Other Population Health Flashcards
Transplant: Prevention of Graft Rejection
1. Define allograft, autograft, and isograft
- When does graft rejection occur, and what are some of the consequences?
- Prior to transplants, immunosuppressants are given to reduce likelihood of reject What are some of the general BBWs from these drugs?
- -Allograft: transplant of organ/tissue from one individual to another of same species w/ different genotype
-Autograft: transplant in same patient from one site to another
-Isograft: transplant from genetically identical donor
- In an allograft - immune response can lead to organ failure support, removal of transplanted organ
- -Infection risk: prophylaxis for infections often required
-Cancer risk: sun protective measures and cancer screenings needed
-“Only Experienced Prescribers…”: especially when drugs are started
Prior to a transplant, tissue typing or cross-matching should be done to access donor-recipient compatibility for _________ and __________ since a mismatch in either would lead to an acute rejection. *Explain further how to read the results. *
Human leukocyte antigen (HLA) and ABO blood group
-Panel reactive antibody (PRA): high PRA indicates need for densitization protocol prior to transplant
-Blood groups:
AB (Universal receiver): can give blood to AB; can receive blood from AB, A, B, or O
A: can give blood to A or AB; can receive blood from A or O
B: can give blood to B or AB; can receive blood from B or O
O (Universal donor): can give blood to AB, A, B, or O; can receive blood from O
**O blood has NO antigens on surface of RBCs; AB blood has no antibodies in serum
Transplant: Induction Immunosuppression
Induction: given immediately before or at time of transplant to prevent acute rejection in early post-transplant period
-Consists of short course of IV medication either polyclonal or MAB with high-dose IV steroids (sometimes steroids alone, high dose usually followed by taper from adrenal suppression)
-Commonly basiliximab is used, an interleukin-2 (IL-2) receptor antagonist which is a receptor critical in organ rejection (ONLY for prevention: cannot deplete immature T-lymphocytes), humanized (infusion rxns unlikely and pre-medication typically NOT needed)
-Alternative to basiliximab: antithyomocyte globulin (polyclonal antibody that depletes both mature and immature T-lymphocytes and can be used for indcution and TX of rejection)
-Alemtuzumab, MAB that targets CD52 for leukemia and MS can beused off-label
Transplant: Maintenance Immunosuppression
Typically a combination of:
-Calcineurin inhibitor (CNIs): cyclosporine, tacrolimus (first line = tacrolimus, alternative: belacept)
-Antiproliferative agent: mycophenolate, azthioprine (first line = mycophenolate, alternative: mTOR inhibitors: everolimus, sirolimus)
-With or without steroids: typically PO prednisone (if low immunological risk, D/C)
**Different MOAs to both lower toxicity risk of individual immunosuppression and reduce risk of graft rejection
Basiliximab:
-Brand
-MOA
-ROA
-TX
-AVEs
-BBW
-Monitoring
Brand: Simulect
MOA: interluekin-2 (IL-2) receptor antagonist - chemeric (murine/human) MAB that inhibits IL-2 on surface of activated T-lymphocytes
ROA: IV
TX: transplant, induction immunosuppression
AVEs: increased BP, fever, stomach upset, N/V, cramping, peripheral edema, dyspnea, upper respiratory irritation/infections, painful urination
BBW: adminster under supervision of physician experienced in immunosuppressive therapy
Monitoring: s/sx of hypersensitivity (witin 24 hours) and infection
Antithymocyte globulin:
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: Atgam (equine), Thyomglobulin (rabbit)
MOA: binds to antigens on T lymphocytes, interfering with their function
ROA: IV
TX: transplant, induction immunosuppression or TX of rejection
Administration:
-Premedicate (Benadryl, APAP, steroids) to lessen infusion-related rxns –> EPI and resucitative equipment should be nearby
-Administer over at least 4 hours (6 hours for first dose of Thymoglobulin) to mimimize immune rxns (infuse w/ an in-line filter)
Antithymocyte globulin:
-AVEs
-BBW
-Monitoring
AVEs: infusion-related rxn/cytokine release syndrome (fever, chills, pruritus, rash, decreased BP - particularly common w/ first dose), infections, leukopenia, thrombocytopenia, chest pain, increased BP, edema
BBW: administer under supervision of physician experienced in immunosuppressive therapy; anaphylaxis can occur (Atgam: intradermal skin testing recommended preior to first dose)
Monitoring: CBC w/ differential, vital signs during administration, lymphocyte profile (T-cell count)
Tacrolimus:
-Brand
-MOA
-ROA
-Administration considerations
-Role in transplant
Brand: Prograf, Envarus XR (ER tablet), Protopic (topical - eczema), Astagraf XL (XR capsule)
MOA: calcineurin inhibitor that suppresses immunity by inhibiting T-lymphocyte activation
ROA: PO, injection, topical
Administration:
-Administer under supervision of physician experienced in immunosuppressive therapy
-Do NOT interchange XL/XR to IR w/o prescriber approval
-Food decreases absorption (can take w/ or w/o food - just be consistent)
-Avoid alcoholic beverages w/ Astagraf XL and Envarsus XR (increased rate of release and AVEs)
-IV adminstered as CIV –> must use non-PVC bag and tubing
Role in transplant: maintenance immunosuppression
Tacrolimus:
-AVEs
-BBW
-Monitoring
AVEs: increased BP, increased BG (more than cyclosporine), hyperlipidemia, nephrotoxicity, hypomagnesemia, hypo/hyperkalemia, alopeica, neurotoxicity (dizzines, HA, parasthesia, tremor), edema, hypo/hyperphosphatemia, QT prolongatoin, diarrhea, UTI, anemia, leukopenia, leukocytosis, thrombocytopenia, elevated liver enzymes, arthralgia
BBW: increased risk of malignancy (lymphoma, skin cancer), increased risk of infections
-Astagraf XL: associated w/ increased moratlity in female live transplant recipients
Monitoring: trough levels, serum electrolytes (K, Phos, and Mg), renal fxn, LFTs, BP, BG, lipid profile
Cyclosporine:
-Brand
-MOA
-ROA
-Administration considerations
-Role in transplant therapy
Brand:
-Modified (increased F): Gengraf, Neoral
-Non-modified (original formulation with variable absorption): Sandimmune
-Restasis for dry eyes
MOA: calcineurin inhibitor that suppresses immunity by inhibiting T-lymphocyte activation
ROA: PO, injection, eye drops (Restasis)
Administration:
-*do NOT administer oral liquid in plastic or Styrofoam cup *–> use syringe provided and do NOT rinse before or after use
-IV: non-PVC sets should be used to minimize leaching of DEHP
Role in transplant: maintenance immunosuppression
Cyclosporine:
-AVEs
-BBW
-Monitoring
AVEs: increased BG, hyperlipidemia (more than tacrolimus), hyperkalemia, hypomagnesemia, hirsuitism, gingival hyperplasia, neurotoxicity (tremor, HA, paresthesia), hyperuricemia (more than tacrolimus), edema, abdominal discomfort, N/D, viral infections, viral associated nephropathy
BBW: increased risk of malignancy (lymphoma, skin cancer), increased risk of infections, nephrotoxicity (can occur at any trough level), increased BP
-Modified and non-modified are NOT interchangeable
-Should ONLY be prescribed by HCPs experienced in immunosuppressive therapy
Monitoring: trough levels, serum electrolytes (K and Mg), renal fxn, LFTs, BP, BG, lipid profile
Azathioprine:
-Brand
-MOA
-ROA
-TX
Brand: Azasan. Imuran
MOA: antiproliferative agent - inhibits T- and B-lymphocyte proliferation by altering pruine nucleotide synthesis
ROA: PO, injection
TX: transplant, maintenance immunosuppression
Azathioprine:
-AVEs
-Warnings
-BBW
-Monitoring
AVEs: GI (severe N/V/D), acute pancreatitis, rash, hepatotoxicity
Warnings: myelosuppression (dose-related or conventional doses due to genetic deficiecny of thiopurine methyltransferase or TPMT which reduces inactivation of azathioprine –> both require dose adjustement and increase risk of infection)
BBW: increased risk of malignancy (lymphoma, skin cancer)
Monitoring: LFTs,CBC, renal function
Mycophenolate:
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: mofetil salt (Cellcept), mycophenolic acid (Myfortic)
MOA: antiproliferative agent - inhibits T- and B-lymphocyte proliferation by altering pruine nucleotide synthesis
ROA: PO, IV
Administration:
-Brands are NOT interchangeable due to differences in absorption (CellCept 500mg = Myfortic 360mg)
-Myfortic: EC to decrease diarrhea and is DR
-CellCept IV: stable in D5W only, do NOT use if allergy to polysorbate 80, begin infusion within 4 hours of reconstitution
-Tablets must be stored from light, dispense in light-resistant container such as original container
TX: transplant, maintenance immunosuppression
Mycophenolate:
-AVEs
-BBW
-Monitoring
AVEs: abdominal pain, N/V/D, leukopenia, anemia, thrombocytopenia, increased or decreased BP, tedema, tachycardia, pain, increased BG, hypo/hyperkalemia, hyopmagnesemia, hypocalcemia, hypercholesterolemia, infections
BBW: increased risk of malignancy (lymphoma, skin cancer), increased risk of infections, increased risk of congenital, malformations and spontaneous abortions when used during pregnancy (REMS Program)
-Should only be prescribed by HCP experienced in immunosuppressive therapy
Monitoring: CBC, intolerable diarrhea, pregnancy tests (can decrease efficacy of OCs), renal fxn, LFTs, signs of infection
Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
Drugs: everolimus (Zortress, Afinitor - for certain cancers), sirolimus (Rapamune)
MOA: inhibits T-lymphocyte activation/proliferation, may be synergistic w/ CNIs
ROA: PO
Administration:
-Everolimus: protect from light and moisture
-Sirolimus: tablets and oral soluation are NOT bioequivalent
TX: transplant, maintenance immunosuppression
Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors:
-AVEs
-Warnings
-BBWs
-Monitoring
AVEs: peripheral edema, increased BP, increased BG, constipation, N/V/D, abdominal pain, HA, fatigue, fever, rash/pruritus, acne, anemia, leukopenia, thrombocytopenia, stomatitis
Warnings: hyperlipidemia, impaired wound healing, pneumonitis (D/C if develops), angioedema, fluid accumulation (surgical site), proteinuria, male infertility
-Everolimus: increased risk of hepatic artery thrombosis can result in graft loss (do NOT use within 30 days of transplant)
-Sirolimus: decline in renal fxn (when used long term w/ cyclosporine), latent viral infections, increased risk of hemolytic uremic syndrome when used w/ CNI
BBWs: increased risk of malignancy (lymphoma, skin cancer), increased risk of infection
-Should only be prescribed by HCP experienced in immunosuppressive therapy
-Everolimus: when used w/ cyclopsorine, reduced doses of cyclosporine are reocmmended (increased risk of renal artery thrombosis can result in graft loss, NOT recommended in heart transplant)
-Sirolimus: NOT recommended for use in liver (hepatic artery thrombosis) or lung transplantation
Monitoring: trough levels, renal fxn, LFTs, lipids, BG, BP, CBC, urine protein, signs of infection
Belatacept
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: Nulojix
MOA: inhibits T-lymphocyte activation and production of inflammatory mediators via binding to CD80 and CD86 on antigen presenting cells, inhibitng costimulation with CD28 on T-lymphocytes
ROA: injection
Administration: use silicone-free disposable syringes that come w/ drug
TX: transplant, maintenance immunosuppression as alternative to CNI
Belatacept:
-AVEs
-Warnings
-BBW
-Monitoring
AVEs: HA, anemia, leukopenia, constipation, D/N, peripheral edema, increased or decreased BP, cough, photosensitivity, insomnia, UTI, pyrexia, increased or decrease K, hypophosphatemia
-Overall well tolerated
-NO nephrotoxocity
Warnings: increased risk of opportunistic infections, sepsis, and/or fetal infections, increased risk of TB (test for latent TB prior to initiation and treat prior to use)
BBW:
-Increased risk of post-transplant lymphoproliferative disorder (PTLD) w/ the highest risk in recipients w/o immunity to Epstein-Barr VIrus –> use in EBV seropositive patients ONLY
-Increased risk of infection and malignancies –> avoid in liver transplant pts due to risk of graft loss and death
-Administer under supervision of experienced physician w/ immunosuppressive therapy
Monitoring: neurological, cognitive, or behavioral s/sx (consider PML, PLTD, or CNS infection), s/sx of infection, TB screening prior to initiation, EBV seropositive verification prior to initiation
Transplant Agents: DDIs
-Cycosporine: CYP3A4 inhibitor, CYP3A4 and P-gp substrate; can increase sirolimus, everolimus, and some statins - do NOT use lovastatin or simvastatin (which often seen in transplant pts)
-Tacrolimus: CYP3A4 and P-gp substrate
-Mycophenolate: decrease levels of hormonal contraceptives; mycophenolate levels decreased by antacids (Al, Mg), multivitamins, metronidazole, PPIs, quinolones, sevelamer, bile acid resins, rifampin and derivatives
-Azathioprine: metabolized into 6-mercaptopurine which is inactivated by xanthine oxidase, avoid use w/ inhibitors (allopurinol - decrease azithropine dose by 75%, febuxostat - CI)
Transplant Agents: Pharmacodynamic Interactions
-Nephrotoxicity
-Raising BG
-Worsening lipids
-Raising BP
-Myleosupression
-Nephrotoxic: CNIs (ex. additive w/ NSAIDs)
-Raise BG: steroids, CNIs, mTOR inhibitors
-Worsen lipids: mTOR inhibitors, steroids, cyclosporine
-Raise BP: CNIs, steroids
-Myleosuppressive w/ azithioprine and mycophenolate
Transplant Agents: Food/Natural Product Interactions
-CNIs: avoid grapefruit juice (increases levels) and St. John’s Wort (decreases levels)
-Tacrolimus absorption decreased by food
Transplant Immunosuppression: What is the main monitoring question?
It is a symptom of drug toxicity, organ rejection, or infection?
Transplant Immunosuppression: S/Sx of acute rejection and TX recommendations
S/Sx: flu-like symptoms (chills, body aches, nausea, cough, SOB, and organ-specific symptoms (ex. HF symptoms or new arrhythmia w/ heart transplant rejection; kidney rejection: decrease in urine output, fluid retention, BP elevation, or graft tenderness)
-*Trough levels: drawn 30 minutes prior to scheduled dose
-Rejection can be T-cell (cellular) or B-cell (humoral or antibody) medicated and should be distinguished via biopsy (can also be mixed)*
-Initial TX of acute cellular rejection (ACR): high-dose steroids and optimizing immunosuppression
-Steroid-resistant or severe ACR: antithymocyte globulin
-Antibody mediated rejection (AMR): more difficult to treat since antibodies against graft must be removed and supressed (plasmapheresis and administration of IV immunoglobulin = IVIG and steroids followed by dose of rituximab - MAB against CD20)
Transplant Immunosuppression: S/Sx of infection, prophylaxis recommendations, and vaccines indicated
Infection s/sx: fever of 100.4F (38C) or higher (lower if elderly), chills, cough (more sputum or change in color), sore throat, pain w/ passing urine, ear or sinus pain, mouth sores or wound that does NOT heal
-Opportunistic Infection prophylaxis (see ID section) –> important especially in first 6 months
-Routine infection control: hand-washing, oral hygiene
Vaccines:
-Required vaccines given pre-transplant if NOT up-to-date
-Inactivated vaccines can be given >/=3-6 months post-transplant except for influenza vaccine which can be administered 1 month post-transplant
-Live vaccines cannot be given post-transplant
-Important vaccines: influenza (innactivated) annually, pneumococcoal in 19 yo and older (PCV20 OR PCV15 then PPSV23 8 weeks or more later), hepatitis B, varicella (pre-transplant and close relatives)
-Varicella: high risk for serious infections (ex. diseminated disease) –> if develop rash, need to be seen immediately and if close contact develops, keep distance and contact physician
Administration of Cyclosporine Counseling
- Use syringe provided by manufacturer to measure dose
- Do NOT rinse syringe before or after use –> just wipe down
- Use compatible diluent (ex. orange juice) at room temperature. Consistently use the same diluent.
- Mix dose and diluent thoroughly in glass container. do NOT admister in plastic or Styrofoam cup
- Administer or drink immediately. Rinse container w/ extra diluent to ensure total dose taken.
Drugs and conditions that increase weight gain
Drugs:
-Antipsychotics: clozapine, olanzapine, risperidone, quetiapine
-Diabetes drugs: insulin, SUs, meglitinides, TZDs
-Divalproex/valproic acid, lithium, mirtazapine, gabapentin, pregabalin
-TCAs: amitriptyline, nortriptyline
-Steroids
Conditions: hypothyroidism, depression, eating disorders
Drugs and conditions that cause weight loss
Drugs:
-ADHD drugs: amphetamine, methylphenidate
-Bupropion, topiramate
-GLP-1a, SGLT2is, tirzepatide, pramlinitide
-Roflumilast
Conditions: hyperthyroidism, celiac disease, IBD
Overweight and Obesity:
-Nonpharmacological TX
TX first (diet - 1lb = 3500kcal and exercise)
-OTC supplements (caffeine, green tea, guarana, bitter orange, yerba mate) generally ineffective and can be harmful especially in CVD –> usually contains stimulants
Overweight and Obesity: When to use medications
Medications indicated when BMI >/=30 OR BMI >/=27 + one weight-related condition (ex. DM, dyslipidemia, HTN, sleep apnea)
-Older stimulants (ex. phentermine, diethylpropion) were used short-term to “jump-start” a diet
-Newest drugs (Qysmia, Contrave, Saxenda, Wegovy, Zepbound) and orlistat formulations can be continued long-term
-D/C weight loss drug if do NOT produce at least 5% weight loss at 12 weeks (steady loss –> if cutting very fast, body goes into starvation mode where weight loss is difficult)
Overweight and obesity: when bariatric surgery indicated and consequences
When BMI >/=35 or BMI >/=30 + T2DM OR BMI >/=30 who cannot achieve or sustain a goal BMI or improvement in on obesity-related comorbidity w/ other methods
-Nutrional deficiencies: pt may require life-long supplementatoin of fat-soluble vitamin ADEK due to fat malabsorption, calcium citrate preferred (non-acid-dependent absorption), vitamin B12 or iron in anemia, iron and Ca++ supplements should be taken 2 hours before or 4 hours after antacids
-Medication concerns: may need dose reduction or to be crushed and put in liquid or transdermal form up to 2 months post-surgery
-Rapid weight loss can cause gallstones –> urosodiol may be needed
-Avoid medications that irritate GI tract (ex. NSAIDs)
Phentermine/Topiramate:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Brand: Qsymia
MOA:
-Phentermine: symphathomimetic (stimulant) that releases NE through satiety center that decreases appetite
-Topiramate: increases satiety and decreases appetite possibly by increasing GABA, blocking stimulants and/or inhibiton of carbonic anhydrase
ROA: PO
TX: excessive weight
*Administration: *
-Take in AM to reduce insomnia
-Taper off due to seizure risk
AVEs: tachycardia, CNS effects (insomnia, depression, SI thoughts, anxiety, HA, paresthesias), vision problems, constipation, dry mouth, decrease HCO3, URTIs, increase SCr
CI: pregnancy (REMS), glaucoma, hyperthyroidism, MAOIs use within past 14 days
Naltrexone/Bupropion
-Brand
-MOA
-ROA
-TX
Brand: Contrave
MOA: naltrexone decreases food cravings and bupropion decreases appetite
ROA: PO
TX: excessive weight
Naltrexone/Bupropion:
-AVEs
-Warnings
-CIs
-BBW
-DDIs
AVEs: N/V, constipation, HA, dizziness, dry mouth, insomnia, increased SCr
Warnings: caution in psychiatric disorders, D/C w/ s/sx of hepatotoxicity, can increase HR and BP, glaucoma
CIs: pregnancy, chronic opioid use or acute opiate withdrawl, uncontrolled HTN, seizure disorder, use of other bupropion-containing products, bulimia/anorexia, abrupt D/C of alcohol/BZDs/barbiturates/anticonvusants, use of MAOIs within 14 days
BBW: NOT approved for TX of MDD or pyschiatric disorders
-Buproprion: increased risk of suicidal ideation and behavior in children, adolescents, and young adults
-NOT approved for pediatric patients
DDIs: naltrexone blocks opioids and buprenorphine –> D/C opioids or buprenorphine 7-14 days prior to use of Contrave
Orlistat:
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: Xenical (RX), Alli (OTC)
MOA: lipase inhibitor that decreases absorption of dietary fats by about 30%
ROA: PO
Administration:
-Take multivitamin ADEK and beta-carotene at bedtime or serparated by >/=2 hours
-Must stick to dietary plan for both weight improvement and to help lessen GI AVEs (must be used w/ low-fat diet)
TX: excessive weight
Orlistat:
-AVEs
-Warnings
-CI
-DDIs
AVEs: GI (flatus w/ discharge, fatty stool, fecal urgency)
Warnings: liver damage (rare), cholelithiasis, increased urinary oxalate/kidney stones, hypoglycemia (in DM)
CI: pregnancy, chronic malabsorption syndrome, cholestasis
DDIs:
-Do NOT use w/ cyclosporine or separate by >/=3 hours (has some fat)
-Separate levothyroxine by >/=4 hours
Appetite Suppressants:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
Drugs: phentermine (Adipex-P, Lomaira), diethylpropion, phendimetrazine, benzphetamine
MOA: sympathomimetics (stimulants) that increase NE in satiety center to decrease appetite
ROA: PO
Administration:
-Use short term up to 12 weeks for “jump-start” diet
-Avoid taking later in day (insomnia)
-Potential for misuse/dependence
Appetite Suppressants:
-AVEs
-Warnings/CIs
-Monitoring
AVEs: tachycardia, agitatoin, increased BP, pulmonary HTN (use >3 months), insomnia, dizziness, tremor, psychosis
Warnings/CIs: CVD (uncontrolled HTN, pulmonary HTN, arrythmias, HF, CAD), hyperthyroidism, glaucoma, pregnancy, breast feeding, hx of drug abuse, MAOIs within 14 days
Monitoring: HR, BP, symptoms of pulmonary HTN (dyspnea, edema)
Weight loss: for the given circumstances, which drugs should be avoided or caution w/ use:
1. Pregnancy
2. Hypertension
3. Depression
4. Seizures
5. Taking opioids
Pregnancy: AVOID ALL weight loss drugs
HTN:
-Avoid: Contrave (contains bupropion), stimulants (ex. phentermine) - CI w/ uncontrolled BP
-Caution: Qysmia (contains phentermine - monitor HR)
Depression: caution in young adults and adolescents w/ Contrave (suicide risk w/ bupropion)
Seizures:
-Avoid: contrave (contains bupropion - lowers seizure threshold)
-Caution: Qsymia: must taper off slowly (contains topiramate)
Taking opioids: avoid Contrave (contains naltrexone which blocks opioid receptors)
What are the age classifications: neonate, infant, child, adolescent?
-Neonate: 0-28 days old
-Infant: 1 month to <2 yo
-Child: 2-11 yo
-Adolscent: 12-18 yo
What are signs that pediatric patients should seek medical care?
-Rectal temperature >/= 100.4F (38C) in pts <3 months old –> typically do NOT have fevers when young, so low threshold
-*Rectal temperature >/= 101F in pts 3 months or older
-Severe rash or any rash w/ fever*
-Allergic reactions
-Others:blood in urine/stool, dehydration (limited/no urine output or unable to tolerate oral liquids), difficulty breathing, limping or unable to move extremity, head injury, ingestions, seizure
Neonates:
1. What is the apgar score?
- What are medications routinely given to neonates after birth?
- When is a neonate considered premature, and what are the potential complications?
- The ability to adapt to extraurterine life assess 1-5 minutes post birth (measures: appearance, HR, grimace - reflex, irritability, newborn’s response to stimulation, activity - muscle tone, and respiratory effort)
-Score >/=7 indicates newborn adapting well
-Score <7 indicates distress and prompt medical intervention needed
-
Vitamin K IM (avoid bleeding), opthalamic erythromycin (prevent conjunctivitis), first dose of hepatitis B series
-In select conditions: analgesia (for circumcision), phototherapy (for jaundice) - Premature when born before 37 weeks of gestation - higher risk of patent ductus aterteriosus (PDA) and respitaratory distress syndrome (RDS)
Neonates: What is the following and basic TX: patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), and presistant pulmonary hypertension of the newborn (PPHN)?
-PDA: the normal opening between aorta and pulmonary artery remains open after birth, TX: medical observation and/or interventions (surgery or drugs: IV NSAIDs such as indomethacin or ibuprofen to inhibit prostaglandins that cause closing of opening – this is also why NOT to use NSAIDs in 3rd trimester as it can cause early closing)
-RDS: deficiency of surfactant production due to collpased alveoli, TX: most neonates born before 35 weeks receive surfactant immediately after birth or within first few days of life (ex. poractant alfa - Curosurf, calfactant - Infasurf)
-PPHN (more risk in term neonates): blood vessels fail to relax which may be due to in utero exposure to SSRIs, TX: supportive care, inhaled nitric oxide, sometimes PDE5is (ex. sildenafil)
Neonatal sepsis considerations and general TX
-Classic symptoms of meningitis (ex. HA, nuchal rigidity) UNCOMMON in neonates
-Pathogens differ due to vertical transmission of organism: E. coli most common, GroupB strep (GBS) most common in meningitis
-GBS screening done during pregnancy and for those positive, ABX prophylaxis w/ PCN G aqueous
-Empiric ABX TX: ampicillin + ceftazidime, cefepime, or gentamicin (do NOT use ceftriaxone: displaces bilirubin from albumin which can cause brain damage and can precipitate w/ Ca++ causing death)
Pediatrics: Broncholitis
-Define/Pathogen
-S/Sx
-Who is most at risk
-TX
Broncholitis: lower respiratory tract condition caused mostly by respiratory syncytial virus (RSV), but can occur w/ other viruses
S/Sx: increased mucus production, significant swelling in airway, respiratory distress
Most risk: neonates, premature infants
TX: primarily supportive care(suction of secretions, hydration, supplemental oxygen, fever management)
-Bronchodilators and systemic steroids are NOT used routinely
-Inhaled ribavirin (Virazole): considered in immunocompromised w/ severe RSV infection
Pediatrics Bronchitis: Prophylaxis
-RSV vaccine: recommended in pregnancy between weeks 32-36
-If mother NOT vaccinated, RSV prophylaxis in infants during RSV season (nirsevimab - Beyfortus, pelivizumab - Synaqis)
-Nirsevimab: single IM dose for neonates and infants OR children
-Pelivizumab: IM once monthly though RSV season (max: 5 doses/season) for preamature infant born at <29 weeks gestation and age 6 months or less or 24 months or less w/ congenital heart disease/chronic lung disease
Pediatrics: CROUP
-Define
-S/Sx
-Differences between bronchiolitis
-TX
CROUP: laryngotracheobronchitis due to viral infection causing significant inflammation of upper airway most common in children <6 yo
S/Sx: high-pitched breathing sounds, barking cough, and hoarseness
Differences from broncholitis:
-Cause: RSV (broncholitis), parainfluenzae typically (GROUP)
-Age of onset:
-GROUP has stridor and barking cough and impacts upper (NOT lower tract)
TX: *systemic steroids (dexamethasone) mainstray of TX for mild to severe cases
-In acute care setting: nebulized racemic EPI (D- and L- isomer; L-isomer = active component) may be given to decrease airway edema –> if racemic NOT available, can give L-epinephrine at HLAF the dose of racemic mixture; observe after when given since short T1/2*
-Severe symptoms may require respiratory support
-ABXs only if bacterial infection present
Pediatrics: Nocturnal Enduresis
-Define
-Nonpharmacological TX
-TX and drug considerations
Nocturnal Enduresis: bed-wetting that is a normal part of child’s development and not generally treated before age 5 years
Nonpharmacological TX: attempt FIRST before drugs –> positive reinforcement, establishing normal daytime voiding pattern, bowel pattern, and hydration pattern (fluid intake should be limited before bedtime)
Drug TX: desmopressin PO tablets - synthetic analog of antidiuretic hormone (ADH) to reduce uring production and shuold be in combination w/ alarm therapy (sounds when bed is wet)
-Limit fluids starting 1 hour before dose and until next morning
-AVEs: HA, hyponatremia
Pharmacist considerations when dispensing liquid pediatric medications to reduce errors
- Verify dose is appropriate for patient’s weight
- Transcribe dose in mL ONLY on the label
- Dispense RX with oral measuring device (dosing syringe or cup) appropriate for age and dose volume –> household spoons should NOT be used
Pediatrics: OTCs
1. Cough and cold medicine is NOT recommended for children under ___ yo per the FDA, but some manufacturers include product labeling to avoid in under ___ yo and some are only for those ___ yo and older.
- Aspirin and salicylate-containing products such as _______ (common OTC) are associated with ____________ and should NOT be used in patients under ____ yo.
- What are the age restrictions and doses for acetaminophen and ibuprofen for fever and mild pain?
- Recommendations for nasal congestion, intestinal gas, and dehydration
- 2 yo; 4 yo; 6 yo
- bismuth subsalicylate; Reye’s syndrome in children recovering from viral infectin (especially influenza and chickenpox); 18 yo
- 6 months and older
-APAP: 10-15mg/kg/dose Q4-6H (max: 75mg/kg/day)
-Ibuprofen: 5-10 mg/kg/dose Q6-8H (max: 40mg/kg/day) - -Nasal congestion: saline drops or spray (ex. Ocrean for Kids, Little Remedies)
-Intestinal gas: simethicone drops (not absorbed and safe to use)
-Diarrhea: oral rehydration solutions (ex. Pedialyte, Enfamil Enfalyte), loperamide NOT recommended in </=6 yo
Pediatrics: OTC recommendations for constipation in children <6 months, >/=6 months, >/=2 yo, and >/=6 yo
*-Under 6 months: glycerin suppositories for quick relief *(off-label: FDA approved for >/=2 yo)
-6 months and older: polyethylene glycol (MiraLax) for intermittent constipation
-2 yo and older: additional options of magnesium hydroxide, docusate, senna, and rectal enema such as sodium phosphate - Fleet Pedia-Lax Enema (rectal enemas NOT used in <2 yo due to dehydration risk and electrolyte abnormalities)
-6 yo and older: additonal options of bisacodyl suppositories or oral mineral oil (caution for risk of aspiration such as neurologic impairment or significant GI reflux, N/V)
Pediatrics: OTCs
1. ______________ is a good resource to determine which medications are considered unsafe for children.
- What drugs are CI in neonates, age <2 yo, and age <12 yo? Why?
- Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List
- CI:
-Neonates (0-28 days): ceftiraxone
-Age <2 yo: promethazine (respiratory depression), OTC teething medications containing benzocaine (methemoglobinemia risk)
-Age <12 yo: codeine and tramadol (respiratory depression risk –> CI in <18 yo after tonsillectomy/adenoidectomy)
Pediatrics: What drugs are not GENERALLY recommended? Why?
-Cough and cold medicine: not effective
-Aspirin: Reye’s syndrome risk
-Quinolones: cartilage, bone, and muscle AVEs (in certain conditions benefit outweighs risk: anthrax, complicated UTIs, cystic fibrosis)
-Tetracyclines: NOT recommended under 8 yo due to tooth discoloration and slowing of bone growth (exception where benefit outweights risk: tick-borne Rickettsial disease ex. Rocky Mountain spotted fever - doxycycline most effective TX)
Cystic Fibrosis (CF):
-Define
-S/Sx
-Diagnosis
-Nonpharmacological TX
CF: incurable, hereditary disease from mutation for protein cystic fibrosis transmembrane conductance receptor (CFTR)
-Mutation causes abnormal transport of chloride, sodium, and bicarbonate across epithelium leading to thick, viscous secretions
-Secretions impact lungs, pancreas, liver and intestines (“Cystic fibrosis” refers to the scarring of the pancreas)
S/Sx: salty tasting skin, poor growth and weight gain despite adequate food intake, thick and sticky mucus production, frequent lung infections, coughing, SOB, steatorrhea (fatty stools), malnutrition, clubbing of fingers
Diagnosis: Sweat test - too much chloride in sweat is positive (screened within first 2-3 days of birth)
Nonpharmacological TX:
-High-fat and calorically dense diet recommended for nutrients and growth
-Vitamin supplements (especially fat-soluble ADEK, calicum + vitamin D)
-Maintaining good health improves chances of lung transplant
Dornase Alfa:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Brand: Pulmozyme
MOA: decreases viscosity of mucus via breaking DNA strands into smaller pieces
ROA: inhaled (nebulizer and compressor system)
*Administration: *
-Store ampules in refrigerator (do NOT expose to room temp for >/=24 hours)
-Protect from light
-Do NOT mix with any other drug in nebulizer
TX: Cystic Fibrosis lung complications
AVEs: chest pain, fever, rash, rhinitis, laryngitis, voice alteration, throat irritation
CIs: hypersensitivity to Chinese Hamster ovary (CHO) products
Cystic Fibrois (CF): Inhaled ABXs
1. Inhaled ABXs should be given for _____ days on and ____ days off.
- Tobramycin has the brand names ____ or _______. It is dosed Q___H, but needs to be at least ___ hours apart. Aztreonam is dosed Q___H, but needs to be at least ___ hours apart.
- TOBI Podihaler comes with capsules that should be stored at ________ temperature and should NOT be swallowed.
- TOBI, Bethkis, and KItabis are recommended to be stored in the frigde, but can be kept at room temperature for ______ days.
- 28; 28
- TOBI; TOBI Podihaler; 12; 6; 8; 4
- Room temperature
- 28
Pancrealipase:
-Brands
-MOA
-ROA
-Dosing
-TX
-AVEs
-Warnings
-Monitoring
Brand: Creon, Viokace, Zenpep, Lip-Prot-Amyl, Pancreaze, Pertzye
MOA: natural product derived from porcine pancreatic glands containing a combination of lipase, amylase, and protease that break down startches, fat, and protein; formulated to dissolve in the more basic pH of duodenum
ROA: PO
Dosing: individualized for each patient based on the lipase component and adjusted Q3-4 days until stools are normalized
-Maximum dose: lipases </=10,000 units/kg/day
TX: cystic Fibrosis - pancreatic insufficiency
AVEs: abdominal pain, flatulence, nausea, HA, neck pain
Warnings: fibrosing colonpathy advancing to colonic strictures (rare: higher risk when lipases above >/=10,000 units/kg/day), mucosal irritation, hyperuricemia
Monitoring: abdominal symptoms, nutritional intake, weight, height (children), stool, fecal fat
*Cystic Fibrois: Pancreatic Enzyme Products (PEP): *
1. True or False: PEP products are interchangeable.
- _____ is the only PEP product that is a tablet. It is non-enteric coated and must be given with ________.
- All other PEPs are capsules. How can the capsules be taken?
- False - all have different lipase amounts
- Viokace; PPI
- Do NOT crush or chew. DO NOT retain capsule contents in mouth. Swallow immediately following with water to avoid mucosal irritation and stomatitis.
-DR capsules w/ enteric-coated microspheres or microtablets can be opened and sprinkled on soft, acidic food (ex. applesauces). Avoid foods w/ high pH (ex. dairy)
Cystic Fibrosis - Pancreatic Enzyme Products (PEP):
1. All PEPs should be taken before or with all meals and snacks. _______ meals may require higher doses. Use _____% of dose with snacks.
- Protect from moisture and store in original container with exception of _____ and some ______ strengths. Do NOT refrigerate.
- High-fat; 50%
- Zenpep, some Creon strengths
Cystic Fibrosis Transmembrane Conductance REgular (CFTR) Modulators
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-Warnings
-DDIs
Drugs: ivacaftor (Kalydeca), lumacaftor/ivacaftor (Orkambi), tazacaftor/ivacaftor (Symbdeko), elexacaftor/tezacaftor/ivacaftor (Trikafta)
MOA:
-Ivacaftor: increases the time the CFTR channels remain open, enhancing Cl transport activity
-Lumacaftor, tazacaftor, elexacaftor: correct CFTR folding defect, increasing amount of CFTR delived to cell surface
ROA: PO
Administration:
-Take with high-fat containing food
-Minimum age cut-off for use varies by product: confirm w/ package labeling
TX: cystic fibrosis, homogzygous F508del mutation and additional responsive mutations except ivacaftor alone
Warnings: increased LFTs, cataracts in children
DDIs: ivacaftor is a major substrate of CYP3A4 and should be avoided w/ strong inhibitors
Cystic Fibrosis:
-TX for CF
-TX for lung complications
-TX in intermittent and chronic infection
-Other TX
No cure for CF - just TX of complications
TX (Lung Complications): medications need to be done in order
-First: inhaled bronchodilator (ex. albuterol) –> opens airways
-Hypertonic saline (ex. HyperSal) –> mobilizes mucus to improve airway clearance (delivered via nebulizer)
-Dornase alfa (Pulmozyme) –> decreases viscosity of of mucus (thins) to improve airway clearance
-Chest physiotherapy (ex. flutter vests): mobilizes mucus to improve airway clearance
-Last: inhaled ABXs –> controls airway infections
Cystic Fibrosis: TX in intermittent infection
-Most common pathogens: S. aureua and H. influenzae > Pseudomonas in adults and adolescents
-Exacrebations: increase in cough, sputum, change in sputum color (greenish), SOB, and rapid decline of FEV1
-TX: two IV ABXs for potential synergy and prevent resistance (aminoglycodsides, beta-lactams, quionolones, and other ABXs that cover Pseudomonas) –> doses tend to be higher in CF due to altered pharmacokinetics
Cystic Fibrosis: TX in chronic infection
Inhaled ABX for chronic Pseudomonas infection cycled w/ 28 days on and 28 days off
-Inhaled options: aztreonam (given TID) or tobramycin (given BID)
-Azithromycin PO: 6 month trial can be done for worsening on conventional TX –> NO direct activity against Pseudomonas, BUT disrupts biofilm formation by bacteria
Cystic Fibrosis: TX in CF-related DM
May require insulin
