text:
Overcrowding turns zoos into wild ghettos | delhi | Hindustan Times
Overcrowding turns zoos into wild ghettos
Roar of lions at Delhi zoo or shriek of crocodiles at Chennai park may excite visitors. But, for zoologists it shows a disturbing trend. Most animals are forced to live in ghetto-like conditions. Chetan Chauhan reports.
delhi Updated: Feb 04, 2013 02:37 IST
Roar of lions at Delhi zoo or shriek of crocodiles at Chennai park may excite visitors. But, for zoologists it shows a disturbing trend. Most animals are forced to live in ghetto-like conditions.
The stinging observation has come from the national body mandated to provide better life to animals in zoos, the Central Zoo Authority. It has found that some of the popular zoos are over-crowded.
India has about 165 zoos and nature parks of which seven such as the National Zoological Park or the Delhi Zoo are considered big and another 16 as medium. Half of the major zoos in India have the problem of over-crowding.
The National Zoological Park or Delhi Zoo has 406 wild animals in excess to its carrying capacity. Sir Peter Scott Nature Park in Jamnagar, Gujarat, has 554 extra animals. Bannerghatta Biological Park new Bangalore has around 450. And, Crocodile Park in Chennai about 2,035 crocks more than needed.
Ravi Chellam, director (research & conservation), Madras Crocodile Bank Trust, said: "Many zoos lack a scientific collection plan, which specifies the species to exhibit and the desired population size. Zoos in general allow unplanned breeding, which results in overcrowding."
"One zoo had 16 tigers in a big cage and another 12 leopard…The zoo directors were emphatic in claiming that they have turned solitary animals into a social being," said an expert, who was not willing to be quoted.
An official at Central Zoo Authority, however, explained that most of the popular zoos are within city limits without much scope for expansion and not many new zoos have opened in the last decade to relocate surplus animals.

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Renal replacement therapy in intens...
1. Drug Dosing in PCRRT Deb Pasko, Pharm.D Pharmacy Clinical Specialist, PICU University of Michigan Health System 2. CRRT Solute Removal

Lots of things removed by CRRT!

Drugs, nutrients… FD&C Blue dye #1…

Crit Care Med, Mar 2002

3.

Dialysate is used (lactated Ringers, PD solution, etc)

Good for small solute removal (<500 Da)

diffusion rate inversely proportional to MW

Efficiency of solute removal dependent on

Blood flow

Dialysate flow

Filter type

Solute molecular weight

Less good for larger solutes (MM, Vancomycin?)

Diffusive Therapies 4. Joy MS, Matzke GR, Frye RF, Palevsky PM. AJKD 1998;31:1019-27 . 5. RRT Drug Removal Mechanisms

Diffusion

Convection

Adsorption

May be important for  2 Microglobulin removal

Especially for PMMA membranes

Rarely important for drugs

6. Vancomycin overdose

16 day old full-term infant presented to OSH hypothermia, bradycardia, and hypovolemia. Progressed to develop cardiac arrest, transferred to U of M. Dry wt. 2kg.

Received 3 doses of vancomycin 100mg/kg

Initial vancomycin serum concentration was 195.5 mg/L (desired peak conc ~35mg/L)

7. Vancomycin overdose case 8. Hemodialyzer differences: Are they important in CVVHD?

Most published drug dosing guidelines assume they are all equal in terms of drug removal

most hemofilters are high-permeability with large pores

frequently high flux hemodialyzers were used for CRRT

Vancomycin CVVHD clearance differences between different hemodialyzers

Joy MS, et al. Am J Kidney Dis 1998 Jun;31(6):1019-27

9.

No dialysate, removes plasma water as it seeps through membrane

Removes small and large molecules easily

as long as they can fit through membrane

Protein binding important determinant – sieving coefficient

<15,000 Da has potential to be removed substantially

Drug removal easy to calculate

based on sieving coefficient – usually a function of PPB

ultrafiltrate concentration/plasma concentration

Convective Therapies (Hemofiltration) 10. Doses Derived Via Sieving Coefficient

Sieving Coefficient (SC) known for many drugs

SC= UF/A

Comes from CAVH or CVVH data

Assumption often made that SC can be used CVVHD when dialysate rate is low.

Saturation coefficient (Sa) more properly used in CVVHD

SC related to protein binding of drugs

Protein binding may differ in critically ill vs. normals

11. Sieving Coefficient & Protein Binding 0.10 0.22 Valproic Acid 0.90 0.80 Vancomycin 0.85 0.78 Ranitidine 0.50 0.68 Penicillin 0.80 0.84 Metronidazole 0.80 0.78 Imipenem 0.95 0.93 Amikacin Free Fraction Reported SC Drug 12. Drug Dosing recommendations based on Sieving Coefficient (SC)

Clearance total = Cl CRRT + Cl residual renal + Cl non-renal

SC equations only account for Cl CRRT

What about other clearances?

Cl residual renal usually not an issue in CRRT patients

Cl non-rena l not always available for drugs

13. Non-renal clearance rates of selected drugs in patients with normal renal function and ESRD 14. CRRT Challenges: Drug Dosing

Does CVVH removal = CVVHDF = CVVHD???

Molecular weight determines whether solute diffuses well

Vancomycin (MW 1450 Da)

Aminoglycosides (MW ~450 Da)

High dialysate flow rates don’t allow sufficient time for diffusion

Probably not an issue when flow = ~1000ml/1.73m2/hr

Does Sieving Coefficient (CVVH) = Saturation Coefficient (CVVHD)???

15. CRRT Challenges: Drug Dosing

NO PEDIATRIC DOSING !!!!!!!

Most CRRT dosing guidelines based on CVVH @ UFR of 1000 mL/hr

Trend is for higher UFR and HD flows

UM uses 2L/1.73m2/hr

Higher flow rates now achievable with new machines

solute removal (H, HD, HDF) mechanisms

16. 17. Pediatric CrCl

CL CR = K x L/S CR

Where Cl CR = creatinine clearance in ml/min/1.73m2

K = constant of proportionality age specific

Age K

LBW ≤ 1yo 0.33

Full-term ≤ 1yo 0.45

2-12 0.55

13-21 female 0.55

13-21 male 0.70

18. Calculating Total Clearance

Example:

2yo, 15kg, L = 60cm, S CR = 1.0 mg/dL, K = 0.55

CrCl = 0.55 x 60/1 = 33ml/min/1.73m2

However, if anuric renal clearance = zero

PCRRT = CVVHD of 2L/1.73m2/hr, BSA of 0.5

Qd = ~578ml/hr

(38.5ml/kg, or 9.6ml/min/0.5 BSA, or 33.2ml/min/1.73ml/min)

If this patient was not anuric and had renal fxn as above = 66ml/min/1.73m2, and we need to adjust accordingly

19. Adjusting doses based on Cl

Using the previous example for vancomycin:

>50ml/min/1.73m2 = q6-8h dosing

30-50ml/min/1.73m2 = q12h dosing

It is easy to under-dose or possibly overdose using this method, need to be careful

Is CrCl the most reliable method for children?

20. What drugs do we care about?

Drugs are “ dialyzable” if :

Small MW

Small volume of distribution

Not highly protein bound

Water soluble

21. Case

10mof, ALL s/p chemo & BMT x60days, now admitted to unit for increased O2 needs requiring vent support, GVHD gut/liver stage IV and in septic shock.

PE: T 39.1, HR 180, BP 60/30, wt. 8.5kg, Ht 60cm

I/O: 900/50 over past 24hrs (0.24cc/kg/hr)

Baseline Scr = 0.3mg/dL, now 0.6mg/dL

Meds: Dopamine, Cefepime, Gentamicin, Linezolid, Voriconazole, Pentamidine, Hydrocortisone, Protonix, TPN/lipids, Dilaudid/Ativan, Phenobarb

22. Case con’t

AM BC shows Pseudomonas aer. and VRE

Order written to start CVVH @ 2L/1.73m2/hr,

Calc. clearance: BSA = 0.38m2 (7.24ml/min, or 33ml/min/1.73m2)

What drugs do we care about?

If you can titrate we don’t necessarily care

For this patient antibiotics are going to save her life

23. So what drugs need adjustment?

Dopamine?

Cefepime?

Gentamicin?

Linezolid?

Voriconazole?

Pentamidine?

Hydrocortsione?

Protonix?

TPN?

Dilaudid?

Ativan?

24. Antibiotic Guidelines UM 25. Linezolid Clearance During CVVHDF

85 yo 90 kg anuric male in the SICU with documented abdominal VRE infection

Linezolid 600 mg IV q12

No published literature on CRRT removal

CVVHDF regimen:

dialysate flow rate 2000 mL/hr

mean ultrafiltrate production rate of 775 mL/hr

26. Linezolid Calculations

Half-life, elimination rate, and volume of distribution

Sieving coefficient (SC) was calculated:

SC= CE / Cp, Cp = (CA + CV) / 2

The clearance from CRRT (Cl CRRT) calculated as:

Cl CRRT = (QD + QF) x SC

CE = the concentration in the effluent

Cp is the linezolid concentration in the plasma

CA is the linezolid concentration in the plasma drawn from the pre-filter sampling port

CV is the linezolid concentration in the plasma drawn from the post-filter sampling port.

27. Linezolid Results

Vd = 60L (normal 40-60L)

T 1/2 = 7.5-9 hrs during CVVHDF (8hrs)

SC = 0.77– 0.81 (PPB 30%)

Cl CRRT = 36.5 mL/min with mean effluent flow rate of 46.2 mL/min

(normal Cl R 40mL/min)

No dosage change necessary

First measured linezolid CRRT report

Kraft MK, Pasko DA, DePestel DD, Ellis JJ, Peloquin CA, Mueller BA. Linezolid clearance during continuous venovenous hemodiafiltration: A case report. Pharmacotherapy. 2003 Aug;23(8):1071-5 .

28. So what drugs need adjustment?

Dopamine?

Cefepime?

Gentamicin?

Linezolid?

Voriconazole?

Pentamidine?

Hydrocortsione?

Protonix?

TPN?

Dilaudid?

Ativan?

29. Gentamicin pharmacokinetics

This patient weighing 8.5kg receives a gent dose of 21mg (2.5mg/kg)

What peak concentration (mg/L) can be expected?

Volume of distribution of gent is 0.2-0.4L/kg

0.25L/kg is normal, but in fluid overloaded patients, expect higher values. If 0.3L/kg =

2.55 Liters = Vd

21mg/2.55L = 8.2 mg/L assuming no drug removal

30. Gent kinetics con’t

30 min after the 21mg dose is done a peak is done = 4.0mg/L

What is the patients actual volume of distribution?

5.1 Liters = 0.6L/kg (actually double!!!!)

31. Gent kinetics con’t

Peak was 4.0 mg/L

12 hours later a random level was done

1.0 mg/L

What is the half-life (t 1/2 ) of gentamicin?

4.0mg/L -> 2.0mg/L -> 1.0mg/L in 12 hours

6 hour half-life

Ln 4 – ln 1 = kel = 0.115

12hrs

32. Gent kinetics FINAL

Half-life = 0.693 / 0.115 = 6 hours

33. So what drugs need adjustment?

Dopamine?

Cefepime?

Gentamicin?

Linezolid?

Voriconazole?

Pentamidine?

Hydrocortsione?

Protonix?

TPN?

Dilaudid?

Ativan?

34. Phenobarbital case

2 wof transferred to UM w/ severe CHF w/ AV valve regurgitation and seizure dx

1/20 had cleft AV valve repair w/ PDA ligation, went on VA ECMO, developed ARF

1/24 went on CVVHD in-line w/ECMO circuit

Wt 3.45kg (dry), Ht 47cm, BSA 0.21m2

Qd set at 300ml/hr (~2400ml/1.73m2/hr)

Quf at 69ml/hr (drips + no net loss)

Hemodiafilter = Mini-Plus, 0.08m2

35. Phenobarbital case

Phenobarbital dose pre dialysis initiation = 25mg q24h = 7.2mg/kg = 35.5mg/L serum concentration

CVVHD started 1/24

1/25 Pb = 14.2 mg/L

1/26 Pb = 9.6

1/28 Pb = 13.9 @ 0700

1/28 1400 sequential levels done

36. Phenobarbital case 25.9 Post-hemodiafilter 11.4 Effluent 26.2 Pre-hemodiafilter 24.7 Post-oxygenator 26.5 Pre-oxygenator Concentration (mg/L) Site 37. Drug dosing problems in high volume hemofiltration

Most drugs have > 2 compartments (pools)

like urea measurements during HD

high volume hemofiltration removes drug from peripheral compartment rapidly

how fast can drug transfer from deeper compartment?

Many drugs rapidly stripped from first pool

38. Phenobarb case final

SC = 0.44

Cl CRRT =

2.7ml/0.21m2/min or 22.3ml/1.73m2/min (40)

Vd = 3.24L/kg (0.9L/kg, normal 0.6)

New maintenance dose to maintain level of 25mg/L =

32.4mg (~10mg/kg) IV q8hrs

Original maintenance dose 25mg q24hrs

39. Mueller BA, Pasko DA. Artif Organs 2003;27:808-14. 40.

Drug is infused into compartment being filtered/dialyzed

reduced ability to distribute into tissues (k 12 )

serum concentrations during infusion higher than usual “therapeutic” serum concentration

6L/hr = 1L/10 min = entire plasma volume/hr

Qb 150 ml/min Quf/hd 33 mL/min =

22% of volume removed

“ first-pass” effect

IV drug administration: Drug removed as it is infused 41. Drug Prescribing in Renal Failure edited by George Aronoff et al

Commonly carried text by pharmacists

http://www.kdp-baptist.louisville.edu/renalbook/

New edition to come out soon

Recommendations for new drugs

IHD and CRRT recommendations

Pediatric recommendations

42. Strength of Evidence

Controlled studies in humans or large case series experience

Small Case Series or Human Uncontrolled Trials

Animal or In Vitro Data

Known Drug Characteristics

Vast majority are of this type

58 drugs are A->C 43. D. “Known drug characteristics“

These recommendations made by panel of nephrologists and pharmacists

Based on:

Protein Binding Information

Volume of Distribution

Molecular Weight

44. When in doubt, start here…

Blood flow, filter type are not very important.

Find out

In CVVHD: Dialysate flow rate (ml/hr)

Usually 2 L/1.73m2/hr (33 mL/1.73m2/min)

In CVVH: Substitution Fluid rate (ml/hr)

Usually 2L/1.73m2/hr (33 mL/1.73m2/min)

Add this to patient’s native Cr Cl (ml/1.73m2/min)

This is patient’s new Cr Cl  dose accordingly

Works in most cases…is good enough for initial estimates. Follow up with drug level monitoring.

45. PCRRT & Roller pump 46. Future research needed

ECMO/PCRRT

MARS

RAD

47. CRRT Dosing should not be confusing! Recommended

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Allen H. Dinsmore (1911-1990) - Find A Grave Memorial
2 Dec 1990 (aged 79)
Section H Lot 361 Grave C-1
147965176 · View Source
Find A Grave Memorial 147965176
Find A Grave, database and images (https://www.findagrave.com : accessed ), memorial page for Allen H. Dinsmore (6 Jul 1911–2 Dec 1990), Find A Grave Memorial no. 147965176, citing Brooklawn Memorial Park, Portland, Cumberland County, Maine, USA ; Maintained by Dale & Patti (contributor 46937639) .
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Predictive 3D modelling of the interactions of pyrethroids with the voltage-gated sodium channels of ticks and mites. - PubMed - NCBI
1 selected item: 23589444
Pest Manag Sci. 2014 Mar;70(3):369-77. doi: 10.1002/ps.3561. Epub 2013 Aug 1.
O'Reilly AO1, Williamson MS, González-Cabrera J, Turberg A, Field LM, Wallace BA, Davies TG.
Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bavaria, Germany.
The pyrethroid insecticides are a very successful group of compounds that target invertebrate voltage-gated sodium channels and are widely used in the control of insects, ticks and mites. It is well established that some pyrethroids are good insecticides whereas others are more effective as acaricides. This species specificity is advantageous for controlling particular pest(s) in the presence of another non-target invertebrate, for example controlling the Varroa mite in honeybee colonies.
We applied in silico techniques to compare the voltage-gated sodium channels of insects versus ticks and mites and their interactions with a range of pyrethroids and DDT analogues. We identified a single amino acid difference within the pyrethroid binding pocket of ticks/mites that may have significant impact on the effectiveness of pyrethroids as acaricides. Other individual amino acid differences within the binding pocket in distinct tick and mite species may provide a basis for future acaricidal selectivity.
Three-dimensional modelling of the pyrethroid/DDT receptor site has led to a new hypothesis to explain the preferential binding of acaricidal pyrethroids to the sodium channels of ticks/mites. This is important for understanding pyrethroid selectivity and the potential effects of mutations that can give rise to resistance to pyrethroids in commercially-important pest species.
DDT; acaricides; mites; pyrethroids; resistance; ticks; voltage-gated sodium channel
Mites/chemistry
Mites/metabolism
Pyrethrins/chemistry*
Ticks/drug effects*
Ticks/metabolism
BB/F009143/1/Biotechnology and Biological Sciences Research Council/United Kingdom

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