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AG dosing Flashcards

1
Q

What is the minimum recommended infusion time for vanco? and why?

Some pts might need?

Dont be afraid to what?

Is Redman and allergy?

A

Minimum for 1 hour any faster puts you at risk for RedMans

Might need even longer infusion times of 90 minutes to 2 hours to avoid those reactions

Dont be afraid to extend the interval

Redman syndrome is not a true allergy

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2
Q

Albumin binds what types of drugs bases or acids?

Who does this more?

A

Acidic drugs

M=W

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3
Q

PK changes of Increased absorption and accelerated absorption

A

Increased- Increased AUC increased Cmax same Tmax

AUC Same, Cmax Same, Tmax shorter

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4
Q

What two hepatic Enzymes have increased activity in females?

What enzyme are they equal?

A

CYP3A4 conflicting studies.

CYP1A2

=CYP2C19

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5
Q

What is the killing of bacteria dependent on for AGs and quinolones?

What is the goal?

What ratio?

A
  • Concentration Dependent killing
  • The goal is to maximize peak concentrations for optimal killing without inducing toxicity
  • 10-12 Peak/MIC ratio
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6
Q

AUC is the same

Cmax is the same or decreases with food

Tmax increases with food?

What type of influence on absorption?

What are the two reasons for this?

A

AUC must be the same

Delayed absorption

Gastric Empyting Rate decreases

Gastric pH changes with food

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7
Q

Examples of drugs complexation interactions?

Examples of the last caused of reduced absorption

A
  • Drugs can complex with dairy products pectins, fibers, Tetracyclines chelate with Ca in milk
  • presence of a viscous chyme can make a physical barrier that reduces absorption
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8
Q

What are the 4 reasons drugs can have increased or accelerated absorption?

A
  1. Decreased First Pass metabolism
  2. P-glycoprotein transporter
  3. Drug Solubility/dissolution increase
  4. Gastric Emptying
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9
Q

Hydrophobic drugs VD m vs. women?

Example of one of these?

A
  • VD greater in women
  • Diazepam
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10
Q

What is Vancomycin Active against also specifically two things and its the drug of choice for what?

A
  • Active against Gram positive MRSA, drug of choice for MRSE
  • Resistance is increasing since 1990s
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11
Q

Where is vanco metabolized and excreted? What is the t1/2 in normal pts?

A

hepatic and biliary

5-8 hours

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12
Q

What type of pharmacodynamics does Vanco display?

How are peaks a troughs established?

A
  • Vancomycin is a time dependent killer and is bactericidal
  • Peaks and troughs are established based mostlyt on clinical observations
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13
Q

What 7 populations is Extended Interval Dosing Not adequately studied?

A
  • Children
  • Cystic Fibrosis
  • Burn pts
  • Dialysis pts
  • Pts with Ascites
  • Significant Renal Impairement
  • Pregnancy
  • Higher levels of dosing are not needed if treating uncomplicated UTIs since AGs are highly concentrated in this area.
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14
Q

What is traditional dosing for normal renal function?

What should be done if a pt is renally impaired?

Who gets a loading dose and what is it?

If the MIC is >? or if a pt has very good renal function and they are unable to get to their goal what do you do?

VANCO VANCO VANCO

A
  • 1g IV q12h
  • Pts with impaired renal function might need an increase in dosing interval based on the pts individual parameters
  • Loading dose in serioud ill pts of 25-30 mg/kg OTO?
  • If MIC is >2 or the pts has great renal function and still not at goal switch to linezolid
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15
Q

PD of Vanco it is what type of killer? Also called what?

Want to be above MIC for as long as possible.

A

Time-dependent killer also called concentration independent

Its about the time above MIC not how high you get

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16
Q

Decreased AUC Decreased Cmax Tmax is unchanged

What type of influence on absorption?

What are the 3 reasons for this? What is the first what explain it and examples given?

A
  • REDUCED absorption
  1. Drug instability- Eating a meal can lower the pH in the stomach benzylpen/erythromycin need to be taken separate from meals
  2. Drug Complexation Interaction
  3. Increased viscosity
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17
Q

What is the standard adult dosing for vanco? 2 ways

What are the larger doses sometimes used and who are the pts they are used for?

What do you need to monitor for Vanco?

A
  • 1 g IV q12h or 15 mg/kg IV q12h
  • In obese and infections of the bone or CNS you can sometimes use 1.25 or 1.5 stil q12h
  • Monitor trough at Css if therapy is still needed get trough right before 4th dose
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18
Q

Vanco Monitoring

When do you get troughs? What are the reasons to do so?

NEVER GET PEAKS

A
  • If the desired trough is 15-20 mg/l recommended for complicated infections
  • Therapy with other nephrotoxic agents
  • Unstable renal function better or worse
  • Long course of therapy more than 5 days
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19
Q

Normal pH of the urine?

What can increase pH of urine what can decrease pH what effect does this have on acidic and basic drugs

A
  • Increase pH Milk and veggies
  • Decrease high protein, meat and fish
  • Increase pH Inceases ionization of acids decrease reabsorption and decreasing t1/2
  • Increase pH decrease ionization of acids Increased reabsorption Increased t1/2
  • Decreased pH decreased ionization acid increase reabsorption increase t1/2
  • Decreased pH increase ionization of basic decrease reabsorption decrease t1/2
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20
Q

As far at GI metabolism goes what do men have?

A

Increase enzymatic activity and greater levels.

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21
Q

Acute alcohol effects on renal clearance

Alcohol inhibits the release of what? what is this chain reaction?

A
  • Inhibits the release of ADH vasopressin
  • Decrease ADH decrease renale tubule permeability to water, decreased passive reabsorption of water and drugs from urine to blood alcohol can decrease halflfe of drugs
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22
Q

For time dependent killers like Fluconazole, Imipenem, Meropenem, Ertapenem, Vancomycin Teicoplanin, Penicillin, Cephalosporins, Macrolides, Linzolid, CLindamycin, streptogrammins, Actreonam

What is the dosing strategy?

When is killing maximized and what is important to note about this when concentrations are greater than this?

A
  • Want to maximize the time serum concentrations exceed pathogen MIC values
  • Best killing when concentration is 2-4 x MIC, there is no increased rate or extent when going above 2-4 x MIC
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23
Q

Two ways gastric emptying rate can increase? Accelerated or Increased?

A
  • Food/Drink temp can increase gastric emptying rate (accelerated)
  • Food/drink volume ab distention increases gastric emptying rate
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24
Q

What two types of things decrease gastric emptying?

A

High energy food (fatty foods and carbs)

Hypertonic Liquids

25
26
Vancomycin dosing guidelines based on creatinine clearance and wt \>60ml/min 30-60 ml/min \<30 ml min For pts \<60kg, \>60kg, Pneumonia CNS infection When do you get trough levels? for each one
* \>60 ml/min, \<60 kg 1g IV q12h, \>60 15 mg.kg q12h, Pneumonia CNS 15mg/kg * Get trough within 48 hours or immed prior to 4th dose * 30-60 \<60kg-1g q24h, \>60 15mg/kg q24hrs same for pneumo, no trough * \<30 ml/min \<60 1 g, \>60 kg 20mg/kg max of 1500, Pneumo (15mg/kg wt\>60), 20mg/kg \<60kg * Get trough within 24 hours
27
What are the ways a drug can have increased solubility/absorption? 4 ways
1. Change in ionization state (pH increased Cs) 2. Addition of bile acids only for hydrophobic drugs like cyclosporin) 3. Enhanced volume Sink Conditions 4. Food induced tablet erosion
28
**Target Trough levels for** General infection Life threatening including MRSA Osteomyelitis CNS infection **INCLUDING** meningitis Pneumonia
* 10-15 mcg/ml * all others are 15-20 mcg/ml
29
Two causes of gastric pH changes and one key point
Increase in pH causes decreased dissolution and solubility of basic drugs, but most food are not basic, this can be caused by PPIs and antacids pH decrease can cause in solubility and dissolution of acidic drugs. cranberry juice
30
Strengths and Weaknesses of Vanco * Great activity against what? also 3 specifics * Has activity vs. what two bacteria? AGs have poor activity against this * Can use if someone has an allergy to? * What type of dosing is available? Weaknesses * Additive? * Does get throug? * Is it used often? * What type of syndrome is common? How do you stop this? * OrallY? * Bacterial killing is? * Monitor what is some cases?
* Excellent activity against gram + resistant bacteria, MRSA, MRSE, PCN-RPneumo * Also has activity against Strepto and Entero * Long T1/2 BID or QD dosing * Can use if a pt has a PCN allergy * Additive nephrotoxicity * NO CNS PEnetration * Overused-Phlebitis * Poor oral F * Slow compared to Beta lactams * Serum concentrations need to be monitored in some cases * Red Man Syndrom occurs if infused too rapidly
31
For adults what are you rounding to for the doses? What about for children LACK OF CORRELATION BETWEEN SERUM CONCENTRATIONS AND EFFICACY
* Rounding doses to nearest units of 250 * 500, 750, 1g,1.25,1.5 * For children dose can be rounded to the nearest units of 25-50 mg when possible
32
What type of diets increase and decrease urinary pH?
Milk and veggies increase pH Protein decreases pH
33
Vancomycin PK monitoring Serum concentration? What are some breakpoints?
Trough range because susceptible organisms have MIC values of \<=2 mcg/ml Susceptible if MIC is \<=2mcg/ml for staph \<=1 for strep
34
renal clearance
* Everything is greater in men * GFR Tubular sectretion and nothing on passive reabsorption.
35
What 4 types of patients might need troughs assessed or random sampling?
36
Effects of Food on drug DISTRIBUTION 2 ways and explain them
1. Competition with albumin binding site 1. High fat meals increase fatty acid levels and compete with albumin binding 2. Malnutrition Lower levels of albumin could increase the VD of weakly acidic drugs that bind to Albumin
37
Serum Concentrations arent needed if? 3 things VANCO VANCO VANCO
* If vanco is for surgical prophylaxis, * Routine dosing in adults with normal renal function * To assess toxicity if normal renal function can be assessed by standard lab tests
38
GFR changes What diet increase GFR and Renal Cl? What diet does the opposite?
High protein diet increase GFR increasing renal clearance Veggies have to opposite affect and allopurinol clearance decreases by 31% when taken with veggies
39
What enzyme is alcohol metabolized by? What does this cause when taken with alcohol?
2E1 this causes an increase in the production of a toxic metabolite of acetaminophen a iminoquinone
40
Rule regarding CrCl * Weight rules * Always use actual weight when? * Use actual weight if within what percentage of Ideal? * Use ABW if actual weight is? * SCr Rules: * If SCr is __ or greater do what? * What is the two step method? * If estimated CrCl is \> ? then what should you do?
* Always use actual weight if \< than IBW * Use actual weight id within 20% of IBW * Use AdjustedBW if actual weight is \> 20% of IBW * If SCr is 1 or great use that * Is SCr value is less than 1 use both "1'' and actual SCr value and record the range of estimated CrCl (2 separate calculations) * Compare to SCr trends when available to making dosing decisions * If SCr is increasing use the lower value which is the most conservative * If SCr is stable and not changing use the higher value * If CrCl is \>100 ml/min then you dont need to do the two step process
41
Adult dosing algorithm for pts receiving thrice weekly hemodiaylsis 1. Loading dose after 1st hemo? 2. Dose after 2nd hemo? 3. What needs to be done after 3rd? 1. \> what do what? 2. \_\_\_-\_\_\_ give what after what? 3. \<\_\_ give what after what? 4. Based on the third step what do you give? 5. Based on step 3 determine what? and then calculate what? If nothing happened what do you give? 6. give ___ or ___ based on step 5 7. Do step 3 8. Give ____ after hemo or ____ based on step 7 9. Give ___ after hemo or ___ based on step 7
1. LD of 1000 mg after 1st hemo 2. give 500 mg after 2nd 3. Draw level prior to 3rd dose 1. \>20mcg/ml hold dose 2. 10-20 give 500 mg after each dialysis 3. \<10 give 1000mg 4. Give 500 or 1000 based on step 3 5. If dose was changed or withheld in step 3 then determine pre dialysis concentration and then calculate post dialysis concentration. If nothing was held or changed give 500 mg 6. give 500 or 1000 based on step 5 7. Determine predialysis concentrtion follow step 3 8. give 500 or 1000mg based on 7 9. Give 500 or 1000 based on step 7 If the dose change in step 3 (3rd hemo session) draw a level prior to the 4th session, if the dose didnt change in step 3 give 500 mg after each diaylsis session and draw level prior to the 7th
42
First pass metaolism decrease example of what type of influence on absorption? What drug has a higher F when taken with food? LIVER Is not effected by this
* Increase in liver bood flow decreases the extraction ration of drugs wiht high extractions ratios * Propranolol * Decrease in GI metabolism Chemicals in food can decrease the expression and activity of intestinal CYp3A4 Grapefruit juice tangellos, seville oranges
43
What is Vancos MOA?
Inhibits cell wall synthesis Dala Dala terminal
44
What are the reference ranges for peaks and troughs of vanco
30-40 peak trough 5-10, 5-15 or 5-20
45
Effects of food on Oxidative metabolism DIETs * Decrease oxidative metabolism * Induce metabolic acitivty like cig smoke CYp1A2 * Accelerate Oxidative metabolism Antipyrine, theophylline propranolol * Contain indoles that increase oxidative metabolism * No impact on drug metabolism
* High carb diets * Charbroiled foods * High protein * Cruciferous Veggies (turnup for turnips) * High Fat diets
46
In women oral bioavailability is ___ in some drugs?
greater than men
47
What is the exclusion criteria for the KUMC AG program? 5 things What are the 6 pts in the exclusion criteria with altered PK?
* Neonates \<12 * CrCl \< 40 * AG dosing for synergy * Renal failure and renal diaylsis pts. * Changing Renal Function Altered PK * Burns * Amputee, Quadraplegic * CF * Hemodynamically unstable (unstable BP) * Ascites or other types of 3rd spacing * Pregnancy
48
What other coverage do AGs have? AGs have poor activity with what?
* Staph GOOD coverage not 1st line but often used as additive therapy * AGs have **poor** activity against Enterococcus and Streptococcus Ags dont penetrate the CNS NO MATTER WHAT
49
effects of opioids are increased in who? Men are more sensitive to?
Increased effects in women propofol more sensitive in men
50
What is the VD of metronidazole and water soluble FQs compared to men?
smaller VD
51
Inhibitors of intestinal transporter? Example of what?
Chemicals in food can either alter the expression of a transporter or compete with it.
52
What is the clinical breakpoint when defining VISA and GISA?
MIC between 4-8 mcg/ml
53
Once Daily AG protocol * What dose for gent and tobra? What about obese pts? * How long should the infusion period be? * When should a random level be obtained? And what does the CrCl need to be? * How do you figure out the interval? * What baseline levels do you need every 3 days? * If CrCl is \> than? when should random levels be taken? What else? * What dont you need if following the protocol?
* 7mg/kg of IBW, Actual BW, Adjusted BW * Infuse of 30-60 minutes * Obtain a random level 6-14 hours from the start of the infusion if CrCl is \< 60 * Determine the interval via the hartford nomogram * Need baseline SCr and repeat every 3 days * If CrCl is \> 60 then get levels 8-10 hours and recommended q4-5days while one protocol or if Serum Creatinine starts to trend upward * Dont need peaks a troughs like with traditional dosing.
54
What time frame should vanco troughs be taken? Levels need to be drawn at what? this is usually around?
Vanco troughs should be taken wihtin 30 minute before infusion trough needs to be taken at SS which is usually before the 4th dose (4-5 t1/2s)
55
What binds to acidic drugs? What binds to basic drugs?
* Albumin Acidic * a1 acid glycoprotein m\>W basic drugs
56
What are the most common clinical uses for Vancomycin? * Its exclusive for what type of infections? * Drug of choice for what two bacteria? Regardless of what? * Often added empirically to? * PO for what? After what else is tried first? * Prophylaxis for what if a pt is allergic to PCN?
* Gram + infections * DOC for MRSA and MRSE regardless of site * To cases of suseptible meningitis * PO for C dif after metronidazole is tried first * Surgical Prophylaxis if PCN allergy
57
For hydrophilic drugs VD is greater in women?
False grreater in men
58
How do you calculate T1/2 for vanco in renally impaired pts?
Kd=ln(conc1/conc2)/ Time between levels

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