ADT Final Flashcards
define Pharmacobezoar
A mass of undissolved drug(s) in the gastrointestinal tract.
effects of Pharmacobezoar
Causes erratic absorption.
Prolongs absorption phase.
examples of Pharmacobezoars
theophylline, diltiazem, carbamazepine.
Sodium Bicarbonate and Cardiotoxicity mechanism
Inhibition of calcium sodium channels.
Sodium bicarbonate reduces free _____ concentrations
TCA
t/F Binding to plasma proteins or tissues makes drug inactive.
true
T/F Increasing plasma concentration of drug can saturate protein binding.
true
how does low blood pressure effect clearance?
impairs clearance
Antidote for Methanol Poisoning
MoA?
fomepizole
Alcohol dehydrogenase inhibitor.
Indications for Hemodialysis (HD)? (AEIOU)
A = Metabolic Acidosis.
E = Electrolyte disturbances.
I = Intoxications.
O = Fluid Overload.
U = Uremia.
As free drug concentration increases, glomerular filtration ________, leading to __________ renal drug clearance.
increases, increased
Activated charcoal can be used to reduce the _______ of a drug that remains in the stomach.
toxicity
Whole bowel irrigation can help clear ______.
toxins
Intrinsic Clearance: The maximum ability of the liver to irreversibly ________ a drug by all pathways.
remove
As the rate of metabolism ________, the plasma drug concentration increases.
increases
As the rate of metabolism increases, the plasma drug concentration _________.
increases
higher Vmax = ______ drug metabolized
more
_______ Vmax = more drug metabolized
higher
Km is the affinity where a lower value requires _____ drug concentration for half-maximal metabolism, where Higher Km requires ______ drug concentration for equivalent half-maximal metabolism.
less,more
High affinity = _______ intrinsic clearance, Low affinity = ______ intrinsic clearance.
faster, slower
_____ affinity = Faster intrinsic clearance, ____ affinity = Slower intrinsic clearance.
high, low
Clearance is affected by changes in ______ binding.
protein
Causes of Altered Hepatic Blood Flow:
CHF, cirrhosis, sepsis, shock, mechanical vent, positive end-expiratory pressure (decrease Q). Vasopressors (increase Q).
what does Q mean?
Q is equivalent to?
liver blood flow/drug delivery to liver.
clearance
ffp = 1 - E, where E= 0 means ____ drug escapes first-pass metabolism (_____ bioavailability). and E=1 means ___ drug escapes first-pass metabolism (_______ bioavailability).
all, good
no, poor
define Vd
Amount of drug binding in plasma vs. in tissue.
Increased Vd indicates the drug is _____ bound to proteins in tissue than plasma.
more
_______ Vd indicates the drug is more bound to proteins in tissue than plasma.
increased
If intrinsic clearance decreases, the amount of drug that escapes first-pass metabolism (ffp) ________.
increases
If intrinsic clearance _______, the amount of drug that escapes first-pass metabolism (ffp) increases.
decreases
Synonymous mutation type means it’s a ______ mutation
silent
Non-synonymous mutation type means ________ or _______ mutation
missense, nonsense
define Pharmacogenetics:
Drug response related to a single or a few ______.
genes
define Pharmacogenomics:
Study of variations of all ___________ related to drug response.
DNA and RNA
list the “Three Rights”
Right Person: Who benefits from the med.
Right Test: Don’t do the wrong one!
Right Interpretation: Give genetic info and inform physicians to make appropriate management decisions.
How many chromosomes are in the human body?
46
How many base-pairs are in the entire genome?
3.2 billion
What percentage of the genome makes proteins?
~1%
Avoid prescribing abacavir in patients with __________ mutation.
HLA-B*5701
Avoid prescribing phenytoin or carbamazepine in patients with _________ mutation.
HLA-B*1502
Mutations in CYP2D6 are common in ________ and can cause _________ metabolism.
Africans, ultrarapid
Mutations in CYP2C19 are most common in ________, causing _____ metabolism of drugs via the 2C19 pathway, such as _________(drug).
Oceanians, poor, clopidogrel
CYP2C19 polymorphism requires a _______ in the initial warfarin dose.
VKORC1 polymorphism also requires a _______ in the initial warfarin dose.
reduction, reduction
Main Resource for Pharmacogenetic Information?
The Clinical Pharmacogenetics Implementation Consortium (CPIC).
what is a major SE of Azathioprine, mercaptopurine, thioguanine.?
Myelosuppression
if low TPMT: Reduce daily dose by _____, frequency to _____ times weekly.
if intermediate TPMT: Reduce dose by ______
if high TPMT: ______ dosing
10X, three
30-80%.
normal
Thioguanine with low NUDT15 activity: ______ dose by 25%.
reduce
Thioguanine with low NUDT15 activity: Reduce dose by _____
25%
Irinotecan Dose Reduction:
Patients Homozygous for UGT1A1*28 allele: Start with ____ of normal dose.
70%
Irinotecan Dose Reduction:
Patients Homozygous for _______ allele: Start with 70% of normal dose.
UGT1A1*28
CYP2D6 and Tamoxifen:
Poor metabolizer (0): ______ concentration.
Intermediate metabolizer (0.5): _____ concentration.
Normal/Intermediate (1): _____ concentration.
Normal (1.5-2): ______ concentration.
Ultrarapid (>2): ______ concentration.
lower
lower
lower
normal
normal
Avoid CYP2D6 inhibitors with tamoxifen (bupropion, fluoxetine, paroxetine, quinidine, terbinafine).
.
Tissue-Agnostic Agent: A drug that targets specific ________ across multiple cancer types.
biomarkers
The two tissue-agnostic agents are Larotrectinib and Entrectinib, which treat _____ solid tumors
NTRK-fusion
what does SMMART do?
allows tracking of cancer progression over time to adjust drug combinations before resistance develops.
phenytoin is used to treat Tonic-clonic seizures, Partial seizures, Generalized status epilepticus and seizure prevention.
what is the MoA?
Increases efflux or decreases influx of sodium ions and Prolongs inactivation of voltage-gated sodium ion channels.
what causes purple glove syndrome?
large- multiple doses of IV phentoin
long-term use of phenytoin may lead to?
lupus erythematosus
what Alters phenytoin plasma binding due to displacement?
hyperbilirubinemia, jaundice, liver disease, renal dysfunction
what Alter phenytoin plasma binding due to hypoalbuminemia?
liver disease, nephrotic syndrome, burns, trauma, malnourishment, elderly.
what drugs influence plasma protein binding of phenytoin?
Warfarin, valproic acid, aspirin (>2g/d), NSAIDs.
Hypoalbuminemia ______ phenytoin Vd.
increases
Coadministration of Valproic Acid ______ Vd and fu plasma of phenytoin.
increases
Renal failure ________ the Vd of phenytoin.
increases
Phenytoin is a ______(extraction) drug.
Protein binding changes that increase fu would cause an _______ in Vd and clearance, with ______ in t1/2.
low E
increase, no change
phenytoin Hypoalbuminemia increases fu plasma, therefore Css,total _________.
decreases
phenytoin Hypoalbuminemia ________ fu plasma, therefore Css,total decreases.
increases
Phenytoin At steady-state, the rate of drug in ______ the rate of drug out.
aka
Rate of drug ________ = Rate of drug elimination.
equals
administration
for phenytoin: Rate of drug administration = Rate of drug ________.
elimination
For oral LD of phenytoin, only ______ can be absorbed at a time.
400mg
what are Initial Immunosuppressants for Organ Rejection Prevention
Thymoglobulin, alemtuzumab, rituximab, basiliximab.
what are Maintenance Immunosuppressants
Cyclosporine, tacrolimus, sirolimus, everolimus, mycophenolate, azathioprine, methylprednisolone, prednisone.
what is the Treatment for Acute Rejection?
Thymoglobulin
Adverse Effects of Cyclosporine
Hirsutism, nephrotoxicity, hypertension, gingival hyperplasia.
Adverse Effect of Mycophenolate?
Gastrointestinal hemorrhage.
Mycophenolic acid is _______.
teratogenic
what drug is an IL-2 inhibitor?
Basiliximab
what drugs Decrease transcription of IL-2?
Cyclosporine, tacrolimus.
Azathioprine Combination with allopurinol causes?
severe myelosuppression
avoid combining azathioprine with ACE-Is due to?
increased risk of myelosuppression.
side effects of azathiioprine?
Pancytopenia (leukopenia, anemia, thrombocytopenia), alopecia, hepatotoxicity, pancreatitis.
SE;s of sirolimus?
Hyperlipidemia, pancytopenia, mouth ulcers.
SEs of tacrolimus?
Nephrotoxicity, hyperglycemia.
Definitions:
Prematurity:
Neonates:
Infants:
Children:
Adolescents:
Prematurity: Born before 37 weeks.
Neonates: Younger than 28 days of life when born full term.
Infants: 28 days to 1 year old.
Children: 1-11 y/o.
Adolescents: 12-16 y/o.
Children have ______ clearance.
increased
Absorption: ______ in neonates and young infants, ________ Tmax.
slower, prolonged
Neonates have _______ gastric pH, ________ bioavailability of drugs like penicillin and ampicillin.
elevated, increasing
Children have ________ percutaneous absorption.
enhanced
Neonates and young infants have _______ bioavailability of rectal metabolism.
enhanced
intramuscular Absorption: ______ in infants due to ______ blood flow.
reduced, reduced
Infants have less body fat, so highly lipid-soluble drugs are distributed _____.
less
Drugs renally eliminated have _______ clearance in neonates and ______ clearance in young children (older than 1 year).
decreased, increased
Promethazine is contraindicated under?
2 y/o
what drug is contraindicated in children under 2?
promethazine
Ceftriaxone contraindicated in _______ (under 28 days of age).
neonates
what cephalosporin is contraindicated in neonates?
ceftriaxone
FDA Warning: Not to use ______ in children under 12.
codeine
Avoid drugs containing benzyl alcohol for kids.
Main ones to watch for are ________ saline and water.
bacteriostatic
Avoid drugs containing __________ for kids.
Main ones to watch for are bacteriostatic saline and water.
benzyl alcohol
