**5. Principles of pharmacotherapy for the pediatric patients**


### **5.1 Major problems of pediatric patients related to drug use**


The drug manufacturers design drugs according to adult population. With the increasing doses on pediatric patients, the drugs used in adults generally cause trouble (Schultheis et al, 2006). Although most drugs in the market are steadily used on pediatric patients today, only one fourth of these drugs have actually been approved by the FDA (Food and Drug Administration) for their use on infants (Pala & Baktr, 2011). FDA has a website in order to give assistance for who might be willing to carry out clinical tests on pediatric patients (Schultheis et al, 2006).

#### **5.1.1 Dose forms**

Regarding new products in the market, drug manufacturers generally take little interest in the production of liquid forms that are to be used on infants and children. Among the

The Administration and Dose of Most Frequently Used Drugs in Pediatrics 303

equipment specific to children, other varying parameters on a long-term study, contribute to

Antibacterial (chemical agents which cease the reproduction of microorganisms or kill them) agents are the most frequently used group of pediatric drugs. These drugs are to be influential as bactericide or bacteriostatic corrupting the structure or the functions of the

Penicillin influences the gram-positive coccus, some gram-negative microorganisms and spirochetes. They are used in order to provide prophylaxis in streptococcus, pneumococcus, staphylococcus, salmonella, shigella infections, venereal diseases and also in rheumatic

*Penicillin G* has a variable absorption level as it is acid-labile. *Penicillin V* is acid-resistant and

400.000 U=250 mg penicillin, 25.000-50.000 U/kg/day rheumatic fever prophylaxis; 400.000

The antibacterial spectrum is limited. It cannot be administered by oral route as it is decomposed in gastric acid and is not well-absorbed by digestive tract (Rang et al, 1998;

*Side effects* are as follows: allergy, shock, anaphylaxis, serum disease, rash, gastrointestinal

After IM injection it is a slowly absorbed, water-insoluble crystal salt of penicillin G. It is used in pneumococcus, streptococcus and meningococcal infections. Newborn: 50.000 U/kg/day IM (single dose); the others 25-50.000 U/kg/day IM (single dose) (Dökmeci,

Newborn: IV 15-30 min. 6 dose/day every 4 hours established optimal treatment.

Higher doses are required in B group streptococcal meningitis (Apak, 1996).

such difficulties (Pala & Baktr, 2011).

microbial cell (Eroğlu, 2002; Oval, 2002).

**6. Drugs** 

**6.1.1 Penicillin** 

Dökmeci 2000).

2000).

**6.1 Antibacterial drugs** 

fever (Kavakl et al, 1998). **6.1.1.1 Oral preparations** 

absorbed better (Eroğlu, 2002).

**6.1.1.2 Parenteral preparations** 

system (GIS) (Eroğlu, 2002). *6.1.1.2.2 Procaine penicillin G* 

U/day (every 12 hours) (Eroğlu, 2002).

*6.1.1.2.1 Benzyl penicillin (crystallized penicillin G)* 

Newborn: <2000g: 50.000 U/kg/day (every 12 hours) In Meningitis: 100.000 U/kg/day (every 12 hours) Newborn: >2000g: 75.000 U/kg/day (every 12 hours) In Meningitis: 150.000 U/kg/day (every 12 hours)

Infant (I), child (C): 100.000-250.000 U/kg/day (every 4-6 hours) In Serious Infections: 200-400.000 U/kg/day (every 4-6 hours)

reasons, likely obligations, limited sources, and the little market share of pediatric drugs can be told. Not having been approved, most of the products are kept being used on the infants and children. Formulation of these medications may not be appropriate for pediatric patients just because they are fit for adults. Liquid forms are preferred for oral use on infants. Infants have difficulty in swallowing capsules and tablets. Besides they are too sized for them, their active ingredients are equally too much. Measuring the appropriate dose becomes, therefore, difficult. Most drugs do not dissolve in the water entirely. To make use of some drugs on the infants orally, suspensions should be formed. Carboxymethylcellulose and methylcellulose are used to achieve this. Most of the intravenous drugs used in adults are very concentrated. Therefore, their use on infants and children are quite difficult. Due to difficulties in dosing, toxic reactions are reported related to digoxin and morphine use on infants. The parenteral drugs to be used on infants, but are used in adults, are diluted in injection water or in 0.9% NaCl. The stability of these drugs should be tested for their active components and sterilities. The excipient components used in drug production are often inert matters, some of which might result in undesired effects. The benzyl alcohol used as preservative show serious toxic properties on infants; sorbitol used in high volumes as excipient may result in diarrhea. In addition, the propylene glycol used in preparations such as Phenytoin, Phenobarbital, digoxin, diazepam, vitamin D, and hydralzine, leads to hyperosmolarity on infants (Pala & Baktr, 2011).

### **5.1.2 Dosing in children**

Calculation according to body weight is a preferred way of measuring the infant dose, especially using the Clark formula (Pala & Baktr, 2011).

#### *Clark Formula:*

#### Infant dose = Infant weight (kg)/ 72 x adult dose

Many clinic experiments show that the dose calculations according to the surface area (m2) are more suitable than those using body weights for their least erroneous, thus, preferred aspect. Respiration metabolism, blood volume, extracellular liquid amount, glomerular filtration speed, and renal blood circulation are among the physiological parameters showing strong correlation with the body surface. Most of these functions have a direct affect on drug elimination (Pala & Baktr, 2011).

Since the metabolism is faster in children, infant doses (per kg. weight) can be greater than that of adults (Pala & Baktr, 2011).

Among the drugs given to infants in greater amount (per kg.) are as follow: Phenytoin, Diazepam, Imipramine, Phenobarbital, Teophylin, Chlomypramin, Carbamazepine, Enprophylin, Haloperidol, Ethosuximide, Digoxin, Chlorpromazine, Clonazepam, some anti-cancerogenic drugs (Pala & Baktr, 2011).

With the lower renal and hepatic functions, infants require longer drug intervals comparing to children and adults. For children to get appropriate doses, thorough clinical tests and drug's blood level studies are required. Due to certain ethical reasons, carrying out clinical studies over the children is difficult. In addition to the outstanding ethical reasons, too little size of the samples resulting in inefficiency in determination, insufficient experimental equipment specific to children, other varying parameters on a long-term study, contribute to such difficulties (Pala & Baktr, 2011).
