Miscellaneous pharmacology

Family Medicine Residency Program
Laura Muller, PharmD (404) 650-4725
ALL patients in the ICU receive DVT prophylaxis:  Heparin 5000 units SC q12h or q8h (This is preferred treatment, recommended by  Bilateral sequential compression devices (SCDs) if heparin is contraindicated (active SELECT patients in the ICU receive GI prophylaxis for stress ulcer:
Proven risk factors:
 Mechanical ventilation Coagulopathy (platelets <50, PT >16) Burns >30% TBSA Head injury or hemorrhage Spinal injury NPO status and "being in the ICU" are NOT risk factors for stress ulcer  IV route Pepcid (famotidine) 20 mg q12h (q24h if CrCl < 50ml/min) NG route Zantac (ranitidine) 150 mg q12 (q24h if CrCl < 50ml/min) Note: Pepcid and Zantac do not cause thrombocytopenia, though you'll be told that a million times. The 1st H2 blocker, cimetidine, caused it and every other one got a bad rap. Pepcid and Zantac are over- the- counter drugs….if they caused it as often as claimed, the FDA would not allow them to be OTC. The thrombocytopenia is most likely due to sepsis in our pt population.
Alternative is proton pump inhibitor (PPI) (if pt was on at home or has GERD):  Omeprazole suspension 40mg q24h (NG route) (Grady only uses omeprazole for NG route because there is no known recipe for esomeprazole suspension)  Esomeprazole capsule 40mg q24h (po route). This is the preferred PPI due to cost. Sucralfate 1gm po/NG q6h is formulary, but more expensive than PPIs at Grady, so it's not preferred as an alternative to H2 blockers.
Esomeprazole (Nexium) 80mg IV bolus over 5-15minutes, then 8 mg/hr for 72 hours for active GI bleeding (must have signs of hematemesis, melena, BRB from NGT) with or without hemodynamic instability, then omeprazole/esomeprzaole 20mg PO/NG QD Electrolyte replacement: important to keep K >4 and Mg > 2 in the ICU, also Po4 >2  KCl (ordered in milliequivalents of K) or Kphos (ordered in millimoles of Po4) Kphos…. order in multiples of 15, 30, or 45 mmoles In normal renal function, if Po4 is 1-2, give 30 mmoles, if Po4 is 2-3, give 15 mmoles.
 In renal failure, I only give about 5-8 mmoles to start and watch.
typical order is KP04 30 mmoles IVPB over 4 hours (usually run K at 10meq/hr)  If you want iv replacement (definitely when P04 ≤ 1), can order KPo4 OR NaPo4 (same doses as above)  Can use Neutraphos for NG replacement of Po4 but remember 1 packet also has 7 meq of K in it. Typical dose is 1 packet qid  If you don't want to give ANY potassium….then your only choice is NaPo4 by the iv route. We don't have a NaPo4 po product.  Mag oxide 400mg tabs (400-800 po/ng bid)….this po product has very poor absorption, you can try it, but you'll find it’s not effective to maintain a Mg level at 2.
 IV route ( 2, 4, or 5 grams come pre-made by pharmacy).
 Replace 1gm for every 0.1 increase you need in the level, i.e. for a level of 1.2, write for 8 grams x1 over 4 hours. This is only in normal renal function, if impaired, need to  Usually infuse it as 2gm per hour, the slower it’s infused, the less the kidney will excrete when it’s presented to the kidney  Important to pay close attention to the result of the first dose when your objective is to diurese the pt. Don't just order a dose q12 and not look at it until the next day….you lose a whole day in the ICU and increase cost and length of stay.  When you give a dose, check back in an hour or two to see the result. If it was adequate, you need to check again in 4 hours to see if the result is maintained. If it is not, order the dose at an interval of when the urine output dropped off. If the initial dose was inadequate, double the dose and evaluate the result. Can continue to double the dose until about 200mg, if you don't see a response there, can add metolazone or chlorothiazide for synergy.  Order "30-60ml ng q4h or q6h, titrate to 3 loose stools/day" The rectal route dose is lactulose 300ml with 700ml H20 rectally (same frequency as 6) For community-acquired pneumonia requiring ICU admission, (per IDSA guidelines), we use Ceftriaxone (Rocephin) 1gm IV q24h + Azithromycin 500 mg IV q24h. It’s also recommended to use Levofloxacin in place of Azithromycin for atypical coverage, but we prefer to reserve levofloxacin use for empiric pseudomonal coverage, and therefore, choose Azithromycin. 7) Levofloxacin has new dosing recommendations, we usually only use it for nosocomial infections, so for this indication, dosing should be as follows: CrCl > 50ml/min 750mg q24hCrCl 20-49 ml/min 750mg Q48h CrCl 10-19 ml/min 750mg x1, then 500mg q48hHemodialysis 750mg x1, then 500mg q48h 8) Zosyn: When you’re using it for nosocomial infections (as we usually are), the correct dose is 4.5 gm q6h not q8h. Please order 4.5gm q6h for CrCl >50, 4.5 gm q8h if CrCl 30-50, 4.5 gm q12h if 10-30, and 3.375gm q12h if on hemodialysis.
Use hydrocortisone 100mg IV q8h OR 50mg IV q6h plus/minus fludrocortisone 50mcg PO (only PO) q24h OR can use dexamethasone equivalent dose is 4mg IV q8h OR 2mg IV q6h plus/minus 10) Steroids for PCP…. methylprednisolone 40mg IV BID or dexamethasone 4mg iv q8h are Steroids for asthma/COPD…usually use methylprednisolone 60-80 mg q q6h or q8h hydrocortisone 20mg = dexamethasone 0.75 mg = prednisone 5mg = methylpred 4mg 12) Remember vasopressin dosing for septic shock is different than the GI bleeding dose. We do not use it anymore for GI bleeding since octreotide has become available since vasopressin can cause coronary ischemia and decrease cardiac output. When using vasopressin for septic shock, the dose is 0.04 units/min and do not titrate it to BP. (GI bleeding dose is much higher at 0.2-0.4 units/min and can Very lipophilic……needs to be weight-based dosing, too often every patient is inappropriately ordered a 1gm load with 100mg q8h maintenance dose  When first starting a patient on dilantin (serum level is zero)  Give 15-18 mg/kg x total body weight (max 2000mg) iv loading dose, then 5 mg/kg/day maintenance divided q8h or q12h. Maintenance dose can start 8-12 hrs after the loading dose. The ONLY formulation you can give once daily is the SR capsules. Since most of our pts can't swallow, we're usually giving suspension per NG or iv route. These 2 routes are immediate-release formulations and need to be split evenly throughout the day q8h (preferably) Also, when ordering the suspension you need to write "hold tube feeds 1 hour before and after phenytoin".
 End-stage renal disease patients have altered protein binding (decreased affinity for albumin, as well as decreased albumin) and may require lower loading and maintenance doses. I give about 12 mg/kg loading dose and a maintenance dose at 3 mg/kg/day empirically to start.
 Always correct the level for a low serum albumin. Phenytoin is 90% protein- bound to albumin, the 10% free form is the "active" form. So pts with low serum albumins have a higher free fraction. Ideally, would like to order a "free dilantin" level but Grady has to send those out and it takes 7days.
 I believe a level should be obtained after a loading dose to document a therapeutic level….this needs to be drawn 8 hours after the dose or the level may come back falsely high if you don't allow for distribution time  When ordering levels after a pt has been on a maintenance dose:  The time it is drawn is important….don't order "dilantin level with AM labs" unless you know it's appropriate. It should be drawn as a "trough" level or immediately before a dose is due. Order it as "Dilantin level before next dose".
 Remember, a level won't reflect a maintenance dose unless the pt has received all the doses for about 5 days. If a level is drawn before then and it is sub-therapeutic, you can give a "partial loading dose" to bump them up to a therapeutic range, but I would leave the maintenance dose the same until the pt has received it for an Equation to get a patient therapeutic when you have a serum level: Dose (mg) = Concentration (mg/L) x Volume (L)Volume of distribution of phenytoin is 0.7 L/kg See how for a 70kg pt, V=49L so dose to get a conc of 20 is 1000mg.
Use this same equation, but when you have a level you can use "Change in Concentration" for Concentration Or say an 85 kg pt has a level of 6 and you want to get them to 15, their V = 0.7 L/kg x 85 kg = 59 L Dose = (15-6) mg/L x 59 L = 531mg round to 500mg  The maximum single dose by the oral route you should give is 400mg due to bezoir formation, as well nausea and vomiting, although in the ER you may see them give  Displays concentration-independent killing. Meaning whether you're 20x or 5x the MIC of the organism, you achieve the same killing rate. So….peaks are NOT important. Do not measure peak levels. All we care about is that the serum level
of the drug stays above 3-5x the MIC of the organism, and this is achieved by
maintaining a level above 10 ug/ml. So appropriate troughs are in the range of 10-20 ug/ml. If a trough is above 25 ug/ml, the interval should be cut in half (this cuts the level in half). In most instances we aim to keep troughs at 15 or 20 ug/ml, this includes pneumonia, endocarditis, meningitis, and osteomyelitis (for theoretically better penetration of the lung, vegetation, blood-brain barrier, or bone respectively.) Lower troughs of 10 are sufficient for bacteremias or UTIs.  To monitor the serum level, if the pt is on a schedule of q12, q24 or q48, order a trough before the 3rd dose (pt is at steady state at that point). Vanco is really relatively non-toxic….so if I think sensitivities to a positive culture will be back in a couple days, I'll wait until I know we're going to continue the drug before I check a level….it may MSSA and we'll switch to nafcillin so the level was a waste of money. If we're using it empirically with no positive cultures, go ahead and check a level cause chances are we won't be stopping it. If pt is on dialysis, we check "random levels".
 Typically give 15mg/kg total body weight (max 2000mg) as your dose, and pick an interval according to their CrCl. Most patients are fine with 1 gram, but I give smaller (50kg) pts 750mg or larger (100kg) 1500mg. Always round to the nearest 250mg.
 If CrCL >50 ml/min give q12h exception is elderly(>65 yo)….give it q24h, they're  If CrCl 30-50 ml/min give q24h If <30 ml/min, but not ESRD, give q48h ESRD pts on dialysis get it q 3-4days. It's not removed by substantially by dialysis…no need to check levels around dialysis. In dialysis patients, I will give 15 mg/kg on day 1 and day 2 to “load” them up to a level of about 30, this will last 3- 4 days before re-dosing. See below.
Same concept here: Dose = Conc x Volume Volume is 0.7 L/kg (like Dilantin) so a 1gm dose in a 70kg pt gives you a level about 20 ug/ml (like Dilantin). It will be 15 ug/ml by the next day, so you always end up re-dosing anyway, that’s why now I just give 2 consecutive doses and then check a level a few days after. (I’ve found that the level usually decreases by 3-4 points/day). When you redose, you're putting a level of about 20 ug/ml on top of whatever level you're redosing at. So, the second dose you give puts a level of 20 ug/ml "on top of " the level of 15 ug/ml to give you a level of 35 ug/ml and then this level lasts 3-4 days. Whatever you do, PLEASE don't give a dose and order a random the next day, I KNOW it will be between 15-20 and you will re-dose. The renal service does this frequently and it is a wast of resources. If they write in their note to check a random, please check with me if it's an appropriate time to  PLEASE call me or the PharmD on-call after hours (404-283-0587) if you start an aminoglycoside. Levels ideally should be ordered with the FIRST dose in the ICU to maximize efficacy and minimize toxicity. If you use the method below and order levels with the first dose as below, then you don’t need to call us, but if you don’t want to figure it out, please call us and don’t use Sanford’s dosing guide.  Display concentration-dependent killing, meaning the higher the peak:MIC ratio achieved, the more extensive and faster the killing you'll achieve. This is why peaks are VERY important for efficacy and need to be measured, and troughs are predictive of renal toxicity and also need to be measured.
 Traditionally, a peak and trough is ordered with the 3rd dose (the trough immediately before the 3rd dose and a peak 1/2 or 1 hour after the end of the infusion). However, in our pt population, their volumes of distribution vary depending on fluid status and drug clearance is not well predicted by their Scr, so I need to get levels with the FIRST dose. When you start an aminoglycoside, levels can only be done with the 1st or 3rd dose, so if you miss getting them with the 1st dose and the pt is on a q24 interval, you have to wait 3 days before you can check levels and that's too long of a time to not know if you're achieving adequate peaks and non-toxic troughs.
 Use tobramycin to empirically cover Pseudomonas Use Amikacin ………………… …Acinetobacter Empiric dosing Tobra/gent have the same desired serum conc Amikacin has different serum conc than tobra/gent For the 1st dose you can use the Dose = Conc x Volume males = (2.3 x inches over 5") + 50 kg females = (2.3 x inches over 5") + 45 kg 3) Use actual body weight UNLESS the pt is obese.
Obese if actual body weight divided by IBW is >130% 4) If pt is obese you use an "adjusted weight" which is 40% of the 5) Calculate their volume of distribution using the appropriate weight determined above….this depends on how sickthey are and how much edema they have Use 0.35 L/kg for none-little edema and no pressors Use 0.5 L/kg if on pressors with or without edema The concentrations you aim for depend on the site of infection and which When using gentamicin for "synergy" for enterococcal infections or in endocarditis, you only need peaks of 3-4 ug/ml 7) Calculate your dose based on CxV and order it x1 dose, order levels as " Send levels 1 hour and 8 hours post infusion, please document times drawn on MAR" 53 yo female with pneumonia and sepsis, empirically wish to start Zosyn and tobramycin for hospital-acquired pathogens. Pt is on Levophed for BP support. Actual weight is 100kg. Est height 5'5".
2) IBW = (2.3 x 5) + 45kg = 56 kg3) Is she considered obese? 100kg/56kg is 178% so yes. You need to adjust her weight. Use 40% of the diff. and add it onto IBWAdjusted weight is (100-56) x 0.4 + 56kg = 74 kg is dosing 4) Estimate her volume using 0.5 L/kg (cause she's on Levophed) x 74 kg 5) Using tobra, aim for a peak of 10 ug/ml for pneumonia, so Dose = 10 mg/L x 37 L = 370mg x1 with levels 1 and 8 hrs post infusion.
 Renal failure and dialysis pts get the same dosing as above….remember you don't give a smaller dose because peaks are so important….you need to fill up their volume just like normal pts….they'll just take longer to excrete the dose, so their interval is altered….they'll require it q3-5 days depending on whether they're on dialysis or not.  Dialysis removes about 40-50% of a dose. So when a pt gets dialyzed 3 times a week, just write the order for a dose after each dialysis session. This dose turns out to last the 48-72 hours between dialysis + removal from the dialysis session.  After levels are evaluated with the first dose and any adjustments are made, I typically follow surveillance levels (peak and trough now) every 3-4 days or sooner if  Bottom line….I'll follow all drug therapy, you don't have to order any levels if you don't want to…I always ensure they're ordered when they need to be. I only included all this in case you wanted to learn it.
16) Please consider an insulin drip in patients with 2 consecutive blood sugars >150. Maintaining tight glucose control (goal 80-110 mg/dl) has been shown to decrease morbidity and mortality. Protocol forms are on the units.
17) Note hydralazine IV and PO doses are not the same. IV doses are 10 IV q6h to max of 20 mg IV q6h.
Approximately 20mg IV = 75 mg PO, so when a pt is on 20mg IV q6h, they’re at the maximum of 300mg/day of PO, can switch them to 100mg PO q8h.
18) The only calcium channel blocker that can be crushed down NGT is amlodipine. Do not order nisoldipine or felodipine for pts with NGT.
Thanks very much for your attention!

Source: http://www.fpm.emory.edu/Family/pdfdocs/ICU--MICU%20Orientation.pdf

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