**3.3 MetabolIsm**

298 Complementary Pediatrics

that of acidic ones (*Ampicillin*) is increased. Moreover, gastro-intestinal motilities are irregular; these are slower in newborn and infants, while they are faster than adults in

Rectal use: It is an alternative route when oral use is not applied due to nausea, vomiting, or other reasons. Some analgesic – antipyretic drugs, valproic acid, Diazepam, Phenobarbital, and some corticosteroids can be administered this way. Absorption of the drugs that are applied as a suppository in the rectum is neither regular, nor exact (Pala & Baktr, 2011).

Intramuscular use (IM): it is weak and irregular for newborns and infants. This is caused by

Percutaneous use: With the stratum corneum layer too thin, skin hydration is excessive in newborns. Therefore, locally applied drugs are absorbed more than that in the adults, making undesired toxicity quite possible. Especially, topical preparations containing

Distribution of a drug may be affected by changes in body composition, such as changes in total body water and adipose tissue, which are not necessarily proportional to changes in total body weight. Plasma protein binding and tissue binding changes arising from changes in body composition with growth and development may also influence distribution (Buxton

Prior to the absorption, drug is carried to organs and tissues through blood-circulation. Composition of body liquids and the drug's level of protein-binding affect the distribution level. Plasma albumin is a primer binding-place for drugs. This binding phenomenon delimits the amount of free drug in circulation, hence, preventing drug to attain at toxic

The amount of binding to plasma protein differs from one drug to another. Therefore, density and the amount of the drug that reached to the receptor zone are not proportional to

Should the active free drugs remain at high levels in blood, the chances for toxic effects to surface become more likely. The water amount in body is a significant parameter used to determine the highest attained drug density. The total water amount of premature infants constitutes the 80-85% of their total weight, whereas this ratio is 75% for interm infants, and it is at adult-like levels (50-60%) by the end of age two. Given the amount of total weight to adjust proportional dose levels, administering drugs that are water-soluble results in insufficient drug density in blood-plasma; thus, more appropriate doses are used for infants

The ability to metabolize drugs in newborns (especially premature infants) is quite limited

Once metabolized, drugs transform into water-soluble compositions for excretion at kidneys. Most of this bio-transfer takes places in the liver. Two-to-three weeks from

dose. Neonatal albumin has lower binding capacity to some drugs (*Phenytoin*).

due to physiological immaturity (Çetinkaya &Tengir, 2006).

the irregularities in blood circulation and vasomotor functions (Pala & Baktr, 2011).

corticosteroid require significant attention (Pala & Baktr, 2011).

children (Pala & Baktr, 2011).

**3.2 Distribution** 

& Benet, 2011).

levels (Çetinkaya &Tengir, 2006).

(Çetinkaya &Tengir, 2006).

Drug metabolism usually occurs in the liver, but may also occur in the blood, gastrointestinal wall, kidney, lung, and skin. Developmental changes in metabolizing capacity can affect both absorption and elimination, depending on the degree to which intestinal and hepatic metabolic processes are involved. Although developmental changes are recognized, information on drug metabolism of specific drugs in newborns, infants, and children is limited. In general, it can be assumed that children will form the same metabolites as adults via pathways such as oxidation, reduction, hydrolysis, and conjugation, but rates of metabolite formation can be different (Buxton & Benet, 2011).

There are qualitative and quantitative differences in biotransformation between a newborn and other age groups. (Pala & Baktr, 2011).

The metabolism capacity of most drugs is rudimental in newborns; on the contrary, various metabolism pathways show significant development during the first one year (Pala & Baktr, 2011).

In some cases, the dominant metabolic route differs at the infants and children. Caffeine synthesis due to the methylation of teophylline is developed well at infants (Pala & Baktr, 2011).

Glucuronidation at infants is insufficient (Pala & Baktr, 2011).

Sulfide conjugation is developed at infants. Paracetamol absorption is similar to adults (Pala & Baktr, 2011).

The Administration and Dose of Most Frequently Used Drugs in Pediatrics 301

also an important neurotransmitter, varies largely in the newborn and adult test animals. Many neurological, psychiatric and behavioral disorders are related to the dopamine at SSS. Among the pharmacodynamic responses of the drugs which are being used against this

Major factors affecting the newborn's response to a treatment: Gestation age, chronological age, weight, development phase, liquid-electrolyte balance, disorder level at the organ systems and functions, presence of co-existing diseases, accompanying other medication (Oval, 2008).

• Confirmation of patient's age, body weight, and dose regime; making out the discrepancies in drug absorption, distribution, metabolism and excretion between the

• Preparation of a stabile and suitable dose form if no commercial package is available, • Using the most affective, safest, and fine tasted economic drugs by use of comparative

• Monitoring adverse effects and drug reactions, recognizing the undesired outcomes on

• Regular communication with the patient and patient relatives during the treatment

• Pharmacokinetics, effectiveness, and reliability data through clinical tests are either

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 parameters regarding primary activity for each age groups should be determined

• Duration of disease, age groups, and maturation period should be considered

• Tablets and capsule sizes should be at appropriate sizes for pediatric patients • Appropriate dose types should be improved for individual use (Pala & Baktr, 2011). 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

type of disorders may show significant differences during infancy and childhood.

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

• Choosing the most suitable dose type and regime,

infants and children,

(Pala & Baktr, 2011).

(Schultheis et al, 2006).

**5.1.1 Dose forms** 

tests,

children,

• Assessment of clinical / laboratory findings regarding to the drugs used,

• Applying changes in the drugs, dose, or dose intervals when necessary,

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

• Dose forms are insufficient for the pediatric population

• They have inadequate prospectus knowledge

insufficient or completely absent

• Oral suspensions should be developed
