A1004 Drug Dose

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By. LUKMAN ARIFIN, dr.,AFK

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Dose is a number of ingredient in a given unit administered within a certain period. It is used for determining the number of drugs/toxic materials, chemicals, bacterial toxin / antitoxin, serum and vaccines that are applied or enter into human body or animal in treatment or experiment to give rise symptoms or not in the human body or the animal.

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THE MEASURE OF DOSE ON THE PRESCRIPTION

a. Weight Units : mcg-mg-g-kgb. Volume units : l-ml-l Small spoontful = 5 ml

Large spoonful = 15 mlCth = Teaspoonful = 5 mlC. = Tablespoonful = 15 mlGuttae (drips) = International standard of drop is one gram destilated water (I ml) = 20 drop at temperature 20OC

c. International units = (I.U)Nystatin 500.000. I.UVitamin A 20.000. I.U

d. PRECENTAGE% b/b Weight per weight% b/v weight per volume% v/v volume per volume% v/b volume per weight

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TERMINOLOGY OF DOSESMINIMAL (MINIMUM DOSE) the smallest Quantity of an agent that is

likely to produce an appreciable effect

EFFECTIVE DOSE the quantity of an agent which will produce the effect for which it is administered

OPTIMUM DOSE the quantity of an agent which will produce the effect desert without unfavorable side effects.

DOSIS CURATIVEVA the minimum amount of a therapeutic agent that will effect a cure

DOSIS TOLERATA the largest amount of a therapeutic agent that can be given with safety

TOXIC DOSE the amount of an therapeutic agent which will cause toxic symptoms.

LETHAL DOSE the amount of agent which will cause death

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USUAL DOSE :AVERAGE DOSE :DAILY DOSE :DIVIDED DOSE :SINGLE DOSE :

LEVEL OF THERAPEUTIC DOSE1. INITIAL DOSE2. ADJUSMENT DOSE3. MAINTENANCE DOSE4. MAXIMUM DOSE

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1. AGE, BODY WEIGHT2. SEX3. ROUTE OF ADMINISTRATION4. ABSORPTION AND EXCRETION5. DISEASE

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LITERATURE OF DOSAGE GUIDELINES

1.FORMAL SOURCES TEXT BOOKS + REFERENCE BOOKS : Pharmacology, pharmacyREFERENCE BOOKS published by Health Dept :

- Indonesia pharmacopea, National - FORMULARIUM- Indonesia Extra Pharmacopea

2.OTHER SOURCES :IIMS - MIMS INDONESIAMEDICAL - PHARMACEUTICAL MAGAZINES.

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No. Indication ADM Usual Dose Max. Dose

each daily each daily

1. Acetamonophenum Analgetic Oral 500mg 500-2g Antipyretic

2. Metampyronum Analgetic Oral 500mg 1.2g

3. Atropinisulfas Parasympatholytics Oral 0.25mg 1-2g 2 mg 4 mg

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CALCULATION OF MAXIMUM DOSER/ Atropinisulfat 1.5 mg

Saccharum lactis qsm.f. pulv dtd no x

4 dd.pulv.I

Single maximum dose : 2 mgDaily maximum dose : 4 mg

CALCULATION :Single M.D = 1.5/2 x 100% = 75%Daily M.D. = 4x 1.5/4 x 100% = 150%MG will surpass when more than 100%Single MD 75% ; MD will not surpassDaily MD 150% ; Daily MD will surpass

Attention that :* At the end of drug statement, brief signature or exclamation sign (!) should be

started the drug can be done* No brief signature or! the drug can not be done ask again the presciriber

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DOSE CALCULATIONR/ sol,.Charcot 200mg

AddeLuminal Na 500 mgPyramidone 1500 mgLargactil 1200 mgM.D. 2 dd C

LUMINALSingle MD 250 mgDaily MD 500 mgMaximum Dose for single use :

15 (1 C = 15 g)x 500 mg = 40 mg203.2 (the number of Liquid and drug)

The proportion = 40/250x 100% = 16%The Daily Maximum Dose = 2 x 40 mg = 80 mgThe proportion = 80/500 x 100% = 16%

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Single MD 1 gDAILY MD 3 gMaximum Dose for Single use :

15 x 500 mg = 115 mg

203.2 (the number of Liquid and drug)

The proportion = 115/1000x 100% = 11.5%The Daily Maximum Dose = 2 x 115 mg = 230 mgThe proportion = 230/3000 x 100% = 77.6%

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The active ingredients are generally similar to those for adultIn contrast, the difference is about the dose variety

Pediatric dosage can be divided into 3 age groups :1. Neonatus 0 -4 weeks2. Infant 5 - 52 weeks3. Childrent 1 - 15 years

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PHARMACOLOGICAL EFFECT OF DRUGS IN DIFFERENT CHILD AGES

The different perceptions of gastrointestinal tract to drugs occur between neonatal and infant periodsNo significant difference between healthy children and adultsThe first week of neonatus : irregular peristaltics6 - 12 months : delayed gastric emptying0 - 3 years : fluctuative gastric pHThe intramuscular administration : irregularly reducedPercutaneous administration : needs larger amount but more rapidly

DISTRIBUTIONThe percentage of total body fluid to the extracellular fluid is higher in neonatus and lesser to equal in the infant age of 12 months than in the adult.Subcutaneous tissues is the most in age 9 months, lesser in 6 years, but increased in adolescence.These affect on weak-soluble drug distribution.

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The plasma protein bounds are lesser in neonatus and reaches the adult level atage of 10-12 months.

In hyperbilirubinemic neonatus, the drugs that have high affinity to bind plasma protein, such as sulfonamide, salicilate and phenytoin, can out the bilirubin toxic to brain tissue

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Drug metabolism in infant is lower than that in adult

The drugs whose elimination depend on liver, their half-life time in plasma are longer, for example diazepam, digoxin, indometacin, acetaminophen, phenobarbitol, salicylate, chloramphenicol, etc.

The rapid ones : theophyline, anticonvulsant.

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The renal excretion function in neonatus and infant are still minimal that later will reach the adult level at ages of 6 - 12 months.Drugs whose their elimination depend on kidney function will be excreted gradually and consequently have prolonged half-life time.

SENSITIVITYThe more sensitive drugs are narcotics and strong laxantives, atropine, and sulfas.On the other hand, more resistant against Phenobarbital, chloral hydrate, and digoxin.

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THE PEDIATRIC DOSES BY AGE

Formula

YOUNG : < 8 years

n (year) x adults dose n-12

DILLING : > 8 years

n (year) x adults dose 20

FREID :

m (month) x adults dose 150

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CLARK :

W (kg)-------------- x adult dose 68

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BODY WEIGHT AND PERCENTAGEThe estimated pediatric doses against adult dose based on body weight

AGE BODY WEIGHT (Kg) PEDIATRIC/ADULT DOSERATIO (%)

PREMATURE INFANT 1.13 2.5 – 51.81 4 – 82.27 5 – 10

NEWBORN INFANTS 2.27 12.52 MONTHS 4.54 154 MONTHS 6.35 2012 MONTHS 9.98 203 YEARS 14.97 337 YEARS 22.68 5010 YEARS 29.94 6012 YEARS 35.52 7514 YEARS 45.36 8016 YEARS 54.43 90

The doses are used in the first 2-3 weeks or when appeared jaundice

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The other calculation is that the drugs dose is determined by a given mg for each mg / body weight kg / times / day body weight per each or per day

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BODY SURFACE AREA

This is the most appropriate calculation though there are some arguments because the body surface area do not related directly to physiologic and metabolic function. However, the application of the formula is impractical

Formula :[1.5 x Weight (kg)] + 10 x adults dose (in

%)

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Using NormogramBody Weight Age Surface Area Dose Percentage

3 Newborn 0.2 126 3 months 0.3 1810 1 year 0.45 2820 5.5 years 0.8 4830 9 years 1.0 6040 12 years 1.3 7850 14 years 1.5 9065 Adult 1.7 10270 Adult 1.76 103

Table of Precentile Danekams (very satisfactory)The Scale of Oediatric DosesNotes : C = Adult dose n% (based on body surface area)This scale can be used in 2 ways :1. Based on Age : read from Ato C, 2. Based on Body Weight : read from B to C (quick)

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When the percentage of the child is less / abnormal, use the average dose from thescale B to C (based on body weight) and D to C (based on height)

(12n + 13)Da = ------------------ Dd (n.g) n = BSA/m2

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Calculation based on Formula AUGSBERGER (more accurate, derived from body surface area) :2 - 12 months (m + 13) % of d.d1 - 11 Years (4n + 20) % of d.d12 - 16 years (5n + 10) of d.d

1.5 W + 10Da = ---------------- Dd (mg) : W = BW/kg

100

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DOSE CALCULATION

1. The adult dose of drug A is 5g. How much is the pediatric dose for infant at 3 years ?

YOUNG : 3 (years)

Pediatric dose : ------------------------ x 10 mg = 1 g 3 + 12

2. Determine the pediatric dose having 20kg body weight, whereas the adult dose is 10 mg in average.

CLARK : 20 kgPediatric dose ------------ x 10 mg = 2.91 mg

68

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If the adult dose of drug B is 50 mg, how much is the pediatric dose for an infant

with 0.57 m2 of body surface area ?

0.57Pediatric dose ------------------- x 50 mg = 16.5mg

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If dose of drug C is 0.5 mg/kg/BW/24 hours, how many gram is it required per week or per 24 hours for a children with 15 kg of body weight ?0.5 mg/kg/24 hrs x 15 = 7.5 mg/24 hrs or 0.0075 g/24 hrs0.0075 g/24 hrs x 7 days = 0.052 g/week

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A drug preparation containing 10 mg/m antibiotics pro injection. How much is the pediatric dose required for a child with 8 kg of body weight ? The dose is considered 1.4 mg/mg/kgBW1.4 mg/kg x 8 kg = 11.2 mg is required 10 mg : 1 ml = 11.2 : Y mlY = 1.12 mg as the pediatric dose needed

One mg antibiotics B contains 250 units, then how many units is the content in 15 mg ?25 unit/mg x 15 = 3750 units.

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Ages are 64 years or moreThe factors occur in elderly :

The drugs via oral have not much changedAbsorption is slow and reduced in the following diseases :

Congestive heart failure Malabsorption Iron enteropathy

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Albumin / albumin (?) ration is changed :At age of 23 years : 1.32At age of 79 years : 0.87

Liver weight :40 years 1930 g90 years 1000 g

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In the general liver function is good, except the hepatic microsome enzyme cythochrom P450 reduced.The hepatic Pathway of drug :

In the "Hepatic First Pass Clearance", drug will be metabolized partiallyThe drug with high Hepatic Extraction Ratio (HER) such as Propanolol-lignocaine --> minor systemic circulation, thus the different route will require different doses tooIntravenous Propanolol : 5 - 10 mgPropanolol per oral : 80 - 90 mgFirst pass effect (FPE) --> low bioavailability of drug up to 4 timesThe drugs having FPE : linoxin, chlorpromazine, beta blocker reserpine, morphine, acetosal, paracetamol, phenylbutazone

HYPERSENSITIVITYThe elderly people tend to expose to the excessive drug effect

"Tissue Sensitivity"

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After 40 years old, the glomerular and tubular filtration rate reduces 1% annually.In Some diseases, renal blood flow also reducesThe renal function of 70-year people is half than that of 25 year peopleThe renal mass generally reduced as many as 30%. The loss of entire nephrone units indicates the lowering of GFR :1. 20 - 90 years old : 123 MVL 65 Mol/ml. 1.73 mg2. 25 - 80 years old : tubular filtration reduced 40%3. 30 - 90 years old : creatinine excretion decreases from 24 to 12 mg/kg/24 hrsAs the cause of lowering renal function, some drugs show heightening in their blood levels --> prolonged t 1/2, example : benzylpenicilline, tetracylline, etc

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Based on renal condition :1. The drug metabolism factor via kidney2. Retaining factor of drugs toxic3. Safety Margin of drugs

In non-toxic active drug, eventhough glomerular rate reduces, the dose should not be altered : walfarin, tolbutam

The drugs having wide safety margin, such as ampicillin, will not appear toxic though the creatinine clearance lesser than 2 mol/min

Whereas aminoglycoside group will result in autotoxic when it increase slightly from the standardized dose.

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