pressure and its cells will release rennin
• Renin cleaves an inactive peptide called angiotensin to make AT-I
• AT-I is then converted to AT-II by ACE (which is found mainly in lung capillaries)
effects of AT-II
• It is a potent vasoconstrictor
• It constricts on the glomerular arterioles
- Efferent >> afferent
• Constriction of the afferent arteriole increases arteriolar resistance raising BP and decreasing blood flow
- But this action on the afferent is overshadowed by the release of NO which will vasodilate the afferent and keep it open
• But, the kidneys must continue to filter enough blood despite this decrease in blood flow
- So, AT-II constricts the efferent arteriole which forces blood to build up in the glomerulus, increasing glomerular pressure
- GFR is thus maintained and blood filtration can continue despite lowered overall kidney blood flow
• AT-II causes release of aldosterone in the adrenal cortex
- Aldosterone acts on the tubules (DCT and collecting ducts) causing them to reabsorb more Na+ and water from the urine → increase volume → increase BP
- K+ is exchanged for the Na+
• AT-II also releases ADH (vasopressin) from the pituitary gland
renal physiology relating to glomerular flow
- Blood enters the afferent arteriole into the glomerulus where it is filtered, and exits through the efferent arteriole.
- Both arterioles work together to maintain adequate hydrostatic pressure to form an ultrafiltrate which is further processed into the urine that leaves the bladder
- If perfusion suffers, the kidneys fail, can lead to cardiac arrest, death
- Acute renal failure is a result of vasoconstriction or vasodilation of either arteriole
- When a patient is on an ACE I or ARB, it reduces intraglomerular pressure and preserve mesangial matrix and filtration of surface area
benefits of use of ACE-I/ARB in patients, how this reduces intraglomerular pressure
• Constriction of the efferent arteriole causes greater resistance due to smaller diameter at basal state.
- Want to open up efferent just a little bit to relieve the pressure
• ATII stimulates nitric oxide production at the afferent arteriole
- Stimulation of ATII receptors at the afferent arteriole results in vasodilation from the nitric oxide
• ATII constricts mesangial cells, tends to lower surface area for filtration
- Prevent ESRD and prevent dialysis (prevent proteinuria)
role of CCB agents in decreasing proteinuria
• Gave inconsistent results
• Non-DHP decrease proteinuria more so than DHP (54% vs. 10% respectively)
- Can significantly reduce it when used with other medications
- May be due to improving flow at the afferent, but not sure
• As a general class, decrease proteinuria 30%
• Proposed mechanism is dubious
- Merely reducing the BP is not enough, because other antihypertensive agents do not produce this effect consistently
- DHP CCB’s cause preferential afferent arteriolar dilatation
- Lowering systemic pressure may not always produce a similar change in intraglomerular pressure
• Clinical Guidelines
- Proteinuric non-diabetic chronic kidney disease
- Use in DM or non-DM
- Add non-dihydropyridine CCB’s for additional BP control OR beta-blocker
- Consider adding a diuretic (use with caution due to the risks of over-dehydration)
MDRD trial
Modification of Diet in Renal Disease
- Almost half of the patients were on an ACE I but its selective efficacy was not assessed
- Results
 The severity of proteinuria correlates with the rate of progression of the kidney disease
 A substantial and statistically significant slowing of the decline is seen with aggressive BP control
• Follow-up MDRD study
- Long-term outcomes
 A lot of patients showed benefits such as a reduction in BP
 BP would be way too low if they were symptomatic (passing out)
• HA, sedated, BP <90
• Do not know when it is too much because there is no magic number
- Lower BP group was significantly less likely to have kidney failure or death
 They lived longer and did not progress to hemodialysis as compared to other counterparts
- Did not assess selective efficacy of ACE I
benazepril trial
o N = 600 with variety of chronic renal diseases
- Randomized to benazepril or placebo and other antihypertensives
- Subjects were already within BP control
- Benazepril group showed:
 Greater reduction in BP
 25% reduction in proteinuria
 Decreased kidney disease progression
REIN trial
Ramipril Efficacy in Nephropathy
- Randomly assigned to ramipril or placebo and other antihypertensives
- Degree of BP were the same in both groups
• May have BP problems as well as other medical conditions (CHF, DM)
- Trial was terminated early for subjects with proteinuria > 3g/day because significant benefit was seen early
• Follow up on REIN Trial
- Principal outcomes:
 Rate of decline of renal function
 Start of dialysis
- Outcomes:
 A greater risk of developing ESRD was seen in placebo group
 A need for dialysis was not observed in patients treated with ramipril for at least 3 years
- Bottom line:
 Most benefit was seen in patients with more prominent proteinuria
REIN-2 trial
- N = 335
- DHP CCB (Felodipine) was used as an add-on to ACE-Is for aggressive BP control LACKED any evidence of renoprotection
- There were inconsistent results with CCB
 Some showed a decrease in proteinuria, but some did not
• Depends on what CCB was used and at what dose
 So, lacks significance due to inconsistency
AASK trial
African American Study of Kidney Disease and HTN
- Generally, practitioners consider this population to respond better to CCB and diuretics
- Results:
 Ramipril was more effective in slowing renal disease progression compared to either amlodipine or metoprolol
- After starting the medications, like an ACE I, African Americans did benefit more from the administration
- Some lacked of economic data
 Some cannot receive the medication
 Some lack information about the medication
• N=263
• Losartan or Trandoloapril or Both
• All three groups received similar BP reduction
• 2 major findings:
- Progression of renal dysfunction was less common in combination group
 Combination has more effect in reducing proteinuria
• Will see synergistic side effects when using a combination
- Hypotension, hyperkalemia, etc.
- Inspra (aldosterone receptor blocker) will increase in SCr and K+
REIN trial in advanced kidney disease pts.
• REIN Trial in advanced Kidney Disease
- Initial GFR of 11-33 ml/min
- 20% decrease in rate of decline
- 33% reduction in ESRD progression
- Acute Situations
 CHF, hemorrhagic shock, or any event that may impair perfusion
 DO NOT initiate ACE I or ARB!!!
 It is not the time to perform RENOPROTECTION
 Instead, you want to prevent RENAL PROGRESSION
ARBs in DM2
• ARBs have shown to be renoprotective in Type 2 DM
- It was not proven in other populations
 Type 2 diabetics have shown to exhibit the MOST benefit
- Some studies show less anti-proteinuria effects compared to ACE I
- Appears likely that ARBs are just as effective as ACE Is
• They are renoprotective in ALL patients
ARB/ACE-I use in acute setting
• Preferential efferent arteriole vasodilation
- Reduces intraglomerular hydrostatic pressure
- GOOD in patients with HIGH glomerular pressure
- BAD in patients with ARF or acute hypoperfusion
 Might reduce perfusion in kidney or glomerular
 Might get synergistic SE when use combination
• Reduced GFR
- Increased of ARF risk in volume-depleted patients
- Should not be recommended in acute situations (hypoperfusion, acute CHF presentations, ARF)
role of diuretics and kay
- Diuretics can be added for volume control and K+ elimination if patient at high risk for K+ increases
- Kayexalate in small doses (5mL) can be useful for outpatients with chronic hyperkalemia
- Can help reduce hyperkalemia effect, cardiac function can remain stable
 The use of this agent can prolong time to dialysis
 D/C Kayexalate when begin dialysis
 Sorbitol can cause diarrhea / laxative
ACE-I and ARB intolerances
• Uncontrollable Hyperkalemia
- Furosemide can replace kayexalate if the patient has CHF to help control K+ levels
• SCr increase signaling renal failure
- Risk of pre-renal azotemia when patients have decrease flow to the kidneys
• Angioedema
- It is an allergy that can re-challenge if another agent is used in the ACE-I class or ARB agent
- weigh benefits >> risks
• Dry cough
- Patients can experience ACE-I induced cough and may benefit from ARB trial
- Tends to go away once the ACE I is change to a ARB
- Combination of ACE and ARB may not see the dry cough
JNC VII goals with proteinuria
- BP less than 130 / 80 mmHg for those with DM
- BP less than 125 / 75 mmHg For those with a significant amount of proteinuria
- Reduce protein excretion to less than 500-1000 mg/day
- Know that ANY reduction in proteinuria from baseline is good
- This will provide significant renal protection
clinical pearls with ARB/ACE-I
• ACEI/ARB’s can cause a decline in renal function and hyperkalemia soon after onset of therapy
- Caution when patients have acute problems
- Monitor within 3-5 days or at next PCP visit
- Usually transient decline in GFR
- Extreme caution in bilateral renal artery stenosis
• Caution with combination therapy
- Hypotension
 Whenever they are teamed with other meds that act on RAAS, may see synergistic side effects
- Elevations in serum creatinine
-- Especially with aldosterone receptor blockers (Inspra)
- Elevations in potassium
-- Especially with aldosterone receptor blockers
what is EPO?
- It is a glycoprotein hormone that is a cytokine for erythrocyte (RBC) precursors in the bone marrow
 It is the hormone that regulates RBC production
- It is produced by the kidney (90%) and some by the liver (10%)
when and how is EPO synthesized?
- EPO production is stimulated by low oxygen levels in the blood
- A lack of oxygenation begets a need to create EPO from the kidneys
 Your body wants to make more EPO and senses the hypoxia
- Hct declines in response to hypoxemia
 H/H are signs of your blood cell health
 A decline in either Hgb or Hct is a sign that anemia is occurring
- EPO acts by binding to a specific erythropoietin receptor (EpoR) on the surface of red cells precursors in the bone marrow
 This stimulates them to transform into mature RBC
 As a result the oxygen level in the blood will rise and EPO production decreases
- Renal damage decreases the production of EPO in the peritubular fibroblast cells of the kidneys
 Without EPO, then there can be no stimulation of the RBC in the bone marrow
 In labs, we will see this as low H/H
• This, however, is not easy to detect in the early stages
• By the time it is detected, the patient will already be in a serious state
- Patients on hemodialysis or RRT are unable to make EPO in response to hypoxemia
 Patients have an attenuated or weakened response
 Normochromic and normocytic anemia presents and can progress to microcytic with time
• Initially: normal size and normal color cells
- This results from a decreased in RBC life to ½ the time
- Before patients were put on dialysis, they have waste built up
 Uremic syndrome where they accumulate other waste and urea
- This accumulation can weaken response to hypoxia and produce even less EPO
iron deficits/nutritional deficits and EPO
- Reduces the benefit of EPO and/or DARBO until the iron is replaced
 Iron is necessary to make Hgb, the substance that carries oxygen through your blood to all the cells in your body
• Hgb is what makes red blood cells red
 With insufficient iron, and therefore not enough Hgb, red blood cells become small and pale and don't carry enough oxygen
- Transferrin will decrease before H/H begins to decrease
 So in lab, will see low iron stores with normal H/H
blood loss tx
- With acute loss of blood, transfusing packed RBC would be a good treatment
 But, have to make sure the patient is on iron supplements if they have iron deficiency
 If there is a GI bleed, then give packed RBC and prophylactic meds (PPI, H2 blockers)
- DO NOT give EPO or DARBO for acute bleeds or iron-deficiency conditions
H/H values
• Hemoglobin: 11-12 g/dl
- Any level above 12 is detrimental because it can cause CV complications
- Stop/hold therapy and re-evaluate the patient if their Hgb is too high
- Increase EPO or DARBO if values are still too low
• Hematocrit: 33-36%
- Hgb is ~1/3 the value of Hct
- Having too much Hct will increase viscosity of the blood
- Thus, this will increase vasculature pressure, increase BP
- Stop/hold therapy and re-evaluate the patient if their Hct is too high
- Increase EPO or DARBO if values are still too low
transferrin and ferritin values
• Transferrin Saturation: 20-50%
- Transferrin is the carrier protein for iron
 Can have normal levels of iron, but would be pointless if transferrin levels are low
- This should be looked at if you suspect complications of anemia
 Tsat indicates the value of iron immediately available for delivery to the bone marow
- If patient is started on EPO, then will see no improvement of their symptoms
- Iron doesn’t replenish patients fast, can take weeks or even months
• Serum ferritin: 100-800 ng/ml
- it is in the serum and is an indirect measure of serum iron
CREATE trial
- Assess the need for early intervention in this disorder
- Assess the end-points in the management of CRI-induced anemia
- Ask: is the patient being treated aggressively enough? Are they having good follow-up?
- Patients who are on meds that prevent CKD have less progression of the condition
- HD does NOT do anything for production of EPO
 In a way it does help because it removes waste and improve response to hypoxia
 HD does not correct any anemia conditions, but it only reverses electrolytes imbalances
• GOALS of the CREATE Trial
- Are we treating this disorder aggressively enough???
When is iron therapy indicated?
- Iron therapy is given when there is a deficit in TSat and/or serum ferritin
 Patients are candidates for iron therapy is there are decrease in either:
• TSat and ferritin together
• TSat alone
parenteral iron tx
• Parenteral – can increase H/H and iron stores quickly
- Requires less frequent dosing than oral forms
- Iron dextran
 Has the worst safety profile compared to other IV iron products
 Requires a test dose to reduce risk of anaphylactic shock
- Sodium ferric gluconate
- Iron sucrose
- Given in 8-10 doses/dialysis session
 Dose per session:
• Max: 500 mg Iron Dextran
• Max: 300 mg Iron Sucrose
• Max: 250 mg Ferric gluconate
oral iron tx
- can take a few weeks or even months for it to start working
- Oral iron is about 10% absorbed in the GI
- Requires more frequent dosing than IV forms
 So compliance is a big issue
- Ferrous sulfate, ferrous gluconate and ferrous fumarate
- Polysaccharide iron complexes
- Iron polypeptide formulations
- Oral iron: Max 200 mg Iron elemental
what to do when TSat and Serum ferritin are different levels
• If TSat and Serum ferritin are:
- Low: 1 gram of parenteral iron IV (given in divided doses at each HD session)
- Normal: consider recommending either IV/PO iron as needed + erythropoietic therapy
- High: consider recommending erythropoietic therapy and recommend stopping current iron therapy (if patient is already on)
• Increase in these levels occur gradually, so have to be patient
• Compliance is a big factor because requires frequent dosing throughout the day
oral iron supplement names, dosing
- Fer-In-Sol: 75mg/0.6ml BID – TID
- Ferrous Fumarate: 300mg BID
- Nephro-Fer: 350mg BID
- Vitron C: 65, 125mg TID
- Hytinic: 150mg QD-BID
IV iron agents available
- Iron Dextran (InFeD) and (DexFerrum) *requires test dose*
- Sodium ferric gluconate (Ferrlecit)
- Iron sucrose (Venofer)
iron dextran
• InFed or DexFerrum
- Can cause anaphylaxis, hypotension , and muscle aches
- This is why a test dose is recommended (25mg test dose)
- It is recommended to slow down the infusion rate to decrease the incidence of hypotension
- Anaphylaxis can cause a leaky body, low EABV
- Anaphylaxis mechanisms are theorized to be due to antibody formation to dextran complexes
- Treat these reactions with Epi (stimulants)
 If the patient has a skin irritation, then can give some benadryl
• Side note: can also give benadryl when amphotericin B is to be administered
K/DOQI guidelines for TSat and Serum ferritin
• Current K/DOQI guidelines recommend not to exceed:
o TSat > 50%
o Serrum ferritin > 800ng/ml
iron DDIs
• Antibiotic Therapy
- Iron decreases the efficacy of antibiotic therapy
• Antacid therapy
- Absorption of iron from the GI is decreased
-- mainly iron in dietary sources
• Calcium supplementation and multiple vitamins
- Supplements can decrease the absorption of iron
• If the patient must be on any of the above medications, then it is best to take iron supplements at least 2 hours before or 2 hours after taking those medication
• They promote and stimulate the growth, division, and differentiation of the erythroid progenitor cells
- They allow reticulocyte cells to be released from the bone marrow into the blood stream
- In the blood stream, the cells mature into erythrocytes (RBC)
• EPO (Procrit & Epogen) or DARBO/DARBE (Aranesp) can stimulate EPO production to normal levels in anemic patients
- EPO (Procrit & Epogen)
 IV or SC therapy
 SC therapy yields a better response on H/H control and maintenance compared to IV therapy
 It is usually dosed 3 times weekly
- DARBO/DARBE (Aranesp)
 IV or SC therapy
 SC therapy lasts longer than IV therapy in the system
 It can be dosed weekly by IV or SC
reasons for EPO/DARBO failure
- Iron deficiency
- Inflammation from infection/sepsis leading to reticuloendothelial blockade
- Chronic loss of blood
- Antibody formation
 Resistance patterns
- Megaloblastic anemia
• Hypertension
- Recommend to stop the medications in the situation that patients develop resistant hypertension that does not response to anti-hypertensive drugs
• Seizures
• Thrombosis
• Neutralizing antibodies
- Resistance
- They only option for these patients is blood transfusion