Other Population Health

Question 1

Transplant: Prevention of Graft Rejection
1. Define allograft, autograft, and isograft

2. When does graft rejection occur, and what are some of the consequences?
3. Prior to transplants, immunosuppressants are given to reduce likelihood of reject What are some of the general BBWs from these drugs?

Answer 1

1. -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

2. In an allograft - immune response can lead to organ failure support, removal of transplanted organ
3. -Infection risk: prophylaxis for infections often required
   -Cancer risk: sun protective measures and cancer screenings needed
   -“Only Experienced Prescribers…”: especially when drugs are started

Question 2

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. *

Answer 2

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

Question 3

Transplant: Induction Immunosuppression

Answer 3

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

Question 4

Transplant: Maintenance Immunosuppression

Answer 4

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

Question 5

Basiliximab:
-Brand
-MOA
-ROA
-TX
-AVEs
-BBW
-Monitoring

Answer 5

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

Question 6

Antithymocyte globulin:
-Brand
-MOA
-ROA
-Administration considerations
-TX

Answer 6

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)

Question 7

Antithymocyte globulin:
-AVEs
-BBW
-Monitoring

Answer 7

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)

Question 8

Tacrolimus:
-Brand
-MOA
-ROA
-Administration considerations
-Role in transplant

Answer 8

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

Question 9

Tacrolimus:
-AVEs
-BBW
-Monitoring

Answer 9

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

Question 10

Cyclosporine:
-Brand
-MOA
-ROA
-Administration considerations
-Role in transplant therapy

Answer 10

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

Question 11

Cyclosporine:
-AVEs
-BBW
-Monitoring

Answer 11

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

Question 12

Azathioprine:
-Brand
-MOA
-ROA
-TX

Answer 12

Brand: Azasan. Imuran

MOA: antiproliferative agent - inhibits T- and B-lymphocyte proliferation by altering pruine nucleotide synthesis

ROA: PO, injection

TX: transplant, maintenance immunosuppression

Question 13

Azathioprine:
-AVEs
-Warnings
-BBW
-Monitoring

Answer 13

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

Question 14

Mycophenolate:
-Brand
-MOA
-ROA
-Administration considerations
-TX

Answer 14

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

Question 15

Mycophenolate:
-AVEs
-BBW
-Monitoring

Answer 15

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

Question 16

Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX

Answer 16

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

Question 17

Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors:
-AVEs
-Warnings
-BBWs
-Monitoring

Answer 17

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

Question 18

Belatacept
-Brand
-MOA
-ROA
-Administration considerations
-TX

Answer 18

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

Question 19

Belatacept:
-AVEs
-Warnings
-BBW
-Monitoring

Answer 19

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

Question 20

Transplant Agents: DDIs

Answer 20

-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)

Question 21

Transplant Agents: Pharmacodynamic Interactions
-Nephrotoxicity
-Raising BG
-Worsening lipids
-Raising BP
-Myleosupression

Answer 21

-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

Question 22

Transplant Agents: Food/Natural Product Interactions

Answer 22

-CNIs: avoid grapefruit juice (increases levels) and St. John’s Wort (decreases levels)

-Tacrolimus absorption decreased by food

Question 23

Transplant Immunosuppression: What is the main monitoring question?

Answer 23

It is a symptom of drug toxicity, organ rejection, or infection?

Question 24

Transplant Immunosuppression: S/Sx of acute rejection and TX recommendations

Answer 24

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)

Question 25

Transplant Immunosuppression: S/Sx of infection, prophylaxis recommendations, and vaccines indicated

Answer 25

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

Question 26

*Administration of Cyclosporine Counseling*

Answer 26

1. Use syringe provided by manufacturer to measure dose 2. Do NOT rinse syringe before or after use --> just wipe down 3. Use compatible diluent (ex. orange juice) at room temperature. Consistently use the same diluent. 4. Mix dose and diluent thoroughly in glass container. do NOT admister in plastic or Styrofoam cup 5. Administer or drink immediately. Rinse container w/ extra diluent to ensure total dose taken.

Question 27

*Drugs and conditions that increase weight gain*

Answer 27

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

Question 28

*Drugs and conditions that cause weight loss*

Answer 28

Drugs: -ADHD drugs: amphetamine, methylphenidate -Bupropion, topiramate -GLP-1a, SGLT2is, tirzepatide, pramlinitide -Roflumilast Conditions: hyperthyroidism, celiac disease, IBD

Question 29

*Overweight and Obesity: -Nonpharmacological TX*

Answer 29

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

Question 30

*Overweight and Obesity: When to use medications*

Answer 30

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)

Question 31

*Overweight and obesity: when bariatric surgery indicated and consequences*

Answer 31

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)

Question 32

Phentermine/Topiramate: -Brand -MOA -ROA -Administration considerations -TX -AVEs -CIs

Answer 32

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

Question 33

Naltrexone/Bupropion -Brand -MOA -ROA -TX

Answer 33

Brand: Contrave MOA: *naltrexone decreases food cravings and bupropion decreases appetite* ROA: PO TX: excessive weight

Question 34

Naltrexone/Bupropion: -AVEs -Warnings -CIs -BBW -DDIs

Answer 34

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

Question 35

Orlistat: -Brand -MOA -ROA -Administration considerations -TX

Answer 35

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

Question 36

Orlistat: -AVEs -Warnings -CI -DDIs

Answer 36

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

Question 37

Appetite Suppressants: -Drugs/Brands -MOA -ROA -Administration considerations

Answer 37

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

Question 38

Appetite Suppressants: -AVEs -Warnings/CIs -Monitoring

Answer 38

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)

Question 39

*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

Answer 39

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)

Question 40

*What are the age classifications: neonate, infant, child, adolescent?*

Answer 40

-Neonate: 0-28 days old -Infant: 1 month to <2 yo -Child: 2-11 yo -Adolscent: 12-18 yo

Question 41

What are signs that pediatric patients should seek medical care?

Answer 41

-*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

Question 42

Neonates: 1. What is the apgar score? 2. What are medications routinely given to neonates after birth? 3. When is a neonate considered premature, and what are the potential complications?

Answer 42

1. *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* 2. *Vitamin K IM (avoid bleeding), opthalamic erythromycin (prevent conjunctivitis), first dose of hepatitis B series* -In select conditions: analgesia (for circumcision), phototherapy (for jaundice) 3. *Premature when born before 37 weeks of gestation - higher risk of patent ductus aterteriosus (PDA) and respitaratory distress syndrome (RDS)*

Question 43

Neonates: What is the following and basic TX: patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), and presistant pulmonary hypertension of the newborn (PPHN)?

Answer 43

-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)

Question 44

*Neonatal sepsis considerations and general TX*

Answer 44

-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)

Question 45

Pediatrics: Broncholitis -Define/Pathogen -S/Sx -Who is most at risk -TX

Answer 45

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

Question 46

*Pediatrics Bronchitis: Prophylaxis*

Answer 46

-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

Question 47

Pediatrics: CROUP -Define -S/Sx -Differences between bronchiolitis -TX

Answer 47

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

Question 48

Pediatrics: Nocturnal Enduresis -Define -Nonpharmacological TX -TX and drug considerations

Answer 48

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

Question 49

*Pharmacist considerations when dispensing liquid pediatric medications to reduce errors*

Answer 49

1. Verify dose is appropriate for patient's weight 2. Transcribe dose in mL ONLY on the label 3. Dispense RX with oral measuring device (dosing syringe or cup) appropriate for age and dose volume --> household spoons should NOT be used

Question 50

*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. 2. Aspirin and salicylate-containing products such as _______ (common OTC) are associated with ____________ and should NOT be used in patients under ____ yo. 3. What are the age restrictions and doses for acetaminophen and ibuprofen for fever and mild pain? 4. Recommendations for nasal congestion, intestinal gas, and dehydration

Answer 50

1. 2 yo; 4 yo; 6 yo 2. bismuth subsalicylate; Reye's syndrome in children recovering from viral infectin (especially influenza and chickenpox); 18 yo 3. 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) 4. -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

Question 51

Pediatrics: OTC recommendations for constipation in children <6 months, >/=6 months, >/=2 yo, and >/=6 yo

Answer 51

*-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)

Question 52

*Pediatrics: OTCs* 1. ______________ is a good resource to determine which medications are considered unsafe for children. 2. What drugs are CI in neonates, age <2 yo, and age <12 yo? Why?

Answer 52

1. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List 2. 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)

Question 53

*Pediatrics: What drugs are not GENERALLY recommended? Why?*

Answer 53

-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)

Question 54

Cystic Fibrosis (CF): -Define -S/Sx -Diagnosis -Nonpharmacological TX

Answer 54

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

Question 55

Dornase Alfa: -Brand -MOA -ROA -Administration considerations -TX -AVEs -CIs

Answer 55

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

Question 56

*Cystic Fibrois (CF): Inhaled ABXs* 1. Inhaled ABXs should be given for _____ days on and ____ days off. 2. 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. 3. TOBI Podihaler comes with capsules that should be stored at ________ temperature and should NOT be swallowed. 4. TOBI, Bethkis, and KItabis are recommended to be stored in the frigde, but can be kept at room temperature for ______ days.

Answer 56

1. 28; 28 2. TOBI; TOBI Podihaler; 12; 6; 8; 4 3. Room temperature 4. 28

Question 57

Pancrealipase: -Brands -MOA -ROA -Dosing -TX -AVEs -Warnings -Monitoring

Answer 57

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), *mucosal irritation*, hyperuricemia Monitoring: abdominal symptoms, nutritional intake, weight, height (children), stool, fecal fat

Question 58

*Cystic Fibrois: Pancreatic Enzyme Products (PEP): * 1. True or False: PEP products are interchangeable. 2. _____ is the only PEP product that is a tablet. It is non-enteric coated and must be given with ________. 3. All other PEPs are capsules. How can the capsules be taken?

Answer 58

1. False - all have different lipase amounts 2. Viokace; PPI 3. 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)

Question 59

*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. 2. Protect from moisture and store in original container with exception of _____ and some ______ strengths. Do NOT refrigerate.

Answer 59

1. High-fat; 50% 2. Zenpep, some Creon strengths

Question 60

Cystic Fibrosis Transmembrane Conductance REgular (CFTR) Modulators -Drugs/Brands -MOA -ROA -Administration considerations -TX -Warnings -DDIs

Answer 60

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

Question 61

Cystic Fibrosis: -TX for CF -TX for lung complications -TX in intermittent and chronic infection -Other TX

Answer 61

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

Question 62

Cystic Fibrosis: TX in intermittent infection

Answer 62

-*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*

Question 63

Cystic Fibrosis: TX in chronic infection

Answer 63

*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*

Question 64

*Cystic Fibrosis: TX in CF-related DM*

Answer 64

May require insulin