PHA 411 Final Exam: Key Terms & Definitions in Medicine

Name 4 drugs in the amino glycoside class

-gentamicin

-tobramycin

-amikacin

-plazomicin

-streptomycin

-neomycin

Name 4 organisms aminoglycosides can be used to treat

gram-negative

-enterobacterales

-acinetobacter

-pseudomonas aeruginosa

-M. catarrhalis

-H. influenzae

gram-positive

-staph

-strep

-enterococci

What is meant by gram-positive synergy?

-combo of aminoglycoside an cell wall-active agents

-have a greater effect against bacteria rather than alone

Name 2 adverse effects of aminoglycosides

-nephrotoxicity

-ototoxicity

What are risk factors for nephrotoxicity?

-dehydration

-use with diuretics, ACEIs, NSAIDs

-age, CKD, diabetes, liver disease

-high trough levels (>1-2 mg/L)

What are risk factors for ototoxicity?

-duration of therapy, cumulative dose, average daily dose

-high peak levels

-loop diuretics

Why is there a boxed warning regarding the use of aminoglycosides in patients on neuromuscular blockers or those that have neuromuscular disorders?

-paralytic agents

-can lead to prolonged paralysis

Is the volume of distribution of aminoglycosides higher or lower than vancomycin?

-higher

What is the primary elimination route for aminoglycosides?

-primarily renal (85-95%)

-mostly via glomerular filtration

What is the post-antibiotic effect?

-persistent suppression of bacterial growth occurring after the drug concentration drops below the MIC

What is the optimal peak:MIC ratio for aminoglycosides?

10:1

Name 3 advantages to large-dose extended interval dosing of aminoglycosides

-high peak=max bactericidal activity

-low trough=less nephrotoxicity

-optimizes post-antibiotic effect

-easier to dose and monitor

When should large-dose extended interval dosing of aminoglycosides not be used?

-acute kidney injury

-synergy dosing for enterococcal endocarditis

-unpredictable Vd/CL

-cystic fibrosis

-end-stage renal disease/dialysis

What are monitoring parameters for aminoglycosides?

Clinical

-getting better

-temperature curve, WBC, improvement in symptoms, radiologic evidence of improvement

Safety

-kidney function

(SCr, BUN, urine output)

-Evidence of ototoxicity

(vertigo, ataxia, tinnitus, hearing loss)

What are the timing of levels for aminoglycosides?

peak

-30-60 minutes after end of infusion

trough

-0-30 minutes before dose

What is the name of a common LDEI amino glycoside dosing nomogram with a dose of 7 mg/kg?

Hartford Nomogram

-gentamycin

-tobramycion

What is Bayesian modeling?

-algorithm using the patient's own data and previous population values to generate more precise estimates of a patient's parameters

-typical PK equations to choose the best dose and predict levels/AUC

What antibiotics can be monitored using Bayesian monitoring?

-aminoglycosides

-vancomycin

Name 3 organisms that vancomycin can be used to treat

-methicillin-resistant staphylococcus aureus

-enterococci

-streptococci

-clostridioides difficile

What are risk factors for vancomycin nephrotoxicity?

-higher doses

-higher trough concentrations

-higher overall exposure

-use with other nephrotoxic drugs

How can vancomycin flushing be managed?

-slowing the infusion rate

-introducing an antihistamine

What is the max infusion rate of IV vancomycin?

-1 g/hr for adults

Why is vancomycin usually given IV?

Vancomycin has poor oral absorption

What is one infection for which vancomycin is given orally?

-C. difficile

-GI infection

In what populations can the Vd of vancomycin often be increased? Decreased?

Increased

-critically ill

-severe kidney impairment

Decreased

-obesity

The 2020 IDSA/ASHP/PIDS/SIDP vancomycin monitoring guideline apply to treating what type of infections?

MRSA infections

Which pharmacodynamic parameter best correlates with vancomycin efficacy?

-AUC/MIC

-ratio of total exposure over 24 hours to MIC

Name 2 strategies for dosing and adjusting vancomycin

-trough based

-AUC based

What are the goals of trough based?

15-20 mg/L

-serious MRSA infections

-no longer recommended due to efficacy and nephrotoxicity

10-15 mg/L

-adequate for less severe MRSA/other infections

What are the goals of AUC based?

AUC (0-24):MIC of 400-600

-assumes MIC <1 mg/L

Which strategy is preferred and why?

-AUC

(Bayesian and AUC calculation)

What is MIC?

minimum concentration needed to be effective

What MIC was assumed when choosing the goal AUC in the guidelines?

< 1 mg/L

What dosing weight should be used for vancomycin?

actual body weight

What are typical loading doses for vancomycin in adults?

-20-35 mg/kg intermittent infusion

-obesity: 20-25 mg/kg

-acute kidney injury: 20 mg/kg

What are typical maintenance doses for vancomycin in adults?

-15-20 mg/kg every 8-12 hours as intermittent infusion

-obesity: <4500 mg/day

What is a typical maintenance dose in children?

-40 mg/kg/day

-split doses every 4-6 hours

In what situations would a modified mg/kg dose be used?

-obese (BMI >30)

-CrCl <30 mL/min

-IHD (hemodialysis)

-CRRT

In what scenarios could a trough-only monitoring strategy be considered for vancomycin?

-limited resources facilities

-patients with vascular access issues

-challenging patient care factors

-non-MRSA or non-severe MRSA infections

-acute kidney injury and dialysis

If a patient's vancomycin trough level is significantly lower than the goal, is better to increase dose by 250 mg or increase the frequency of dosing?

Increase the frequency of dosing

When are vancomycin levels typically drawn for patients receiving intermittent hemodialysis?

levels drawn before the start of hemodialysis

When should a hemodialysis patient be redosed?

-at the end of the session

-higher dose if given during the last 60-90 minutes

-higher dose if 72 hr. vs. 48 hr until next session

What are the advantages of Bayesian modeling for vancomycin?

-steady state not required

-can be done using only a single drug level

-accuracy theoretically improves as more data added to the model

What are the disadvantages of Bayesian modeling for vancomycin?

-cannot be done by hand

-software programs costly

-could be inaccurate if patient does not fit the chosen model

What are the monitoring parameters for vancomycin?

-calculate AUC

-SCr at least every 72 hours, daily if unstable

-CBC at least weekly

-culture and sensitivities

-clinical improvement

When should levels be obtained for patients on antipileptics?

-trough levels drawn before the morning dose

Phenytoin/Fosphenytoin

- >2 hr after end of then IV infusion

- >4 hr after for IM injection

-oral 24 hr after LD

What are some common adverse effects of antiepileptics?

-drowsiness

-dizziness

-slurred speech

-blurry vision

-serious skin reactions

-lab abnormalities

What is the difference between a "reference range" and an "individual therapeutic range"

reference range

-best response

-general guide

individual therapeutic range

-after clinical response is reached

-used to individualize patient's therapy/dosing

What are reference total and free level ranges for phenytoin?

Total

- 10-20 mg/L

Free

- 1-2 mg/L

Which antiepileptics are inducers?

-phenobarbital

-carbamazepine

-phenytoin

What do antiepileptics do to the concentration of drugs that they interact with?

-decrease concentration

What are the max adult infusion rates of phenytoin and fosphenytoin?

Phenytoin

50 mg/min

Fosphenytoin

150 mg PE/min

What are severe adverse effects of IV administration?

Propylene glycol excipient

-cardiac toxicity

-hypotension, arrythmias

Extravasation

-purple glove syndrome

How does chronic kidney disease affects phenytoin free fraction?

-increases phenytoin free fraction

-low albumin levels

-displacement by uremic substances

-binding site alteration

What is meant by Michaelis-Mentin/capacity-limited/saturation kinetics?

-dose dependent non-linearity

-steady state is not proportional to dose

-time to steady state may vary greatly

-make adjustments to dose in small increments

A deficiency in CYP2C9 would lead to (blank) risk of phenytoin toxicity

-increases

-SJS/TEN

What percentage of digoxin is eliminated renally?

- 50-70%

-via glomerular filtration

What is the most appropriate dosing weight for digoxin?

ideal body weight

The accepted therapeutic range for digoxin in heart failure is (blank) than the range for atrial fibrillation.

lower

HF: 0.5-0.8 mcg/L

Afib: 0.8-2 mcg/L

How long does it typically take to reach a steady state digoxin concentration?

-5 half lives

-typically 5-7 days

How long after a dose should we wait to draw a digoxin level?

-at least 6-8 hours after oral or IV dose

What are risk factors for digoxin toxicity?

-decreased kidney function

-polypharmacy/ interacting drugs

-increased age

-multiple comorbid medical conditions

-electrolyte imbalances

What are the monitoring parameters for digoxin toxicity?

-arrythmias

-bradycardia

-vomiting/diarrhea

-heart rate

-ECG

-SCr

-K, Mg, Ca

What drug can be used to acutely treat digoxin toxicity?

-Digoxin immune Fab

-patient must have symptoms

-calculated based on amount ingested and steady state serum concentrations

The risk of systemic exposure from topical products is highest in which pediatric population?

Neonates

(birth to 4 weeks)

What is the concern with the use of codeine and tramadol in pediatric patients?

-pharmacogenomic variation in CYP2D6 activity

-poor metabolizers will not convert to active drug

-ultra rapid metabolizers will increase conversion to active drug

Renal elimination of digoxin, aminoglycosides, and vancomycin is (blank) in children and adolescents.

faster

What equation is commonly used to estimate kidney function in children aged 1-16?

-Bedsaide Schwartz equation

-eGFR=0.413(L/SCr)

Why is empiric dosing of aminoglycosides higher in cystic fibrosis patients?

-potential for reduced oral absorption

-larger apparent Vd

-increased metabolic and renal clearance

-altered protein binding

High risk medications in older adults

-drugs with narrow therapeutic ranges

-diabetes medications

-anticoagulants

-cardiac medications

-psychotropic medications

-pain medications

Examples of drugs with narrow therapeutic ranges

-phenytoin

-theophylline

-AGs

-lithium

Examples of diabetes medications

-sulfonylureas

-long acting

Examples of anticoagulants

warfarin

Examples of cardiac medications

-digoxin

-blood pressure meds

Examples of psychotropic medications

-benzodiazepines

-tricyclic antidepressants

Examples of pain medications

-opioids

-muscle relaxants

-antispasmodics

Pharmacokinetic changes in absorption in aging

DECREASED

-gastric acid production

-gastric emptying rate

-GI motility

-GI blood flow

-absorptive surface

Pharmacokinetic changes in distribution in aging

DECREASED

-total body mass

-body water percentage

-albumin/altered binding

-altered tissue perfusion

INCREASED

-body fat percentage

Pharmacokinetic changes in metabolism in aging

DECREASED

-liver mass

-liver blood flow

-liver metabolism

-enzyme activity

-enzyme induction

Pharmacokinetic changes in elimination in aging

DECREASED

- renal blood flow

-glomerular filtration

-renal tubular secretion

Altered tissue sensitivity related to:

-receptor number

-receptor affinity

-second messenger function

-cellular response

-cellular nuclear response

Characteristics of good IV to PO candidates

-good bioavailability

-Similar PK

-well tolerated

Considerations when switching IV to PO

-GI issues

-CNS issues

-CV issues

-Infection issues