Tid Bits of Knowledge

Drugs with HLA testing action

Abacavir (Ziagen; also Triumeq, Epzicom) HLA-B*5701 (+) = do not use d/t fatal hypersensitivity (must test prior to use)

allopurinol (Zyloprim, Aloprim) HLA-B*5801 (+) = do not use d/t risk of SJS; DC if rash develops (consider testing African, Asian, Native Hawaiian/Pacific Islander)

carbamazepine (Tegretol) (test all Asians)

oxcarbazepine (Trileptal) (testing optional)

phenytoin (Dilantin) (testing optional)

Fosphenytoin (Cerebyx) (testing optional)

HLA-B*1502 (+) = do not use d/t risk of SJS/TENS

What CYP polymorphism impacts citalopram metabolism?

CYP2C19 (*2 and *3 are loss of fx alleles —> MDD 20mg)

What CYP polymorphism impacts clopidogrel metabolism?

CYP2C19 (*2 and *3 are loss of fx alleles —> consider alternative Tx)

What CYP polymorphism impacts codeine metabolism?

CYP2D6 (UM at risk of OD; PM at risk of subtherapeutic mgmt)

What CYP polymorphisms impact warfarin metabolism?

CYP2C9 *2 & *3 & VKORC1 G>A are both loss of Fx —> increase bleeding risk

use lower starting dose

What polymorphic enzyme impact azathioprine safety?

TPMT (thioprine methyltransferase)

low/absent activity —> increased frisk atal myelosuppression (start very low dose or use alternative)

intermediate activity —> risk still present but not as severe

What polymorphic enzyme impacts capecitabine (Xeloda)/ fluorouracil safety?

DPD (dihydropyrimidine dehydrogenase)

deficiency = increase risk severe neurotoxicity, diarrhea, and neutropenia (do not use)

Avoid a drug when these PGx tests are (+)

HLA-B (hypersensitivity)

KRAS mutation (poor response to EGFR inhibitors)

HER2 (-) or (1+ ie weakly positive) (poor response to HER2i like trastuzumab)

What drugs require PGx testing prior to use?

CACAT

carbamazepine

abacavir (and abacavir containing drugs)

cetuximab (and other EGFRi)

azathioprine

trastuzumab (and other HER2i)

Name the site of action for these diuretics in the nephron:

A. SGLTi

B. Loops

C. Thiazides

D. K+ sparing

A. proximal tubule

B. ascending loop of henle

C. distal convoluted tubule

D. distal convoluted tubule + collecting duct

listed in order of proximity to the glomerulus

What are the 2 ways to define CKD

>/3 months of either eGFR <60 OR albuminuria

where albuminuria = urine albumin excretion rate >/30mg/24 hrs OR albumin to cr ratio >/= 30 mg/gW

What is the expected % increase in SCr after starting an ACEi or ARB?

30%; stop if > 30%

How do ACEi/ARBs help with albuminuria in comorbid HTN?

inhibit RAAS —> efferent arteriole dilation —> reduced glomerular pressure —> decreased albuminuria —> delayed progression to ESRD

Name anti-infectives that have to be dose reduced or have the dosing interval increased in CKD

aminoglycosides

beta-lactams (except antistaph PCNs ie naficillin, oxacillin, CTX)

fluconazole

quinolones (except moxi)

vancomycinN

Name anticoagulants that require dose reduction or increased dosing interval in CKD

enoxaparin

rivaroxaban (AFib only)

apixaban (AFib only)

dabigatran (AFib only)

Name GI drugs that require dose reduction or increased dosing interval in CKD

famotidine

ranitidine

metoclopramide

T/F: bisphosphonates and lithium require dose reduction in CKD

T; bisphosphonates depend on indication

Name the abx contraindicated w/ CrCl <60

nitrofurantoin

Name 2 anti-invectives contraindicated w/ CrCl <50

TDF containing products (Complera, Delstrigo, Stribild, Symfi)

voriconazole IV (d/t vehicle)

Name 3 drugs highlighted to be contraindicated w/ CrCL <30

TAF containing products (Biktarvy, Descovy, Genvoya, Odefsey, Symtuza)

NSAIDs

dabigatran (DVT/PE)

T/F: metformin is safe to start in patients w/ CrCl <45

F; can continue use if already on when CrCl <45 but have to stop if drops <30

T/F: meperidine, rivaroxaban, and SGLT2i have CrCl cutoffs

T; product specific

Name the 4 lab values that need to be monitored in CKB-MBD

phosphorus, PTH, Ca, vit D

chronic hyperphosphatemia causes secondary hyperparathyroidism

T/F: ferric sulfate (phosphate binder) avoids systemic absorption

F, it is absorbed systemically

Name the 3 major points of origin of problems with Ca, phosphate, vit D, PTH, and anemia in CKD

1. reduced renal clearance of phosphate

2. inability for kidneys to activate vit D to the active 1,25-dihydroxy vitamin D

3. educed renal production of EPO

What is the dosing schedule for each phosphate binder?

a. aluminum hydroxide (suspension)

b. calcium acetate (tab, cap, suspension)

c. calcium carbonate (tab, chew tab)

d. sucroferric oxyhydroxide (chew tab)

e. ferric citrate (tab)

f. lanthanum carbonate (chew tab, powder)

g. sevelamer carbonate (Renvela; tab, powder)

h. sevelamer HCl (Renagel; tab)

a. aluminum hydroxide (suspension) — TID w/ meals

b. calcium acetate (tab, cap, suspension) — TID w/ meals

c. calcium carbonate (tab, chew tab) — TID w/ meals

d. sucroferric oxyhydroxide (chew tab) — TID w/ meals

e. ferric citrate (tab) - TID w/ meals

f. lanthanum carbonate (chew tab, powder) — TID w/ meals

g. sevelamer carbonate (Renvela; tab, powder) — TID w/ meals

h. sevelamer HCl (Renagel; tab) — TID w/ meals

ALL TID W/ MEALS; SKIP DOSE IF ATE MEAL W/O BINDER

SEPERATE ADMIN OF ANY W/ CATION FROM LEVOTHYROXINE, QUINOLONES, & TETRACYCLINES TO AVOID CHELATION

T/F: cinacalcet (Sensipar) can be used in CKD patients not on dialysis

F, calcimimetics are only indicated in dialysis patients to reduce PTH

Name the drug that is the active form of vit D3

calcitriol

Serum calcium is reduced or increased with the following class of drugs?

a. vit D analogs (ex. calcitriol, calcifediol, doxercalciferol, paricalcitol)

b. calcimimetics

a. increased —> vit D analogs cause hypercalcemia

b. decreased —> calcimimetics cause hypocalcemia

Name the Hgb cutoffs for when ESAs can be initiated and when they need to be stopped, as well as the specific cardiovascular risk associated with/ ESAs and higher Hgb

*initiate only if Hgb <10

*hold/stop if Hgb >11

HTN, thrombosis

What lab panel must be collected and corrected if abnormal in order for ESAs to work?

iron panel (can only make RBCs if adequate iron is present)

what is the general K+ level to be concerned about hyperK+ on the exam

>5

FITB: diabetics are at _______ risk of hyperkalemia because ______ deficiency reduces the ability to push K+ _______

increased, insulin, intracellular

What are the overall Tx options for HepA

supportive care; prevent w/ vax

What are the overall Tx options for hep B?

PEG-IFN or NRTI (TDF or TAF or entecavir or lamivudine but not pref’d); prevent w/ vax

What are the overall Tx options for hep C?

DAA combo or DAA combo + RBV (in cirrhosis or prior Tx failure); no vax but can cure w/ Tx

8-12 wks of Tx

DAA combo should be 2-3 drugs w/ dif MOAs

What are the 2 DAA combo drugs w/ indication for HCV Tx in Tx-naiive patients without cirrhosis or with compensated cirrhosis, regardless of genotype

Mavyret (glecaprevir/pibrentasvir) 3 tabs once daily w food x 8 weeks

Epclusa (sofosbuvir/velpatasvir) 1 tab once daily x 12 weeks

previr = NS3/4A protease inhibitor FOOD

asvir = NS5A replication complex inhibitor

buvir = NS5B polymerase inhibitor

*genotype dependent drugs = Harvoni, Vosevi, Zepatier

boxed warning for all DAAs

HBV reactivation —> test for HBV before starting DAA

Name 3 pearls for Epclusa

1. sofosbuvir intrx w/ amiodarone (symptomatic bradycardia)

2. dispense in original container

3. avoid/minimize acid suppression therapy (antacids, H2RAs, & PPIs)

FITB: stronge CYP3A4 _______ should be avoided with all DAAs

inducers

How do DAAs impact statin levels? blood glucose levels?

increase statin levels (Mavyret contraindicated w/ atorva, lova, simva)

quick drop in viral load can improve glucose metabolism and cause hypoglycemia

T/F: ribavirin mono therapy is a safe and effective Tx to cure hep C

F, never use as monotherapy for hep C

What type of patient populations would ribavirin be contraindicated or cautioned in according to the boxed warning?

pregnant, significant or unstable cardiac disease d/t risk of delayed onset hemolytic anemia

T/F: only females on ribavirin carry the risk of teratogenicity

F, males carry teratogenic risk too —> 2 forms of contraception needed during Tx and 6-9 months after

Why do we test patients with hep B for HIV before Tx?

NRTI monotherapy to Tx hep B can cause HIV resistance if the person also has HIV

T/F: NRTI monotherapy is safe and effective for Tx hep B?

T

Name 2 boxed warnings for hep B NRTIs

fatal lactic acidosis & severe hepatomegaly w/ steatosis

HBV exacerbation upon Tx DC

What is the CrCl cutoff for needed dose or frequency adjustment of hep B NRTIs?

<50

FITB: entecavir (Baraclude) must be taken on a ______ stomach

empty

FITB: TDF (Viread) and TAF (Vemlidy), must be dispensed ______

in the original container

CYP ______ cannot be used with TAF

inducers (phenobarbital, phenytoin, oxcarbazepine, rifampin, st johns wort)

What is the dosing schedule of PEG-IFN in chronic hep B and what are the boxed warnings?

SC once weekly (thanks PEG);

can cause or exacerbate neuropsych/autoimmune/ischemic/infections disorders

also causes myelosuppression, increased LFTs, flu-like syndrome

What are the 2 most common causes of cirrhosis in the US?

hep C and alcohol

What are the 4 overall complications from cirrhosis

ascites

portal HTN

esophageal varices

hepatic encephalopathy

albumin will increase or decrease in liver disease?

decrease since it is a protein produced by the liver

how are prothrombin time and INR impacted in liver disease?

both increase (so increase the risk of bleeding)

How do the Child-Pugh and MELD scores work?

Child-Pugh is a scale of 0-15 that correlates to class A, B, or C; higher number = increase severity of liver disease

MELD = model for end-stage liver disease, score 6-40; higher number = greater risk of death in the next 3 months

____ is a hepatotoxic natural product; ___ is a natural product used in liver disease although limited efficacy

kava; milk thistle

avoid NSAIDs in people w/ cirrhosis d/t risk of ______

bleeding and decompensation

drugs with boxed warning for liver damage

APAP

amiodarone

isoniazid

ketoconazole

MTX

nefazodone

nevirapine

PTU

valproic acid

zidovudine

____ is the splanchnic vessel- specific constrictor used for bleeding varies, while ____ is the non-selective constrictor used for bleeding varices

octreotide (somatostatin analog), vasopressin (antidiuretic hormone analog)

What 2 abx are used for PPX in patients w/ cirrhosis and an active variceal bleed?

CTX or cipro

what are the 3 non-selective BB in portal HTN and their dosing schedule

nadolol (Corgard) - once daily

propranolol (Inderal LA, Inderal XL) - BID

carvedilol (Coreg) - once daily to BID

What are 3 Tx methods for hepatic encephalopathy

lactulose (converts ammonia to ammonium for excretion)

rifaximin as add on (decreases Ammonia production by inhibiting activity of urease-producing bacteria)

animal protein restriction in the diet (for everyone)

What are the 2 diuretic therapy methods used in ascites?

1. spironolactone monotherapy

2. spironolactone + furosemide in 100:40 ratio for K+ balance titrated to weight loss of 0.5kg/day

*furosemide monotherapy is ineffective

when does albumin need to be given in ascites Tx?

when paracentesis is performed to avoid progression to hepatorenal syndrome and avoid paracentesis-induced circulatory dysfunction from the significant fluid shift

What is the 1st line abx for SBP and what are the 2 secondary PPX Tx options?

CTX (covers strep and enteric G(-)); oral cipro or SMX/TMP

What is the time period required between IVIG (or other antibody) administration and live vaccine administration?

if antibody 1st, then wait >/=3 months to give live vaccine

if live vaccine 1st, then wait 2 weeks to give antibody

At what age can live vaccines be given to children and what is the reasoning for the delay?

12 months since this is the time when antibodies given by the mother before birth are gone and therefore will not be present to counteract a live vaccine

exception is rotavirus vaccine bc it’s proven efficacious even in infants w/ maternal antibodies

if two different live vaccines are not given on the same day, how much time needs to pass between administration?

4 weeks

Name the 2 egg-free flu vaccines w/ appropriate ages

Flucelvax (>/= 6 months)

Flublok (>/= 18 years)

T/F: children <2 yo have good immune response to polysaccharide vaccines

F; this is why <2 yo cannot get the PPSV-23 (Pneumovax 23) vaccine, and rather need to get the conjugate vaccines PCV15 (Vaxneuvance) or PCV20 (Prevnar 20)

T/F: travelers diarrhea is most commonly cause by viral pathogens

F, most commonly bacterial (e coli being the most common)

What is the PPx of choice for traveler’s diarrhea

bismuth subsalicylate 524-1050mg PO QID w/ meals and HS; abx PPx (rifaximin pref’d, azithro, rifamycin) only if immunocompromised or significant comorbidities exist

Outline the Tx pathways for traveler’s diarrhea

mild: loperamide or bismuth (loperamide more effective)

moderate: loperamide ± abx (low resistance - azithro OR quinolone; alt - rifaximin)

severe (including dysentery ie bloody stool): azithro pref’d; alt if no dysentery- quinolone OR rifaximin OR rifamycin

Name the type and route of administration for these typhoid vaccines:

1. Vivotif

2. Typhim Vi

1. oral, live (give >1 week before travel)

   1. IM, inactivated (give >2 weeks before travel)

Cholera is a bacterial infection characterized by this type of stool, and has a (live/inactivated) vaccine, Vaxchora, available to be taken (route) >/=10 days before travel

rice-water stool, live, orally

What is the guideline for polio vaccine boosters when traveling to endemic regions?

a single lifetime booster dose in previously vaccinated adults given at least 4 weeks before travel to the endemic area

What are the 2 meningococcal vaccine options recommended when traveling to hyper endemic or epidemic areas of meningococcal meningitis?

Menveo and MenQuadfi (both menACWY); no rec for men B vax

What 5 pathogens do mosquitoes act as vectors for?

dengue - best way to avoid is mosquito prevention since the vax is only given to those w/ previous dengue infection

malaria

Japanese encephalitis

yellow fever

zika virus

Name the quick start (3) and advanced start (3) regimens for malaria PPx

quick start (1-2 days before travel, taken daily; avoid in pregnancy):

• doxycycline

• atovaquone/proguanil

• primaquine

advanced start (1-2 weeks before travel, taken weekly; safe for pregnancy/children):

• chloroquine

• mefloquine

  • tafenoquine (initially loading dose, then weekly)

T/F: NSAIDs/aspirin increase the risk of bleeding in yellow fever and therefore cannot be used

T

the yellow fever vaccine, YF-VAX, is (live/inactivated) and must be given at least ___ days before travel. it is contraindicated in people with hypersensitivity to ___ or who are _______

live, 10, eggs, immunocompromised

No vaccine for Zika virus exists, but it can be prevented by 2 methods

avoid contact w/ mosquitos

use condoms during sexual encounters w/ people possibly infected

zika virus causes birth defects — pregnant women should not travel to endemic areas and male partners should use condoms or avoid sex w/ their pregnant partners

What allergy is a contraindication to acetazolamide for altitude sickness?

sulfa

Wetting agents (levigating agents) are used to combine ____ & ____. ____ is a levigating agent commonly used for lipophilic compounds, while ____ or ____ are used for aqueous compounds

solids & liquids. mineral oil, glycerin, propylene

What is a suspension, and what are some names for suspending agents?

Suspension = solid dispersed in a liquid; dispersants, dispersing agents, plasticizers (sorbitol for gelatin capsules)

What are Ora-Plus, Ora-Sweet, and Ora-Blend?

Ora-Plus - bland suspending agent that requires flavoring

Ora-Sweet - the flavoring, similar to simple syrup

Ora-Blend - mix of plus and sweet

Sweet and Blend are available as sugar-free, sweetened w/ saccharin

T/F: simethicone is a foaming agent (surfactant) used to foam compounds

F, simethicone is an anti-foaming agent to prevent foaming

PEG and poloxamer serve 2 purposes

drug delivery vehicles AND surfactants

why? both hydrophilic and lipophilic partsW

What is an emulsion?

mixture of 2+ immiscible liquids; the surfactant is called an emulsifier

can be o/w (oil in water)

or w/o (water in oil, generally unpalatable and only used topically)

emulsifier is determined by the hydrophilic-lipophilic balance (HLB)

What is the HLB range for an emulsifier to be used in w/o and o/w emulsions?

w/o: 0 - <10 (more lipophilic) ex: Span 65 has HLB of 2.1

o/w: >10 - 20 (more hydrophilic) ex: PEG 400 has HLB of 11.4, Tween 85 has HLB of 11

Example of a binder excipient

starch paste

Example of diluent/filler excipients

tabs/caps: lactose, starches, calcium salts, cellulose powder

liquids: water, glycerin, alcohol

topicals: petrolatum, mineral oil, lanolin

Examples of disintegrant excipients

alginic acid

cellulose

starchesE

Examples of flavoring/coloring excipients

flavoring:

aspartame

glycerin

dextrose

mannitol

sorbitol

xylitol

stevia

coloring:

D&C red no 3

yellow no 6

caramel

ferric oxide (red)

Examples of lubricant excipients (ie glidants in powders)

magnesium stearate

Examples of preservative excipients

chlorhexidine

povidone iodine

sodium benzoate/benzoic acid

benzalkonium chloride

sorbic acid/potassium sorbate

methyl/ethyl/propyl parabens

EDTA

thimerosal

cetylpyridinium chloride

Examples of buffers to maintain acidic pH

hydrochloric acid

acetic acid/sodium acetate

citric acid/sodium citrate

Examples of buffers to maintain alkaline pH

sodium hydroxide

boric acid/sodium borate

sodium bicarbonate/sodium carbonate