pharm / ethics / stats Flashcards
what is the bioavailability with IV administration?
100%
What is ‘absorption’
Movement of a drug from site of administration into systemic circulation
which properties favor absorption?
lipid soluble, small molecule, unionized molecules
how can liver damage impact pharmacokinetics?
can decrease first-pass metabolism (making it more bioavailable), and decrease metabolism in general making it less ready to be eliminated
What is volume of distribution
the theoretical volume that would be necessary to contain the administered dose of drug at the same concentration observed in the plasma
V(d) - D (dose)/C (Concentration)
which drug qualities have a larger V(d)
lipophilic drugs, not protein bound drugs
PT babies have larger Vd
which proteins bind what kind of drugs
albumin binds acidic drugs, alpha 1 acid glycoprotein binds basic drugs
serum drug concentration includes which type of drugs
both bound and free
what is ‘metabolism’
biotransformation of a drug to a more water-soluble compound to facilitate elimination. Primarily occurs in liver. Primarily through cyp 450 system
what is ‘elimination’
removal of a drug or metabolite from the body, primarily via renal excretion
how should you change management in renail impairment?
decrease dose of drugs that are time-dependent (pnc), decrease interval of drugs that are concentration dependent (aminoglycosides)
describe first order elimination
drug clearance is based on concentration, fraction of drug cleared is constant.
looks like a curved line, linear when logarithmic
describe zero order elimination
constant amount of drug is cleared, fraction of clearance is variable.
looks like a linear line, curved when logarithmic
what is saturation kinetics
drugs can display zero order kinetics when they are overdosed or have poor clearance.
What are drugs contraindicated in breastfeeding
illicit drugs
radiopharmaceuticals
antineoplastic chemo agents
What is a relative infant dose?
dose that baby will receive in BM compared to maternal dose. If <10%, okay to use
how do you calculate loading dose
cv/Fs
what is the teratogenic effect of ACEi
renal dysfunction, iugr, skull ossification, fetal death
1st tri: CHD, CNS malformation
what is the teratogenic effect of ARBs
renal dysfucntion, limb contractions, fetal death, skull ossification defects
1st tri: data shows no risk
what is the teratogenic effect of AEDs
over all causes CHD, cleft lip/palate
carbamazepine: NTD, iugr, craniofacial defects, fingernail hypoplasia
lamotrigine: facial cleft
phenytoin: fetal hydantoin syndrome, facial cleft, hypertelorism, short nose, short neck, microcephaly iugr, mental deficiency
topiramate: oral cleft, hypospadias
valproic acid: NTD, cardiac defect, FHS features. most likely to have cognitive impairment*
teratogenic effetc of antiretroviral drugs?
zidovudine: chd, neuromitochndrial disease
teratogenic effects of cyclophosphamide
cns malformations, facial defects, absent digits, single coronary artery, imperforate anus, eye defects
teratogenic effects of cocaine
fetal loss, microcephaly, growth retardation, lmb reduction, urinary tract malformation, cardiac anomalies, placental abruption, poor neurodevelopment
teratogenic effects of ethanol
FAS, iugr, microscephaly, growth retardation, developmental delay, behavioral abnormalities
isotretinoin (Retinoids) teratogenic effect?
spontaneous aborption, cardiac defects (TGA), craniofacial defects, thypmic hypoplasia
lithium teratogenic effects
ebstein anomaly
teratogenic effect of methotrexate
NTD, anencephaly, microcephaly, iugr, craniofacial, craniosynostosis, ToF
misoprotstol teratogenic effect
NTD, limb defect, mobius syndrome
teratogenic effect of tetracycline
malformation of tooth enamel and bone
teratogenic effect of thalidomide
limb shortening defect, hearing loss, facial paralysis
teratogenic effect of warfarin
nasal hypoplasia, epipyseal stippling, limb/digit hypoplasia, pthalmic anomlaies, LBW, CNS defects
what is the correct concentration of iv epi
1:10,000 (0.1 mg/ml)
what is the MOA of aminoglycosides
inhibit protein synthesis by binding to 30S ribosomal subunit
MOA of penicillins and cephalosporins
b-lactam, bacteriocidal action by binding to penicillin binding proteins and inhibiting bacterial wall synthesis
MOA of vancomycin
inhibits bacterial cell wall synthesis by inhibiting peptidoglycan synthesis. bacteriocidal at higher doses.
MOA of amphotericin
binds ergosterol in fungal cell wall, leading to alteration of cell membrane permeability, leakage of cell components, cell death
MOA of fluconazole
decreases ergosterol synthesis in fungal cell membrane by interrupting fungal cytochorme p450 activity, inhibiting fungal cell membrane formation
moa of acyclovir
acyclovir triphosphate acts as inhibitor of HSV dna polymerase, inhibiting dna synthesis and viral replication
what is the adverse effect off SSRI
pphn, less commonly nas
where does furosemide act
on ascending loop of henle. binds to chloride receptor of na/k/cl channel
where does chlorothiazide act
what are the side effects
distal convoluted tubule by blocking na/cl transporter.
side effects of intrahepatic cholestasis, hyperglycemia, and hyperuricemia
what is the criteria for a level II nicu
> 32 weeks, >1500g, ventilation for <24 hours
What does STABLE stand for
sugar, temperature, airway, blood pressure, emotional support
what are six characteristics when implementing QI?
safety, effectiveness, patient centeredness, timeliness, efficiency, equitable
define perinatal death
fetal death + neonatal death (most commonly death >20 weeks + death <28d)
define perinatal mortality
still birth + neonatal death
define fetal death
death > 8 weeks (prior is an embryo) 8-20 miscarriage 20-27 early 28-term late >28 still birth
define infant death
death any time after birth - 365 days
define early neonatal death and late neonatal death
early <7 d, lat 7-28 days
define postneonatal death
28d-365d
what is parens patriae
common law that states gvt intervention on behalf of incompetent individual is allowed protecting safety and well being, may challenge surrogate authority
what is the doctrine of double effect
that something can have both good and bad effects. permissable if
1) action is not wrong
2) good effect is intended and direct result of action
3) good > bad
what are the four principles of ethical analysis?
beneficience, non-maleficence, autonomy, justice
what is EMTALA
law in 1986 that requires provision of emergency care to all, despite ability to pay
what is the difference between a systematic review and a meta-analysis?
Systematic Review: looks at the literature and identifies all articles meeting criteria to avoid inclusion bias.
Meta-analysis: Combines data from several articles to increase power of comparisons. Results in forest plot
What is the Receiver operating characteristic curve (ROC), AUC, and what are one the axis?
ROC curve is compares sensitivity and specificity of a test. The closer the ‘shoulder’ of the curve is to top left corner, the more perfect is.
AUC is the area under the curve. 1 is perfect, 0.5 is a flat line which is no better than chance.
X axis is 1-specficity, Y is sensitivity.
What is the likelihood ratio?
Looks at the chance of a positive or negative result based on sensitivity and specificty, use a nomogram once you know the LR.
LR calculation for positive change: sensitivity/(1-sp) (positive, positive is on top)
LR calculation for negative change: (1-sensitivity)/sp. (negative things is on top)
Tells you how much the odds of an outcome are changed if a test is positive/negative
which tests are affected by prevalence?
PPV and NPV. If prevalence is low, you are going to have increased FP, PPV will decrease. If prevalence is very high, you are going to have FN, NPV will decrease.
what is a hazard ratio
a specific type of relative risk comparing outcome rates
which studies use odds ratio vs relative risk
Odds ratio is used in case control studies. ‘A’ and ‘O’ are different. Odds are 1:1 so in the calculation it’s a/c over b/d
Relative Risk is used in cohort studies. Relatives are similar, just like ‘o’ and ‘o’ in cohort are similar. This is 1/2 in the calculation. a/a+b over c/c+d.
What are the three kinds of variables?
Continuous: ie weight
Ordinal: apgars
Categorical/nominal: ie. sex
when do you use t-test
continuous, normal data, two variables
when do you use x2 test
categorical. Fisher test if small sample size. ‘cat’, Chi, ‘fish’.
how does prevalence of an outcome affect odds ratio vs relative risk
If prevalence is low, OR and RR are similar.
If prevalence is high, O > R
What kinds of paired tests are used?
paired t test for continuous variables
McNemar test for pair categorigal variables (nemar like lemur, animals.. cat)
when do you use an anova test
3+ variables, just tells you if there is a difference in the mean (rejecting the null hypothesis)
when do you use non-parametric tests and what are examples
ordinal data, non-normal distribution
man whittney U and wilcox RANK sam test
what is the method to correct for multiple comparisons
Bonferroni method, divide the p value by number of comparisons.
what is standard error
measure of precision of an estimate of the mean of a population
what are the different stages of trials
preclinical: animal, looking at pharmacokinetics and adverse events –> results reported in investigational brochure. Apply for IND if want to go to clinical trials.
stage 1: 20-100 healthy individuals, looking for pharmacokinetics and adverse events in humans
stage 2: 20-300 individuals, looking at efficacy
stage 3: 300-3000 individuals, looking at efficacy and adverse events
stage 4: post-marketing looking at long term adverse events
what is ‘determination’
the ability of a test to correctly risk stratify. determined by ‘c statistic’ which = AUC in ROC.
what is ‘calibration’
a model’s ability to correctly predict outcome.
what is ‘coefficient of correlation’
-1 to 1, how well two variables correlate to each other
what is ‘coefficient of determination’
r squared: fraction of variation explained by variables in a regression model
what is absolute risk reduction?
a/(a+b) - c/(c+d)
when are OR and RR similar, when are they different?
when the outcome is rare, they are similar. When it is large, OR > RR
what are the axis in an ROC curve
sensitivity on y axis, 1-sp on x axis. making x=0 and y=infinity the best test.
what electrolyte imbalance can amphotericin cause?
hypomagnesemia
which side effect of aminoglycosides is reversible vs non-reversible?
renal toxicity (due to ATN) is reversible ototoxicity is irreversible
