1

(renal)
disorder)

content
14.1
14.2

14.3

14.4

(IV admixture)

14.5 (Drug
induced nephrotoxicity)

3:

: ..
..
..
..
..
..

Pharmacy Khon Kaen University

15

14.
1

(Acute renal failure and

Chronic kidney disease)
(Kidney)

- 2 200 g 0.5 %

renal artery renal vein

- functional unit nephron 2

1. Cortical nephron 20 %

2. Juxtamedullary nephron 80 %
nephron
1. Glomerulus bowman s

capsule (filtration)

2. Proximal tubule
(reabsorbtion)
,Na+,K+,H+,CL 60 70 %
isotonic

16

Renal disorder

3. Loop of Henle medullary interstition

hypo-osmolar

4. Distal tubule hormone aldosterone (

) parahormone ( Ca salt) , ADH ( )

5. Collecting duct nephron

andosterone

Na K+ , H+ ADH
Urea ( concentration gradient)

Juxtaglomerular apparatus

renal blood flow

- renin Juxtaglomerular cell -receptor

sympathetic

inhibit pressure ()

- macula densa

1.

Endocrine function

rennin Juxtaglomerular Apparatus

Prostaglandins Kinins
Erythropoietin

2.

Metabolic function

Activated vitamin D3 active

Ca&PO4 balance

Pharmacy Khon Kaen University

17

Gluconeogenesis
3.

Exogenous compound insulin steroid

Excretory function

metabolic waste product

Electrolyte -

GFR Glomerulus
(L/hr, ml/min)

Creatinine GFR Creatinine

SCr = 0.6-1.3 mg/dL

, body mass, protein intake SCr

CrCl

CrCl = (140-

) x (IBW)
72 x SCr

(IBW)

72 x SCr

CrCl = (140- ) x
0.85

18

Renal disorder

BUN (Blood Urea Nitrogen) Creatinine BUN

12-20 mg/dL SCr 0.6-1.3 mg/dL
2
1.
2.

1. (Acute Renal Failure)

(Acute Renal Failure, ARF)

metabolism Urea Creatinine
serum creatinine (Scr) urine output (UOP)
primary criteria
Azotemia

uremia

1. Pre-renal ARF

GFR
prerenal ARF

Pharmacy Khon Kaen University

19

anaphylaxis sepsis vasoactive agents

Norepinephrine, Cyclosporine, NSAIDs ACEi

2. Intrinsic ARF (parenchymal)

Renovascular diseases arteritis, vasculitis, renal artery

occlusion, renal vein thrombosis

Acute glumerulonephritis

Acute tubular necrosis (ATN) (ischemia)

NSAIDs, AGs, radiocontrast media, anphotericin B ,
cyclosporine endogenous toxin
myoglobin rhabdomyolysis, hemoglobin

intravascular hemolysis,bilirubin severe jaundice

Acute intestinal nephritis (ATN)
penicillins, rifampicin, NSAIDs, diuretics acyclovir,

sulfonamides, methotrexate, indinavir triamterene

Renal allograft rejection

3. Post-renal ARF

prostatic hypertrophy

Uric acid sulfonamides oxalate

tubules

20

Renal disorder

Lab

Scr BUN

ARF
GFR
UOP ARF

Acute anuric urin output < 50 ml/day

Oliguria urin output 400-500 mL/day prerenal

parenchymal

non-oligric renal failure urin output > 400-500 mL/day

parenchymal

urinalysis ARF

Pharmacy Khon Kaen University

21

Sige : edema,colored or foamy urine (

),proteinuria

Symptoms : change in urinary habits

(nocturia) ,

, ,. acute glomerolonephritis
interstitial nephritis (flank pain)

22

Renal disorder

ARF

metabolic,electrolytes fluid

ARF ARF
Acute intestinal nephritis (ATN)

radiocontrast dye
oral acetylcysteine 600 mg every 12 hours for four

doses.,amphotericin B
infusion rate
NSS 5%dextrose 1/2NSS

500 1,000 ml in 30-60 min

diuretic ARF
loop
diuretic mannital

Low dose dopamine infusion

diuretic

Furosemide

20 40 mg

urine output

( tablet 40,500 30 60
mg, amp 20

serum electrolyte

mg/2ml)

80 100 mg IV

ototoxicity

4 mg/min

Pharmacy Khon Kaen University

23

fluid replacement
Mannitol ( inj

12.5 25 g IV 3-5 min

fluid status, urine

ml)

20 ml/hr

electrolyte serum

20% 250, 500

1 hr
furosemide

output, serum

osmolarity > 310 mOsm/L

Dopamine (inj

1-5 ug/kg/min IV infusion

50mg/5ml,

250mg/10ml,

urine output,

extravasation

500mg/10 ml)
Prevention
ARF ARF

tubules concentrate urine

nephrotoxin CCB
afferent aterioles

vasoconstrictive agents GFR

efferent arterioles.

Renal Replacement Therapy

dialysis

dialysis

24

Renal disorder

dialysis

(Insensible loss - water of metabolism

= 500-600 ml/day)

Extrarenal loss

0.2-0.3 kg/day

sodium bicarbonate

K
+

K
+

K
phosphate binder

Pharmacy Khon Kaen University

25

K K


2.
(Chronic Renal Failure)

(SCr CrCl )

irrreversible
3
Azotemia (BUN,SCr ) , Uremia( Azotemia + )
Stages of CKD
Stag

Description

GFR
(ml/min/1.73
2

m)

Kidney damage with normal or 90

Kidney damage with mild

60-89

Moderate decreased GFR

30-59

Severe decreased GFR

15-29

Kidney failure

< 15 or on

increased GFR

decreased GFR

dialysis

26

Renal disorder

5-10% ( End State Renal Disease
: ESRD

1. (Peritoneal dialysis)
2. (Hemodialysis)

3. ( Renal transplantation )

Pharmacotherapy

Furosemide

CRF

mg )

40-250 mg/day

ACEi(Captopril CRF

, Enalapril,

Azotemia

(tablet 40,500

SCr > 4-5

mg/L

Lisinopril)

Microalbumine

mia

Hyperkalemia

SCr > 4
ml/L

Sodium

CRF

15 g

Polystyrene

3-4

Pharmacy Khon Kaen University

Sulfonate

27

>6 mEq/L

(Kayexalate

powder 454 g)
Sodium

bicarbonate

0.5 mEq/kg/day

Hct <30-33%

IV SC 25-100

BP,

(tablet 300 mg
= 3.6 mEq)

Erythropoietin
(prefilled

u/kg 2-3

Hct, serum

syringe, vial ;

ferritin &
Hct

transferin Hct

3000, 4000,

33-36

1000, 2000,
10000 IU)

1.5-3.5 2
wk

Calcitriol(1,25(

Hypocalcemia

OH)2D3 0.25

Folic acid (tab

mEq)

5 mg)

0.25 ug/day

dialysis

1 mg/day

Folate
Al(OH) 3 ( gel

Hyperphosphat 300-600 mg tid

600 mg/5 ml)

emia CRF

Al

GFE < 25-30

with meal

ml/min
Calcium

Hyperphosphat 0.5 -1 g tid with

Carbonate

emia in ESRD

meal

28

Renal disorder

(tab 500, 600,

650 mg)
Complication
1.

130/80140/80 mmHg

125/75 mmHg ( Mean Arterial Blood Pressure MAP
92 mmHg)

2. ACEI

ACE inhibitor

Creatinine

K ACEI
+

ACEI Creatinine

30 ACEi
+

ACEI ACEI K

K ( K-exchange resin)

K ACEI

ACEi ACEI
Angiotensin II Receptor Blockade
(ARB)
ACEI

3.Dietary protein restriction

Non Hemodialysis Pt. 0.6-0.75
gm/kg/day

Hemodialysis Pt. 1.2 gm/kg/day

Pharmacy Khon Kaen University

29

Peritoneal dialysis 1.2-1.3

gm/kg/day

4.

(atherosclerosis)
,
(atherosclerosis),

5. Metabolic acidosis

(Sodium Bicarbonate)
(Shohls Solution) HCO3 23 mEq/L
6. Hyperphosphatemia / Hypocalcemia

3-

serum PO4

3-

5 mg/dL PO4

binder Ca Al

30

Renal disorder
x
[Calcium] x [Phosphate] 55 mg/dL

7.

Dyslipidemia

LDL > 100 mg/dL HDL < 40 mg/dL

Triglyceride > 180 mg/dL

Simvastatin

8. Anemia

Erythropoetin (EPO) , Uremic toxin , Iron

deficiency , Folic acid deficiency
Blood loss

EPO supplement IV or SC

Iron supplement : 200 mg/day

Vit. B, Vit.C, Folic acid

CKD GFR 30-59 Ca , Parathyroid hormone
,

ERSD = CKD stage 5 dialysis / renal replacement therapy

stage

Pharmacy Khon Kaen University

31

complications

(HD)

30-35 Kcal/Kg/day 1,700-

2,400 Kcal/day

50
30

1-1.2 g/Kg/day 60-70 g/day

(CAPD)

30 Kcal/Kg/day dialysate

1.2-1.4 g/Kg/day 70-84 g/day

HD

Fluid intake(ml/d) = 500 + (Dialysate out Dialysate in) + urine

(ml)

Na intake (NaCl) 4-6 g/day K

32

Renal disorder

(SrCl 2-6 ,
CrCl 30-10)

30-35 Kcal/Kg/day

0.6 g/Kg/day
7 g/day

:
4-6 /

Pharmacy Khon Kaen University

33

. 3-4
pharmacotherapy of acute renal failure and

chronic kiney disease

2551

14.
2

(Fluid and Electrolyte

34

Renal disorder

disorder)

(Total body water, TBW) 2

(Intracellular fluid, ICF)
(extracellular fluid, ECF)

Plasma osmolarity

Na osmolarity

Plasma osmolarity (mOsm/L) = 2 x Plasma Na (mmol/L)

uremia hyperglycemia
glucose
Plasma osmolarity (mOsm/L)

= [2 x Plasma Na (mmol/L)] + Plasma glucose (mmol/L)

+Plasma urea (mmol/L)

Plasma osmolarity (mOsm/L)

= [2 x Plasma Na (mmol/L)] + [Plasma glucose

(mg/dL)/18] + [BUN (mg/dL) /2.8)

plasma 500

mOsm/L

150
mOsm/L
1.

Pharmacy Khon Kaen University

35

= Maintenance water requirement + Deficit water + Continuing
water loss Excess water

Water requirements Hollidays & Segar

24 .

10 .

100 ./ .

10-20 .

1,000 . + [50 ./ .
10 .

10 .

1,500 . + [20 ./ .
20 .

intake output 24 .
Intake

Output

1,200

1,400 .

1,000

100 .

.
.

300

(insensible loss)

2,500
.

500 .
500 .
2,500 .

36

Renal disorder

1. (fluid overload/ water excess)

:

2. (fluid deficit/ dehydration)

hyperthyroidism 1 C
37 C 10% 10
ml/kg

:
3
. 3

oral

rehydrate solution (ORS)

- 2
1. 8 . 1 3 daily

maintenance fluid deficit

fluid

Pharmacy Khon Kaen University

37

2. 16 . 2 3
daily maintenance fluid defecid fluid
deficit fluid 4-6 . 48 .

135-145 mEq/L mmol/L

Hyponatremia (serum sodium < 135 mEq/L) Na <

120 mEq/L
hyponatremia

1 Euvolumic hypotonic hyponatremia:

ADH
syndrome of inappropriate secretion fo ADH SIADH
2 Hypervolumic hypotonic hyponatremia:

dilutional

hyponatremia

3 Hypovolumic hypotonic hyponatremia:

thiazide loop diuretics

hypotonic hyponatremia

38

Renal disorder

1. antidiuretic

hormone

Oxytocin, Vasopressin

exogenous:

Carbamazepine, chlorpropamide,

endogenous:

clofibrate, cyclophosphamide, vincristine,

bromocriptine, morphine, nicotine

2.

Chlorpropamide, cyclophosphamide,

NSAIDs

antidiuretic
hormone

3.

Diuretics

(diuting capacity)
4.

Antipsychotics, antidepressants, MAO

inhibitors, adenosisne arabinoside,
clonidine

hyponatremia
1. euvolemia hypervolemia :

600-800 ml/day furosemide

IV 0.5-1 mg/kg

Excess water = TBW (TBW (Observed serum Na/ Desired serum

Na)

TBW = 50% BW

Pharmacy Khon Kaen University

39

2. hypovolemia:
-: TBW ICF, ECF
Sodium deficit

= (Desired serum Na Observed serum Na) x TBW

= (Desired serum Na Observed serum Na) x 0.5 BW

Hypernatremia (serum sodium > 150 mEq/L) Na

160-170 mEq/L

1. hypernatremia :

- 5% dextrose solution

0.5 mEq/Lhr
50% hypotonic solution 12-24 .
50%
24-48 .

2.
: furosemide 1 mg/kg/day
IV D5W

3.

:

sodium chloride solution dextrose solution

Sodium deficit
BW

= (Desired serum Na Observed serum Na) x 0.5

40

Renal disorder

membrane polarization



-

Metabolic acidosis

Respiratory acidosis

Metabolic alkalosis
Respiratory alkalosis
Adrenergic

Beta-2 agonist

epinephrine

Beta- blocker

propranolol
Insulin

Hyperosmolality

Nutrition

Anabolism

Pharmacy Khon Kaen University

Catabolism

41

Na, K-ATPase pump

catecholamines

digitalis

toxicity

hypokalemia

Predisposing factors

Aminoglycosides

hypomagnesemia

Amphotericin B

distal

Barium

Intoxication

Beta2-agonists

Cisplatinum

hypomagnesemia

Corticosteroids

tubule permeability

Diuretics (non-K-

sparing)

Laxative/purgatives

42

Renal disorder

Levodopa

Lithium

Cellular redistribution

Nifedipine

Penicillins: carbenicillin,

Non-reabsorbable

Rifampin

Theophylline

ticarcillin

anions distal tubule

hyperkalemia, hypokalemia
Hypokalemia
- EKG finding : T waves
, ST segment

Hyperkalemia
- EKG findings: peaked T
waves, ST segment , P
wave QRS complex

- reflect

- Paralysis

- Paresthesis

-
-
-
-

- Flaccid paralysis

Pharmacy Khon Kaen University

43

-
hypokalemia

K 3 mEq/L 200
mEq/L K 3 mEq/L 1 mEq/L
200-400 mEq/L 0.27 mEq/L
100 mEq/L

serum K = 3-3.5 mEq/L

K+ 100-150 mEq/day serum K = 2-3 mEq/L
40 mEq/L NSS

10 mEq/hr serum K 2 mEq/L

60 mEq/L 40 mEq/hr

potassium chloride
potassium acetate hypophosphatemia
potassium phosphate

potassium hypokalemia
1. loop thiazide diuretics :

CHF digitalis, MI,

2. aldosterone
3.

4. Potassium-losing nephropathy

hypokalemia
potassium

44

Renal disorder

1. : K>3 mEq/L
K < 3 mEq/L
potassium chloride 50-60 mEq/day
serum K

2. : potassium

potassium sparing diuretics hypokalemia

potassium 40-80 mEq/day 100-120 mEq/day

hyperkalemia (K > 5 mmol/L)

hyperkalemia

ACE inhibitors

Hypoaldosteronism

Predisposing factors

Alpha adrenergic

agents

Arginine

Beta adrenergic

blockers

beta1-

Cyclosporine

Digitalis

Na+/K+ pump

Potassium

supplements

receptor

Pharmacy Khon Kaen University

Potassium

penicillins

Heparin

45

aldosterone
NSAIDs

hypoaldosteronism
Pentamidine

Succinylcholine

Head trauma,

46

Renal disorder

hyperkalemia

10% Calcium

membrane

10-20 ml

calcium

50-100 ml 15-60

1- hypernatr

2 .

gluconate
chloride

antagonism
neuromuscular

1-3

membrane

potential
7.5% Sodium
bicarbonate

insulin

50 g + 15-30
regular

insulin 10 U

Cation

exchange

Kayexalate

K exchan

Kayexalate

sorbital 20 ml 1 .

2 mEq, K+ 1

resin

(1 g Na+
mEq)

2 .

40 g + 70%

6 .
Kayexalate
50 g +

Pharmacy Khon Kaen University

47

200 ml
6 .
Dialysis

-Peritoneal

2 .

dialysis

15

Hemodialysis

excitation-contraction
coupling stabilize cell membrane permeability
excitability

active transport

Vitamin D parathyroid hormone

phosphate, oxalate

(>98%) serum calcium 2.2-2.6

mmol/L 8.8 10.2 mg/dL (conversion factor 0.25)
serum calcium

1. Parathyroid hormone (PTH)

calcitriol bone resorption

tubular
reabsorption

2. Vitamin D tubular
reabsorption vitamin D

cholecalciferol (Vitamin D3) hydroxyl group

25-hydroxyvitamin D calcidiol hydroxyl group

48

Renal disorder
1,25-dihydroxycholecalciferol calcitriol
major active vitamin D

3. Calcitonin (bone absorption)

4.
-

3 40%

complexed 5-15% 47%

albumin
albumin

albumin

albumin 1 g/dL 0.8 mg/dL

Correct Ca = Observed Ca + [0.8 (normal serum albumin

observed serum albumin)]
-

pH ()
inonzed calcium ionized calcium

Hypocalcemia (Total Ca < 8.8 mg/dL 2.2 mmol/L ionized

calcium < 4 mg/dL 1.0 mmol/L)

Hormone/vita

Calcitonin

bone

Vitamin D

min

absorption

Pharmacy Khon Kaen University

PTH (

49

Vitamin D)

hypocalcemia hypercalcemia
Hypocalcemia

Hypercalcemia

Chvosteks sign

Hyperactive reflexes

Trousseaus sign

(tetany)

Hypocalcemia

1.
-
carbonate,

25-100 mmol/day

chloride,

chronic hypocalcemia
( CaCO3
)

gluconate,
gluceptate
phosphate

2.5-5 mmol

acute hypocalcemia

50

Renal disorder
IV infusion 0.075-

CaCl2

0.1 mmol/kg/hour

thrombophlebitis

1.25-5 mg/day

2-4

- Ergocalciferol

50,000-200,000 IU/day

25-200 ug/day

chloride,
gluconate,

gluceptate
2. Vitamin D

(D2)

Dihydrotachysterol

0.25 1 mg/day
0.25 1 ug/day

(DHT)

- Calcifediol [25-

2-4

(OH)D]

- Calcitriol [1,25(OH)2D]
Hypercalcemia

1. Furosemide

1 mg/kg (80-120 mg) IV

2-6 .

NSS 1-2 L

2. Calcitonin

4 IU/kg SC IM

uptake

12 . (

8 IU/kg 6 hr)

2-4 .

Pharmacy Khon Kaen University

51

3. Plicamycin

25 ug/kg/day IV infuse

mithramycin

4 . hypercalcemia
150 ug/kg/week

bone

resorption
48 .
3-7
4.
Biphosphosphonat
es

-disodium

etidronate
-disodium

7.5 mg/kg/day NSS

250 ml IV infusion 2
. 3

15-90 mg NSS

bone resorption

24-48 .
Onset

pamidronate

D5W

etidronate

5. Corticosteroid

15-100 mg/day

calcitonin

prednisolone

2-4

resistance hypocalcemic

calcitoin antagonize
activation vitamin D

bone
resorption
6.

10-100 mmol/day IV acute hypercalcemia

hypophosphatemia

52

Renal disorder

calcium phosphate complexe

buffer

75%

800-1,500 mg/day

0.8-1.6 mmol/L 2.5-5 mg/dl (conversion

factor = 0.3229)

Hypophosphatemia (<0.8 mmol/L 2.5 mg/dl 1 mg/dL

)

diabetic ketoacidosis, chronic alcoholism, burn

malnutrition, renal tubular acidosis,
hypomagnesemia,

: paresthesia,
respiratory distress, hemolytic anemia, cardiomyopathy

Pharmacy Khon Kaen University

53

:
sodium
phosphate potassium phosphate IV
infusion 12 .

Hyperphosphatemia (>1.6 mmol/L 5 mg/dl)

, hyperparathyroidism, acromegaly

vitamin D

: calcium phosphate soft tissue

renal osteodystrophy

:
aluminium hydroxide peritoneal dialysis
hemodialysis

cofactor
Na+/K+ ATPase

polarization,
repolarization cardiac arrthymia

Hypomagnesemia (< 0.8 mmol/L 1.8 mg/dl)

:
hyperactive reflexes

: magnesium oxide capsule

magnesium sulfate solution
magnesium
sulfate solution empirical 1 mEq/kg

54

Renal disorder
0.5 mEq/kg 2-5

Hypermagnesemia (>1.2 mmol/L 3 mg/dl)

:
furosemide
0.45% NaCl KCl peritoneal dialysis

hemodialysis CHF renal failure

-
pH extracellular fluid 7.4 intracellular
fluid 7.1

Buffer base system H pH

buffer hemoglobin, protein, carbonic acid

phosphate

bicarbonate/carbonic acid buffer

+

H2CO3

K = [H ] [HCO3 ]

equilibrium carbon dioxide

H2CO3

H2O+ CO2

Pharmacy Khon Kaen University

55
+

catalyte carbonic anhydrase H HCO3

H2CO3 H2CO3

H2O+ CO2 CO2 pCO2 paCO2

(carbon dioxide partial pressure)
H

pH

pH = pK + log [bicarbonate] , pK carbonic acid /

bicarbonate buffer = 6.1

carbonic acid

H2CO3 CO2
pCO2

pH HCO3

pCO2

buffer plasma protein, hemoglobin buffer

phosphate, ammonium ion,

bicarbonate H 70 mmol
Acid Base Balance
+

H proteinc metabolite

( H2O+ CO2 )

- buffer 2

Quick-reacting buffer system Slower-reacting compensatory

buffer system

1. Respiratory Control HCO3 - H2CO3 buffer system

56

Renal disorder
H2O + CO2

H2CO3

H + HCO3 CO2

H pCO2 CO2 pCO2

aterial blood gas -

pH (ventilation)
- ventilation CO2

- ventilation

,pH

CO2

,pH

pulmonary ventilation peripheral chemoreceptor

carotid arteries central aorta chemoreceptor medulla

peripheral chemoreceptor arterial acidosis, hypercapnia
(pCO2 ) hypoxia (pCO2 ) central chemoreceptor
cerebrospinal fluid acidosis CO2 cerebrospinal fluid

chemoreceptor medulla

CO2

2. Renal Control buffer acid load

+

H H HCO3 H c ell proximal

+

distal tubule H active process

+

Na reabsorption ( H Na )
+

2.1 bicarbonate-carbonic acid system H lumen

-

HCO3 proximal tubule H2CO3 H2O+

CO2 CO2 cell carbonic anhydrase H2CO3
+

H HCO3 H Na lumen H
+

tubular lumen Na HCO3

+

H Na

2.2 Phosphate system distal tubule

-

proximal tubule HCO3 Phosphate

proximal tubule distal tubule Phosphate Phosphate

Pharmacy Khon Kaen University

+

57
-

H HCO3 H
non bicarbonate buffer

2.3 Ammonia system H distal tubule metabolize

+

glutamine ammonia lumen buffer H NH4

tubular cell
3. Intracellular acid-base control -
-

permeable anions HCO3 uncharged molecule

H2O, CO2 cation active transport

pCO2 pH
+

H extracellular fluid

acid-base balance
- arterial blood gas, serum electrolyte, ,
,

Laboratory Assessment
Laboratory tests
1. Arterial blood gas(ABG)
- pH

- pO2

paO2

- pCO2 paCO2

Normal range of Laboratory tests

7.36-7.44( 7.35-7.45)
90-100 mmol
34-45

2. Total CO2 content 24-30

7-14

mmHg
mEq/l mmol/l

mEq/l mmol/l

58

Renal disorder

3. Anion gab

Arterial blood gas(ABG) pH, pCO2 ( CO2

), pO2 ( O2 ) pH
-

pCO2 HCO3

pH=pK+[HCO3 ]

0.03*pCO2

Arterial blood gas(ABG) pH<

7.35 academia pH> 7.45 alkalemia
( pO2 , pCO2 gas )
-

Total CO2 [HCO3 ] 95 % Total CO2

-

HCO3 Total CO2 acidify serum HCO3 serum

CO2 pCO2

Serum Total CO2 = pCO2 + CO2 HCO3 serum solubility

constant pCO2= 0.03

-

serum HCO3 = serum Total CO2 - pCO2*0.03 serum Total

-

CO2 HCO3
Anionic gab

anion cation

Anion gab = unmeasured anion - unmeasured cation

total anion

total cation

Pharmacy Khon Kaen University

59

measured anion+ unmeasured anion =

measured cation+ unmeasured

cation

unmeasured anion - unmeasured cation

measured

cation-

measured anion

Anion gab = measured cation-measured anion

+

measured cation

measured anion

= Cl , HCO3

2-

unmeasured anion

= protein, SO4 , phosphate

2+

unmeasured cation
+

= Na ( K )

= Ca ,Mg
+

2+

Anion gab = (Na + K ) (Cl , HCO3 )

Anion gab unmeasured anion

Anion gab unmeasured anion
Anion gab

1. metabolic acidosis
Anion gab anion

salicylate, lactic acidosis, diabetic ketoacidosis

2. anion gab

bicarbonate mixed-acid acidosis 1

metabolic acidosis 1.2 0.8
mixed acid-base disorder

acid-base balance

Metabolic aciacidosis metabolic alkalosis

+

H HCO3 buffer

respiratory acidosis respiratory alkalosis

pCO2

60

Renal disorder

1. Metabolic acidosis pH

HCO3

1. H lactic acid
lactic acidosis, ketoacid ketoacidosis
endogenous acid phosphate, sulfate

2. aspirin

aspirin salicylic acid

+

3. H
-

4. HCO3

CO2

pCO2
Metabolic acidosis 2

1.1 Normal anion gap hyperchloremic metabolic acidosis

bicarbonate anion
chloride anion gap anion gap

1.2 Elevated anion gap metabolic acidosis organic acid

nonvolatile acids nonvolatile acids
bicarbonate unmeasured anions
anion gap

1. Hyperventilation

2. Periphreal vasodilation
3. Gastrointestinal symptoms
4. serum potassium acidosis

Pharmacy Khon Kaen University

61

1.

2. 3 bicarbonate,
lactic, acetate, citrate THAM (tromethamine)

sodium bicarbonate metabolic

acidosis

Dose (mEq)= 0.5l/Kg(body weight in Kg)(Desired increment in

mEq/L of icarbonate)
2. Metabolic alkalosis serum bicarbonate serum total
CO2 pH

- bicarbonate bicarbonate precursors carbonate,

citrate, acetate
+

- H fluid chloride bicarbonate

- pyloric sodium
potassium sodium
+

potassium H sodium

paradoxical aciduria metabolic alkalosis

pCO2
respiratory acidosis

-Diuretic metabolic alkalosis sodium chloride

extra cellular

aldosterone distal tubular sodium reabsorption hydrogen

potassium alkalosis hypokalemia
diuretic NaCl

62

Renal disorder
+

- chemical buffer H potassium

sodium

- 2 carbon dioxide
pCO2

tetany ionized calcium
hypokalemia

metabolic alkalosis
saline

1. saline metabolic alkalosis

, ,

citrate

2. saline metabolic alkalosis

mineralcorticosteroid
potassium
hypercalcemia

- sodium potassium NaCl,

KCl chloride ammonium chloride arginine
chloride precursor metabolized HCl+urea

- NaCl
KCl 0.1-0.2 N HCl in D5W Dose HCl
(mEq)=0.2*BW(Kg)*(103-Obsered chloride)

Pharmacy Khon Kaen University

63

- Ammonium chloride NaCl KCl

hypochloremia

Dose

NH4Cl(mEq)=0.2l/Kg*BW(Kg)*(103-observed serum Cl )
*

refractory

hypochloremia

metabolic

alkalosis

Dose

NH4Cl(mEq)=0.2l/Kg*BW(Kg)*(103-observed serum HCO3 -24 )

-arginine chloride NaCl , KCl NH4Cl

Arginine dose (g)= 0.1*BW(Kg)* (observed serum HCO 3 -24)

1/2 -1/3

hypochloremia 10 % arginine dose

(ml)=0.4*BW(Kg)*(103-Obsered chloride)

3. Respiratory acidosis
CO2

CO2
CO2, ,
neuromuscular trauma

neuromuscular spasm, cardiac contractility

, serum potassium

non carbonate system

+

respiratory acidosis 12-24 . H

bicarbonate
-

oxygen CO2

hypoxia

- acute respiratory acidosis

64

Renal disorder

- sodium bicarbonate CO2

-

CNS-mediated

hypoventilation

medroxyprogesterone acetate 20 mg 3
chronic respiratory acidosis

4. Respiratory alkalosis CO2

+

H pH

chemical buffer
+

bicarbonate H

respiratory alkalosis 6 . bicarbonate

- light
headness, confusion

- Cardiac arrhythmia tachycardia

- ,Paper bag
CO2

5. Mixed acid-base disorders

- Mixed respiratory acidosis metabolic acidosis pCO2

sodium bicarbonate
oxygen

- Mixed respiratory alkalosis metabolic alkalosis NaCl

KCl

Pharmacy Khon Kaen University

65

- Mixed respiratory alkalosis metabolic acidosis

- Mixed metabolic alkalosis respiratory acidosis

pCO2 O2

serum bicarbonate NaCl KCL

bicarbonate

arterial blood gas 2-4 . acute

phase
12 -24 .

. .
: , , , .
Advanced pharmacotherapeutics. :
..
.
2546: 48-78.

. -. : ,
, , . Advanced

pharmacotherapeutics. :
.. . 2546: 79-92

66

14.
3

Renal disorder

( IV product and
Plasma expander)

1.

Pharmacy Khon Kaen University

67

(KVO = keep vein opened) 5% Dextrose

in 1/2 N.S.S.

2. (maintenance fluid)

( insensible loss)

3.
(replacement
fluid)

4. (nutrition supplement)

68

Renal disorder

5. (Blood supplement)
(hypovolemia)

1.
2.
3.
4.

Crystalloid

Crystalloids 1 phase solution electrolyte

water solution

Pharmacy Khon Kaen University

69

-
-

- hypersensitivity
-

isotonic distribute interstitial cell

(1
250 ml)

- oncotic pressure keep

volume

-
1. NaCl solution

1.1 Isotonic NaCl solution

+

0.9 NaCl, NSS (Na ,Cl

pH 4.5-7.0)

154 mEq/L

osmolarity 308 mOsm/L

- Cl Na
-

- metabolic alkalosis

-

Cl

- NSS

70

Renal disorder

- (hypernatremia)
90-250 mEq
15 mEq
400 mEq NSS 3 5%

dextrose NSS 462 mEq (154

mEq/L x 3)

- Acidosis NSS 1 1/3

NSS

acidosis

- (hypokalemia) NSS
+

K
+

- Circulatory overload NSS

Pharmacy Khon Kaen University

71

NSS

1.2 hypotonic NaCl solution

1/2, 1/3, 1/4, 1/5 NSS

- hypotonic NaCl dextrose solution

hypokalemia

1.3 hypertonic NaCl solution

3%, 5% NaCl

- severe dilutional hyponatremia (water intoxification)

osmolarity pressure

- (severe sodium depletion)

+

Na

72

Renal disorder
NaCl

pulmonary

edema 1 . 1
..

2. Dextrose solution
isotonic

5% (D5W)

hypotonic 2.5% (D2.5W)

hypertonic 10% (D10W), 20% (D20W), 50% (D50W)

-
-
-

Dextrose hypertonicsolution

- 2.5% 5%
5% osmolarity = 290
mOsm/L

(metabolized)
osmotic pressure

Pharmacy Khon Kaen University

73

- D5W

- 20%, 50%

(anabolism)

-
metabolize

osmolarity

- Hyperinsulinism
beta cell

D5W

74

Renal disorder

- Water intoxication isotonic

hypotonic

antidiuretic (ADH)

( 0.5 g/kg/hr)

osmolarity

3. Lactated Ringers solution (LRS)

LRS lactate

bicarbonate lactate bicarbonate

calcium bicarbonate calcium carbonate

lactate

- 2

- lactate bicarbonate
lactic acidosis

Pharmacy Khon Kaen University

75

acetates Ringers solution
metabolic acidosis

4. Acetate Ringers solution (ARS)

LRS pH (ARS

pH = 7.4 , LRS pH = 6.8) osmolarity

LRS 1) pathway acetate

acetyl CoA citric acid cycle

2) acetate

lactate 3) acetate buffer

ARS

Colloids

Colloid 2 phase particle

Colloid cryatalloid colloid ,

oncotic pressure colloid

(central line) clot
Ideal properties of Colloid

Osmotic pressure plasma

O2 organ

(Ag-Ab reaction)

76

Renal disorder

Colloid 2

1. Natural Protein solution

Human plasma serum albumin (Albutein , Albuminar ,

Albumin Kit )

sterile preparation 5 25% serum albumin

5% solution isoosmotic

plasma vials 250, 500 ml 25% solution

20,50,100 ml hepatitis B virus

heat human plasma protein fraction

vial
5% solution volume expander
25% solution protein 5 plasma
protein protein replacement

Human plasma protein fraction (Plasmonate , Plasmaplex ,

Plasmatein )

sterile aqueous solution 5% human plasma

proteins NSS

solution albumin 83%

alpha, beta globulin osmolarity equivalent

plasma hepatitis B virus
0

heat 60 C 10 . vial
250, 500 ml

2. Synthetic complex sugars

Dextran

branched polysaccharide glucose

20,000 unti Dextran solution
2 form

Pharmacy Khon Kaen University

77

molecular weight 75,000 2 MW 40,000 2

plasma volume MW
hypovolemia
microcirculation
shock

ideal plasma expander antigenicity

hypovolemia

plasma plasma expander

Hetastarch

dextran protein colloid

plasma expander ( 4

)

20 ml/kg/d 1500 ml/d

dilutional effect anemia, bleeding, coagulation

monitor PTT bleeding time

Blood product

colloid
carry O2
anemia O2

colloid blood Hemoglobin ( 7 g/dl)

Hematocrit( 20%)

Ag-Ab rejection

Matching serious reaction

78

Renal disorder

1. Whole blood

O2

2.

whole blood

O2

O2

whole blood
+

Na citrate
ABO compatible
ABO antibody

3.

O2

Ab

(leukoagglutinin) febril reactions

4.

Pharmacy Khon Kaen University

O2

79

1%

Ab

Ab IgA IgE
paroxysmal nocturnal hemoglobulinuria (PNH)
5.

whole blood

stable clotting factors

hypovolemia

IX

6. ()
0

5. 4 C

7. cryoprecipitate

cryoprecipitate

stable clotting factors 6.

8.

whole blood 4

0

-30 C 6

80

Renal disorder

labile factor massive transfusion

dilutional hypocoagulability
fibrinogen
9.

lyophilisation

stable factors

10.

4
(fresh whole

blood) 1
lyophilisation

labile factors
( )

11.

whole blood

2-3

hypovolemia

Pharmacy Khon Kaen University

12.

81

megakaryocyte cytoplasmic fragments

2-3 .

5.5X10

10

(bleeding)

- (thrombocytopenia)

(thrombocytopathy)

20,000/ul bone marrow hypoplasia

chemotherapy, tumor invasion, or primary aplasia

- (

50,000/ul)
13.

fresh whole blood buffy

coat

20-40 ml 20-50

ml

granulocyte 0.5-2 X10

granulocyte

granulocyte

14.

Cryoprecipitate

82

Renal disorder

+4 C

Factor VIII: (procoagulant activity) Factor

VIII:vWF(von Willebrands Factor) Fribrinogen, Factor XIII, fibrinectin

VIII, XIII, fibrinogen, fibrinectin

fibrinogen
cryoprecipitate

Hemophilia A, von Willebrand

discase, fibrinogen, Factor XII

fibrinogen DIC

14.
4

(IV admixture)

( IV admixture
system )

aseptic technique

( Contamination )

( Compatibility )

Pharmacy Khon Kaen University

83

pyrogen

particulate matter

1. ( contamination ) clean area

laminar air flow hood

2. ( compatibility )

3. ( stability )

sterility

4. ( cost )
5. ( error )
medication error

84

Renal disorder

6. ( quality )

7. ( process )

8. ( pharmaceutical care )

9. ( safety )

3
1. ( procurement ) ( selection )

2. ( procedure )

3. ( quality control )

Aseptic Handwashing
1.
(

Pharmacy Khon Kaen University

85

2.
3. ( disinfecting agent )

4.

()

5. vertical position

6.

7.
Laminar Airflow Hood
Horizontal Laminar Airflow
Hood

Horizontal Laminar Airflow Hood

86

Renal disorder

sterile product Horizontal Laminar Airflow Hood

HEPA filter Hood Horizontal Laminar
Airflow Hood

hood 6
mix air hood

hood hood 30

Hood

(working area) hood

hood

hood

HEPA filter
mask

hood

hood

hood

hood

HEPA filter

hood

Horizontal Laminar Airflow Hood

Pharmacy Khon Kaen University

87

Horizontal Laminar Airflow Hood

hood 30

70 % alcohol
Horizontal Laminar Airflow Hoodh

hood hood


overlap

spray hood
hood
Vertical Laminar Airflow

Hood

Vertical Laminar Airflow Hood

88

Renal disorder
Sterile product Vertical Laminar Airflow Hood

HEPA filter hood sterile product

Vertical Laminar Airflow Hood

Vertical Laminar Airflow Hood

8

3
HEPA filter

spray liquid hood

HEPA filter

hood
Hood

hood

hood
hood


hood

Vertical Laminar Airflow Hood

hood 30

hood
HEPA filter

Pharmacy Khon Kaen University

89

Vertical

hood
horizontal

Airflow Hood

1.

hood

Laminar

90
2.

3.
Laminar Airflow Hood

critical point
( ,

, plunger
)

4.

( plunger
)

Renal disorder

Pharmacy Khon Kaen University

5.

6.
plunger

barrel (

plunger )
7.
plunger

8.
plunger

( plunger )
barrel

9.

plunger barrel

91

92

Renal disorder

10.

vial

Pharmacy Khon Kaen University

93

94

Renal disorder
1.
hood

2. vial (
forcep )

3.
alcohol pad
4.
(

10 ml.

5.

HEPA filter

6. plunger

7. vial

barrel 60

Pharmacy Khon Kaen University

95

(vertical)

8. vial

vial

vial

9.

plunger

10.
vial

11. barrel

plunger

96

Renal disorder

12. plunger

HEPA filter HEPA filter

13.

14. filter

15. filter

Pharmacy Khon Kaen University

16. filter
laminar air flow
17.

18.

19. plunger

97

98

Renal disorder

20.
plunger

21. (
Steri-Drape)

Pharmacy Khon Kaen University

99

Ampule

1.
hood

2.

plunger )

3. ampule alcohol pad

4. ampule ampule

ampule
ampule

10
0

Renal disorder

ampule

5. ampule HEPA filter

6.

7. ampule

ampule 20

8. plunger
ampule

9.
plunger

ampule

Pharmacy Khon Kaen University

10
1

, .
. : ; 2547. 42-54
.

(Aseptic dispensary in
Khon Kaen Hospital). : ; 2544. 81-104.

10
2

Renal disorder

14.
5

( Drug induced
nephrotoxicity)

30

1. 25 cardiac output

2.
(tubular epithelium)

glomerulus

Pharmacy Khon Kaen University

10
3

3.

(proximal tubule)

4.

(proximal tubular epithelial cell) metabolite

5.

6.

amphotericin B

7. hydrogen ion

tubular lumen

1, 2

multiple myeloma
proteinuria lupus

(volume depletion)

(uric acid)

10
4

Renal disorder

shock

Pharmacy Khon Kaen University

1.Hemodynamic

renal failure

hypovolemia,

ally-mediated

-
afferent
arteriole
efferent
arteriole
glomerulus

glomerulus

10
5

1.1 Angiotensin-converting enzyme inhibitors,

Angiotensin II receptor blockers
- Angiotensin II

efferent arteiole renal artery

stenosis
Scr > 1.6 mg/dl
Scr > 3.0 mg/dl

, nephrotic
syndrome
-ACEIs, ARBs Angiotensin II efferent
arteriole glomerulus
Scr

- ACEIs

ACEIs
K

-


hyperkalemia

10
6

Renal disorder
1.2

- NSAIDs

PGs

-PGs PGE2

PGI2 afferent arteriole

hypoxia

-NSAIDs PGs

glomerulus

ibupr

selective COX-2 inhibitors

4 3
3 3

- re

, decompens

CHF, SLE NSAIDs ACE

ARBs

PGs parace

sulindac

PGs

Pharmacy Khon Kaen University

10
7

1.3 Cyclosporine, Tacrolimus

- ARF

- afferent

arteriole

thromboxane A2, endothelin1,

PGs, nitric oxide

- Scr BP, K, Na , Mg
, tubular acidosis, oliguria
-

- CCBs

mycophenolate mofetils, sirolimus

10
8
2.Tubular
epithelial cell

damage: Acute

tubular necrosis

Renal disorder
ATN

2.1 Aminoglycosides

6-10

- GFR Scr 3-5 Clcr

glomerulus

pinocytosis

cell membrane

lysosome Phospholipids

(PLs) PLs lysosome

lysosomal enzyme

cytoplasm

cell membrane neomycin

> gentamicin, tobramycin > amik

> netilmicin, streptomycin

fluoroquinolones, cephalosporins

AMGs

once daily extended-interval dosing

- Scr

0.5 mg/dl

Pharmacy Khon Kaen University

10
9

2.2 Amphotericin B
- cumulative dose
300-400 mg

K, Na, Mg

GFR Scr, BUN

-

0.9% NaCl 1

CHF







24 .
4 .
-

11
0

Renal disorder
2.3

- ARF cisplatin

glomerulus

mithramycin, cyclophosphami

methotrexate

-
AMGs, alcohol abuse

slow continuous infusion (0.9%

NaCl) 1-4 24 . cisplatin 3

24 . ciplatin
12 . infusion mannitol

furosemide 10

ml/hr volume homeostasis

(antidote) amifostine, sodium thiosulfate

cisplatin
-
2.4 Radiocontrast agents

osmolarity

0.45 0.9%NaCl 1 ml/kg/hr

acetylcysteine antioxidant 600 mg bid

Pharmacy Khon Kaen University

3.Tubulointerstiti

ARF

Acute (allergic)

al disease:
interstitial
nephritis,
Chronic

interstitial

nephritis
papillary

hypersensitivity

/ immune
complex

reactions

necrosis
interstitial tissues

gross
hematuria,
eosinophilia
ARF nonoliguria

11
1

3.1 Beta-lactam ampicillin,

amoxicillin, pen G, piperacillin cephalosporins

- AIN
- AIN ciprofloxacin, rifampicin,
sulfonamides, furosemide, pheytoin, allopurinol,
cimetidine, omeprazole NSAIDs
3.2 NSAIDs
- hypersensitivity
6
- prednisolone 0.5-1 mg/kg
1-4

11
2
4.Glomerular
disease:

Glomerulonephri
tis
nephrotic

syndrome

Renal disorder

4.1

papillary necrosis analgesic nephropathy

- chronic interstitial nephritis

aspirin, paracetamol, NSAIDs

- medulla

medulla NSAID

paracetamol

carcinoma
4.2 Cyclosporin, Tacrolimus

(arteriolar endothelial cells)

chron

interstitial fibrosis 6-12

4.3 Lithium

- BUN, Scr R
WBC

- lithium

Pharmacy Khon Kaen University

5.

5.1 Membranous

tis

Glomerulonephri
-

glomerulonephriti
-antigen

antiboddy
immune

complex
glomerulus
capillaries
capillary

11
3

5.1.1 Gold compound

- 2-19 % 6

proteinuria
5.1.2 D-penicillamine

- proteinuria 30% 12


6-12

basement
membrane

5.2 Minimal-

- glomerulus

glomerulonephriti

nephrotic syndrome 2

change
s
5.3 Lupus
nephritis

NSAIDs
2 steroid

- hydralazine
slow acetylator
100 . hematuria, proteinuria,
positive titer antinuclear factor

6.Renal

thrombosis

microthrombi

vasculitis

hemolytic-uremic arteriole
syndrome

glomerulus

- cyclosporine, mitomycin C, ciplatin

, quinine

11
4

Renal disorder
hemolytic
anemia,
thrombocytopeni
a,

7.Obstructive
nephropathy

7.1 Intratubular

obstruction

glomerulus

tissue
degradation
products

7.1.1 Sulfonamides sulfadiazine

toxoplasmosis

sulfamethoxazole

albumin

sulfonamide

7.1.2 Acyclovir (500 / )

collecting tubule

7.1.3

allopurinol
pH

7.2 Extrarenal

- retroperitoneal fibrosis

- bladder fibrosis cyclophosphamide

obstruction

8.Electrolytes

- Scr

abnormalities

and Acid-base

methysergide, dihydroergotamine, atenolol

ifosfamide

1. K Mg : AMGs, cisplatin,
carboplatin,
2. Na : Thiazide diuretics,

Pharmacy Khon Kaen University

11
5

chlorpropamide, cyclophosphamide
3. K : ACEIs, cyclosporine, NSAIDs, Ksparing diuretics

4. Ca : Cisplatin

5. Nephrogenic diabetes insipidus : Lithium,

cyclophosphamide, ifosfamide

Lithium
(antidiuretic hormone;

ADH)
polyuria


6. : Amphotericin B, cyclosporine,
tetracycline HCl
7. : Loop and thiazide diuretics

drug-induced nephrotoxicity

Scr 3
3 Nephrotoxicity: usual definition is based on changes in Scr
If the baseline value is

The required change in Scr is

Normal 1.9 mg/dL

Increase of 0.5 or greater

2.0-4.9 mg/dL

Increase of 1.0 or greater

5.0-10 mg/dL

Increase of 1.5 or greater

drug-induced nephrotoxicity

1. nephropathy

2. nephropathy

11
6

Renal disorder

3. dehydration
renal ischemia

4. Sodium chloride drug-induced

nephrotoxicity cisplatin sodium chloride
tubular flow renin renal blood
flow
0.9%NaCl hydration
sodium chloride

5. furosemide drug-induced nephropathy

renal blood flow
chloride co-transport thick

ascending limb hypovolemia electrolyte

imbanance

Drug induced nephrotoxicity

Pharmacy Khon Kaen University

11
7

. Drug-induced nephrotoxicity : ,
, ,

. Drugs and the kidney. : .2538

. . : ,

. . :
. 2547

11
8

Renal disorder